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Home , Acylphosphatase, ADCY8, Aminopeptidase I, Anion exchanger family, Aspartyl aminopeptidase, ATBF1

Tables Index

Receptor 1337 -gated channels 1337 Receptors with intrinsic function 1339 tyrosine kinases (RTKs) 1339 Receptor /threonine kinases 1341 Receptor tyrosine 1342 Receptor-linked guanylyl 1342 G- coupled receptors (GPCRs) 1343 receptors (Jak/STAT-coupled) 1353 TNF receptor superfamily 1354 IL-1/toll-like receptors 1355 Other surface receptors 1356 Plexins 1356 LDL receptor family 1357 Nuclear receptors 1357

Membrane transport proteins 1359 Channel proteins 1359 -channels 1359 Potassium channels 1360 Voltage-dependent Ca2+-channels 1363 channels 1364 Cation channels 1365 TRP channels 1365 Cyclic nucleotide-gated cation channels 1366 Calcium release channels 1366 Water channels 1367 Solute carriers 1367 Transport (ATP-powered pumps) 1383 P-type ATPases 1383 V-type ATPases 1384 F-type ATPases 1385 ABC-transporter 1385

Adhesion molecules 1387 Cadherins 1387 Classic cadherins 1387 Protocadherins 1388 1389 Selectins 1390 Syndecans 1391 Immunoglobulin superfamily 1391 1334

Enzymes 1393 1393 (EC 1.14.99.1) 1393 Lipoxygenases (EC 1.13.11.-) 1393 Nitric oxide synthases (NOS; EC 1.14.13.39) 1393 (EC 1.14.-) 1394 hydroxylases (NOS; EC 1.14.16.-) 1396 1396 Lipid kinases 1396 PI-3-kinases (EC 2.7.1.137) 1396 PI-4-kinases (EC 2.7.1.67) 1396 PI-5-kinases (EC 2.7.1.68) 1397 PI-5P-kinases (EC 2.7.1.149) 1397 Sphingosine kinases (EC 2.7.1.91) 1397 Diacyl glycerol kinases (EC 2.7.1.107) 1397 Serine/threonine kinases 1397 AGC group (containing PKA, PKG and PKC families) 1397 CAMK group 1399 CK1 group () 1400 CMGC group (containing Cdk, MAPK, GSK3, Clk families) 1401 RGC group (Receptor Guanylyl Cyclases; Guanylyl Cyclases) 1402 STE Group (homologues of Sterile-7, -11, -20 kinases; MAP kinase cascades) 1402 TKL group (-like families) 1403 Atypical group 1404 Other groups 1405 Tyrosine kinases 1406 RTK group (Receptor Tyrosine Kinases; see also under “Receptors”) 1406 NRTK group (Non-Receptor Tyrosine Kinases; tyrosine kinases) SH2 domain proteins 1408 PTB domain proteins 1411 Transglutaminases (EC 2.3.2.13) 1413 1413 1413 Heterotrimeric G-proteins 1413 RGS proteins 1414 Small GTPases 1415 GTPase activating proteins (GAPs) 1419 Guanine nucleotide exchange factors (GEFs) 1422 Phosphodiester hydrolases 1424 (EC 3.1.4.17) 1424 1425 1426 Phosphatases 1426 Non-protein phosphatases 1426 Protein phosphatases 1428 Protein serine/threonine phosphatases (EC 3.1.3.16) 1428 Protein tyrosine phosphatases 1429 Dual specificity phosphatases (PSP) or VH1-like 1430 Cyclases 1432 Adenylyl cyclases (EC 4.6.1.1) 1432 Guanylyl cyclases (EC 4.6.1.2.) 1432 1335

Peptidases 1433 peptidases 1433 Cysteine 1434 Metallopeptidases 1437 Serine proteases 1442 Threonine peptidases 1447 Decarboxylases (EC 4.1.1.-) 1447 1448 synthases (EC 5.3.99.-) 1448

Transcription factors 1449 Superclass: basic domains 1449 zipper factots (bZIP) 1449 Helix-loop-helix factors (bHLH) 1450 Helix-loop-helix/ factors (bHLH-ZIP) 1452 NF-1 1453 RF-X 1453 Helix-span-helix factors (bHSH) 1453 Zinc-coordinating DNA-binding domains 1453 Cys4 of nuclear type 1453 Diverse Cys4 zinc fingers 1454 Cys2His2 zinc finger domain 1455 Superclass: helix-turn-helix 1456 Homeo domain 1456 Paired box 1460 Fork head/winged helix 1460 Heat shock factors 1461 Tryptophan clusters 1461 TEA domain 1462 Beta-scaffold factors with minor groove contacts 1463 RHR (Rel homology region) 1463 STAT 1463 1463 MADS-box 1463 TATA-binding-proteins 1464 HMG 1464 Heteromeric CCAAT factors 1464 Grainyhead 1464 Cold-shock domain factors 1465 Runt 1465 Other factors HMGI(Y) 1465 HMGI(Y) 1465 Pocket domain 1465

List of established drugs 1467 Receptor Proteins

Receptor proteins are specialized structures, which are Receptors without intrinsic effector function interact able to recognize mostly but not exclusively diffusible with proteins, which are effectors themselves, or which molecules with very high specifity and to bind them can regulate effectors. The largest group of these reversibly with high affinity. Binding of a ligand to the receptors are the G-protein coupled receptors (GPCRs), receptor initiates a process, which which via heterotrimeric G-proteins are able to regulate propagates the message of the ligand. There are many the activity of a variety of effector proteins (, different types of receptors, which differ especially in ion channels). Other receptors like the cytokine their mode of signal propagation. Most receptors are receptors interact with and activate cytosolic protein cell-surface receptors, which respond to ligands, which kinases (Jak-family) upon ligand binding. Another usually cannot enter the cell. Lipophilic molecules (e.g. group of receptors (TNF-receptor superfamily, IL-1/ ), in contrast, enter the cell and can act on Toll-like receptors) recruit adaptor proteins (e.g. intracellular receptors. TRADD, MyD88) after ligand-dependent activation, The group of ▶cell-surface receptors can be which then serve as a platform for the formation of an subdivided in those, which have an intrinsic effector effector complex consisting of various other proteins. function (enzymes, ion channels) and others without The majority of ▶intracellular receptors are so-called intrinsic effector function. The first group consists of “nuclear receptors,” which are transcription factors, receptor operated ion channels or receptors with which reside in the or nucleus and upon intrinsic enzymatic activity. In both cases the intrinsic ligand binding translocate to the nucleus and become effector function is regulated by ligand binding. transcriptionally active. Receptors linked to an intrinsic enzymatic activity are receptor tyrosine kinases, receptor serine/threonine kinases or receptor guanylyl cyclases. Ligand-Gated Ion Channels Ligand-operated ion channels generate electrical sig- pentamer contains different subunits of which two are nals in response to specific chemical . ligand-binding. Each subunit has four transmembrane They are specialized for mediating the fast chemical regions. Heteropentameric channels are formed by synaptic transmission. Depending on their ion selectiv- GABAA-, - nicotinic acetylcholine and, 5-HT3- ity, ligand-gated ion channels are either excitatory receptors. In contrast, the cation-selective ionotropic (glutamate-, P2X-, nicotinic, 5-HT3-receptors) or inhib- glutamate receptors have four subunits. Each subunit is itory (GABAA-, glycine-receptors). Ligand-gated ion able to bind glutamate. Finally, P2X purinoceptors channels can be grouped in three distinct families based subunits, which have two transmembrane segments, on the architecture of the channel. Most known ligand- form trimeric channels. operated ion channels consist of five subunits. This

Cation Channels

Receptor-subunit Ion selectivity Endogenous ligand Ionotropic glutamate receptors NMDA receptors (tetrameric) NR1 Na+/K+/(Ca2+) Glutamate, glycine NR2A Na+/K+/(Ca2+) Glutamate, glycine NR2B Na+/K+/(Ca2+) Glutamate, glycine NR2C Na+/K+/(Ca2+) Glutamate, glycine 1338 Receptor Proteins

Cation Channels (Continued)

Receptor-subunit Ion selectivity Endogenous ligand

NR2D Na+/K+/(Ca2+) Glutamate, glycine NR3 Na+/K+/(Ca2+) Glutamate, glycine AMPA receptors (tetrameric) GluR1 (GluR-A) Na+/K+ Glutamate GluR2 (GluR-B) Na+/K+ Glutamate GluR3 (GluR-C) Na+/K+ Glutamate GluR4 (GluR-D) Na+/K+ Glutamate Kainate receptors (tetrameric) GluR5 Na+/K+ Glutamate GluR6 Na+/K+ Glutamate GluR7 Na+/K+ Glutamate KA1 Na+/K+ Glutamate KA2 Na+/K+ Glutamate Purinoceptors (P2X) (trimeric) + + 2+ P2X1 Na /K /(Ca )ATP + + 2+ P2X2 Na /K /(Ca )ATP + + 2+ P2X3 Na /K /(Ca )ATP + + 2+ P2X4 Na /K /(Ca )ATP + + 2+ P2X5 Na /K /(Ca )ATP + + 2+ P2X6 Na /K /(Ca )ATP + + 2+ P2X7 Na /K /(Ca )ATP Nicotinic acetylcholine receptors (nAChR) (pentameric) Ligand-binding α1Na+/K+ Acetylcholine α2Na+/K+ Acetylcholine α3Na+/K+ Acetylcholine α4Na+/K+ Acetylcholine α6Na+/K+ Acetylcholine α7Na+/K+ Acetylcholine α8Na+/K+ Acetylcholine α9Na+/K+ Acetylcholine α10 Na+/K+ Acetylcholine Non-ligand-binding β1Na+/K+ β2Na+/K+ β3Na+/K+ β4Na+/K+ γ Na+/K+ δ Na+/K+ ε Na+/K+

Ionotropic serotonin receptors (5-HT3) (pentameric) + + 5-HT3A Na /K Serotonin + + 5-HT3B Na /K Serotonin

Anion Channels

Receptor-subunit Ion selectivity Endogenous ligand

GABAA receptors (pentameric) Ligand-binding α1 Cl¯ γ-Aminobutyric acid, (benzodiazepines) α2 Cl¯ γ-Aminobutyric acid, (benzodiazepines) α3 Cl¯ γ-Aminobutyric acid, (benzodiazepines) Receptor Proteins 1339

Anion Channels (Continued)

Receptor-subunit Ion selectivity Endogenous ligand

α4 Cl¯ γ-Aminobutyric acid α5 Cl¯ γ-Aminobutyric acid, (benzodiazepines) α6 Cl¯ γ-Aminobutyric acid Non-ligand-binding β1 Cl¯ β2 Cl¯ β3 Cl¯ γ1 Cl¯ γ2 Cl¯ γ3 Cl¯ δ Cl¯ ε Cl¯ θ Cl¯ ρ1 Cl¯ ρ2 Cl¯ ρ3 Cl¯ Glycine receptors (GlyR) (pentameric) Ligand-binding α1 Cl¯ Glycine α2 Cl¯ Glycine α3 Cl¯ Glycine α4 Cl¯ Glycine Non-ligand-binding β Cl¯

Receptors with Intrinsic Enzyme Function Receptor Tyrosine Kinases (RTKs) Receptor tyrosine kinases (RTKs) are a group of results in autophosphorylation of their cytoplasmic transmembrane receptors which are endowed with an domains. Tyrosine autophosphorylation of RTKs induces intrinsic tyrosine kinase activity. RTKs posses an the recruitment and activation of various signaling extracellular ligand binding domain and an intracellular molecules via interaction of SH2 (src homology 2) or conserved tyrosine kinase domain. Almost 60 PTB (phosphotyrosine binding) domains with tyrosine encoding RTKs have been identified in the mammalian autophosphorylation sites at the cytoplasmic portion. genome (Robinson et al. (2000) Oncogene 19:5548– Some RTK ligands (e.g. FGFs) require accessory 5557). With the exception of the -receptor family molecules for receptor activation. While some RTKs which form α2β2 heterodimers, all known RTKs are homodimerize, heterodimerization is a common feature monomers which dimerize upon ligand binding which among different RTK subfamilies.

Receptors Tyrosine Kinases (RTKs)

Receptor Endogenous ligand(s) ErbB receptor family ErbB1 (EGFR) Epidermal (EGF), heparin-binding (HB)-EGF, transforming growth factor α (TGFα), (AR), (BTC), (EPR) ErbB2 (Neu, Dimerization partner for ErbB1,3,4, no ligand binding HER2) ErbB3 (HER3) -1 (heregulin), neuregulin-2 ErbB4 (HER4) Neuregulin-1, -2, -3, -4; BTC, HB-EGF, EPR 1340 Receptor Proteins

Receptors Tyrosine Kinases (RTKs) (Continued)

Receptor Endogenous ligand(s)

Insulin-receptor family InsR Insulin IGF-1R Insulin-like growth factor-1 (IGF-1), IGF-2 InsRR (IRR) ? Platelet-derived growth factor-receptor family PDGFR-α/ PDGF-CC, PDGF-AA, PDGF-AB, PDGF-BB PDGFR-α PDGFR-β/ PDGF-BB, PDGF-DD PDGFR-β PDGFR-α/ PDGF-AA, PDGF-AB PDGFR-β CSF-1R Colony stimulating factor (CSF) Kit/SCFR (SCF, steel factor) Flk2/Flt3 Flt3 Ligand Vascular endothelial growth factor (VEGF) receptor family VEGF-R1 growth factor (PlGF), VEGF-A, VEGF-B (Flt-1) VEGF-R2 VEGF-A, VEGF-C, VEGF-D (Flk-1) VEGF-R3 VEGF-C, VEGF-D (Flt-4) (FGF) receptor family FGF-R-1 FGF-1, -2, -3, -4, -5, -6, -8, -10, -19, -21, -22, -23 FGF-R-2 FGF-1, -2, -3, -4, -5, -6, -7, -9, -10, -16, -19, -20, -21, -22, -23 FGF-R-3 FGF-1, -2, -4, -8, -9, -15, -16, -17, -18, -19, -20, -21, -23 FGF-R-4 FGF-1, -2, -4, -6, -8, -17, -18, -19, -21, -23 KLG/CCK receptor family CCK4/PTK7? (NGF) receptor family TrkA Nerve growth factor (NGF) TrkB derived neurotrophic factor (BDNF), 4 (NT4), neurotrophin 5, (NT5) TrkC Neurotrophin 3 (NT3) (HGF) receptor family Met HGF (scatter factor) Ron/Skt Macrophage-stimulating protein (MSP) Eph family receptors EphA1 -A1 EphA2 Ephrin-A1, -A3, -A4, -A5 EphA3 Ephrin-A1, -A2, -A3, -A5 EphA4 Ephrin-A1, -A2, -A3, -A5, -B2, -B3 EphA5 Ephrin-A1, -A2, -A3, -A4, -A5 EphA6 Ephrin-A1, -A2, -A3, -A4, -A5 EphA7 Ephrin-A1, -A2, -A3 EphA8 Ephrin-A2, -A3, -A5 EphB1 Ephrin-A3, -B1, -B2 EphB2 Ephrin-B1, -B2, -B3 EphB3 Ephrin-B1, -B2, -B3 EphB4 Ephrin-B1, -B2 EphB5 EphB6 Axl Axl Growth arrest-specific protein 6 (Gas6) Mer Gas6 Tyro3 (Sky, Rse) Gas6, protein S Receptor Proteins 1341

Receptors Tyrosine Kinases (RTKs) (Continued)

Receptor Endogenous ligand(s) Tie Tie-1 ? Tie-2 (Tek) -1, -4 (agonists); angiopoietin-2, -3 (antagonists) Ryk Ryk Wnt Dicoid domain receptor (DDR) family DDR1 DDR2 Collagen Ret Ret Glial cell derived neurotrophic factor (GDNF; + GFRα1), neuturin (+GFRα2), (+GFRα3), (+GFRα4) Ros Ros ? Leukocyte tyrosine kinase (Ltk) family Ltk ? Alk Ror Ror1 ? Ror2 ? MuSK MuSK Agrin LMR AATYK ? AATYK2 (Brek, ? Lmtk2) AATYK3 ? Others RTK106 ?

Receptor Serine/Threonine Kinases Receptor serine/threonine kinases are functioning as which then specifically phosphorylate receptor hetero-oligomeric complexes, consisting of type II and regulated Smad-proteins (R-Smads). R-Smads then type I serine/threonine kinase receptors. Ligand binding dimerize with Co-Smads in the . The R-Smad/ induces the oligomerization. Type II-receptors primari- Co-Smad complex translocates to the nucleus where it ly bind the ligand and phosphorylate type I-receptors binds to regulatory sequences in combination with (also termed “activin receptor-like kinases” (ALK)), specific transcription factors.

Type II Ligand(s) Type I receptor R-Smads Co- receptor Smads

TβR-II TGFβ-1/2/3 TβR-I (ALK-5) Smad 2/3 Smad 4 ActR-II A ALK-1 ActR-II A Activins ActR-I B (ALK-4) Smad 2/3 Smad 4 ActR-II B Activins, nodals ActR-I B (ALK-4), ALK-7 Smad 2/3 Smad 4 BMPR-II BMP-6/7 ActR-I A (ALK-2) Smad 1/5 BMPR-II BMP-2/4/7 BMPR-I A (ALK-3) Smad 1/ Smad 4 5/8 BMPR-II GDF-5, BMP-2/4/7 BMPR-I B (ALK-6) Smad 1/ Smad 4 5/8 AHMR-II MIS/AMH (anti-Müller ) ALK-2, ALK-3, BMPR-I B (ALK-6) Smad 1/5 Smad 4 1342 Receptor Proteins

Receptor Tyrosine Phosphatases The protein tyrosine phosphatases with transmembrane Although only for a few members of this family ligands domains are called “receptor-like protein tyrosine have been described they are supposed to function as phosphatases (Alonso et al. (2004) Cell 117:699–711; receptors. activity may be regulated by Tonks (2006) Nat Rev Mol Cell Biol 7:833–846). ligand dependent dimerization.

Receptor Synonyms Ligand

PTPRA PTPα PTPRB PTPβ PTPRC CD45, LCA PTPRD PTPδ PTPRE PTPε PTPRF LAR Homophilic interaction, syndecan? PTPRG PTPγ PTPRH SAP1 PTPRJ DEP1, CD148 PTPRK PTPκ PTPRM PTPμ Homophilic interaction PTPRN IA-2 (islet cell antigen 512) PTPRN2 IA-2β, phogrin, PTPπ PTPRO GLEPP1, PTP-U2 PTPRQ/P PTPS31 PTPRR PCPTP1, PTP-SL PTPRS PTPσ Agrin, collagen XVIII PTPRT PTPρ PTPRU PTPλ PTPRV OST-PTP PTPRZ PTPζ Pleiotrophin

Receptor-Linked Guanylyl Cyclases Receptor-linked guanylyl cyclases belong to the group of They share a conserved intracellular catalytic domain but receptor-linked enzymes. The Receptor-linked (mem- differ in their extracellular ligand-binding domains brane-bound) Guanylyl cyclases have one transmem- (▶Guanylyl cyclases). brane-spanning region and function as homodimers.

Receptor Endogenous ligand(s) Expression

GC-A Atrial natriuretic (ANP), B-type (BNP) Endothelium, smooth muscle, , adrenals, , , GC-B C-type natriuretic peptide (CNP) Fibroblast and other tissues GC-C Guanylin, uroguanylin, (E. coli heat-stable enterotoxin) Intestinal epithelium, regenerating GC-D ? Olfactory neuroe- pithelium GC-E ? Retina, pineal gland GC-F ? Retina GC-G ? Skeletal muscle, , intestine Receptor Proteins 1343

G-Protein Coupled Receptors (GPCRs) G-protein coupled receptors (GPCRs) represent the currently not well defined and may be in the range of largest family of transmembrane receptors. The majori- 130–150. On the basis of structural similarity to ty of GPCRs in mammalian organisms belong to the (type A), / receptors (type group of olfactory, and taste receptors B) and metabotropic glutamate receptors (type C), which respond to exogenous stimuli. There are more GPCRs can be grouped into several major classes than 1,000 olfactory receptors in mice while the number (Schioth, Fredriksson (2005) Gen Comp Endocrinol in is considerably lower. Currently almost 400 142:94–101). The cellular and physiological effects cDNAs encoding distinct mammalian GPCRs which induced by activation of GPCRs are determined by the are supposed to function as non-sensory receptors can specific coupling of the receptor to subgroups of be found in public databases (see ▶http://www.gpcr. heterotrimeric G-proteins (Gs,Gi/o,Gq/11,G12/13). A org/ and ▶http://www.expasy.org/cgi-bin/lists?7tmrlist. comprehensive list of drugs acting specifically on txt; Bjarnadottir et al. (2006) Genomics 88:263–273; GPCRs can be found under ▶http://pdsp.cwru.edu/ IUPHAR GPCR database (▶http://www.iuphar-db.org/ PDSP.asp as well as in the TIPS Nomenclature GPCR/index.html)). For about 240 of these GPCRs Supplement published by Trends in Pharmacological endogenous ligands have been identified (see list Sciences (▶http://research.bmn.com/ptbase). See also below). GPCRs for which no endogenous ligand has IUPHAR GPCR database (▶http://www.iuphar-db.org/ been found are “orphan” GPCRs. Their number is GPCR/index.html).

Class A (Rhodopsin-Like)

Receptor Endogenous ligand(s) Coupling

(Rhod)

Rhodopsin 11-cis-retinal Gt-r Blue-sensitive 11-cis-retinal Gt-c Green-sensitive opsin 11-cis-retinal Gt-c Red-sensitive opsin 11-cis-retinal Gt-c 11-cis-retinal ? Encephalopsin Orphan Peropsin Orphan RGR Orphan GPR136 (neuropsin) Orphan Amines Adrenoceptors

α1A Adrenaline = noradrenaline Gq/11 α1B Adrenaline = noradrenaline Gq/11 α1D Adrenaline = noradrenaline Gq/11 α2A Adrenaline > noradrenaline Gi/o α2B Adrenaline > noradrenaline Gi/o α2C Adrenaline > noradrenaline Gi/o β1 Noradrenaline > adrenaline Gs β2 Adrenaline > noradrenaline Gs β3 Adrenaline = noradrenaline Gs Histamine receptors

H1 Histamine Gq/11 H2 Histamine Gs H3 Histamine Gi/o H4 Histamine Gi/o receptors

D1 Dopamine Gs D2 Dopamine Gi/o D3 Dopamine Gi/o 1344 Receptor Proteins

Class A (Rhodopsin-Like) (Continued)

Receptor Endogenous ligand(s) Coupling

D4 Dopamine Gi/o D5 Dopamine Gs Acetylcholine receptors

M1 Acetylcholine Gq/11 M2 Acetylcholine Gi/o M3 Acetylcholine Gq/11 M4 Acetylcholine Gi/o M5 Acetylcholine Gq/11 Serotonin receptors

5-HT1A Serotonin Gi/o 5-HT1B Serotonin Gi/o 5-HT1D Serotonin Gi/o 5-HT1E Serotonin Gi/o 5-HT1F Serotonin Gi/o 5-HT2A Serotonin Gq/11 5-HT2B Serotonin Gq/11 5-HT2C Serotonin Gq/11 5-HT4 Serotonin Gs 5-HT5A Serotonin Gi/o,Gs 5-HT5B Serotonin ? 5-HT6 Serotonin Gs 5-HT7 Serotonin Gs receptors

MT1 Melatonin Gi/o MT2 Melatonin Gi/o GPR50 Orphan, heterodimerizes with MT1 Trace amines

TA1 Tyramine, Gs β-phenylethylamine

TA2 Tryptamine, Gs β-phenylethylamine

Nucleotide-like Adenosine receptors (P1)

A1 Adenosine Gi/o A2A Adenosine Gs A2B Adenosine Gs A3 Adenosine Gi/o Purinoceptors (P2)

P2Y1 ADP > ATP Gq/11 P2Y2 UTP/ATP Gq/11 P2Y4 UTP > ATP Gq/11 P2Y6 UDP Gq/11 P2Y11 ATP Gq/11,Gs ADP Gi/o P2Y13 ADP Gi/o P2Y14 UDP- Gi/o Peptide receptors Opioid receptors

δβ-Endorphin, met/leu- Gi/o κ A Gi/o μβ-Endorphin > dynorphin A > met/leu-enkephalin Gi/o ORL1 Nociceptin/orphanin FQ Gi/o Somatostatin receptors

SST1 Somatostatin-14 = somatostatin-28 Gi/o SST2 Somatostatin-14 = somatostatin-28 Gi/o Receptor Proteins 1345

Class A (Rhodopsin-Like) (Continued)

Receptor Endogenous ligand(s) Coupling

SST3 Somatostatin-14 = somatostatin-28 Gi/o SST4 Somatostatin-14 = somatostatin-28 Gi/o SST5 Somatostatin-28 > somatostatin-14 Gi/o Melanin-concentrating hormone receptors

MCH1 Melanin-concentrating hormone Gi/o MCH2 Melanin-concentrating hormone Gq/11 Y receptors

Y1 (NPY) > peptide YY (PYY) Gi/o Y2 NPY > PYY Gi/o Y4 (PP) > NPY = PYY Gi/o Y5 NPY > PYY > PP Gi/o Y6 NPY = PYY > PP Gi/o receptors

B1 Bradykinin Gq/11 B2 Bradykinin Gq/11 receptors

AT1 Angiotensin II > angiotensin III Gq/11, G12/13,Gi/o AT2 Angiotensin II = angiotensin III ? Vasopressin/oxytocin receptors

V1a Vasopressin > oxytocin Gq/11 V1b Vasopressin > oxytocin Gq/11 V2 Vasopressin > oxytocin Gs OT Oxytocin > vasopressin Gq/11,Gi/o receptors

ETA Endothelin-1 = endothelin-2 Gq/11, G12/13,Gs ETB Endothelin-1 = endothelin-2 = endothelin-3 Gq/11, Gi/o /hypocretin receptors

OX1 OrexinA/B Gs,Gq/11 OX2 OrexinA/B Gs,Gq/11 Neuropeptide FF receptor

NPFF1 RFamide-related peptide 1 and 3, NPFF Gi/o NPFF2 Neuropeptide FF and AF (NPFF and NPAF) Gi/o receptors

GAL1 Galanin > galanin-like peptide Gi/o GAL2 Galanin-like peptide > galanin Gq/11, Gi/o,G12/13 GAL3 Galanin Gi/o -activated receptors

PAR-1 , , factor Xa, APC Gq/11, G12/13,Gi/o PAR-2 Trypsin, factor Xa, TF/factor VIIa Gq/11 PAR-3 Thrombin, trypsin Gq/11 PAR-4 Thrombin, trypsin Gq/11, G12/13,Gi/o P2RY8 Orphan receptors

BB1 > bombesin Gq/11 BB2 -releasing peptide > bombesin Gq/11 BB3 Orphan Gq/11 Tachykinin receptors

NK1 Substance P Gq/11 NK2 Neurokinin A (substance K) Gq/11 NK3 Neurokinin B, neuromedin K Gq/11 1346 Receptor Proteins

Class A (Rhodopsin-Like) (Continued)

Receptor Endogenous ligand(s) Coupling Melanocortin receptors

MC1 α-Melanocortin (α-MSH) > β-MSH Gs MC2 Adrenocorticotrophin (ACTH) Gs MC3 γ-MSH = β-MSH Gs MC4 β-MSH > α-MSH = ACTH Gs MC5 α-MSH > β-MSH Gs receptors

NTS1 Neurotensin Gq/11 NTS2 Neurotensin Gq/11 Cholecystokinine receptors

CCK1 (CCK-8) Gq/11,Gs CCK2 CCK-8, gastrin Gq/11 Thyrotropin-releasing hormone

TRH-1 Thyrotropin-releasing hormone (TRH) Gq/11 TRH-2 Thyrotropin-releasing hormone (TRH) Gq/11 receptor

GPR154 Neuropeptide S Gs,Gq/11 Prokineticin receptors

PK-R1 Prokineticin-1, -2 Gq/11 PK-R2 Prokineticin-1, -2 Gq/11 Neuropeptide W receptors

GRP7 Neuropeptide W-23, W-30, Gi/o GPR8 Neuropeptide W-23, W-30 Gi/o Others

GnRH Gonadotropin-releasing hormone Gq/11 PrRP (GPR10) -releasing peptide Gq/11 GPR54 Metastin, kisspeptins Gq/11 UT-II (GPR14) Urotensin II Gq/11 APJ Apelin Gi/o NMU1 (FM-3) Gq/11 NMU2 (FM-4) Neuromedin U Gq/11 GHS-R Ghrelin Gq/11 GPR38 Gq/11 receptors CC chemokine receptors

CCR1 CCL3, CCL5, CCL7, CCL8, CCL13, CCL14, CCL15, CCL23 Gi/o CCR2 CCL2, CCL7, CCL8, CCL13 Gi/o CCR3 CCL5, CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL24, CCL26 Gi/o CCR4 CCL17, CCL22 Gi/o CCR5 CCL3, CCL4, CCL5, CCL8, CCL11, CCL13, CCL14 Gi/o CCR6 CCL20 Gi/o CCR7 CCL19, CCL21 Gi/o CCR8 CCL1, CCL16 Gi/o CCR9 CCL25 Gi/o CCR10 CCL27, CCL28 Gi/o CXC chemokine receptors

CXCR1 CXCL5, CXCL6, CXCL8 Gi/o CXCR2 CXCL1, CXCL2, CXCL3, CXCL5, CXCL7, CXCL8 Gi/o CXCR3 CXCL9, CXCL10, CXCL11 Gi/o CXCR4 CXCL12 Gi/o CXCR5 CXCL13 Gi/o CXCR6 CXCL16 Gi/o CXCR7 CXCL12 Gi/o Receptor Proteins 1347

Class A (Rhodopsin-Like) (Continued)

Receptor Endogenous ligand(s) Coupling

CX3C chemokine receptors CXCL12 CX3CR1 XCL1, XCL2 Gi/o XCR1 CX3L1 Gi/o MAS group () MAS Orphan MRG Orphan MRGD β-alanine MRGE Orphan MRGF Orphan MRGG Orphan MRGX1 BAM 22 MRGX2 PAMP12, cortistatin MRGX3 Orphan MRGX4 Orphan

(Glyco)protein hormone receptors

FSH Follicle-stimulating hormone (FSH) Gs LSH Luteinizing hormone (LH), choriogonadotropin Gs,Gi TSH Thyrotropin (TSH) Gs,Gq/11,Gi, G12/13 receptors

LGR7 Relaxin Gs LGR8 Relaxin, relaxin-like factor Gs LGR4 Orphan LGR5 Orphan LGR6 Orphan

Cannabinoid receptors

CB1 Anandamide, Gi/o 2-arachidonoyl glycerol

CB2 Anandamide, Gi/o 2-arachidonoyl glycerol Prostanoid receptors

FP F2α(PGF) Gq/11 TP Thromboxane A2 (TXA2)Gq/11,G12/13 DP1 Prostaglandin D2(PGD2)Gs DP2 (CRTH2) Prostaglandin D2(PGD2)Gi IP Prostacyclin (PGI2)Gs EP1 Prostaglandin E2(PGE2)Gq/11 EP2 Prostaglandin E2(PGE2)Gs EP3 Prostaglandin E2(PGE2)Gs,Gq/11,Gi EP4 Prostaglandin E2(PGE2)Gs receptors

BLT1 Leukotrinene B4 (LTB4)Gi/o,Gq/11 BLT2 Leukotrinene B4 (LTB4)Gi/o,Gq/11 CysLT1 LTC4 =LTD4 Gq/11 CysLT2 LTC4 >LTD4 Gq/11 Platelet-activating factor receptor

PAF Platelet-activating factor (PAF) Gq/11 Chemotactic substances

C3a C3a Gi/o C5a C5a Gi/o 1348 Receptor Proteins

Class A (Rhodopsin-Like) (Continued)

Receptor Endogenous ligand(s) Coupling

FPR Formyl-Met-Leu-Phe (fMLP) Gi/o FPRL1 (ALXR) LXA4 Gi/o FPRL2 Orphan Lysophospholipid receptors

S1P1 (Edg1) Spingosine-1-phosphate (S1P) Gi S1P2 (Edg5) S1P Gi,Gq/11, G12/13 S1P3 (Edg3) S1P Gi,Gq/11, G12/13 S1P4 (Edg6) S1P, apingosylphosphorylcholine (SPC) Gi S1P5 (Edg8) S1P, SPC Gi LPA1 (Edg2) (LPA) Gi,Gq/11, G12/13 LPA2 (Edg4) LPA Gi,Gq/11, G12/13 LPA3 (Edg7) LPA Gi,Gq/11 LPA4 (GPR23) LPA Gs LPA5 (GPR92) LPA Gi,Gq/11, G12/13 Proton-sensing receptors + SPC1 (OGR1) H , SPC Gq/11 + SPC2 (GPR4) H , SPC, lysophosphatidylcholine (LPC) Gs + LPC1 (G2A) H Gq/11,G12/13 + PSY1 (TDAG8) H Gs Free receptors

GPR40 Fatty acids (C12-C20)Gq/11 GPR120 Fatty acids (C14-C22)Gq/11 GPR41 Fatty acids (C2-C5)Gi GPR43 Fatty acids (C2-C5)Gi,Gq/11 GPR84 Fatty acids (C9-C14)Gi Dicarboxylate receptors

GPR99 α-Ketoglutarate (adenosine, AMP) Gq/11 GPR91 Succinate Gi,Gq/11 Bile acid receptor

GPBA Bile acid Gs Ketone body receptor

GPR109A (HM74a) β-Hydroxybutyrate Gi GPR109B (HM74) Orphan Gi GPR81 Orphan

Other receptors

GPR119 Oleolylathanolamide Gs GPR18 N-arachidonylglycine Gi GPR35 Kynurenic acid Gi QRFP QRFP, 26RFa GPR30

OXE (TG1019) 5-oxo-ETE Gi Other class A orphan receptors EBI2 Orphan GPR Orphan GPR3 Orphan GPR6 Proteins 1349

Class A (Rhodopsin-Like) (Continued)

Receptor Endogenous ligand(s) Coupling

GPR12 Orphan GPR17 Orphan GPR19 Orphan GPR20 Orphan GPR21 Orphan GPR22 Orphan GPR26 Orphan GPR27 Orphan GPR31 Orphan GPR33 Orphan GPR34 Orphan GPR37 Orphan GPR37L1 Orphan GPR39 Orphan GPR45 Orphan GPR52 Orphan GPR57 Orphan GPR58 Orphan GPR61 Orphan GPR62 Orphan GPR63 Orphan GPR72 Orphan GPR75 Orphan GPR78 Orphan GPR82 Orphan GPR85 Orphan GPR87 (GPR95) Orphan GPR101 Orphan GPR102 Orphan GPR148 Orphan GPR153 Orphan GPR161 Orphan GPR162 Orphan GPR171 (H963) Orphan GPR173 Orphan GPR174 Orphan P2RY5 Orphan P2RY10 Orphan PGR11 Orphan PNR Orphan TA3 Orphan TA4 Orphan

Class B (Calcitonin/Secretin-Like)

Receptor Endogenous ligand(s) Coupling

Secretin Secretin Gs GHRH releasing hormone Gs GIP Gastric inhibitory peptide Gs PTH/PTHrP (related peptide) Gs,Gq/11 1350 Receptor Proteins

Class B (Calcitonin/Secretin-Like) (Continued)

Receptor Endogenous ligand(s) Coupling

Calcitonin/CGRP-receptors

CT Calcitonin Gs,Gq/11 AMY1 (CT + RAMP1) Gs AMY2 (CT + RAMP2) Amylin Gs AMY3 (CT + RAMP3) Amylin Gs CGRP1 (CL + Calcitonin -related peptide (CGRP) Gs,Gq/11 RAMP1)

AM1 (CL + RAMP2) Gs AM2 (CL + RAMP3) Adrenomedullin Gs Corticitropin-releasing factor

CRF1 Corticitropin-releasing factor (CRF), Gs CRF2 CRF, urocortin, urocortin II Gs /glucagon-like peptide receptors

Glucagon Glucagon Gs GLP1 Glucagon-like peptide Gs GLP2 Glucagon-like peptide Gs VIP/PACAP receptors

VPAC1 Vasoactive intestinal peptide (VIP), pituitary adenylyl activating peptide Gs (PACAP)

VPAC2 VIP, PACAP Gs PAC1 PACAP Gs

Class C (Metabotropic Glutamate-Like)

Receptor Endogenous ligand(s) Coupling

CaSR Calcium Gq/11,Gi/o Metabotropic GABA receptors

GABAB1 (binding) γ-Aminobutyric acid GABAB2 (signaling) γ-Aminobutyric acid Gi/o Metabotropic glutamate receptors

mGluR1 Glutamate Gq/11 mGluR2 Glutamate Gi/o mGluR3 Glutamate Gi/o mGluR4 Glutamate Gi/o mGluR5 Glutamate Gq/11 mGluR6 Glutamate Gi/o mGluR7 Glutamate Gi/o mGluR8 Glutamate Gi/o Taste receptors (T1R)

T1R1 Umami (taste quality) Ggust? T1R2 Sweet (taste quality) Ggust? T1R3 Umami, sweet (taste quality) Ggust? Orphan receptors GPRC6A L-, cations PGR28, Orphan GABABL GPRC5A (RAIG1) Orphan GPRC5B (RAIG-2) Orphan GPRC5C (RAIG-2) Orphan GPRC5D Orphan GPR158 Orphan GPR179 (GPR158L1) Orphan Receptor Proteins 1351

Adhesion Receptors

Receptor Endogenous ligand(s) Coupling

EGF LAG seven-pass G-type receptor 1 Orphan EGF LAG seven-pass G-type receptor 2 Orphan EGF LAG seven-pass G-type receptor 3 Orphan Brain-specific angiogenesis-inhibitory receptor 1 Orphan Brain-specific angiogenesis-inhibitory receptor 2 Orphan Brain-specific angiogenesis-inhibitory receptor 2 Orphan CD97 CD55, chondroitin sulfate EGF-like module containing receptor 1 Orphan EGF-like module containing receptor 2 Chondroitin sulfate EGF-like module containing receptor 3 Orphan Iatrophilin-related receptor Orphan GPR97 Orphan GPR110 Orphan GPR111 Orphan GPR112 Orphan GPR113 Orphan GPR114 Orphan GPR115 Orphan GPR116 Orphan GPR123 Orphan GPR124 Orphan GPR125 Orphan GPR126 Orphan GPR127 Orphan GPR128 Orphan GPR133 Orphan GPR144 Orphan GPR64 Orphan Iatrophilin 1 Orphan Iatrophilin 2 Orphan Iatrophilin 3 Orphan GPR56 Orphan VLGR1 Orphan

Frizzled/Taste2 Receptors

Receptor Endogenous ligand(s) Coupling receptors

Frizzled 1 Wnt1, 3, 3a Gq/11? Frizzled 2 Wnt5a Frizzled 3 Wnt Frizzled 4 Wnt, Wnt5a Frizzled 5 Wnt, Wnt5a Frizzled 6 Wnt Frizzled 7 Wnt, Wnt5a Frizzled 8 Wnt, Wnt1 Frizzled 9 Wnt, Wnt2 Frizzled 10 Wnt 1352 Receptor Proteins

Frizzled/Taste2 Receptors (Continued)

Receptor Endogenous ligand(s) Coupling Taste receptors (humanT2R)

T2R1 Ggust? T2R3 Ggust? T2R4 Denatonium, 6-n-propyl-2-thiouracil Ggust? T2R5 Ggust? T2R7 Strychnine, papavarine, quinacrine Ggust? T2R8 Ggust? T2R9 Ggust? T2R10 Strychnine Ggust? T2R13 Ggust? T2R14 Aristolochic acid, naphthoic acid, picrotin Ggust? T2R16 Salicin, helicin, arbutin, amygdalin, esculin Ggust? T2R38 6-n-Propyl-2-thiouracil Ggust? T2R39 Ggust? T2R40 Ggust? T2R41 Ggust? T2R42 Ggust? T2R43 Aristolochic acid, saccharin Ggust? T2R44 Aristolochic acid, saccharin, acesulfame K Ggust? T2R45 Ggust? T2R46 Ggust? T2R47 Denatonium, 6-nitrosaccharin Ggust? T2R48 Ggust? T2R49 Ggust? T2R50 Ggust? T2R60 Ggust?

V1 Pheromone Receptors

Receptor Endogenous ligand(s) Coupling

VN1R1 Orphan ? VN1R2 Orphan ? VN1R3 Orphan ? VN1R4 Orphan ? VN1R5 Orphan ?

Other Orphan Receptors

Receptor Endogenous ligand(s) Coupling Orphans CD234 (Dfy) GPR88 GPR135 GPR137 PGR3 PGR13 PGR2 PGR8 PGR5 GPR160 GPR151 (PGR7) Receptor Proteins 1353

Other Orphan Receptors (Continued)

Receptor Endogenous ligand(s) Coupling

PGR10 (IEDA) GPR143 (OA1) GPR172A GPR172B GPR137B GPR137C TM7SF3 GPR175

Cytokine Receptors (Jak/STAT-Coupled) The group of cytokine receptors directly coupled to the results in the activation of cytosolic tyrosine protein Jak/STAT pathway is subdivided in class I-cytokine kinases of the Jak-family (Jak1, Jak2, Tyk2) and receptors (also known as “hematopoietin receptors”) subsequent of the receptor as well as and class II-cytokine receptors (also known as the of transcription factors (STAT1-6). The class II cytokine “ receptor family”). The class I receptors fall receptor subfamily consists of at least two subunits, into four subgroups which are functioning as homo- which are unassociated in the absence of ligand. Ligand dimers or heterooligomers. The heterooligomeric group results in dimerization or oligomerization, and via the consists of the ligand binding receptor, which hetero- activation of a preassociated tyrosine kinase of the Jak- oligomerizes with a second subunit, which is required family to the activation of the Jak/STAT-pathway for signaling (gp130, βc-subunit/gp140, γc-subunit). (▶;▶; ▶Jak/STAT pathway; ▶He- Binding of the ligand results in homodimerization or matopoietic growth factors). heterooligomerization of receptor components, which

Cytokine Receptors (Jak/STAT-Coupled)

Receptor Endogenous Tyrosine kinase ligand(s) Homodimeric receptors EPO-R Jak2 STAT5 GH-R, Growth hormone Jak2 STAT1/3/5 PRL-R Prolactin Jak2 STAT5 Mpl Jak2 STAT1/3/5 Receptor-heterooligomers (gp130) IL-6-R -6 (IL-6) Jak1/2,Tyk2 STAT1/3 IL-11-R Interleukin-11 (IL-11) Jak2 STAT1/3 LIF-R Leukemia inhibitory factor (LIF), Cardiotrophin-1 Jak1/2 STAT1/3 CNTFR-R Ciliary neurotrophic factor (CNTFR), BSF3 Jak1/2,Tyk2 STAT1/3 OSM-R Jak1/2 STAT1/3 G-CSF-R Granulocyte-colony stimulating factor (G-CSF) Jak2 STAT3 Ob-R STAT3 Jak2 STAT3 Receptor-heterodimers (βc-subunit) GM-CSF-R GM-CSF Jak2 STAT5 IL-3-R Interleukin-3 (IL-3) Jak2 STAT5 IL-5-R Interleukin-5 (IL-5) Jak2 STAT5 Receptor-heterodimers (γc-subunit) IL-2-R Interleukin-2 (IL-2) Jak1/3 STAT3/5 IL-4-R/IL-13-R Interleukin-4 (IL-4), Interleukin-13 (IL-13) Jak1/3 STAT3/5/6 IL-7-R Interleukin-7 (IL-7) Jak1/3 STAT5 IL-9-R Interleukin-9 (IL-9) Jak1/3 STAT1/3/5 IL-15-R Interleukin-15 (IL-15) Jak1/3 STAT6 IL-21-R Interleukin-21 (IL-21) Jak1/3 STAT1/3/5 1354 Receptor Proteins

Cytokine Receptors (Jak/STAT-Coupled) (Continued)

Receptor Endogenous Tyrosine kinase Transcription factor ligand(s) Receptor-heterodimers (IL12-subunit) IL-12-R1/2 Interleukin-12 (IL-12) Jak2,Tyk2 STAT4 IL-23-R/IL-12-R1 Interleukin-23 (IL-23) Jak2,Tyk2 STAT4 Interferon receptors INFα-R1/2 INF α/β Jak1/Tyk2 STAT1/2/3/5 INFγ-R1/2 INF γ Jak1/Jak2 STAT1/5 IL-10-like receptors IL-10-R1/2 Interleukin-10 (IL-10) Jak1/Tyk2 STAT1/3 IL-20-R1/2 Interleukin-19/20/24 (IL-19/20/24) Jak1/? STAT3 IL-20-R1/IL-10-R2 Interleukin-26 (IL-26) STAT3 INFλ-R1/ IL-10-R2 INF-λ STAT1/2 IL-22-R/IL-20-R2 Interleukin-20/24 (IL-20/24) STAT3 IL-22-R/IL-10-R2 Interleukin-22 (IL-22), IL-TIF Jak1/Tyk2 STAT3 IL-28-R/IL-10-R2 Interleukin-28/29 (IL-28/29)

TNF Receptor Superfamily The TNF receptor superfamily comprises currently domain protein (TRADD), which serve as a platform to about 25 receptors, which share some structural features recruit several other mediators including receptor- (Locksley et al. (2001) Cell 104:487–501; Baud, Karin interacting protein 1 (RIP1), Fas-associated death (2001) Trends Cell Biol 11, 372–377; ▶http://www. domain protein (FADD) and TNF-receptor-associated gene.ucl.ac.uk/nomenclature/genefamily/tnftop.html). factor 2 (TRAF2). TNFR2-activation results in the The signaling mechanism of this receptor family has recruitment of TRAF1 and TRAF2. TRAF2 plays a recently been elucidated by exemplary studies on the central role in the induction of downstream events like TNF and the Fas receptor. Binding of the inherently activation of IκB-kinase (IKK) and MAP-kinases. Fas trimeric ligand TNFα or FasL induces receptor activation does not result in the recruitment of TRAF2 trimerization and recruitment of several signaling but recruits FADD and subsequently leads to the proteins to the cytoplasmic domains of the receptors. activation of 8 (▶). TNF receptors recruit the TNFR1-associated death

TNF Receptor Superfamily

Receptor Aliases Ligand Interacting protein

CD27 TNFRSF7, S152, Tp55 CD27L TRAF 2, (CD 70) 3, 5 CD40 TNFRSF5, p50, Bp50 CD40Ligand (CD40L/CD154) TRAF 2, 3, 5, 6 FAS(CD 95) CD95, APO-1, FAS1, APT1, TNFRSF6, (FasL) FADD LTBR TNFCR, TNFR-RP, TNFR2-RP, TNF-R-III, LIGHT, LTα, β(LTβ) TRAF 3, 5 TNFRSF3, D12S370 NGFR TNFRSF16, CD271 Nerve growth factor (NGF) TRAF 2, 4, 6 EDAR Ectodysplasin-A1 (EDA-A1) TRAF 1, 3 XEDAR Ectodysplasin-A2 (EDA-A2) TRAF 3, 6 TNFRSF1A TNF-R, TNFAR, TNFR60, TNF-R-I, CD120a, TNFα,LTα TRADD, TNF-R55 FADD TNFRSF1B TNFR2, TNFBR, TNFR80, TNF-R75, TNF-R- Tumour necrosis factor α (TNFα), LTα TRAF1, 2 II, p75, CD120b TNFRSF4 ACT35, OX40, CD134, TXGP1L OX40Ligand (OX40L) TRAF 1, 2, 3, 5 TNFRSF6B DcR3, DCR3, TR6, M68 FasL, LIGHT, TL1A Receptor Proteins 1355

TNF Receptor Superfamily (Continued)

Receptor Aliases Ligand Interacting protein TNFRSF8 KI-1, CD30, D1S166E CD30L (CD153) TRAF 1, 2, 3, 5 TNFRSF9 CD137, 4-1BBL (CDw137L) TRAF 1, 4-1BB, ILA 2, 3 TNFRSF10A DR4, Apo2, TRAILR-1, CD261 TRAIL FADD TNFRSF10B DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, TRAIL FADD CD262 TNFRSF10C DcR1, TRAILR3, LIT, TRID, CD263 TRAIL TNFRSF10D DcR2, TRUNDD, TRAILR4, CD264 TRAIL TNFRSF11A RANK, CD265 RANKL TRAF 1, 2, 3, 5, 6 TNFRSF11B OCIF, TR1, OPG RANKL, TRAIL? TNFRSF12A FN14, TweakR, CD266 TWEAK TNFRSF13B TACI, CD267 APRIL, BAFF TRAF 2, 5, 6 TNFRSF13C BAFFR, CD268 BAFF TNFRSF14 HVEM, ATAR, TR2, LIGHTR, HVEA LIGHT, lymphotoxin α(LTα) TRAF 1, 2, 3, 5 TNFRSF17 BCM, CD269, BCMA APRIL, BAFF TRAF 1, 2, 3 TNFRSF18 AITR, GITR AITRLigand (AITRL) TRAF 1, 2, 3 TNFRSF19 TAJ-alpha, TROY, TAJ, TRADE ? TRAF 1, 2, 3, 5 TNFRSF19L FLJ14993, RELT TNFRSF21 DR6 RANKL, “TNF receptor-related, apoptosis- TRADD inducing ligand” (TRAIL) TNFRSF25 DR3, TRAMP,WSL-1, LARD, WSL-LR, DDR3, TL1A FADD TR3, APO-3

IL-1/Toll-Like Receptors The interleukin-1/toll-like receptor superfamily is IL-1/toll-like receptors involves association of the recep- involved in the rapid defense response to infection and tors with adaptor proteins like MyD88, TIRAP and others, injury. Currently, 11 human Toll-like receptors have been which recruite various proteins including IRAK-1, IRAK- identified, TLRs 1–11. They share structural homologies 2 and TRAF-6, which eventually results in the activation and are involved in innate immunity by recognizing of NF-κB and MAP kinases (Lee, Kim (2007) Annu Rev microbial particles. Their intracellular domains show Biochem; Pulendran, Ahmed (2006) Cell 124:849–863; homology with that of the IL-1 receptor subfamily (TIR- Takeda, Akira (2005) Int Immunol 17:1–14). domain). Activation of downstream signaling events via

IL-1/Toll-Like Receptors

Receptor Ligand Adaptor proteins Toll-like receptors TLR1 MyD88, TIRAP TLR2 , peptidoglycan, , zymosan, lipoarabinomannan, bacte- MyD88, rial lipopolysaccharide (LPS) TIRAP TLR3 Viral dsRNA TRIF TLR4 Bacterial lipopolysaccharide (LPS) MyD88, TIRAP, TRAM, TRIF 1356 Receptor Proteins

IL-1/Toll-Like Receptors (Continued)

Receptor Ligand Adaptor proteins TLR5 Flagellin MyD88 TLR6 Diacyl lipopeptides, LTA, zymosan MyD88, TIRAP TLR7 ssRNA MyD88 TLR8 ssRNA MyD88 TLR9 Unmethylated CpG DNA MyD88 TLR10 ? TLR11 Uropathogenic bacteria, profilin (T. gondii) MyD88 IL-1/IL-18 receptor subfamily IL-1RI/IL- Interleukin-1α, interleukin-1β MyD88 RacP IL-1RII/IL- Interleukin-1β RacP IL-18R/IL- Interleukin-18, IL-1F7 18RacP T1/ST2 ? IL-1Rrp2 IL-1F5, IL-1F6, IL-1F8, IL-1F9 APL ? TIGIRR ? (APL-2) SIGIRR ? (TIR8)

Other Cell Surface Receptors Plexins Plexins serve as receptors for semaphorins and are semaphorins in solution. The interaction between grouped into four subfamilies (A-D) on the basis of semaphorins and plexins are mediated by the Sema structural similarities. Semaphorins are secreted from domains. However, the class 3 semaphorins do not bind membrane-associated . In the mammalian directly to plexins but to neuropilins, which interact system, five different subclasses of semaphorins (3–7) with plexins of the class A. While neuropilins bind class have been found which in addition to plexins use also 3 semaphorins, class A plexins function as partners of other transmembranes proteins as receptors. Since neuropilins and are required for transferring the signal semaphorins are found both in a membrane-bound over the plasma membrane. In contrast to the class A form as well as in a soluble-bound form, plexins can plexins, class B, C, and D plexins bind semaphorins interact with semaphorins on other cells or with directly via their Sema domain.

Plexins

Receptor Ligand Alias

Plexin A family Plexin-A1 Sema6D NOV Sema3A (neuropilin-1) Sema3F (neuropilin-2) Plexin-A2 Sema3A (neuropilin-1) OCT Plexin-A3 Sema3A (neuropilin-1) SEX, XAP-6 Sema3F (neuropilin-2) Plexin-A4 Sema6A, Sema6B Sema3A (neuropilin-1) Sema3F (neuropilin-2) Receptor Proteins 1357

Plexins (Continued)

Receptor Ligand Alias

Plexin B family Plexin-B1 Sema4D SEP Plexin-B2 Sema4C, Sema4D MM1 Plexin-B3 Sema5A

Plexin C family Plexin-C1 Sema7A VESDPR, CD232

Plexin D family Plexin-D1 Sema3E, Sema4A

LDL Receptor Family The “low-density lipoprotein” (LDL) receptor family e.g. through the association of the receptors with PTB was originally described as a group of endocytotic domain containing proteins. For recent review see: receptors. However, binding of various ligands to Nykjaer, Willnow (2002) Trends Cell Biol 12:273–280; members of this family can induced signaling processes May et al. (2005) Cell Mol Life Sci 62:2325–2338.

Receptor Ligands Expression

LDLR E, apolipoprotein B, LDL Ubiquitous, e.g. hepatocytes, macrophages, central nervous system LRP1 Apolipoprotein E, chylomicron remnants, α2-macro- Wide expression, e.g. hepatocytes, , vascular (LPR) globulin, amyloid precursor protein (APP), tPA, prote- smooth muscle cells, macrophages, , ase/protease inhibitor complexes, lipoprotein , embryonic tissues PDGF, TGFβ VLDLR Apolipoprotein E, , , tissue Developing and adult brain, heart and endothelial factor pathway inhibitor cells, ApoER2 Apolipoprotein E, reelin Developing and adult brain, testis Megalin Apolipoprotein B, apolipoprotein E, apolipoprotein J, Apical plasma membrane of absorptive and secretory apolipoprotein H, albumin, cubilin, retinol-binding epithelia (e.g. renal proximal tubule), thyroid and protein, D-binding protein, sonic hedgehog, parathyroid gland, tropho-ectoderm, BMP-4, sex hormone-binding protein visceral yolk sac, neuroectoderm LRP1b , receptor precursors Restricted expression pattern (central nervous system) MEGF7 Unknown Restricted expression pattern, embryogenesis, adult CNS LRP5/6 Wnt

Nuclear Receptors Nuclear receptors are able to bind to DNA as either target gene transcription. Nuclear receptors are acti- homodimers or heterodimers. They function as ligand- vated by a variety of small hydrophobic molecules, activated gene regulatory proteins. In the inactive including and intracellular metabolites. For state they reside in the nucleus or in the cytoplasm, a variety of nuclear receptors, the so called “orphan usually associated with an inhibitory protein. Ligand nuclear receptors,” the physiological ligands are not binding to the receptor results in the activation, trans- known (▶Gluco-/Mineralocorticoid-Receptor; ▶Sex location to the nucleus, binding to specific receptor receptor; ▶Selective sex steroid receptor binding elements on the DNA and activation of modulators). 1358 Receptor Proteins

Nuclear Receptors

Receptor Gene name Ligand

Homodimers ERα NR3A1 ERβ NR3A2 Estradiol PR NR3C3 Progestins AR NR3C4 Androgens MR NR3C2 Mineralocorticoids GR Glucocorticoids RXR (α,β,γ)-heterodimers RXRα NR2B1 RXRβ NR2B2 RXRγ NR2B3 RARα NR1B1 Retinoic acids RARβ NR1B2 Retinoic acids RARγ NR1B3 Retinoic acids

TRα NR1A1 Thyroid hormone (T3) TRβ NR1A2 Thyroid hormone (T3) VDR NR1I1 1,25 (OH)2 Vitamin D3 FXR NR1H4 Bile acids LXRα NR1H2 Oxysterols, glucose LXRβ NR1H3 Oxysterols, glucose CAR NR1I3/4 Xenobiotics, phenobarbital, androstane metabolites SXR/PXR NR1I2 Xenobiotics, steroids, rifampicin,

PPARα NR1C1 Fatty acids, fibrates, leukotriene B4 PPARβ NR1C2 Fatty acids, carboprostacyclin

PPARγ NR1C3 Fatty acids, thiazolidinediones, prostaglandin J2 Orphan receptor SF-1, FTZ-F1 NR5A1 Phosphatidylinositols LRH-1, FTZ-F1β NR5A2 Phosphatidylinositols DAX-1 NR0B1 SHP NR0B2 TLL, TLX NR2E1 PNR, RNR NR2E3 NGFI-Bα NR4A1 NGFI-Bβ NR4A2 NGFI-Bγ NR4A3 RORα NR1F1 , cholesteryl sulfate RORβ NR1F2 Retinoic acid RORγ NR1F3 Retinoic acid ERRα NR3B1 Diethylstilbestrol, 4-hydroxytamoxifen ERRβ NR3B2 ERRγ NR3B3 Rev-erbα NR1D1 Rev-erbβ NR1D2 GCNF NR6A4 TR 2 NR2C1 TR 4 NR2C2 HNF-4α NR2A1 Palmitic acid HNF-4γ NR2A3 COUP-TFα NR2F1 COUP-TFβ NR2F2 COUP-TFγ NR2F6 Membrane Transport Proteins

Membrane transport proteins are integral transmembrane gradient (uniporters). Other carriers function as coupled proteins and transport substances with a high degree of carriers, in which the transfer of one solute striktly specificity. The rate of transport differs considerably depends on the transport of a second. Coupled transport between different types of transport proteins due to involves the simultaneous transfer of two or more differences in their mechanism of action. solutes in the same direction (/) ▶Channel proteins transport water or specific or in opposite directions (/exchanger). Cou- down their concentration or electric potential gradients. pled solute transporters usually couple the movement of In the open state they form passages across the one type of ion or molecule against its concentration membrane through which multiple water molecules or gradient to the movement of a different ion or molecule ions can move simultaneously. The transport rate of down its concentration gradient. In this case an channel proteins is very high (107–108 ions/s). energetically unfavorable reaction is coupled to an In contrast to channel proteins, ▶solute carriers energetically favorable reaction. (transporters) bind only one or a few The third major group of membrane transport proteins molecules at a time. In order to transport a substrate is able to move ions or small molecules across the molecule across the plasma membrane, the transporter membrane against a chemical concentration gradient or has to undergo a conformational change. Their transport electric potential by using the energy of ATP . rate is much lower than that of ion channels being in the They are called “▶transport ATPases,”“▶ATP-powered range of 102–104 molecules/s. Solute carriers can pumps” or simply “pumps.” ATP-powered pumps have a transport specific molecules down a concentration relatively low transport rate (100–103 molecules/s).

Channel Proteins Sodium-Channels Sodium channels can be divided in voltage-dependent Non-voltage-dependent Na+-channels belong to the channels and non-voltage-dependent channels. ▶Voltage- family of ▶degenerin/epithelial Na+-channel family. dependent Na+-channels (Catterall et al. (2005) Epithelial sodium channels (ENaC) mediate Na+-transport Pharmacol Rev 57:397–409) are mainly found in excitable in epithelia and are essential for sodium . Acid cells where they become activated by membrane sensing channels (ASIC) are proton-gated cation channels depolarization and are involved in the generation of action with a preference for Na+ ions, which are present both potentials. They consist of a pore-forming α-subunit, in the central and peripheral nervous system. Epithelial + which is structurally related to the pore forming α1-sub- Na -channels are heteromultimeric channels, whose pore unit of voltage-gated Ca2+-channels. In addition, the may be formed by three ENaC subunits. However, other voltage-dependent Na+-channels contain auxillary β models for their subunit arrangement have been proposed subunits (▶Voltage-dependent sodium channels). (Kellenberger, Schild (2002) Physiol Rev 82:735–767).

Sodium-Channels

Gene symbol Name Aliases Expression

Voltage-dependent Na+-channels Pore forming subunits

SCN1A Nav1.1 Rat I, HBSCI, GPBI, SCN1A CNS, PNS SCN2A Nav1.2 Rat II, HBSCII, HBA CNS SCN3A Nav1.3 Rat III CNS SCN4A Nav1.4 SkM1, µ1 Skeletal muscle 1360 Membrane Transport Proteins

Sodium-Channels (Continued)

Gene symbol Name Aliases Expression

SCN5A Nav1.5 SkM2, H1 Uninnerv. skeletal muscle, heart SCN8A Nav1.6 NaCh6, PN4, Scn8a, CerIII CNS, PNS SCN9A Nav1.7 NaS, hNE-Na, PN1 PNS, Schwann cells SCN10A Nav1.8 SNS, PN3, NaNG Small- and medium-sized DRG neurons SCN11A Nav1.9 NaN, SNS2, PN5, NaT, SCN12A C-type DRG neurons β-subunits SCN1B β1 GEFSP1 SCN2B β2 SCN3B β3 HSA243396 SCN4B β4

(ENaC)/degenerin family Epithelial Na+-channels SCNN1A ENaCα Epithelial cells SCNN1B ENaCβ Epithelial cells SCNN1D ENaCδ Epithelial cells SCNN1G ENaCγ PHA1 Epithelial cells Acid-sensing channels ACCN1 ASIC1 BNC1, BNaC1, MDEG CNS, PNS ACCN2 ASIC2 BNaC2 CNS, PNS ACCN3 ASIC3 TNaC1, DRASIC CNS, PNS ACCN4 ASIC4 BnaC4 ACCN5 INAC, HINAC

Potassium Channels Potassium channels are a diverse family of mem- transmembrane segments and a conducting pore between brane proteins, which selectively conduct K+ ions across segment five and segment six with a voltage sensor the along its electrochemical gradient. (positive charge of amino acid residues) located at S4 (e.g. More than 80 genes have been identified, which encode KCNA-KCNH, KCNM-KCNT). The inward rectifier K+ subunits of potassium channels, including non-pore channels (Kir; KCNJ) (Kubo et al. (2005) Pharmacol Rev forming auxiliary subunits. As a general feature of 57:509–526) consist of four subunits, each containing two potassium channels, their conducting pore is composed of transmembrane segments with a P-loop between the four α subunits. In some cases, additional auxiliary transmembrane segments. Ca2+-activated K+ channels subunits are required for proper function and/or regula- (Wei et al. (2005) Pharmacol Rev 57:463–472) consist of tion of the tetrameric K+ channel. Based on their primary subunits containing six transmembrane segments while amino acid sequence, potassium channels can be the KCNK subgroup of subunits classified into four major families. The voltage-gated K+ (Goldstein et al. (2005) Pharmacol Rev 57:527–540) has channels (Gutman et al. (2005) Pharmacol Rev 57:473– four putative transmembrane with two pore forming 508) are composed of four subunits, each containing six domains.

Potassium Channels

Gene Name Aliases Expression symbol

Voltage-gated K+ channels

Kv1 () Kv1.1 KCNA1 AEMK, RBK1, Neurons, heart, HUK1, MBK1 retina, , skeletal muscle

Kv1.2 KCNA2 HK4 Brain, heart, pancreas Membrane Transport Proteins 1361

Potassium Channels (Continued)

Gene Name Aliases Expression symbol

Kv1.3 KCNA3 MK3, HLK3, HPCN3 Lymphocyte, brain, lung, platelets, osteoclasts, macrophages, microglia

Kv1.4 KCNA4 HK1, HPCN2 Brain, heart, pancreas, skeletal muscle

Kv1.5 KCNA5 HK2, HPCN1 Brain, heart, lung, skeletal muscle Kv1.6 KCNA6 HBK2 Brain, colon, heart, lung, ovary

Kv1.7 KCNA7 HAK6 Heart, pancreas, skeletal muscle, placenta Kv1.8 KCNA10 Aorta, brain, kidney, heart, adrenal + β subunits (associate with Kv1K -channels) Kvβ1 KCNAB1 Kvβ2 KCNAB2 Kvβ3 KCNAB3 Kv2 (Shab) Kv2.1 KCNB1 DRK1 Brain, heart, kidney, retina, skeletal muscle, cochlea Kv2.2 KCNB2 CDRK Brain, heart, kidney, retina, skeletal muscle, smooth muscle Kv3 (Shaw) Kv3.1 KCNC1 NGK2, Raw2 Brain, muscles, lymphocytes Kv3.2 KCNC2 Raw1 Brain Kv3.3 KCNC3 Brain, liver Kv3.4 KCNC4 HKSHIIIC Brain, skeletal muscle, parathyroid

Kv4 (Shal) Kv4.1 KCND1 mShal Brain, heart, liver, kidney, lung, placenta, pancreas, thyroid

Kv4.2 KCND2 RK5 Brain Kv4.3 KCND3 Brain, heart, smooth muscle Kv10 Kv10.1 KCNH1 Ether-á-go-go (eag) Brain Kv11.1 KCNH2 LQT2, HERG Heart, brain, liver, kidney Kv12.2 KCNH3 BEC1 Brain, lymphocytes

Kv12.3 KCNH4 BEC2 Brain, pituitary, lung Kv10.2 KCNH5 Eag2, Brain Kv11.2 KCNH6 HERG2 Brain, uterus Kv11.3 KCNH7 HERG3 Brain Kv12.1 KCNH8 Sympathetic ganglia, brain, colon Kv7 (slow delayed rectifyer) Kv7.1 KCNQ1 KVLQT1, LQT1 Heart, kidney, lung, placenta, colon, cochlea Kv7.2 KCNQ2 KQT2 Brain, heart Kv7.3 KCNQ3 KvEBN2 Brain, retina, colon

Kv7.4 KCNQ4 Outer hair cells, inner , central auditory pathway Kv7.5 KCNQ5 Brain, skeletal muscle, sympathetic ganglia Auxillary subunits for Kv7, Kv3, Kv4, Kv10 and Kv11 K+-channels Mink/Isk KCNE1 AM- KCNE1L MECR2 MiRP1 KCNE2 MiRP2 KCNE3 MiRP3 KCNE4 1362 Membrane Transport Proteins

Potassium Channels (Continued)

Gene Name Aliases Expression symbol

+ Kv5/6/8 (modifier of Kv2 family of K channels) Kv5.1 KCNF1 IK8, kH1 Brain, heart, skeletal muscle, liver Kv6.1 KCNG1 K13, kH2 Brain, skeletal muscle Kv6.2 KCNG2 KCNF2 Heart Kv6.3 KCNG3 Brain, pituitary, adrenal Kv6.4 KCNG4 Brain, liver, intestine Kv8.1 KCNV1 KCNB3 Brain, kidney Kv8.2 KCNV2 Lung, liver, kidney, spleen Kv9.1 KCNS1 Brain Kv9.2 KCNS2 Brain Kv9.3 KCNS3 Brain, lung, artery, heart, kidney, colon Inwardly rectifying K+ channels

Kir (inward rectifyer) Kir1.1 KCNJ1 ROMK1 Kidney, pancreas, spleen, brain, heart Kir2.1 KCNJ2 IRK1 Heart, brain, smooth muscle, skeletal muscle, lung, placenta, kidney

Kir2.2 KCNJ12 IRK2 Heart, brain, skeletal muscle

Kir2.3 KCNJ4 HIR, HRK1, HIRK2 Heart, brain, skeletal muscle, kidney

Kir2.4 KCNJ14 IRK4 Brain, retina, heart Kir3.1 KCNJ3 GIRK1 Brain, atrium Kir3.2 KCNJ6 BIR1, GIRK2 , brain

Kir3.3 KCNJ9 GIRK3 Brain Kir3.4 KCNJ5 CIR, GIRK4 Heart, pancreas, brain Kir4.1 KCNJ10 Kir1.2 Glia, retina, ear, kidney Kir4.2 KCNJ15 Kir1.3 Kidney, lung, brain, pancreas Kir5.1 KCNJ16 Brain, pancreas, thyroid, liver Kir6.1 KCNJ8 Vascular smooth muscle Kir6.2 KCNJ11 BIR, IKATP B-cells (pancreas), heart, brain Kir7.1 KCNJ13 Brain, intestine, lung Two-P K+ channels

K2P1.1 KCNK1 DPK, TWIK1 Brain, kidney, heart, liver K2P2.1 KCNK2 TREK-1 Brain, heart K2P3.1 KCNK3 TASK Brain, heart, pancreas, placenta

K2P4.1 KCNK4 TRAAK Brain, retina, kidney, intestine

K2P5.1 KCNK5 TASK2 Kidney, brain, intestine K2P6.1 KCNK6 TOSS, TWIK2, Eyes, lung, KCNK8 stomach, embryo, pancreas

K2P7.1 KCNK7 Brain K2P9.1 KCNK9 TASK-3 Brain K2P10.1 KCNK10 TREK2 Kidney, pancreas, heart, liver K2P12.1 KCNK12 THIK2 Brain, heart, lung, kidney K2P13.1 KCNK13 THIK-1 Brain, heart, lung, kidney K2P15.1 KCNK15 TASK5, KCNK11, 14 Brain, heart, lung, kidney K2P16.1 KCNK16 TALK1 Heart, lung, liver K2P17.1 KCNK17 TALK2, TASK4 Heart, lung, liver K2P18.1 KCNK18 – Brain Membrane Transport Proteins 1363

Potassium Channels (Continued)

Gene Name Aliases Expression symbol Ca2+-activated K+ channels

KCa1 (large conducted channel) KCa1.1 KCNMA1 SLO Ubiquitous KCa4 KCa4.1 KCNT1 Slack, Slo2.2 Brain, kidney KCa4.2 KCNT2 Slick, Slo2.1 Ubiquitous KCa5 KCa5.1 KCNU1 Slo3 Testis, spermatocytes β-subunit slo-beta KCNMB2 KCNMB3 KCNMB3L KCNMB4

KCa2/3 (small/intermediate conductance channels) KCa2.1 KCNN1 hSK1 Brain, heart KCa2.2 KCNN2 hSK2 Brain, , Jurkat T cells KCa2.3 KCNN3 hSK3 Brain, heart, liver, skeletal muscle KCa3.1 KCNN4 hSK4, hKCa4, hIK- Lymphocytes, intestine, smooth muscle, prostate, red blood cells, Ca1 neurons, placenta, thyroid gland

Voltage-Dependent Ca2+-Channels Voltage-dependent Ca2+-channels are a family of multi- the voltage-sensor, the selectivity filter and the interac- subunit complexes, consisting of five proteins, which tion sites for regulatory proteins. The electrophysiolog- allow the influx of Ca2+ into a cell in response to ical properties of voltage-dependent Ca2+-channels are membrane depolarization. The five subunits of these mainly determined by the identity of their α1 subunit channels are encoded by four different gene families. (Catterall et al. (2005) Pharmacol Rev 57:411–425) 2+ The α1 subunit is the pore-forming unit, which contains (▶Voltage-dependent Ca -channels).

Voltage-Dependent Ca2+-Channels

Gene symbol Name Aliases Expression

L-type channel (α1-subunit) CACNA1S Cav1.1 α1S, α1Skm, CaCh1 Skeletal muscle CACNA1C Cav1.2° α1C-a, rbC, CaCh2 Heart Cav1.2b α1C-b Smooth muscle Cav1.3c α1C-c Brain, pituitary, adrenal CACNA1D Cav1.3 α1D, rbD, CaCh3 Brain, pancreas, kidney, ovary, cochlea CACNA1F Cav1.4 α1F Retina

P/Q-type channel (α1-subunit) CACNA1A Cav2.1a α1A, rbA, CaCh4, BI1 Brain, cochlea, pituitary

Cav21b BI2 Brain, cochlea, pituitary

N-type channel (α1-subunit) CACNA1B Cav2.2a α1B-1, rbB, CaCh5, BIII Brain, nervous system

Cav2.2b α1B-2 Brain, nervous system 1364 Membrane Transport Proteins

Voltage-Dependent Ca2+-Channels (Continued)

Gene symbol Name Aliases Expression

R-type channel (α1-subunit) CACNA1E Cav2.3a α1E, rbB, CaCh6, BII Brain, cochlea, pituitary, retina, heart Cav2.3b BII2 Brain, cochlea, retina

T-type channel (α1-subunit) BII CACNA1G Cav3.1 α1G Brain, nervous system

CACNA1H Cav3.2 α1H Brain, heart, kidney, liver CACNA1I Cav3.3 α1I Brain

α2δ-subunit CACNA2D1 α2δ1 Ubiquitously CACNA2D2 α2δ2 Heart CACNA2D3 α2δ3 Brain β-subunit CACNB1 β1 Skeletal muscle, brain, spleen CACNB2 β2 Heart, aorta, lung, brain CACNB3 β3 Brain, smooth muscle CACNB4 β4 Brain

γ-subunit CACNG1 γ1 Skeletal muscle CACNG2 γ2 Brain CACNG3 γ3 Brain CACNG4 γ4 CACNG5 γ5 CACNG6 γ6 CACNG7 γ7 CACNG8 γ8

Chloride Channels Several classes of chloride channels have been found: proven. The CLC chloride channels form a large family these include ▶ligand-gated chloride channels of which many are gated in a voltage-dependent (GABAA- and glycine-receptors; ▶Ligand-gated ion manner. There are nine different CLC genes found in channels), the cystic fibrosis transmembrane conduc- . CLC channels are present in the plasma tance regulator (CFTR; ▶ABC-transporters), and the membrane as well as in intracellular organelles. They ▶CLC family of chloride channels. CLIC proteins and function as dimers, with each monomer having its own CaCC proteins are proposed chloride channels, howev- pore. Some CLC channels have accessory β-subunits er their function as chloride channels has not yet been (▶Chloride channels).

Gene symbol Name Alias Expression

CLCN1 ClC-1 Skeletal muscle CLCN2 ClC-2 Broad CLCN3 ClC-3 Brain, kidney, liver etc. CLCN4 ClC-4 Brain, muscle etc. CLCN5 ClC-5 DENTS, XLRH Kidney, intestine, liver etc. CLCN6 ClC-6 Broad CLCN7 ClC-7 Broad CLCNKA ClC-Ka Kidney, inner ear CLCNKB ClC-Kb Kidney, inner ear Membrane Transport Proteins 1365

Cation Channels TRP Channels The TRP superfamily includes a variety of non-voltage- TRP channels, which are related to the vanilloid gated cation channels, that are distinguished by their receptor1 (VR1). Members of this family can be selectivity and mode of action. They all have regulated by heat, osmolarity and other stimuli. The similarities to the first member of family, the Drosphila third subfamily, TRPM, is related to the first member TRP (“travsient receptor potential”). TRP cation of this family melastatin and is structurally character- channels are subdivided in three families, the TRP- ized by its increased length compared to the other canonical (TRPC) subfamily, which are most highly subfamilies. For details of the nomenclature and recent related to Drosphila TRP. At least some of the members review: Mol Cell 9:229–231 (2002); Cell 108:595–598 of the TRPC subfamily play a role as Ca2+ store- (2002); Pharmacol Rev 57:427–450 (2005). operated channels. The TRPV subfamily comprises

TRP Channels

Name Alias Expression

TRPC subfamily TRPC1 TRP1 Heart, brain, testis, ovaries TRPC2 TRP2 VNO, testis TRPC3 TRP3 Brain TRPC4 TRP4 Brain, endothel, adrenal gland, retina, testis TRPC5 TRP5 Brain TRPC6 TRP6 Lung, brain TRPC7 TRP7 Eye, heart, lung

TRPV subfamily TRPV1 VR1, OTRPC1 Trigeminal and dorsal root ganglia (DRG) TRPV2 VRL-1, OTRPC2 DRG, spinal cord, brain, spleen, intestine TRPV3 TRPV4 OTRPC4, VR-OAC, TRP12, VRL-2 Kidney, lung, spleen, testis, endothelium, liver, heart TRPV5 ECaC1, CaT2 Kidney, duodenum, jejunum, placenta, pancreas TRPV6 CaT1, EcaC2, CaT-L Small intestine, pancreas, placenta, prostate

TRPM subfamily TRPM1 Melastatin Eye, melanocytes TRPM2 TRPC7, LTRPC2 Brain TRPM3 KIAA1616, LTRPC3 ? TRPM4 TRPM4, LTRPC4 Prostate, colon, heart, kidney TRPM5 MTR1, LTRPC5 Small intestine, liver, lung TRPM6 Chak2 TRPM7 TRP-PLIK, Chak1, LTRPC7 Kidney, heart

TRPP subfamily TRPP1 PC2, PKD2, TRPP2 Widely TRPP2 PKD2L1, TRPP3 Eye, kidney, testis TRPP3 PKD2L2, TRPP5 Nearly ubiquitously TRPA subfamily TRPA1 ANKTM1 Sensory neurons TRPML subfamily TRPML1 Mucolipin 1 Widely TRPML2 Mucolipin 2 Widely TRPML3 Mucolipin 3 Widely 1366 Membrane Transport Proteins

Cyclic Nucleotide-Gated Cation Channels The activation of cyclic nucleotide-gated cation chan- nucleotide-gated (HCN) channels are primarily nels is regulated or modulated by cyclic AMP or cyclic activated by membrane hyperpolarization and are GMP. While the cyclic nucleotide-gated (CNG) chan- modulated in their activity by cyclic nucleotides nels obligatorily require binding of cyclic nucleotides (Hofmann et al. (2005) Pharmacol Rev 57:455–462) in order to activate, hyperpolarization-activated cyclic (▶Cyclic nucleotide-regulated cation channels).

Gene symbol Activator Alias Expression

Cyclic nucleotide-gated channels α-subunits CNGA1 cGMP >> cAMP RCNC1, CNG1 Rod outer segments, some neurons CNGA2 cGMP > cAMP CNG2, OCNC1 Olfactory epithelium, brain CNGA3 cGMP >> cAMP CCNC1, CNG3 Cones, brain, sperm CNGA4 OCNC2, CNG5 Olfactory epithelium, brain β-subunits CNGB1 RCNC2, GARP, GAR1 Rods, olfactory epithelium, sperm CNGB3 Retina (cones), testis

Hyperpolarization-activated cyclic nucleotide-gated channels HCN1 cAMP > cGMP BCNG-1, HAC-2 Heart, brain HCN2 cAMP > cGMP BCNG-2, HAC-1 Brain, heart HCN3 BCNG-4, HAC-3 Brain, retina, heart HCN4 cAMP > cGMP BCNG-3, HAC-4 Heart, retina, thalamus

Calcium Release Channels The Ca2+ release channels are abundant in some regions ▶Inositol-1,4,5-triphosphate receptors have a general of the sarcoplasmic or . ▶Rya- structure similar to ryanodine receptors. They mediate nodine receptors (which bind the alkaloid the release of intracellularly stored Ca2+ in response ryanodine) consist of homotetramers which can be to the production of Inositol-1,4,5-triphosphate (IP3). opened by Ca2+ (Ca2+-induced Ca2+ release). In skeletal Calcium release channels have a low selectivity for muscle, the ryanodine Ca2+ release channel is gated by a individual cations, but under physiological conditions 2+ conformational change of a voltage sensor, the α1S mainly allow the passage of Ca ions (▶Ryanodine subunit of voltage-dependent calcium channels. receptor).

Gene symbol Name Alias Expression

Ryanodine receptor Type I RYR1 RyR1 Type I, MHS1 Skeletal muscle (high levels) RYR2 RyR2 Type II Cardiac muscle, brain RYR3 RyR3 Type III Ubiquitous (low levels)

Inositol-1,4,5-triphosphate receptors

ITPR1 IP3 receptor 1 Type I IP3 receptor CNS, ubiquitous ITPR2 IP3 receptor 2 Type II IP3 receptor Widely ITPR3 IP3 receptor 3 Type III IP3 receptor Kidney, brain, gastrointest. tract, pancreas Membrane Transport Proteins 1367

Water Channels The (AQPs) are a family of small integral transmembrane helices. AQPs increase the water membrane proteins which function as water-selective permeability of biological membranes, thereby allow- channels. A subgroup, AQP3, AQP7, AQP9 and ing rapid transcellular movement of water. AQPs are AQP10 is also permeable for neutral solutes such as constitutively active. Several hormones control AQP glycerol and urea. The membrane topology of AQPs functions by regulating their expression and cellular is characterized by intracellular N- and C-termini localization. (see aquaporins; vasopressin/oxytocin). and two tandem repeats, each formed from three

Name Gene Alias Expression

Aquaporin 1 AQP1 -CHIP Brain, kidney, eye, lung AQP2 WCH-CD, Kidney (collecting duct), inner ear aquaporin-CD AQP3 Kidney, , eye, urinary bladder, skin, gastrointestinal tract Aquaporin 4 AQP4 MIWC Kidney, brain, retina, inner ear, skeletal muscle Aquaporin 5 AQP5 salivary glands, respiratory tract Aquaporin 6 AQP6 AQP2L Kidney Aquaporin 7 AQP7 AQP7L, AQPap, AQP9 Testis, adipose tissue Aquaporin 8 AQP8 Pancreas, colon Aquaporin 9 AQP9 liver, brain, reproductive system, skin, gastrointestinal tract Aquaporin 10 AQP10 gastrointestinal tract Aquaporin 11 AQP11 testis, liver, kidney Aquaporin 12 AQP12 pancreas Aquaporin 0 AQP0 MIP lens

Solute Carriers Solute carriers comprise a huge family of membrane other solute. In this way the free energy released during transport proteins, which specifically bind a variety of the movement of an inorganic ion down its electro- ions and molecules. The solute carrier then undergoes a chemical gradient is used as a driving force to pump conformational change, which results in the transport of other solutes uphill, against their electrochemical the ion or molecule across the membrane. Solute gradient. This principle is called “secondary active carriers are not directly coupled to an energy consuming transport” in contrast to “primary ” process. If two or more ions/molecules are transported carried out by transport ATPases (see below), which in a coupled fashion in one direction, the solute carrier is carried out by transporters, which generate the is called ▶cotransporter (symporter). If ions/molecules required energy directly. The third type of solute carrier are transported in opposite directions, the solute carrier transports certain molecules just down a concentration is called ▶antiporter (exchanger). The tight coupling gradient (▶uniporter)(▶Glucose transporters; ▶Neu- between the transport of two solutes allows these rotransmitter transporters; ▶Organic cation transpor- carriers to use the energy stored in the electrochemical ters; ▶Vesicular transporters). gradient of one solute, typically an ion, to transport the

Solute Carriers

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC1: the high affinity glutamate and neutral amino acid transporter family SLC1A1 EAAC1, EAAT3 L-Glu, D/L-ASP C/Na+,H+ and K+ Brain (neurons), intestine, kidney, liver, heart

SLC1A2 GLT-1 EAAT2 L-Glu, D/L-ASP C/Na+,H+ and K+ Brain (astrocytes), liver SLC1A3 GLAST EAAT1 L-Glu, D/L-ASP C/Na+,H+ and K+ Brain (astrocytes), heart, skeletal muscle, placenta 1368 Membrane Transport Proteins

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC1A4 ASCT1SATT L-Ala, L-Ser, L-Thr, C/Na+, E/amino acids Widely L-Cys, L-Gln SLC1A5 ASCT2AAAT L-Ala, L-Ser, L-Thr, C/Na+, E/amino acids Lung, skeletal muscle, large L-Cys, L-Gln intestine, kidney, testis, adipose tissue

SLC1A6 EAAT4 L-Glu, D/L-ASP C/Na+,H+ and K+ Cerebellum (Purkinje cells) SLC1A7 EAAT5 L-Glu, D/L-ASP C/Na+,H+ and K+ Retina

SLC2: the facilitative GLUT transporter family SLC2A1 GLUT1 Glucose, galactose, F Erythrocytes, brain, blood mannose, brain barrier, blood-tissue glucosamine barrier SLC2A2 GLUT2 Glucose, galactose, F Liver, islet of Langerhans, , mannose, intestine, kidney, brain glucosamine

SLC2A3 GLUT3 Glucose, galactose, F− Brain (neurons), testis mannose, xylose

SLC2A4 GLUT4 Glucose, glucosamine F Adipose tissue (white and brown), skeletal and cardiac muscle

SLC2A5 GLUT5 Fructose F Small intestine, kidney SLC2A6 GLUT6/GLUT9 Glucose F Brain, spleen, leukocytes SLC2A7 GLUT7 O SLC2A8 GLUT8/GLUTX1 Glucose, fructose, ga- F Testis, brain, adrenal, liver, lactose spleen, , lung SLC2A9 GLUT9/GLUTX O Kidney, liver, small intestine, placenta, lung, leukocytes SLC2A10 GLUT10 Glucose, galactose F Heart, lung, brain, liver, skeletal muscle, pancreas, placenta, kidney SLC2A11 GLUT11/GLUT10 Glucose, fructose F Heart, muscle SLC2A12 GLUT12 O Heart, prostate, skeletal muscle SLC2A13 HMIT/GLUT13 Myo-inositol C Brain, adipose tissue SLC2A14 GLUT14 O Testis

SLC3: the heavy subunits of the heteromeric amino acid transporters SLC3A1 rBAT/NBAT D2 Heterodimerizes with E (see details in SLC7 Epithelial cells in kidney and light subunit SLC7A9 table) small intestine > liver, pancreas (apical plasma membrane) SLC3A2 4F2hc/CD98hc With light subunits E (see details in SLC7 Ubiquitous. In epithelial cells SLC7A5-8 and table) (basolateral plasma SLC7A10-11 membrane)

SLC4: the bicarbonate transporter family SLC4A1 AE1/Band3 Chloride bicarbonate E Erythrocytes, intercalated cells of renal collecting duct, heart, colon Membrane Transport Proteins 1369

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC4A2 AE2 Chloride bicarbonate E Widely, basolateral in most epithelial cells SLC4A3 AE3 Chloride bicarbonate E Brain, retina, heart and smooth muscle, epithelial cells of kidney and GI tract SLC4A4 NBCe1/NBC, NBC1 Sodium bicarbonate C NBCe1-A: renal proximal (and/or carbonate) tubule, eye. NBCe1-B: widely distributed, pancreas, heart, eye. NBCe1-C: brain SLC4A5 NBCe2/NBC4 Sodium bicarbonate C Liver, testes, spleen (and/or carbonate) SLC4A6 SLC4A7 NBCn1/NBC2, NBC3 Sodium bicarbonate C Widely distributed, spleen, testes, brain, heart, lung, liver and kidney; not skeletal muscle SLC4A8 NDCBE/kNBC3 Sodium bicarbonate C and E Brain, testes, kidney and chloride ovary SLC4A9 -/AE4 Inconclusive ? At least kidney SLC4A10 -/NCBE Inconclusive ? Brain SLC4A11 -/BTR1 Unknown O Kidney, salivary gland testis, thyroid, trachea

SLC5: the sodium glucose cotransporter family SLC5A1 SGLT1/None Glucose and galac- C/Na+ (H+) F/Na+ (H+) Small intestine > trachea, tose (urea and water) channel urea and wa- kidney and heart. Plasma ter membranes SLC5A2 SGLT2/None Glucose C/Na+ Kidney cortex SLC5A3 SMIT/none Myoinositol (glucose) C/Na+ Brain, heart, kidney and lung. Plasma membranes SLC5A4 SGLT3/SAAT1 Na+ (H+) Small intestine (Cholinergic neurons), skeletal muscle, kidney, uterus, testis SLC5A5 NIS I− (ClO4−,SCN−,NO3−, C/Na+, uniporter Na+ Thyroid, breast, colon and Br−) channel urea water ovary SLC5A6 SMVT Biotin, lipoate and C/Na+ Brain, heart, kidney, lung, panthothenate placenta SLC5A7 CHT/CHT1 Choline C/Na+/Cl− Spinal cord and medulla SLC5A8 AIT Iodide Thyroid, apical plasma membrane SLC5A9** SGLT4 Small intestine, kidney, liver, lung, brain SLC5A10 SGLT5/rabbit RK-D Kidney SLC5A11 SGLT6/KST1Rabbit, Rabbit ortholog: myo- C/Na+ Small intestine, brain, ST1Rabbit, SMIT2 inositol, chiro-inositol, kidney, liver, heart, lung glucose and xylose

SLC6: the sodium- and chloride-dependent transporter family SLC6A1 GAT1 GABA C/Na+,Cl− GABAergic neurons SLC6A2 NET/NAT1, NET1 , dopa- C/Na+,Cl− Central and peripheral mine nervous system, adrenal gland, placenta 1370 Membrane Transport Proteins

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC6A3 DAT/DAT1 Dopamine C/Na+,Cl− Brain (dopaminergic neurons) SLC6A4 SERT/5-HTT Serotonin C/Na+,Cl−,K+ Central and peripheral nervous system, epithelial cells, platelets SLC6A5 GLYT2/NET1 Glycine C/Na+,Cl− Spinal cord, brain (glycinergic neurons) SLC6A6 TAUT Taurine C/Na+,Cl− Brain, retina, liver, kidney, heart, spleen, pancreas SLC6A6P + − SLC6A7 PROT L- C/Na ,Cl Brain (glutamatergic neurons) SLC6A8 CT1/CRTR Creatine C/Na+,Cl− Ubiquitous SLC6A9 GLYT1 Glycine C/Na+,Cl− GLYT1a: brain, pancreas, uterus, stomach, spleen, liver, and lung. GLYT1b, GLYT 1c: nervous system. GLYT1e, GLYT1f, retina SLC6A10 CT2 Creatine Testis SLC6A11 GAT3 GABA, β-alanine C/Na+,Cl− Brain (GABAergic neurons, glia) SLC6A12 BGT1 Betaine, GABA C/Na+,Cl− Kidney, brain SLC6A13 GAT2 GABA, β-alanine C/Na+,Cl− Brain (meninges, ependyma, choroid plexus), retina, liver and kidney SLC6A14 ATB(0+) Neutral, cationic ami- C/Na+,Cl− Lung, trachea, salivary no acids gland, mammary gland, stomach, pituitary. SLC6A15 v7-3/NTT73 Unknown Brain (amygdala, putamen, ) SLC6A16 NTT5 Unknown Testis, pancreas, prostate

SLC7: the cationic amino acid transporter/-associated amino-acid transporter family 1 2 SLC7A1 CAT-1/ATRC1, ERR , Cationic L-amino acids F (non-obligate E) Ubiquitous except for liver, REC11 plasma and intracellular membranes, in epithelial cells basolateral 2 SLC7A2 CAT-2(A or B)/TEA, ATRC2 Cationic L-amino acids F CAT-2A: liver, skeletal muscle, pancreas CAT-2B: inducible in many cell types 2 SLC7A3 CAT-3/ATRC3 Cationic L-amino acids F , ovary, testis, brain (neurons) plasma membrane SLC7A3P ––P Placenta SLC7A4 -/CAT-4 Unknown O Brain, testis, placenta plasma and intracellular membranes SLC7A5 LAT Large neutral L-amino E (similar intra-and Brain, ovary, testis, placenta,

acids, T3,T4, L-dopa, extracellular blood-brain barrier, fetal liver, BCH (system L) selectivities, low activated lymphocytes, intracellular apparent tumor cells; lower affinity) expression in many other tissues/plasma membrane Membrane Transport Proteins 1371

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC7A6 y+LAT2/[associated with E (preferentially intra- Brain, small intestine, testis, 4F2hc] cellular ationic amino parotis, heart, kidney, lung, acid against extracel- liver/basolateral in epithelial lular neutral amino cells acid + Na+) SLC7A7 y+LAT1/[associated with Na+ independent: E (preferentially Small intestine, kidney, 4F2hc] cationic amino acids; intracellular cationic leukocytes, placenta, lung/ Na+ dependent: large amino acid against basolateral in epithelial cells neutral L-amino acids extracellular neutral (system y+L) amino acid + Na+) SLC7A8 LAT2/[associated with Neutral L-amino acids E (similar intra-and Small intestine, kidney, 4F2hc] (large and small), BCH extracellular selectiv- brain, placenta, ovary, testis, (system L) ities, lower intracellu- skeletal muscle/basolateral lar apparent affinity) in epithelial cells SLC7A9 b0,+AT/[associated with Cationic amino acids, E (preferentially extra- Small intestine, kidney, lung, rBAT] large neutral amino cellular cationic amino placenta, brain, liver/apical in acids (system acid against intracel- epithelial cells b0,+-like) lular neutral amino acid) SLC7A10 Asc-1/[associated with Small neutral L- and Preferentially E Brain, heart, placenta, 4F2hc] D-amino acids skeletal muscle and kidney (Na+-independent: (human). Brain, lung, small system asc) intestine and placenta/ basolateral in epithelial cells (mouse) SLC7A11 xCT/[associated with Cystine (anionic), E (preferentially extra- Macrophages, brain, retinal 4F2hc] L-glutamate cellular cystine pigment cells, liver, kidney/ − (system Xc against intracellular basolateral in epithelial cells glutamate) SLC7A13 Orphan

SLC8: the Na+/Ca2+ exchanger family SLC8A1 NCX1/NACA, NCE Sodium, calcium Exchanger/Na+,Ca2+ Ubiquitous tissue distribu- tion. Plasma membrane of various cell types. In brain mainly in neurons and their dendrites SLC8A2 NCX2 Sodium, calcium Exchanger/Na+,Ca2+ Predominantly in brain (glial cells) and skeletal muscle. Low transcript levels in various other tissues SLC8A3 NCX3 Sodium, calcium Exchanger/Na+,Ca2+ Exclusively in brain (subpopulations of neuronal cells) and skeletal muscle

LC9: the Na+/H+ exchanger family + + + + + + SLC9A1 NHE1/APNH Na ,H ,Li ,NH4 E: Na /H (1:1) Ubiquitous (plasma mem- brane; basolateral surface of epithelia) + + + + + + SLC9A2 NHE2 Na ,H ,Li ,NH4 E: Na /H (1:1) Stomach, intestine > skeletal muscle >>> kidney, brain, uterus, testis >> heart, lung 1372 Membrane Transport Proteins

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC9A2L + + + + + + SLC9A3 NHE3 Na ,H ,Li ,NH4 E: Na /H (1:1) Intestinal tract, stomach > kidney, gall bladder, epididy- mis, >>> brain; (apical surface and recycling endosomes of epithelia) + + + + + + SLC9A4 NHE4 Na ,H ,Li ?, NH4 ? E: Na /H (1:1) Stomach >>> kidney, brain; (plasma membrane; basolateral membrane of epithelia) + + + + + + SLC9A5 NHE5 Na ,H ,Li ,NH4 ? E: Na /H (1:1) Brain (neurons); (plasma membrane and recycling endosomes/synaptic vesicles) SLC9A6 NHE6/KIAA0267 ? E: ? Ubiquitous; (recycling endosomes) + + + + + + + + SLC9A7 NHE7 Na ,K ,H ,Li ,NH4 ? E: Na ,(K )/H Ubiquitous; (trans-Golgi network and endosomes) SLC9A8 NHE8/KIAA0939 ? E. ? Ubiquitous; (plasma membrane and possibly oth- er endomembrane compartments) SLC9A9

SLC10: the sodium bile salt cotransport family SLC10A1 NTCP/LBAT Bile acids C/Na+ Liver, pancreas SLC10A2 ASBT/IBAT, ISBT Bile acids C/Na+ Ileum, kidney, iliary tract SLC10A3 P3 O Ubiquitously (based on EST data) SLC10A4 Hypothetical protein O Brain neuroblastoma (based MGC29802 on ESTdata) SLC10A5 Similar to O Fetal brain (based on EST data) SLC11: the proton coupled metal family SLC11A1 NRAMP1/NRAMP, LSH Mn2+, Fe2+ and other C/H+ Phagolysosomes of divalent metal ions phagocytes (macrophages, neutrophils) SLC11A2 DMT1, NRAMP2, DCT1 Fe2+,Cd2+,Co2+,Cu1+, C/H+ Widespread, including intes- Mn2+ tine, erythroid cells, kidney, lung, brain, testis (Sertoli cells), thymus

SLC12: cation coupled chloride SLC12A1 NKCC2/BSC1 Sodium, potassium, C/Na+/K+/2Cl− Kidney-specific: apical chloride membrane of the thick as- cending limb SLC12A2 NKCC1/BSC2 Sodium, potassium, C/Na+/K+/2Cl− Ubiquitous: basolateral chloride membrane of epithelial cells. Also in non-epithelial cells SLC12A3 NCC/TSC Sodium, chloride C/Na+/Cl− Kidney-specific: apical membrane of the ; ? Membrane Transport Proteins 1373

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC12A4 KCC1 Potassium, chloride C/K+/Cl− Ubiquitous SLC12A5 KCC2 Potassium, chloride C/K+/Cl− -specific SLC12A6 KCC3 Potassium, chloride C/K+/Cl− Widespread SLC12A7 KCC4 Potassium, chloride C/K+/Cl− Widespread, minimal in brain SLC12A8 CCC9 Unknown Unknown Widespread SLC12A9 CIP Unknown Unknown Widespread

SLC13: cation sodium sulphate/carboxylate cotransporters + 2− SLC13A1 NaS1/NaSi-1, Na-sulfate Sulfate, selenate, thio- C/Na /SO4 /S2O3- Kidney, proximal tubular 2− sulfate SeO4 cells, brush border membrane SLC13A2 NaC1/NaDC-1, SDCT1, Succinate, citrate, C/Na+/succinate/cit- Kidney, intestine, brush NaDC-2 α-keto glutarate rate border membrane SLC13A3 NaC2/NaDC-3, SDCT2 Succinate, citrate, C/Na+/succinate/cit- Kidney proximal tubule α-keto glutarate rate basolateral membrane, liver, pancreas, brain, placenta + 2− SLC13A4 NaS2/SUT-1 Sulfate C/Na /SO4 Placenta, tonsillar high en- dothelial venules, testis, heart SLC13A5 NaC2/NaCT Citrate C/Na+/citrate/succi- Liver, brain, testis nate/pyruvate

SLC14: the family SLC14A1 UT-B1 (43)/UT3, JK, Kidd, Urea F/- Kidney (vasa recta, papillary UT11 epithelia) Erythrocytes, testes, brain, spleen SLC14A2 UT-A1 (97, 117)/UT1 Urea F/- Kidney (luminal membrane of inner medullary collecting duct, IMCD)

SLC15: the proton oligopeptide cotransporter family SLC15A1 PEPT1/oligopeptide C/H+ Intestine, kidney apical, ly- transporter 1, H+/peptide sosomal membrane transporter 1 SLC15A2 PEPT2/oligopeptide C/H+ Kidney, lung, brain, transporter 2, H+/peptide mammary gland, bronchial transporter 2 epithelium SLC15A3 PHT2 hPTR3/peptide/ Histidine, di- and C/H+ Lung, spleen, thymus (faintly histidine transporter 2, hu- tripeptides, protons in brain, liver, gland, heart) man peptidetransporter 3 SLC15A4 Peptide/histidine Histidine, di- and C/H+ Brain, retina, placenta transporter 1, peptide tripeptides protons transporter4

SLC16: the monocarboxylate transporter family SLC16A1 MCT1 Lactate, pyruvate, ke- C/H+ or E/monocar- Ubiquitous tone bodies boxylate SLC16A2 MCT8/XPCT (*was MCT7) T3, T4 (unpublished) F Liver, heart, brain, thymus, intestine, ovary, prostate, pancreas, placenta SLC16A3 MTC4/(*was MCT3) Lactate, pyruvate, ke- C/H+ Skeletal muscle, tone bodies chondrocytes, leukocytes, testis, lung, placenta, heart 1374 Membrane Transport Proteins

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC16A4 MTC5/(*was MCT4) O Brain, muscle, liver, kidney, lung, ovary, placenta, heart SLC16A5 MTC6/(*was MCT5) O Kidney, muscle, brain, heart, pancreas, prostate, lung, placenta SLC16A6 MTC7/(*was MCT6) O Brain, pancreas, muscle SLC16A7 MTC2 Pyruvate, lactate, ke- C/H+ Kidney, brain tone bodies SLC16A8 MTC3/REMP Lactate C/H+ (pH dependent) Retinal pigment epithelium, choroid plexus SLC16A9 MTC9 O Endometrium, testis, ovary, breast, brain, kidney, adrenal, retina SLC16- TAT1 Aromatic amino acids F Kidney, intestine, muscle, A10 (W,Y,F,L-Dopa) placenta, heart SLC16- MTC11 O Skin, lung, ovary, breast, A11 lung, pancreas, retinal pigment epithelium, choroid plexus SLC16- MTC12 O Kidney A12 SLC16- MTC13 O Breast, bone marrow stem A13 cells SLC16- MTC14 O Brain, heart, ovary, breast, A14 lung, pancreas retinal pigment epithelium, choroid plexus SLC17: the vesicular family SLC17A1 NPT1/NaPi1 Organic acids Unknown Na+ channel Kidney, liver phosphate chloride SLC17A2 NPT3 Unknown Heart, muscle, brain, pla- centa, lung, liver, kidney, pancreas SLC17A3 NPT4 Unknown Liver, kidney small intestine, testis SLC17A4 Na+/PO4− cotransporter Unknown Small intestine, colon, liver, homologue pancreas SLC17A5 /AST Sialic acid C/H+ Heart, brain, liver, lung, pancreas, placenta, muscle, uterus, bladder, kidney, spleen SLC17A6 vglut2/DNPI Glutamate E/H+ Brain (neurons only), endocine SLC17A7 vglut1/BNPI Glutamate E/H+ Brain (neurons only), endocine SLC17A8 vglut3 Glutamate E/H+ Brain (neurons and glia), liver, kidney

SLC18: the vesicular amine transporter family SLC18A1 VMAT1/CGAT, VAT1 5HT, Dopamine, E/H+ Adr gl(medulla), sympathetic adrenaline, ganglia (SIF-cells), carotid noradrenaline, body, skin (Merkel cells), GI histamine tract (EC cells) Membrane Transport Proteins 1375

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC18A2 VMAT2/SVAT, SVMT, VAT2 5HT, dopamine, E/H+ Brain (neurons), adr (MAT) adrenaline, gl(medulla), sympathetic noradrenaline, ganglia (neurons, SIF cells), histamine carotid body, intestine (neurons), stomach (neurons and ECL-cells), endocrine pancr, basoph, mast cells, dendritic cells and platelets SLC18A3 VAChT Acetylcholine E/H+ Brain (neurons), peripheral nervous system (neurons), intestine (neurons) SLC19: the / transporter family SLC19A1 RFT/RFC, FOLT N5-methyltetrahydro- E/OH− Ubiquitous/plasma mem- folate brane, also in mitochondrial membrane SLC19A2 ThTr1/ThT1 Thiamine E/H+ Ubiquitous/plasma membrane SLC19A3 ThTr2 Thiamine E/H+ Ubiquitous/plasma membrane SLC20: the type III Na+-phosphate cotransporter family + + SLC20A1 PiT/Gibbon ape leukemia Pi,Na C/Na /Pi Widely expressed-highest virus receptor 1; GLVR1; in bone marrow; likely Glvr-1 expressed on basolateral membranes of` polarized epithelia SLC20A2 + + SLC20A3 PiT-2/amphotropic murine Pi,Na C/Na /Pi Widely expressed-highest leukemia virus receptor; in bone marrow; likely Gibbon ape leukemia virus expressed on basolateral receptor 2; GLVR2; Glvr-2; membranes of` polarized MLVAR epithelia SLC21 family/organic anion transporting family: see OATP/SLCO family (below) Slco1a1 Oatp1a1 Bile salts, organic Liver (basolateral anions, organic membrane of hepatocytes), cations kidney (apical membrane of proximal tubule), choroid plexus (apical) SLCO1A2 OATP1A2 Bile salts, organic Brain (endothelial cells), anions, organic kidney, liver, ciliary body cations Slco1a3 Oatp1a3_v1 Oatp1a3_v2 Bile salts, organic Kidney anions Slco1a4 Oatp1a4 Digoxin, bile salts, Liver, blood-brain barrier, organic anions, choroid plexus, ciliary body, organic cations retina Slco1a5 Oatp1a5 Bile salts, organic Jejunum, choroids plexus anions Slco1a6 Oatp1a6 SLCO1B1 OATP1B1 Bile salts, organic Liver anions Slco1b2 Oatp1b2 Bile salts, organic Liver, ciliary body anions 1376 Membrane Transport Proteins

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLCO1B3 OATP1B3 Bile salts, organic an- Liver, lines ions, digoxin SLCO1C1 OATP1C1 Oatp1- T4, rT3, BSP Brain, testis (Leydig cells) Slco1c1 c1Oatp1c1 SLCO2A1 OATP2A1 Oatp2a1 Ubiquitously Slco2a1 Oatp2a1 SLCO2B1 OATP2B1 Oatp2b1 E-3-S, DHEAS, BSP Liver, placenta, ciliary body Slco2b1 SLCO3A1 OATP3A1 Oatp3a1 E-3-S, prostaglandin Ubiquitously Slco3a1 SLCO4A1 OATP4A1 Oatp4a1 Taurocholate, T3, Ubiquitously Slco4a1 prostaglandin SLCO4C1 OATP4C1 Kidney SLCO5A1 OATP5A1 SLCO6A1 OATP6A1 Testis Slco6b1 Oatp6b1 Oatp6b1 Taurocholate, T3, T4, Testis, epididymis, ovary, DHEAS adrenal gland Slco6c1 Oatp6c1 Taurocholate, T3, T4, Testis DHEAS Slco6d1 Oatp6d1

SLC22: the organic cation/anion/zwitterion transporter family SLC22A1 hOCT1 Organic cations, F Liver, sinusoidal membrane polyspecific of hepatocytes SLC22A2 hOCT2 Organic cations, F Kidney, basolateral mem- polyspecific brane of proximal tubules; brain, neurons SLC22A3 hOCT3/hEMT Organic anions, F Liver, skeletal muscle, polyspecific placenta, kidney, heart, lung, brain SLC22A4 hOCTN1 Organic anions, F or E/H+ Kidney, skeletal muscle, polyspecific placenta, prostate, heart + SLC22A5 hOCTN2/CT1 L-carnitine, organic C/Na and L-carnitine, Skeletal muscle, kidney cations, polyspecific F (for organic cations) (luminal membrane of proximal tubules), prostate, lung, pancreas, heart, small intestine, adrenal gland, thyroid gland, liver etc SLC22A6 hOAT1 Organic anions, E/organic anions Kidney, basolateral polyspecific membrane of proximal tubules; placenta, brain SLC22A7 hOAT2 Organic anions, F or E Liver, sinusoidal membrane polyspecific of hepatocytes; kidney, basolateral membrane of proximal tubules SLC22A8 hOAT3 Organic anions, E/organic anions Kidney, basolateral mem- polyspecific brane of proximal tubules; brain, luminal membrane of choroids plexus; skeletal muscle, developing bone SLC22A9 hUST3 Not determined O Liver SLC22A10 hOAT5 Not determined O Liver SLC22A11 hOAT4 Organic anions, poly- F or E Kidney, luminal membrane of specific proximal tubules, placenta Membrane Transport Proteins 1377

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC22A12 hURAT1 Urate E/organic anions Kidney SLC22A13 OCTL1/hORCTL3 Not determined O Kidney, colon, small intestine SLC22A14 OCTL2/hORCTL4 Not determined O Kidney, colon, small intestine SLC22A15 FLIPT1 Not determined O Kidney, brain, liver, skeletal muscle, heart, placenta, lung, spleen SLC22A16 hCT2/hFLIPT2, hOCT6 Carnitine F Testis, Sertoli cells and epididymdal duct cells, bone marrow, leukocytes, kidney SLC22A17 BOIT/BOCT Not determined O Brain

SLC23: the Na+-dependent ascorbic acid transporter family + SLC23A1 SVCT1/YSPL3, NCBT2 L-ascorbic acid C/Na Epithelial tissues including kidney, intestines, liver, ova- ry, prostate, and thymus, and in B-lymphocytes + SLC23A2 SVCT2/YSPL2, KIAA0238, L-ascorbic acid C/Na Widespread including brain NBTL1, NCBT1 (neurons), retina, placenta, spleen, prostate, testis, ova- ry, (rat SVCT2 also in lung, adrenal, osteoblast) SLC23A3 SVCT3/YSPL1, FLJ31168 SLC23A4 SVCT4

SLC24: the Na+/(Ca2+–K+) exchanger family SLC24A1 NCKX1 Na+,Ca2+,K+ E/4Na+,Ca2+,K+ Rod photoreceptors, platelets SLC24A2 NCKX2 Na+,Ca2+,K+ E/4Na+,Ca2+,K+ Brain, retinal cone photoreceptors, retinal ganglion cells SLC24A3 NCKX3 Na+,Ca2+,K+ E/4Na+,Ca2+,K+ Brain, aorta, uterus, intestine SLC24A4 NCKX4 Na+,Ca2+,K+ E/4Na+,Ca2+,K+ Brain, aorta, lung, thymus SLC24A5 NCKX5 Na+,Ca2+,K+

SLC25: the family SLC25A1 CIC (citrate carrier)/CTP, Citrate, malate, PEP E/citrate?H+/malat Liver, kidney, pancreas (also tricarboxylate carrier in brain, lung, heart)/inner mitochondrial membrane SLC25A2 ORC2 (ornithine carrier 2)/ Ornithine, citrulline, ly- E/ornithine/citrulline + Liver, testis, spleen, lung, ORNT2 sine, arginine, H+; ornithine/H+ pancreas, small intestine, histidine brain, kidney/inner mito- chondrial membrane SLC25A3 PiC (phosphate carrier)/ Phosphate C/phosphate + H+ Isoform A: heart, skeletal PTP E/phosphate/OH? muscle and diaphragm; isoform B: liver, kidney, brain, thymus, lung, heart, skeletal muscle, diaphragm/inner mitochondrial membrane 1378 Membrane Transport Proteins

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC25A4 AAC1 (ADP/ATP carrier 1)/ ADP, ATP E/ADP/ATP Heart, skeletal muscle, much ANT 1, T1, PEO2, PEO3, less in brain, pancreas, adenine nucleotide prostate, kidney, lung, translocator 1 thymus/inner mitochondrial membrane SLC25A5 AAC2 (ADP/ATP carrier 2)/ ADP, ATP E/ADP/ATP Brain, lung, kidney, ANT 2, T2 adenine pancreas, heart, skeletal nucleotide translocator 2 muscle, spleen/inner mitochondrial membrane SLC25- Pseudogene A5P1 SLC25A6 AAC3 (ADP/ATP carrier 3)/ ADP, ATP E/ADP/ATP Brain, lung, kidney, liver, ANT3, T3 adenine pancreas, heart, skeletal nucleotide translocator 3 muscle, spleen, thymus/in- ner mitochondrial mem- brane SLC25A7 UCP1 ( H+ F Brown adipose tissue/inner 1)/thermogenin, proton mitochondrial membrane carrier SLC25A8 UCP2 (uncoupling protein H+ F Brain, lung, kidney, spleen, 2)/proton carrier, UCPH heart/inner mitochondrial membrane SLC25A9 UCP3 (uncoupling protein H+ F Skeletal muscle, lung/inner 3) proton carrier mitochondrial membrane SLC25A10 DIC (dicarboxylate carrier) Malate, phosphate, E/malate/phosphate Liver, kidney, heart, brain, succinate, sulfate, lung, pancreas/inner thiosulfate mitochondrial membrane SLC25A11 OGC (oxoglutarate carrier)/ Oxoglutarate, malate E/oxoglutarate/malate Heart, skeletal muscle, liver, oxoglutarate/malate carrier kidney, brain, pancreas/inner mitochondrial membrane SLC25A12 AGC1 (aspartate/glu? Aspartate, glutamate E/aspartate/glutamate Brain, heart, skeletal tamate carrier 1)/aralar1 +H+ muscle, lung, pancreas, kidney, but not in liver/inner mitochondrial membrane SLC25A13 AGC2 (aspartate/glu? Aspartate, glutamate E/aspartate/glutamate Liver, kidney, pancreas, tamate carrier 2)/ +H+ heart, skeletal muscle, brain/ inner mitochondrial membrane SLC25A14 UCP5 (uncoupling protein H+ (?)homologous to Unknown Widely expressed, with 5)/BMCP1, brain mito- UCP1/2/3 highest levels in brain and chondrial carrier protein testis SLC25A15 ORC1 (ornithine carrier 1)/ Ornithine, citrulline, ly- E/ornithine/citrulline + Liver, pancreas, lung, ORNT1 sine, arginine H+; ornithine/H+ testis, small intestine, spleen, kidney, brain, heart/inner mitochondrial membrane SLC25- Pseudogene A15P SLC25A16 GDC (Graves’ disease CoA or a precursor of Unknown Liver, kidney, thyroid, lung, carrier)/GP CoA (?) heart, skeletal muscle, brain/ inner mitochondrial mem- brane Membrane Transport Proteins 1379

Solute Carriers (Continued)

Human Protein name/aliases Predominant Transport type/ Tissue distribution and gene name substrates coupling ions* cellular/subcellular expression

SLC25A17 ANC1 (peroxisomal ade- ATP E/ATP/AMP Brain, kidney, lung, heart, nine nucleotide carrier)/ liver, pancreas/peroxisomal ANT1, PMP34 membrane SLC25A18 GC2 (glutamate carrier 2) Glutamate C/glutamate + H+, Brain, testis, heart, pancre- E/glutamate/OH? as, kidney, lung/inner mito- chondrial membrane SLC25A19 DNC (deoxy? nucleotide dNDPs, dNTPs, E/dNDPs/ATP Brain, testis, lung, kidney, carrier)/MUP1 NDPs, ATP, ddNTPs liver, spleen, skeletal mus- cle, heart/inner mitochondri- al membrane SLC25A20 CAC (carnitine/acyl?carni- Carnitine, E/carnitine/acylcarni- Heart, skeletal muscle, liver tine carrier)/CACT, acylcarnitines tines F (at slow rate) (also in lung, kidney, brain, carnitine carrier pancreas, lung, placenta)/in- ner mitochondrial membrane SLC25- pseudogene A20P SLC25A21 ODC (oxoadipate carrier) Oxoadipate, E/oxoadipate/oxoglu- Kidney, gall bladder, colon, oxoglutarate tarate liver, placenta, testis, lung, spleen, skeletal muscle, brain, heart/inner mitochon- drial membrane SLC25A22 GC1 (glutamate carrier 1) Glutamate C/glutamate E+ H+ E/ pancreas, brain, liver, testis, glutamate/OH? spleen, kidney, heart, lung, small intestine/inner mito- chondrial membrane

SLC26: The Multifunctional Human gene Aliases Reported substrates Tissue distribution

2− SLC26A1 Sat-1 SO4 , oxalate Liver, kidney 2− − SLC26A2 DTDST SO4 ,Cl Widespread 2− − − SLC26A3 DRA, CLD SO4 ,Cl HCO3-, OH , oxalate Intestine, sweat gland, pancreas, prostate − − SLC26A4 Cl , HCO3-, I , formate Inner ear, kidney, thyroid SLC26A5 ? Inner ear 2 − − SLC26A6 CFEX, PAT-1 SO4,Cl , HCO3-, OH , oxalate, formate Widespread 2− − SLC26A7 None SO4 ,Cl , oxalate Kidney 2 − SLC26A8 Tat1 SO4,Cl , oxalate Sperm, brain 2− − SLC26A9 None SO4 ,Cl , oxalate Lung SLC26A10P None Pseudogene 2− SLC26A11 None SO4 Widespread SLC27: The Fatty Acid Transport Human gene Protein name/ Predominant substrates Transport type/ Tissue distribution and cellular/sub- name aliases coupling ions* cellular expression

SLC27A1 FATP1 Long-chain fatty acids Unknown Adipose tissue, muscle, brain, heart SLC27A2 FATP2/ Long-chain fatty acids Unknown Kidney cortex, liver VLACS SLC27A3 FATP3 Long-chain fatty acids Unknown Lung, multiple organs SLC27A4 FATP4 Long-chain fatty acids Unknown Intestine, brain, adipose tissue, muscle SLC27A5 FATP5/ Long-chain fatty acids Unknown liver VLCS-H2 1380 Membrane Transport Proteins

Solute Carriers (Continued)

Human gene Protein name/ Predominant substrates Transport type/ Tissue distribution and cellular/sub- name aliases coupling ions* cellular expression SLC27A6 FATP6/VLCS- Long-chain fatty acids Unknown heart H1 SLC28: the Na+-coupled nucleoside transport family SLC28A1 CNT1 Pyrimidine nucleosides, C/Na+/pyrimidine Liver, kidney, small intestine, adenosine nucleosides (epithelia apical membrane) SLC28A2 CNT2/SPNT Purine nucleosides, C/Na+/purine nu- Kidney (apical membrane), liver, uridine cleosides heart, brain, placenta, pancreas, skeletal muscle, colon, rectum, small intestine SLC28A3 CNT3 Broadly selective for C/2Na+/pyrimi- Pancreas, trachea, bone marrow, pyrimidines and purines dine and purine and mammary gland, intestine, lung, nucleosides placenta, prostrate, testis, and liver

SLC29: the facilitative family SLC29A1 ENT1 Purine and pyrimidine F Ubiquitous, plasma membrane (ba- nucleosides solateral in polarized renal epithelial cells) and perinuclear membranes SLC29A2 ENT2 Purine and pyrimidine F Ubiquitous, plasma membrane (ba- nucleosides and solateral in polarised renal epithelial nucleobases cells). Particularly abundant in skeletal muscle SLC29A3 ENT3 Purine and pyrimidine Not determined Widely distributed, possibly intracel- nucleosides and some lular nucleobases SLC29A4 ENT4 Adenosine Not determined Widely distributed

SLC30: the zinc efflux family SLC30A1 ZNT1 Zinc Unknown Widespreada SLC30A2 ZNT2 Zinc Unknown Widespreada SLC30A3 ZNT3 Zinc Unknown Glutamanergic neutrons SLC30A4 ZNT4/Dri27 Zinc Unknown Widespreada Secretory glands SLC30A5 ZNT5/ZTL1 Zincd Unknown Widespread; b cells SLC30A6 ZNT6 Zincd Unknown Widespreada SLC30A7 ZNT7/ZNTL2 Zinc Unknown Widespreada

aBy RNA analysis in rodents. bIn mouse. cOrphan transporter. dBy association only, no zinc-dependent described in mammalian cells.

SLC31: The Copper Transporter Family SLC31A1 hCtr1/hCtr1, Copper (I) Energy- Ubiquitous mRNA expression; high- Ctr1 independent/ est in liver, lowest in brain, and potassium skeletal muscle. Protein localized to dependent plasma membrane and intracellular vesicles of cultured cells SLC31A1P Pseudogene SLC32: the vesicular inhibitory amino acid transporter family SLC32A1 VIAAT/VGAT GABA, glycine E/H+ CNS SLC33: the acety-CoA transporter family SLC33A1 ACATN/AT-1 Acetyl-CoA F Brain, spinal cord, prostate, placenta, uterus, testis, thymus, trachea/ endoplasmic reticulum Membrane Transport Proteins 1381

Solute Carriers (Continued)

SLC34: the type II Na+-phosphate cotransporter family =- SLC34A1 NaPi-lla/NaPi-3 Inorganic phosphate C/Na/HPO4 Kidney (proximal tubules; apical) osteoclasts, neurons =- SLC34A1P NaPi-llb Inorganic phosphate C/Na/HPO4 Sall intestine, lung, testis, liver, se- creting mammary gland =- SLC34A2 NaPi-llc inorganic phosphate C/Na/HPO4 Kidney (proximal tubules, apical) SLC35: the nucleoside-sugar transporter family SLC35A1 CMP-Sia trans- CMP-sialic acid E/CMP Ubiquitous/golgi porter/CST SLC35A2 UDP-Gal trans- UDP-galactose, UDP-N- E/UMP Ubiquitous/golgi porter/UGT acetylgalactosamine SLC35A3 UDP-GlcNAc UDP-N-acetylglucosamine E/UMP Ubiquitous/golgi transporter/ UGTrel2 SLC35C1 GDP-Fuc GDP-fucose E/GMP Ubiquitous/golgi transporter/ FUCT1 SLC35D1 -/UGTrel7 UDP-glucuronic acid, E/ Ubiquitous/ER UDP-N-acetylgalactosamine

SLC36: the proton-coupled amino acid transporter family SLC36A1 PAT1/LYAAT1 Gly, Ala, Pro, GABA, D-Ala, C/H+ Brain (neurons), intestine, colon, MeAIB kidney, lung, liver, spleen/lysosomes (neurons), apical membrane (Caco- 2 cells) SLC36A2 PAT2/tramdor- Gly, Ala, Pro C/H+ Lung, heart, kidney, muscle, testis, in1 spleen, adrenal gland, thymus, sci- atic nerve (Schwann cells)

SLC37: the sugar-phosphate/phosphate exchanger family SLC37A1 SPX1/G3PP Glycerol 3-phosphate (?) E/inorganic Adult bone marrow, colon, small phosphate (?) intestine, kidney, liver and other tissues. Fetal liver, spleen and other tissues SLC37A2 SPX2/Ci2 Unknown Unknown ESTs from several tissues SLC37A3 SPX3 Unknown Unknown EST from several tissues, high level in breast and stomach SLC37A4 SPX4/G6PT1 Glucose-6-phosphate E/inorganic Strongly expressed in liver, kidney phosphate and hematopoietic progenitor cells SLC38: the system A and N, sodium-coupled neutral amino acid transporter C/Na+ Brain (glutamatergic and GABAergic neurons, ependyma), retina, heart, placenta and adrenal grand SLC38A2 SNAT2/ATA2 Alanine, asparagine, C/Na+ Widespread, including brain and KIAA1382 SA1 cysteine, glutamine, glycine, spinal cord (neurons), placenta, SAT2 histidine, , proline, adrenal glands, testis, thymus, serine muscle, liver, intestine, kidney, lung, adipose, spleen, skin SLC38A4 SNAT4/ATA3 Alanine, asparagine, C/Na+ Liver, skeletal muscle, kidney, pan- FLJ10191 cysteine, glycine, serine, creas NAT3 PAAT threonine SAT3 SLC38A3 SNAT5/JM24 Glutamine, histidine C/Na+ + Astrocytes in the brain and retina; SN2 E/H+ liver, kidney, and adipose SLC38A5 SNAT5/JM24 C/Na+ + Stomach, brain, liver, lung, small SN2 E/H+ intestine, spleen, colon, kidney 1382 Membrane Transport Proteins

Solute Carriers (Continued)

SLC39: the metal ion transporter family SLC39A1 hZIP1/ZIRTL Zinc Unknown Widespread/plasma membrane and intracellular vesicles SLC39A2 hZIP2/6A1 Zinc Unknown Prostate, uterus, cervical epithelium, optic nerve, monocytes,/plasma membrane SLC39A3 hZIP3 Unknown Unknown Widespread SLC39A4 hZIP4 Zinc Unknown Small intestine, stomach, colon, cecum, kidney/plasma membrane SLC39A5 Unknown Unknown Kidney, liver, spleen, colon, stomach, pancreas SLC39A6 LIV-1 Unknown Unknown Widespread/unknown SLC39A7 KE4 Manganese Unknown Widespread/endoplasmic reticulum SLC39A8 BIGM103 Zinc Unknown Widespread/unknown SLC39A9 Unknown Unknown Widespread/unknown SLC39A10 Unknown Unknown Widespread/unknown SLC39A11 Unknown Unknown Widespread/unknown SLC39A12 Unknown Unknown Brain, lung, testis, retina/unknown SLC39A13 Unknown Unknown Widespread/unknown SLC39A14 Unknown Unknown Widespread/unknown

SLC40: the basolateral iron transporter family SLC40 IREG1/ferro- Ferrous iron Facilitated? Basolateral membrane in duodenum, portin, MTP1 spleen red pulp macrophages plasma membrane, liver Kupffer cells PM, Placenta, kidney

SLC41: MgtE-like magnesium transporter family SLC41A1 Mg2+,Sr2+,Zn2+,Cu2+,Fe2+, Heart, testis, skeletal muscle, Co2+,Ba2+,Cd2+ prostate, adrenal gland, thyroid - low expression in most tissues SLC41A2 Mg2+,Ba2+,Ni2+,Co2+,Fe2+, Mn2+ SLC41A3 SLC42: Rh ammonium transporter family + + SLC42A1 RhAG NH4 H Red blood cells (cell membrane) + SLC42A2 RhBG NH4 Kidney, Liver (basolateral mem- brane) + SLC42A3 RhCG NH4 ? Kidney (apical membrane), Brain, Testis, Placenta, Pancreas, Prostate

SLC43: Na+-independent, system-L like amino acid transporter family SLC43A1 Neutral amino acids F Pancreas and liver SLC43A2 Neutral amino acids F Placenta, kidney, and intestine SLC43A3 Fetal liver, lung, placenta, and kid- ney

SLC44: choline-like transporter family SLC44A1 Choline Na+- Cerebrocortical neurons independent SLC44A2 SLC44A3 SLC44A4 SLC44A5

SLC45: putative sugar transporter family SLC45A1 DNB5 SLC45A2 AIM-1 Membrane Transport Proteins 1383

Solute Carriers (Continued)

SLC45A3 IPCA-6, pros- tein SLC45A4

SLC46: Heme transporter family SLC46A1 HCP1 Fe-heme Intestine/apical membrane SLC46A2 TSCOT SLC46A3 *Transport type: C, Cotransporter; E, exchanger; F, facilitated transporter; O, orphan transporter.

Transport ATPases (ATP-Powered Pumps) Transport ATPases are primarily active transporters, mitochondria. Both transport protons (H+) in a process which use the energy of ATP hydrolysis to move ions or that does not involve a phosphoprotein intermediate. small molecules across the membrane against a While V-class pumps use the energy derived from ATP chemical concentration gradient or electric potential. hydrolysis to pump protons into vesicles, F-class pumps There are two major groups of active transport ATPases, function to power the synthesis of ATP from ADP and Pi those which actively transport ions (P-ATPases, V- by movement of protons from the exoplasmic to the ATPases, F-ATPases) and the superfamily of ATP- cytosolic of the membrane down the proton electro- binding cassette (ABC) transporters, which couple the chemical gradient. They are important in ATP synthesis hydrolysis of ATP with the transport of a huge variety of in mitochondria. The class of ▶ATP-binding cassette small molecules as well as ions. Many ▶P-class ion (ABC) transporters is much larger and more diverse than pumps (P-ATPases) are tetramers, composed of two the ion pumps. Each ABC transporter is specific for a α and two β subunits. The α subunit contains an single substrate or a group of related substances ATP-. During the transport process, at least including ions and many small molecules. ABC one of the α subunits is phosphorylated (P), and the transporters share a common organization, consisting transported ions are thought to move through the of four “core” domains: two transmembrane domains, phosphorylated subunit. The smaller β subunit may have which form the passageway used by transported regulatory functions. ▶F-class and V-class ion pumps molecules, and two cytosolic ATP-binding domains. (F-ATPases and V-ATPases) have much more compli- These four “core” domains can be present on four cated structures than P-class pumps. They contain at least separate proteins or the “core” domains are fused into three kinds of transmembrane proteins and five kinds of one or two multidomain proteins. In all ATP-powered extrinsic polypeptides that form the cytosolic domain. pumps, the hydrolysis of ATP is tightly coupled to the V-class pumps are mainly found in lysosomes and other transport process (▶Multidrug transporter). acidic vesicles, whereas F-class pumps are found in

P-Type ATPases

Gene Name/aliases Function ATP1A1 NaKα1Na+/K+ transporting ATPase, α1 polypeptide ATP1A2 NaKα2Na+/K+ transporting ATPase, α2 (+) polypeptide ATP1A3 NaKα3Na+/K+ transporting ATPase, α3 polypeptide ATP1A4 NaKα4Na+/K+ transporting ATPase, α4 polypeptide ATP1B1 Na+/K+ transporting ATPase, β1 polypeptide ATP1B2 Na+/K+ transporting ATPase, β2 polypeptide ATP1B3 Na+/K+ transporting ATPase, β3 polypeptide ATP1B4 Na+/K+ transporting ATPase, β4 polypeptide ATP1BL1 Na+/K+ transporting ATPase, β polypeptide-like 1 ATP2A1 SERCA1 Ca2+ transporting ATPase, cardiac muscle, fast twitch 1 ATP2A2 SERCA2 Ca2+ transporting ATPase, cardiac muscle, slow twitch 2 ATP2A3 SERCA3 Ca2+ transporting ATPase, ubiquitous 1384 Membrane Transport Proteins

P-Type ATPases (Continued)

Gene Name/aliases Function

ATP2B1 PMCA1 Ca2+ transporting ATPase, plasma membrane 1 ATP2B2 PMCA2 Ca2+ transporting ATPase, plasma membrane 2 ATP2B3 PMCA3 Ca2+ transporting ATPase, plasma membrane 3 ATP2B4 PMCA4 Ca2+ transporting ATPase, plasma membrane 4 ATP2C1 PMR1 Ca2+ transporting ATPase, type 2C, member 1 ATP3 Mg2+ transporting ATPase ATP4A ATP6A H+/K+ exchanging ATPase, α polypeptide ATP4B ATP6B H+/K+ exchanging ATPase, β polypeptide ATP7A MNK Cu2+ transporting ATPase, α polypeptide (Menkes syndrome) ATP7B WND Cu2+ transporting ATPase, β polypeptide (Wilson disease) ATP8A1 ATPIA, APLT ATPase, aminophospholipid transporter, Class I, 8A/1 ATP8A2 ATPIB, ML-1 ATPase, aminophospholipid transporter-like, Class I, 8A/2 ATP8B1 ATPIC, PFIC ATPase, Class I, type 8B, member 1 ATP8B2 ATPID ATPase, Class I, type 8B, member 2 ATP8B3 ATPIK ATPase, Class I, type 8B, member 3 ATP8B4 ATPIM ATPase, Class I, type 8B, member 4 ATP8B5 ATPIN ATPase, Class I, type 8B, member 5 ATP9A ATPIIA ATPase, Class II, type 9A ATP9B ATPIIB ATPase, Class II, type 9B ATP10A ATPVA ATPase, Class V, type 10A ATP10B ATPVB ATPase, Class V, type 10B ATP10C ATPVC ATPase, Class V, type 10C ATP10D ATPVD ATPase, Class V, type 10D ATP11A ATPIH, ATPIS ATPase, Class VI, type 11A ATP11B ATPIF, ATPIR ATPase, Class VI, type 11B ATP11C ATPIG, ATPIQ ATPase, Class VI, type 11C ATP12A ATP1AL1 H+/K+ transporting ATPase, nongastric, α polypeptide

V-Type ATPases

Gene Name/aliases Function

ATP6IP1 ORF, XAP-3 H+ transporting ATPase, lysosomal interacting protein 1 ATP6IP2 APT6M8-9 H+ transporting ATPase, lysosomal interacting protein 2 ATP6V0A1 a1, Vph1 H+ transporting ATPase, lysosomal V0 subunit a isoform 1 ATP6V0A2 TJ6, ATP6a2 H+ transporting ATPase, lysosomal V0 subunit a isoform 2 ATP6V0A4 VPP2 H+ transporting ATPase, lysosomal V0 subunit a isoform 4 ATP6V0B VMA16 H+ transporting ATPase, lysosomal 21 kDa, V0 subunit c’ ATP6V0C VATL, Vma3 H+ transporting ATPase, lysosomal 16 kDa, V0 subunit c ATP6V0D1 VATX H+ transporting ATPase, lysosomal 38 kDa, V0 subunit d 1 ATP6V0D2 H+ transporting ATPase, lysosomal 38 kDa, V0 subunit d 2 ATP6V0E Vma21p H+ transporting ATPase, lysosomal 9 kDa V0 subunit e ATP6V1A1 Vma1 H+ transporting ATPase, lysosomal 70 kDa, V1 subunit A 1 ATP6V1B1 VATB, Vma2 H+ transporting ATPase, lysosomal 56/58 kDa, V1 subunit B1 ATP6V1B2 VATB, Vma2 H+ transporting ATPase, lysosomal 56/58 kDa, V1 subunit B2 ATP6V1C1 VATC, Vma5 H+ transporting ATPase, lysosomal 42 kDa, V1 subunit C1 ATP6V1C2 H+ transporting ATPase, lysosomal 42 kDa, V1 subunit C2 ATP6V1D VATD, VMA8 H+ transporting ATPase, lysosomal 34 kDa, V1 subunit D ATP6V1E1 P31, Vma4 H+ transporting ATPase, lysosomal 31 kDa, V1 subunit E1 ATP6V1E2 MGC9341 H+ transporting ATPase, lysosomal 31 kDa, V1 subunit E-like 2 ATP6V1El1 H+ transporting ATPase, lysosomal 31 kDa, V1 subunit E-like 1 Membrane Transport Proteins 1385

V-Type ATPases (Continued)

Gene Name/aliases Function

ATP6V1F VATF, Vma7 H+ transporting ATPase, lysosomal 14 kDa, V1 subunit F ATP6V1G1 Vma10 H+ transporting ATPase, lysosomal 13 kDa, V1 subunit G1 ATP6V1G2 Vma10 H+ transporting ATPase, lysosomal 13 kDa, V1 subunit G2 ATP6V1G3 Vma10 H+ transporting ATPase, lysosomal 13 kDa, V1 subunit G3 ATP6V1H SFD, VMA13 H+ transporting ATPase, lysosomal 50/57 kDa V1 subunit H

F-Type ATPases

Gene Name/aliases Function

ATP5A1 hATP1 H+ transporting ATP synthase, mitochondrial F1 complex, ε 1 (cardiac) ATP5A2 H+ transporting ATP synthase, mitochondrial F1 complex, α 2, (non-cardiac) ATP5AL1 H+ transporting ATP synthase, mitochondrial F1 complex, α1 cardiac-like 1 ATP5AL2 H+ transporting ATP synthase, mitochondrial F1 complex, α 2, non-cardiac-like 2 ATP5B ATPSB H+ transporting ATP synthase, mitochondrial F1 complex, β polypeptide ATP5BL1 ATPSBL1 H+ transporting ATP synthase, mitochondrial F1 complex, β polypeptide -like 1 ATP5BL2 ATPSBL2 H+ transporting ATP synthase, mitochondrial F1 complex, β polypeptide -like 2 ATP5C1 ATP5CL1 H+ transporting ATP synthase, mitochondrial F1 complex, γ polypeptide 1 ATP5C2 ATP5CL2 H+ transporting ATP synthase, mitochondrial F1 complex, γ polypeptide 2 ATP5D H+ transporting ATP synthase, mitochondrial F1 complex, δ subunit ATP5E H+ transporting ATP synthase, mitochondrial F1 complex, ε subunit ATP5F1 H+ transporting ATP synthase, mitochondrial F0 complex, subunit b, isoform 1 ATP5G1 ATP5G H+ transporting ATP synthase, mitochondrial F0 complex, subunit c, isoform 1 ATP5G2 H+ transporting ATP synthase, mitochondrial F0 complex, subunit c, isoform 2 ATP5G3 H+ transporting ATP synthase, mitochondrial F0 complex, subunit c, isoform 3 ATP5H ATPQ, ATP5JD H+ transporting ATP synthase, mitochondrial F0 complex, subunit d ATP5I H+ transporting ATP synthase, mitochondrial F0 complex, subunit e ATP5J H+ transporting ATP synthase, mitochondrial F0 complex, subunit F6 ATP5J2 F1Fo-ATPase H+ transporting ATP synthase, mitochondrial F0 complex, subunit f, isoform 2 ATP5L ATP5JG H+ transporting ATP synthase, mitochondrial F0 complex, subunit g ATP5O OSCP, ATPO H+ transporting ATP synthase, mitochondrial F1 complex, O subunit

ABC-Transporter

Gene Name/aliases Function ABCA1 ABC1 Cholesterol efflux onto HDL ABCA2 ABC2 Drug resistance ABCA3 ABCC ABCA4 ABCR Rod photoreceptor retinoid transport ABCA5 ABCA6 ABCA7 ABCA8 ABCA9 ABCA10 ABCA12 ABCA13 1386 Membrane Transport Proteins

ABC-Transporter (Continued)

Gene Name/aliases Function

ABCB1 PYG1, MDR Multidrug resistance ABCB2 TAP1 Peptide transport ABCB3 TAP2 Peptide transport ABCB4 PGY3 Phosphatidylcholine (PC) transport ABCB5 ABCB6 MTABC3 Iron transport ABCB7 ABC7 Fe/S cluster transport ABCB8 MTABC1 ABCB9 ABCB10 MTABC2 ABCB11 SPGP Bile salt transport

ABCC1 MRP1 Drug resistance, LTC4 transport ABCC2 MRP2 Organic anion efflux ABCC3 MRP3 Drug resistance, organic anion transport ABCC4 MRP4 Nucleoside transport, cyclic nucleotide transport ABCC5 MRP5 Nucleoside transport, cyclic nucleotide transport ABCC6 MRP6 ABCC7 CFTR Chloride ABCC8 SUR Sulfonylurea receptor ABCC9 SUR2 ABCC10 MRP7 ABCC11 ABCC12 ABCD1 ALD Very long chain fatty acid transport regulation ABCD2 ALDL1 ABCD3 PXMP1 ABCD4 PMP69 ABCE1 OABP Oligoadenylate binding protein ABCF1 ABC50 ABCF2 ABCF3 ABCG1 White Cholesterol transport? ABCG2 ABCP Toxin efflux, drug resistance ABCG4 White2 ABCG5 White3 Sterol transport ABCG8 Sterol transport Adhesion Molecules

Adhesion molecules are transmembrane proteins, which some adhesion molecules are passive in their adhesive through their extracellular part mediate the interaction of function, the adhesiveness of other adhesive molecules cells with other cells or with extracellular components can be regulated. Some adhesive proteins are very similar like the extracellular matrix. On the basis of structural and to receptors, in that they not only bind other molecules functional similarities, most adhesion molecules can be with high selectivity and affinity, but are also able to grouped into families like cadherins, integrins, selectins, transduce the binding into an intracellular signal. the immunoglobulin superfamily or the syndecans. While

Cadherins Cadherins are characterized by the presence of 4–7 cadherins are subdivided into four subfamilies, the type I cadherin repeats of about 110 amino acids, which are classic cadherins, the type II classic cadherins, the present in the extracellular part of the protein. Cadherins desmosomal cadherins and the so-called “other classic mediate Ca2+-dependent homophilic adhesion. The cadherins”. The protocadherins represent a recently specificity of this homophilic interaction is generated discovered subfamily, which contain more than five by sequence differences at the adhesive face of the N- extracellular cadherin domains. This subfamily, which terminal cadherin domain. Cadherins have to dimerize in consists of far more than 50 protocadherins are less well order to bind cadherins in a Ca2+-dependent manner on studied, but may also mediate Ca2+-dependent homo- different cell. Cadherins are divided into two subfamilies, philic adhesion (▶Cadherins). the classic cadherins and the protocadherins. Classic

Classic Cadherins

Cadherin Symbol Distribution Type I E-cadherin CDH1 Non-neural epithelial cells during development N-cadherin CDH2 Adult neural tissue, cardiac and skeletal muscle, lens, endothelial cells in the embryo P-cadherin CDH3 Placenta, epidermis and mammary gland R-cadherin CDH4 Developing epithelia in the kidney, lung, thymus, early optic nerve glia Type II VE-cadherin CDH5 Endothelium, intercellular junctions K-cadherin CDH6 Kidney, brain, cerebellum Cadherin-7 CDH7 Cadherin-8 CDH8 Brainstem, cerebellum, thymocytes T1-cadherin CDH9 T2-cadherin CDH10 OB-cadherin CDH11 Bone Br-cadherin CDH12 Central nervous system Cadherin-14 CDH14 Central nervous system M-cadherin CDH15 Myoblasts, regenerating skeletal muscle myoblasts Ey-cadherin CDH18 Cadherin-19 CDH19 Cadherin-20 CDH20 1388 Adhesion Molecules

Classic Cadherins (Continued)

Cadherin Symbol Distribution Other H-cadherin CDH13 Heart and breast epithelium, vascular smooth muscle cells Ksp-cadherin CDH16 Kidney LI-cadherin CDH17 Liver and intestine Desmosomal Desmocollin 1 DSC1 Epidermis Desmocollin 2 DSC2 Epithelia, lymph nodes, heart Desmocollin 3 DSC3 Desmoglein 1 DSG1 Keratinizing epodermis Desmoglein 2 DSG2 Simple and stratified epithelia Desmoglein 3 DSG3 Epidermis, tongue, tonsil, esophagus

Protocadherins

Protocadherins Symbol Alias

Protocadherin 1 (cadherin-like 1) PCDH1 PC42 BH-protocadherin (brain-heart) PCDH7 BH-PCDH Protocadherin 8 PCDH8 PAPC, ARCADLIN Protocadherin 9 PCDH9 Protocadherin 10 PCDH10 OL-PCDH, KIAA1400 Protocadherin 11 PCDH11 Protocadherin 12 PCDH12 LOC51294, VE-cadherin-2 Protocadherin 14 PCDH14 Protocadherin 15 PCDH15 Protocadherin 16 PCDH16 FIB1 Protocadherin 17 PCDH17 PCDH68, PCH68 Protocadherin 18 PCDH18 KIAA1562, PCDH68-like Protocadherin 19 PCDH19 Protocadherin 20 PCDH20 PCDH13 Protocadherin α PCDHA@ CNRS1 Protocadherin β locus PCDHB@ PCDH3 Protocadherin γ locus PCDHG@ PCDH2, PCDH4 Protocadherin α 1 PCDHA1 Protocadherin α 2 PCDHA2 Protocadherin α 3 PCDHA3 Protocadherin α 4 PCDHA4 Crnr1, Cnr1 Protocadherin α 5 PCDHA5 Crnr6, Cnr6, CNRS6 Protocadherin α 6 PCDHA6 Crnr2, Cnr2, CNRS2 Protocadherin α 7 PCDHA7 Crnr4, Cnr4, CNRS4 Protocadherin α 8 PCDHA8 Protocadherin α 9 PCDHA9 Protocadherin α 10 PCDHA10 Crnr8, Cnr8, CNRS8 Protocadherin α 11 PCDHA11 Crnr7, Cnr7, CNRS7 Protocadherin α 12 PCDHA12 Protocadherin α 13 PCDHA13 Crnr5, Cnr5, CNRS5 Protocadherin α subfamily C1 PCDHAC1 Protocadherin α subfamily C2 PCDHAC2 Protocadherin α constant PCDHACT PCDHAC Protocadherin β 1 PCDHB1 Protocadherin β 2 PCDHB2 Protocadherin β 3 PCDHB3 Protocadherin β 4 PCDHB4 Adhesion Molecules 1389

Protocadherins (Continued)

Protocadherins Symbol Alias

Protocadherin β 5 PCDHB5 Protocadherin β 6 PCDHB6 Protocadherin β 7 PCDHB7 Protocadherin β 8 PCDHB8 Protocadherin β 9 PCDHB9 Protocadherin β 10 PCDHB10 Protocadherin β 11 PCDHB11 Protocadherin β 12 PCDHB12 Protocadherin β 13 PCDHB13 Protocadherin β 14 PCDHB14 Protocadherin β 15 PCDHB15 Protocadherin γ subfamily A, 1 PCDHGA1 Protocadherin γ subfamily A, 2 PCDHGA2 Protocadherin γ subfamily A, 3 PCDHGA3 Protocadherin γ subfamily A, 4 PCDHGA4 Protocadherin γ subfamily A, 5 PCDHGA5 Protocadherin γ subfamily A, 6 PCDHGA6 Protocadherin γ subfamily A, 7 PCDHGA7 Protocadherin γ subfamily A, 8 PCDHGA8 Protocadherin γ subfamily A, 9 PCDHGA9 Protocadherin γ subfamily A, 10 PCDHGA10 Protocadherin γ subfamily A, 11 PCDHGA11 Protocadherin γ subfamily A,12 PCDHGA12 KIAA0588 Protocadherin γ subfamily B, 1 PCDHGB1 Protocadherin γ subfamily B, 2 PCDHGB2 Protocadherin γ subfamily B, 3 PCDHGB3 Protocadherin γ subfamily B, 4 PCDHGB4 Protocadherin γ subfamily B, 5 PCDHGB5 Protocadherin γ subfamily B, 6 PCDHGB6 Protocadherin γ subfamily B, 7 PCDHGB7 Protocadherin γ subfamily C, 3 PCDHGC3 PCDH2, PC-43 Protocadherin γ subfamily C, 4 PCDHGC4 Protocadherin γ subfamily C, 5 PCDHGC5 Protocadherin γ constant PCDHGCT PCDHGC

Integrins Integrins consist of an α and β subunit, which form a systems (“inside-out signaling”), which are mediated dimer. They mediate the interaction of cells with the through complex cytoskeletal interactions with the extracellular matrix or with proteins on other cells. cytoplasmic tails of the subunits. Binding of a Both, the α and the β subunit take part in binding of the ligand to an integrin can result in an intracellular signal ligands. The function of the integrin is modulated by (“outside-in signaling”)(▶Integrins). signals from within the cell delivered via other receptor

Integrins

Integrin Ligand Distribution

α1β1 Collagen, laminin Widespread, embryogenesis, smooth muscle cells and liver, hemopoietic cells

α2β1 Echovirus 1, , collagen types I-IV, laminin, E-cadherin, Stimulated T cells, fibroblasts, endothelium, tenoscin peripheral nerves, platelets

α3β1 Epiligrin, fibronectin, invasin, thrombospondin, netrin-1 Monocytes, B and T cells, kidney, thyroid, most non-lymphoid adherent cell lines 1390 Adhesion Molecules

Integrins (Continued)

Integrin Ligand Distribution

α4β1 Fibronectin, invasin, VCAM-1, thrombospondin, ICAM-4, Leucocytes, hemopoietic precursors, muscle

α4β7 Fibronectin, MAdCAM-1, VCAM-1, osteopontin Mucosal lymphocytes, NK cells, eosinophils α5β1 Fibronectin, fibrinogen, invasin, denatured collagen, COMP, Widespread in embryonic and adult tissues fibrillin, L1, thrombospondin, osteopontin

α6β1 Invasin, laminin, sperm fertilin, Cyr61, thrombospondin Epithelia, hemopoietic tissues α6β4 Laminin, netrin-1 Stratified epithelia, Schwann cells and some endothelia

α7β1 Laminin types 1,2,4 Expression during , developing nervous system

α8β1 Cytotactin/tenascin-C, fibronectin, osteopontin, LAP-TGFβ, Smooth muscle, kidney nephronectin, POEM

α9β1 Cytotactin/tenascin-C, VEGF-C, VEGF-D, osteopontin Epithelia, muscle, liver α10β1 Collagen type II, laminin Chondrocytes, skeletal muscle, heart αEβ7 E-cadherin Intraepithelial lymphocytes, subpopulation of T cells in the lamina propria

αLβ2 ICAM-1, ICAM-2,3,4,5, ESM-1, ICAM-4 Lymphocytes, monocyte lineage cells and other leucocytes, during activation

αMβ2 Candida albicans, , fibrinogen, complement fragment Neutrophils, monocytes, eosinophils and ba- iC3b, ICAM-1, neutrophil inhibitory factor, ICAM-4 sophils, NK cells

αDβ2 ICAM-3, VCAM-1, Cyr61, fibrinogen, fibronectin, plasminogen, Peripheral leucocytes, tissue macrophages

αxβ2 Fibrinogen, complement fragment iC3b, ICAM-4 Tissue macrophages and monocytes αvβ1 Fibronectin, vitronectin, L1, LAP-TGFβ αvβ3 Adenovirus penton base protein, bone sialoprotein, denatured Endothelium, smooth muscle, some activated collagen, cytotactin/tenascin-C, disintegrins, fibronectin, macrophages and T cells, platelets fibrinogen, HIV Tat protein, laminin, matrix metalloproteinase-2, osteopontin, prothrombin, thrombospondin, vitronectin, von Willebrand factor, ICAM-4, MMP-2, L1, LAP-TGFβ

αvβ5 Adenovirus penton base protein, bone sialoprotein, fibronectin, More widely than αvβ3, regulated in HIV Tat protein, vitronectin, LAP-TGFβ, osteopontin angiogenesis

αvβ6 Cytotactin/tenascin-C, fibronectin, LAP-TGFβ, osteopontin Epithelial cells αvβ8 Fibronectin, LAP-TGFβ Placenta, kidney, brain, ovary, uterus, synapses, glia

αIIbβ3 Fibrinogen, plasminogen, prothrombin, , Borrelia Platelets, megacaryocytes burgdorferi, denatured collagen, decorsin, disintegrins, fibronectin, thrombospondin, vitronectin, von Willebrand factor, Cyr61, ICAM-4, L1

Selectins The three selectins are related both structurally and repeat and a variable number of complement control functionally. They are transmembrane proteins, with an protein (CCP) domains. Selectins bind carbohydrates, N-terminal C-type actin domain, followed by an EGF which are present of various glycoproteins.

Selectin Ligands Distribution E-selectin ESL-1, PSGL-1, leucocyte L-selectin Activated endothelial cells L-selectin CD34, GlyCAM-1, MAdCAM-1, PSGL-1 Leucocytes Adhesion Molecules 1391

Syndecans Syndecans are transmembrane proteins, which are chains. Binding specificities may vary depending on modified by the addition of heparan sulfate glycosamino- cell-type specific modifications of the heparan sulfate glycan (GAG) chains and other sugars. Syndecans bind a chains. wide variety of different ligands via their heparan sulfate

Syndecan Ligands Distribution

Syndecan-1 Growth factors, extracellular matrix components Epithelial cells, vascular smooth muscle cells, (fibronectin, laminin, collagens), other adhesion endothelium, neural cells, pre-B cells, immature receptors (L-selectin, NCAM, CD31) and enzymes B cells and plasma cells Syndecan-2 Growth factors, extracellular matrix components Fibroblasts during development, primary human (fibronectin, laminin, collagens), other adhesion monocytes, in response to differentiation/ receptors (L-selectin, NCAM, CD31) and enzymes activation Syndecan-3 Growth factors, extracellular matrix components Neuronal cells, during development (fibronectin, laminin, collagens), other receptors (L-selectin, NCAM, CD31) and enzymes Syndecan-4 Include growth factors, extracellular matrix components Many epithelial and fibroblastic cells, localized to (fibronectin, laminin, collagens), other receptors focal adhesion (L-selectin, NCAM, CD31) and enzymes

Immunoglobulin Superfamily The immunoglobulin superfamily represents a very large of all transmembrane proteins belong into this super- group of transmembrane proteins, which are chara- family. However, not all of them function as adhesion cterized by the presence of one or more extracellular molecules. Examples of immunoglobulin superfamily immunoglobulin domains of about 100 amino acids proteins which function as adhesion molecules are listed each. This structural motif is very widely used in below. transmembrane proteins. It is estimated that up to 1/3

Immunoglobulin Superfamily

Integrin Ligand Distribution

AMOG Not known Glia ALCAM CD6, homophilic adhesion, NgCAM Neurons, epithelial cells, fibroblasts, activated T cells, activated monocytes BL-CAM CD45 B-lymphocytes CD22 Sialoglycoconjugate NeuAcα2-6Galβ1-4GlcNAc Mature peripheral B cells present on N-linked carbohydrates

CD31 Homophilic adhesion, integrin αvβ3, Endothelial cells, platelets, monocytes, (PECAM-1) glycosaminoglycans granulocytes and other leucocytes CD33 Sialoglycoconjugate NeuAcα2-3Galβ1-3(4) Myelomonocytic precursors GlcNAc and NeuAcα2-3Galβ1-3GlcNAc on glycoproteins CD44 Hyaluronin, , fibronectin, osteopontin Lymphocytes, epithelial cells CD96 Not known Up-regulated following T cells activation, expressed by most T cell lines CD147 Interstitial collagenase (MMP-1) Widely expressed in embryonic and adult tissues CEACAM Mediates homophilic cell-cell adhesion, E-selectin Granulocytes, epithelial cells family Contactin-1 CASPR Adult brain

ICAM-1 Integrins αLβ2, αMβ2 and αXβ2, rhinoviruses, Wide range of both hematopoietic and Plasmodium falciparum-infected erythrocytes non-hematopoietic cells 1392 Adhesion Molecules

Immunoglobulin Superfamily (Continued)

Integrin Ligand Distribution

ICAM-2 Integrins αLβ2 and αMβ2 Subpopulation of lymphocytes, monocytes, splenic sinusoids, dendritic cells, platelets, stromal cells and at high levels on vascular endothelium

ICAM-3 Integrins αLβ2 and αDβ2, DC-SIGN Leucocytes, epidermal Langerhans cells ICAM-4 Integrins αLβ2, αMβ2 and αXβ2 Erythrocytes, subsets of both B and T cells ICAM-5 Integrins αLβ2 Brain JAM Presumed to be homotypic Endothelial and epithelial cells, mesothelial cells, megacaryocytes

L1 Homophilic binding, integrins αVβ3 and α5β1 Adult and embryonic nervous system, 10–20% of peripheral blood lymphocytes L1CAM Axonin Neuronal LFA-2 (CD2) LFA-3 Lymphocytes, thymocytes LFA-3 (CD58) LFA-2 Leucocytes, stroma endothelial cells

MAdCAM-1 Integrin α4β7, L-selectin High endothelial venules of Peyer’s patches and mesenteric lymph nodes, vascular endothelium MAG Sialoglycoconjugate NeuAcα2-3Galβ1-3GlcNAc Oligodendrocytes, Schwann cells on N- and O- linked oligosaccharides and gangliosides, CD22, CD33, collagens I-VI MUC18 None identified Endothelial, smooth muscle, trophoblast, subpopulation of activated T cells NCAM Homophilic binding, chondroitin sulfate Adult neural tissue and muscle, NK cells proteoglycans P(0) Homophilic interaction Schwann cells PMP-22 PMP-22 Sialoadhesin Sialoglycoconjugate NeuAcα2-3Galβ1-3(4) Subsets of macrophages in bone marrow and GlcNAc and NeuAcα2-3Galβ1-3GlcNAc on secondary lymphoid organs glycoproteins and glycolipids TAG-1 L1 family members Neural tissue

VCAM-1 Integrins α4β1 and α4β7, integrin αDβ2 Activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts Enzymes

Oxidoreductases Cyclooxygenases (EC 1.14.99.1) The cyclooxygenases-1 and -2 (COX-1 and COX-2; to individual . While COX-1 is almost also prostaglandin endoperoxide H synthases-1 and -2, ubiquitously and constitutively expressed, COX-2 is PGHS-1 and PGHS-2) catalyze a critical step in the an inducible enzyme which is found in kidney, synthesis of prostanoids by converting arachidonic bone, brain and endothelium but can under certain acid to the prostaglandin endoperoxide PGG2 which conditions be expressed in various other cells espe- is then further converted to prostaglandin H2 (PGH2). cially in the or in tumor cells PGH2 is metabolized by specific prostanoid synthases (▶Cyclooxygenases).

Name Gene Protein length (AA) Expression

Cyclooxygenase-1 (COX1) PTGS1 599 Ubiquitous -2 (COX2) PTGS2 604 Immune cells, endothelial cells, tumor cells (inducible); kidney, bone, brain

Lipoxygenases (EC 1.13.11.-) The lipoxygenases are metalloenzymes containing iron fatty acids with two oxygen atoms. Important substrates atoms in their catalytic centre which belong to the group are , or 12R-HPETE of dioxygenases being able to oxidize polyunsaturated (▶).

Name Gene Protein length (AA) Expression

5-Lipoxygenase ALOX5 674 Widely 12-Lipoxygenase ALOX12 663 Widely 12-Lipoxygenase, 12R type ALOX12B 701 B-cells, hair follicles, keratinocytes 15-Lipoxygenase ALOX15 662 15-Lipoxygenase, type B ALOX15B 676 Lipoxygenase 3 ALOXE3 711 Skin

Nitric Oxide Synthases (NOS; EC 1.14.13.39) Nitric oxide synthase (NOS) is responsible for the characterized by their expression pattern as well as by synthesis of nitric oxide (NO) from the terminal their inducibility (▶NO synthases). nitrogen of L-arginine. The three NOS isoforms are

Name Gene Protein length (AA) Expression

Neuronal NO-synthase (nNOS) NOS1 1434 Neuronal Inducible NO-synthase (iNOS) NOS2 1153 Macrophages, liver, bone Endothelial NO-synthase (eNOS) NOS3 1203 Endothelial cells, platelets 1394 Enzymes

Cytochrome P450 Monooxygenases (EC 1.14.-) Cytochrome p450 (CYP) is a huge family of enzymes compounds. They act in a multicomponent electron- found in a wide variety of species. It is typically involved transfer chain called the p450 containing mono- in the of many exogenous and endogenous system (▶p450 mono-oxygenase system).

Cytochrome P450 Monooxygenases (EC 1.14.-)

Gene Name(s) Previous symbols, Substrates aliases

CYP1A1 Cytochrome P450 1A1 P450DX, P1-450, Steroids, fatty acids, and xenobiotics P450-C CYP1A2 Cytochrome P450 1A2 P3-450, CP12 Steroids, fatty acids, and xenobiotics CYP1B1 Cytochrome P450 1B1 CP1B, GLC3A Steroids, fatty acids, and xenobiotics CYP2A6 Cytochrome P450 2A6, coumarin CPA6, CYP2A, CYP2A3 Coumarin 7, xenobiotic 7-hydroxylase CYP2A7 Cytochrome P450 2A7 CYP2A Steroids, fatty acids, and xenobiotics CYP2A13 Cytochrome P450 2A13 CPAD, CYP2A Coumarin 7, xenobiotic CYP2B6 Cytochrome P450 2B6 CPB6, CYPIIB6, Steroids, fatty acids, and xenobiotics CYP2B CYP2C8 Cytochrome P450 2C8 CPC8 Steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid CYP2C9 Cytochrome P450 2C9, limonene P450IIC9, CYP2C10 Steroids, fatty acids, and xenobiotics 6- CYP2C18 Cytochrome P450 2C18 CYP2C17, CPCI, Steroids, fatty acids, and xenobiotics CYP2C CYP2C19 Cytochrome P450 2C19, limonene P450IIC19, CPCJ Xenobiotics 6-monooxygenase, mephenytoin 4-hydroxylase CYP2D6 Cytochrome P450 2D6, debrisoquine CPD6, P450-DB1, Xenobiotics 4-hydroxylase P450C2D CYP2E1 Cytochrome P450 2E1 CYP2E Xenobiotics CYP2F1 Cytochrome P450 2F1 CYP2F Xenobiotics CYP2J2 Cytochrome P450 2J2, arachidonic acid Arachidonic acid epoxygenase CYP2R1 Cytochrome P450 2R1, Vitamin D(2) and D(3) 25-hydroxylase CYP2S1 Cytochrome P450 2S1 Xenobiotics CYP2U1 Cytochrome P450 2U1 Arachidonic acid, docosahexaenoic acid CYP2W1 Cytochrome P450 2W1 CYP3A4 Cytochrome P450 3A4 CYP3A3 Steroids, fatty acids, and xenobiotics CYP3A5 Cytochrome P450 3A5 PCN3, P450PCN3, Steroids, fatty acids, and xenobiotics CP35 CYP3A7 Cytochrome P450 3A7 CP37, P450-HFLA Steroids, fatty acids, and xenobiotics CYP3A43 Cytochrome P450 3A43 6-β CYP4A11 Cytochrome P450 4A11, fatty acid CYP4AII, CYP4A2 Laurate, myristate, palmitate, ω-hydroxylase prostaglandin A1 and E1 CYP4A22 Cytochrome P450 4A22 CYP4B1 Cytochrome P450 4B1 Steroids, fatty acids, and xenobiotics

CYP4F2 Cytochrome P450 4F2, leukotriene-B(4) LTB4, steroids, fatty acids, and ω-hydroxylase xenobiotics Leukotriene-B(4) 20-monooxygenase

CYP4F3 Cytochrome P450 4F3, leukotriene-B(4) CYP4F, LTB4H LTB4 ω-hydroxylase Leukotriene-B(4) 20-monooxygenase CYP4F8 Cytochrome P450 4F8 CYP4F11 Cytochrome P450 4F11 Enzymes 1395

Cytochrome P450 Monooxygenases (EC 1.14.-) (Continued)

Gene Name(s) Previous symbols, Substrates aliases

CYP4F12 Cytochrome P450 4F12 LTB4, arachidonic acid CYP4F22 Cytochrome P450 4F22 FLJ39501 CYP4V2 Cytochrome P450 4V2 CYP4AH1 CYP4X1 Cytochrome P450 4X1 MGC40051 CYP4Z1 Cytochrome P450 4Z1 CYP4A20 CYP7A1 Cytochrome P450 7A1, cholesterol CYP7 Cholesterol 7-alpha-hydroxylase CYP7B1 Cytochrome P450 7B1, Cholest-5-ene-3-β,25-diol 25-hydroxycholesterol 7-α-hydroxylase Oxysterol 7-α-hydroxylase CYP8B1 Cytochrome P450 8B1, CYP12 7 α-Hydroxy-4-cholesten-3-one, 7-α-hydroxycholest-4-en-3-one 7-α-hydroxylated C27 steroids 12-α-hydroxylase Sterol 12-α-hydroxylase CYP11A1 Cytochrome P450 11A1, cholesterol P450SCC, CYP11A Cholesterol side-chain cleavage enzyme CYP11B1 Cytochrome P450 11B1, steroid CYP11B, P450C11, Steroids 11-β-hydroxylase FHI, CPN1 CYP11B2 Cytochrome P450 11B2, aldosterone CYP11BL, CPN2, 11-deoxycorticosterone synthase, steroid 18-hydroxylase P-450C18, P450aldo, ALDOS CYP17A1 Cytochrome P450 17A1, steroid P450C17, CYP17, Pregnenolone and 17-α-monooxygenase S17AH Steroid 17-α-hydroxylase/17,20 CYP19A1 Cytochrome P450 19A1, , CYP19, ARO, CPV1, C19 androgens estrogen synthetase ARO1, CYAR CYP20A1 Cytochrome P450 20A1 CYP-M CYP21A2 Cytochrome P450 20A2, steroid CYP21, P450c21B, Steroids 21-hydroxylase CA21H, CPS1, CAH1 CYP24A1 Cytochrome P450 24A1,vitamin D(3) CP24, P450-CC24 25-Hydroxyvitamin D(3) 24-hydroxylase CYP26A1 Cytochrome P450 26A1, retinoic P450RAI, CP26, All-trans-retinoic acid (RA) and acid-metabolizing cytochrome CYP26, P450RAI1 9-cis-RA CYP26B1 Cytochrome P450 26B1, P450 retinoic P450RAI-2 All-trans-retinoic acid (RA) acid-inactivating 2 CYP26C1 Cytochrome P450 26C1 All-trans-retinoic acid (RA) and 9-cis-RA CYP27A1 Cytochrome P450 27A1, sterol CYP27, CTX, CP27 5-Beta-cholestane-3-alpha,7-alpha, 26-hydroxylase 12-alpha-triol Sterol 27-hydroxylase Vitamin D(3) 25-hydroxylase CYP27B1 Cytochrome P450 27B1, calcidiol VDD1, PDDR, CYP1, 25-Hydroxyvitamin D3 (25(OH)D) 1-monooxygenase P450c1 25-OHD-1 alpha-hydroxylase CYP27C1 Cytochrome P450 27C1 FLJ16008 CYP39A1 Cytochrome P450 39A1, 24-Hydroxycholesterol 24-hydroxycholesterol 7-alpha-hydroxylase Oxysterol 7-alpha-hydroxylase CYP46A1 Cytochrome P450 46A1, cholesterol CYP46 Cholesterol 24-hydroxylase CYP51A1 Cytochrome P450 51A1, sterol 14-alpha CYP51, CYPL1, Lanosterol demethylase P450L1, LDM, Lanosterol 14-alpha demethylase P450-14DM 1396 Enzymes

Amino Acid Hydroxylases (NOS; EC 1.14.16.-) Amino acid hydroxylases contain iron and use tetra- and cosubstrate. They play important roles in the hydrobiopterin and molecular oxygen as cosubstrate biogenesis of biogenic amines.

Name Gene Protein length (AA)

L-phenylalanine hydroxylase PAH 452 Tyrosine L-tryptophan hydroxylase TPH1 444 5-Hydroxytryptophan L-tyrosine hydroxylase TH 528 DOPA

Transferases Lipid Kinases Lipid kinases are enzymes which transfer phosphate (Fruman et al. (1998) Annu Rev Biochem 67:481– groups onto lipids. Depending on their substrates 507). Sphingosine kinases catalyze the phosphoryla- they can be divided in various subgroups like tion of sphingosine to sphingosine-1-phosphate (S1P), a ▶phosphoinositide kinases, ▶sphingosine kinases or bioactive sphingolipid metabolite (Spiegel, Milstein ▶diacyl glycerol kinases. Phosphatidylinositol, a com- (2007) J Biol Chem 282:2125–2129; Alemany et al. mon component of cellular membranes, (2007) Naunyn Schmiedeberg’s Arch Pharmacol can be phosphorylated at multiple free hydroxyl groups. 374:413–428). Diacylglycerol kinases phosphorylate Phosphoinositides with characteristic phosphorylation the second messenger diacylglycerol (DAG) to phos- patterns play important roles in cellular signaling. phatidic acid which by itself also has signaling proper- Phosphorylation of phosphatidylinositol is catalyzed ties. They terminate signaling by DAG (Topham, by a variety of enzymes of which the phosphatidylino- Prescott (2002) Thromb Haemost 88:912–918; Kanoh sitol-3-kinases, phosphatidylinositol-4-kinases and et al. (2002) J Biochem 131:629–633) (▶phospholipid phosphatidylinositol-5-kinases are most important kinases; ▶lysophospholipids; ▶ C).

Lipid Kinases

Name Gene Previous symbols, Protein length (human) Substrate(s) aliases (AAs)

PI-3-kinases (EC 2.7.1.137)

Class IA/B catalytic subunits PI-3-K p110α, class Ia PIK3CA ca PI3K 1068 PtdIns PI-3-K p110β, class Ia PIK3CB PIK3C1 1070 PtdIns-4-P

PI-3-K p110δ, class Ia PIK3CD p110D 1044 PtdIns-4,5-P2 PI-3-K p110γ, class Ib PIK3CG 1102 PtdIns-4,5-P2 Class IA/B regulatory subunits PI-3-K p85α PIK3R1 GRB1, p85-ALPHA 724 PI-3-K p85β PIK3R2 P85B 728 PI-3-K p55γ PIK3R3 461 PI-3-K p50α 454 PI-3-K p101 class Ib 880 Class II PI-3-K C2α PIK3C2A PI3K-C2alpha 1686 PtdIns PI-3-K C2β PIK3C2B C2-PI3K, PI3K- 1634 PtdIns-4-P C2beta PI-3-K C2γ PIK3C2G 1448 Class III PI-3-K catalytic subunit PIK3C3 Vps34 887 PtdIns PI-3-K regulatory subunit PIK3R4 VPS15, P150 1358

PI-4-kinases (EC 2.7.1.67) PI-4-K type II PI4K2A 845 PI-4-K type II β PI4K2B 481 PI-4-K type II β PIK4CA 2044 PtdIns PI-4-K type III β PIK4CB 801 PtdIns Enzymes 1397

Lipid Kinases (Continued)

Name Gene Previous symbols, Protein length (human) Substrate(s) aliases (AAs) PI-5-kinases (EC 2.7.1.68) PI-4-P-5-K type I α PIP5K1A 540 PtdIns-4-P PI-4-P-5-K type I β PIP5K1B STM7 549 PtdIns-4-P PI-4-P-5-K type I γ PIP5K1C 668 PtdIns-4-P

PI-5P-kinases (EC 2.7.1.149) PI-4-P-5-K type II α PIP5K2A 406 PtdIns-5-P, PtdIns-3-P PI-4-P-5-K type II β PIP5K2B 416 PtdIns-5-P, PtdIns-3-P PI-5-P-4-K type II γ PIP5K2C 421 PtdIns-5-P, PtdIns-3-P PI-5-K type III PIP5K3 1026

Sphingosine kinases (EC 2.7.1.91) Sphingosine kinase 1 SPHK1 SphK1 384 Sphingosine Sphingosine kinase 2 SPHK2 SphK2 654 Sphingosine Diacyl glycerol kinases (EC 2.7.1.107) DGK α DGKA DAGK, DAGK1 735 sn-1,2-Diacyl-glycerol DGK β DGKB DAGK2 804 sn-1,2-Diacyl-glycerol DGK δ DGKD DAGK4 1170 sn-1,2-Diacyl-glycerol DGK ε DGKE DAGK6 564 sn-1,2-Arachidonoyl-diacyl- glycerol DGK γ DGKG DAGK3 791 sn-1,2-Diacyl-glycerol DGK η DGKH 1220 sn-1,2-Diacyl-glycerol DGK ι DGKI 1065 sn-1,2-Diacyl-glycerol DGK θ DGKQ DGK7 942 sn-1,2-Diacyl-glycerol DGK ζ DGKZ DAGK5 928 sn-1,2-Diacyl-glycerol DGK κ DGKK 1271 sn-1,2-Diacyl-glycerol

Serine/Threonine Kinases Protein kinases catalyze the transfer of the terminal (γ) (▶Tyrosine Kinases). Protein occur phosphoryl group of ATP to a hydroxyl residue on an inside cells where the substrate ATP is abundant. amino acid side-chain. Phosphorylation of proteins by The effects of protein kinases are reversed by protein kinases represents the most prevalent reversible protein phosphatases which remove phosphoryl groups modification which regulates the activities of many from proteins by catalyzing the hydrolysis of the enzymes, ion channels and other proteins. Reversible phosphate bond. is involved in basically all Protein kinases represent one of the largest families cellular processes including signal transduction, metab- of genes in . The protein kinase complement olism, transcription, progression, cell move- of the has recently been catalogued ment, apoptosis or cell differentiation. There are two (Manning et al. (2002) Science 298:1912). The principal classes of protein kinases: Those which following list of protein kinases is based on the transfer phosphoryl groups to specific serine and classification used by Manning et al. for the description threonine residues (▶Serine/threonine kinases)on of the human “kinome.” those which transfer it to specific tyrosine residues

AGC Group (Containing PKA, PKG and PKC Families)

Family Subfamily Name

PKA () PKA-Cα PKA-Cβ PKA-Cγ PRKX PRKY 1398 Enzymes

AGC Group (Containing PKA, PKG and PKC Families) (Continued)

Family Subfamily Name

AKT/PKB () AKT1 (PKB α) AKT2 (PKB β) AKT3 (PKB γ) PKC (protein kinase C) Alpha PKCα PKCβ PKCγ Delta PKCδ PKCθ Eta PKCη PKCε Iota PKCι PKCζ PKG (cGMP-dependent protein PKG1 (cGK-I) kinase) PKG2 (cGK-II) PKN (protein kinase N) PKN1 PKN2 PKN3 DMPK (dystrophia myotonica protein GEK (Genghis Khan) DMPK1 kinase) DMPK2 MRCKβ ( kinase-related Cdc42-binding kinase) MRCKα ROCK (Rho-kinase) ROCK2 ROCK1 CRIK (citron) GRK (G-protein coupled receptor ki- βARK (β-adrenoceptor βARK1 (GRK2) nase) kinase) βARK2 (GRK3) GRK RHOK (rhodopsin kinase; GRK1) GRK4 GRK5 GRK6 GRK7 MAST (microtubule-associated serine/ MAST3 threonine kinase) MAST2 MAST1 MASTL MAST4 PDK1 (phosphoinositide-dependent PDK1 kinase 1) NDR NDR1 LATS1 LATS2 NDR2 RSK (ribosomal protein S6 kinase) MSK (mitogen and MSK1 stress-activated kinase) MSK2 p70 p70S6K p70S6Kb RSK RSK1 RSK2 RSK3 RSK RSK4 SgK494 RSKL RSKL2 RSKL1 Enzymes 1399

AGC Group (Containing PKA, PKG and PKC Families) (Continued)

Family Subfamily Name

SGK (serum/glucocorticoid regulated SGK kinases) SGK2 SGK3 YANK YANK1 YANK2 YANK3

CAMK Group

Family Subfamily Name

CaMK I (calcium- dependent protein kinase) CaMK Iγ CaMK Iα CaMK IV CaMK Iδ CaMK Iβ CaMK II CaMK IIα CaMK IIβ CaMK IIγ CaMK IIδ CaMKL AMPK (AMP-activated AMPKα1 kinase) AMPKα2 BRSK BRSK2 BRSK1 CHK1 CHK1 HUNK HUNK LKB LKB1 MARK MARK3 MARK2 MARK1 MARK4 MELK MELK NIM1 NIM1 NuaK NuaK1 NuaK2 PASK PASK QIK QSK QIK SIK SNRK SNRK CaMK-Unique VACAMKL STK33 SgK495 CASK (Ca2+/calmodulin-dependent serine protein kinase) CASK DAPK (death associated protein kinase) DAPK1 DAPK2 DRAK1 DRAK2 DAPK3 DCAMKL (double cortin and Ca2+/calmodulin-dependent protein DCAMKL1 kinase-like) DCAMKL3 DCAMKL2 1400 Enzymes

CAMK Group (Continued)

Family Subfamily Name

MAPKAPK (MAP kinase-activated protein kinase) MAPKAPK MAPKAPK2 MAPKAPK3 MAPKAPK5 MINK MNK1 MNK2 MLCK ( light chain kinase) smMLCK Titin caMLCK skMLCK sgMLCK PhK (phosphorylase kinase) PhKγ1 PhKγ2 Pim (proviral integration site) Pim3 Pim1 Pim2 PDK PDK1 PDK2 PDK3 Psk (putative protein-serine kinase) PskH1 PskH2 RAD53 CHK2 (checkpoint ki- nase 2) Trbl Trb1 Trb2 Trio Trio Trad SPEG Obscn TSSK (testis specific serine/threonine kinase) TSSK3 TSSK2 SSTK TSSK4 TSSK1

CK1 Group (casein kinase 1)

Family Name

CK1 (casein kinase 1) CK1α CK1δ CK1ε CK1γ2 CK1γ3 CK1α2 CK1γ1 TTBK (Tau kinase) TTBK2 TTBK1 Vrk (vaccinia related kinase) Vrk1 Vrk2 Vrk3 Enzymes 1401

CMGC Group (Containing Cdk, MAPK, GSK3, Clk Families)

Family Subfamily Name

Cdk (cyclin-dependent kinase) Cdc2 Cdc2 Cdk2 Cdk3 Cdk10 Cdk10 Cdk4 Cdk4 Cdk6 Cdk5 Cdk5 Cdk7 Cdk7 Cdk8 Cdk8 Cdk11 Cdk9 Cdk9 Crk7 Ched Crk7 PITSLRE PITSLRE TAIRE PCTAIRE1 PCTAIRE2 PCTAIRE3 PFTAIRE1 PFTAIRE2 CCRK Cdkl (cyclin-dependent kinase-like) Cdkl2 Cdkl1 Cdkl5 Cdkl4 Cdkl3 Clk (cdc2/CDC28-like kinase) Clk1 Clk2 Clk3 Clk4 Dyrk (dual-specificity tyrosine-(Y)-phosphorylation Dyrk1 Dyrk1A regulated kinase) Dyrk1B Dyrk2 Dyrk2 Dyrk3 Dyrk4 HIPK (homeodomain-interacting protein kinase) HIPK1 HIPK2 HIPK3 HIPK4 PRP4 PRP4 GSK (glycogen synthase kinase 3) GSK3α GSK3β MAPK (mitogen activated protein kinase) Erk Erk1 Erk2 Erk3 Erk4 Erk5 Erk7 Erk7 Jnk Jnk1 Jnk2 Jnk3 nmo NLK P38 p38α p38β p38γ p38δ 1402 Enzymes

CMGC Group (Containing Cdk, MAPK, GSK3, Clk Families) (Continued)

Family Subfamily Name

RCK (related to the cdc2 kinase) Mak ICK MOK SRPK (serine/arginine-rich protein specific kinase) SRPK1 SRPK2 MSSK1

RGC Group (Receptor Guanylyl Cyclases; Guanylyl Cyclases)

Family Name

RGC (receptor guanylyl cyclases) GC-A (ANPa) GC-B (ANPb) GC-D (CYGD) GC-F (CYGF) GC-C (HSER)

STE Group (Homologues of Yeast Sterile-7, -11, -20 Kinases; MAP Kinase Cascades)

Family Subfamily Name

STE11 (sterile 11) MAP3K1 (Mekk1) MAP3K2 (Mekk2) MAP3K3 (Mekk3) MAP3K4 (Mekk4) MAP3K5 (Mekk5) MAP3K6 (Ask2) MAP3K7 MAP3K8 (Tpl2) STE20 (sterile 20) FRAY OSR1 STLK3 KHS (kinase homologous To SPS1/STE20) GCK (MAP4K2) HPK1 (MAP4K1) KHS1 (MAP4K5) KHS2 MSN ZC1/HGK (MAP4K4) ZC2/TNIK (Traf2) ZC3/MINK (Misshapen) ZC4/NRK (Nesk) MST MST1 (Stk4; Krs-2) MST2 (Stk3; Krs-1) NinaC MYO3B MYO3A PAKA (p21-activated kinase) PAK1 PAK2 PAK3 PAKB PAK6 PAK4 PAK5 SLK SLK LOK (Stk10) Enzymes 1403

STE Group (Homologues of Yeast Sterile-7, -11, -20 Kinases; MAP Kinase Cascades) (Continued)

Family Subfamily Name

STLK STLK5 STLK6 TAO (Thousand-and-one amino acid kinase) TAO2 TAO3 TAO1 YSK MST3 (Stk24) YSK1 (Sok1; Stk25) MST4 (Mask) STE7 (sterile 7) MAP2K1 (Mek1) MAP2K2 (Mek2) MAP2K5 (Mek5) MAP2K6 (Mek6) MAP2K7 (Mek7) MAP2K3 (Mek3) MAP2K4 (Mek4) STE-Unique COT NIK (MAP3K14)

TKL Group (Tyrosine Kinase-Like Families)

Family Subfamily Name IRAK (interleukin-1 receptor-associated kinase) IRAK1 IRAK2 IRAK3 IRAK4 LISK (LIMK/TESK) LIMK Limk2 Limk1 TESK (testis-specific protein Tesk1 kinase) Tesk2 LRRK LRRK2 LRRK1 Mlk (mixed lineage kinase) HH498 HH498 ILK ILK (integrin linked kinase) LZK DLK (MAP3K12) LZK (MAP3K13) Mlk Mlk1 (MAP3K9) Mlk2 (MAP3K10) Mlk3 (MAP3K11) ZAK (Mltk) Mlk4 TAK1 TAK1 (TGF-β activated-kinase 1) Raf A-Raf B-Raf KSR1 (Kinase suppressor of ras-1) Raf1 (C-Raf) KSR2 RIPK (receptor-interacting protein kinase) RIPK1 RIPK2 RIPK3 ANKRD3 SgK288 1404 Enzymes

TKL Group (Tyrosine Kinase-Like Families) (Continued)

Family Subfamily Name

STKR (receptor serine/threonine kinases (see also Type I ALK-1 “Receptors”) ActR-I A (ALK-2) BMPR-I A (ALK-3) ActR-I B (ALK-4) TGFβR-I (ALK-5) BMPR-I B (ALK-6) ALK-7 Type II ActR-II A ActR-II B MISR-II BMPR-II TGFβR-II TKL Unique MLKL

Atypical Group

Family Subfamily Name A6 A6 A6r ABC1 ABC1-A ADCK4 ADCK3 ABC1-B ADCK1 ADCK5 ABC1-C ADCK2 Alpha ChaK ChaK1 ChaK2 eEF2K eEF2K AlphaK2 AlphaK3 AlphaK1 BCR (breakpoint cluster region) BCR BRD BRD2 BRD3 BRD4 BRDT FAST FASTK G11 G11 H11 H11 PDHK (pyruvate dehydrogenase kinase) BCKDK PDHK1 PDHK2 PDHK3 PDHK4 PIKK ATM ATM ATR ATR DNAPK DNAPK FRAP FRAP SMG1 SMG1 TRRAP TRRAP RIO RIO1 RIOK1 RIO2 RIOK2 RIO3 RIOK3 Enzymes 1405

Atypical Group (Continued)

Family Subfamily Name

TAF1 TAF1 TAF1L TIF1 TIF1α TIF1β TIF1γ

Other Groups

Family Subfamily Name

AUR AurC AurB AurAC BUB (budding uninhibited by benzimidazoles 1 homolog) BUBR1 BUB Bud32 PRPK CAMKK (Ca2+/calmodulin-dependent protein kinase kinase) Meta CaMKK2 Meta CaMKK1 Cdc7 Cdc7 CK2 (casein kinase 2) CK2α1 CK2α2 Haspin (-specific gene 2) Haspin IKK (IκB kinase) IKKα IKKβ IKKε TBK1 Ire (inositol-requiring) Ire1 (Ern1) Ire2 (Ern2) Mos (moloney sarcoma oncogene) Mos Nak (numb-associated kinase) Gak Aak1 MPSK1 BIKE Nek (nimA-related expressed kinase) Nek1 Nek2 Nek3 Nek4 Nek6 Nek7 Nek9 Nek8 Nek5 Nek11 Nek10 NKF1 SgK069 SgK110 SBK NKF2 PINK1 NKF3 SgK223 SgK269 NKF4 CLIK1L CLIC1 1406 Enzymes

Other Groups (Continued)

Family Subfamily Name

NKF5 SgK307 SgK424 NRBP NRBP1 NRBP2 Other-unique SgK493 SgK496 SgK071 SgK196 SgK396 KIS RNAseL PEK GCN2 GCN2 PEK PEK PKR HRI Plk (Polo-like kinase) Plk1 Plk3 Plk4 Plk2 SCY1 SCYL1 SCYL3 SCYL2 Slob Slob TBCK TBCK Tlk (tousled-like kinase) Tlk1 Tlk2 TOPK PBK Ttk (embryonal carcinoma kinase) Ttk Ulk (Unc-51-like kinase) Fused Ulk1 Ulk2 Ulk3 Ulk4 VPS15 PIK3R4 Wee (Wee 1 homolog) MYT1 Wee1 Wee1B Wnk (with-no-lys kinase) Wnk2 Wnk1 Wnk4 Wnk3

Tyrosine kinases RTK Group (Receptor Tyrosine Kinases; see also under “Receptors”)

Family Name EGFR (epidermal ; ErbB) EGFR/ErbB1 HER2/ErbB2 HER3/ErbB3 HER4/ErbB4 Enzymes 1407

RTK Group (Receptor Tyrosine Kinases; see also under “Receptors”) (Continued)

Family Name

InsR () IGF1R INSR IRR PDGFR (platelet derived growth factor) FMS Flt3/Flk2 Kit/SCFR PDGFRα PDGFRβ VEGFR (vascular endothelial growth factor) VEGF-R1; Flt1 VEGF-R3; Flt4 VEGF-R2; Flk1; KDR FGFR (fibroblast growth factor) FGFR1 FGFR2 FGFR3 FGFR4 KLG/CCK (kinase-like gene) CCK4/PTK7 NGF (nerve growth factor; Trk) TrkA TrkB TrkC HGF (hepatocyte growth factor; Met) Met Ron/Skt Eph (kinase detected in erythropoietin-producing hepatoma) EphA1 EphA2 EphA3 EphA4 EphA5 EphA8 EphB1 EphB2 EphB3 EphB4 EphB6 EphA7 EphA10 EphA6 Axl (anexelekto) Axl Mer Tyro3 Tie (tyrosine kinase with Ig and EGF homology) Tie2 (tek) Tie1 Ryk Ryk DDR (discoid domain receptor) DDR1 DDR2 Ret Ret Sev (sevenless) Ros Alk (anaplastic lymphoma kinase) Alk Ltk (leukocyte tyrosine kinase) Ror Ror1 Ror2 Musk Musk LMR LMR1 (AATYK) LMR2 (AATYK2) LMR3 (AATYK3) TK-unique SuRTK106 1408 Enzymes

NRTK Group (Non-Receptor Tyrosine Kinases; Tyrosine Kinases)

Family Name

Abl (Abelson murine leukemia oncogene) Abl Arg (Abl-related gene) Ack (activated Cdc42- Ack (Tnk2) associated kinase) Tnk1 (tyrosine kinase, non-receptor 1) Csk (C-terminal Src kinase) Csk Ctk (Csk-type protein tyrosine kinase) Fak (focal adhesion kinase) Fak Pyk2 Fer (Fps/Fes-related tyrosine kinase) Fer (TYK3) Fes () JAKA Jak1 (-1) Jak2 (Janus kinase-2) Jak3 (Janus kinase-3) Tyk2 (transducer of interferon α/β signals) Src (Rous sarcoma virus oncogene) Blk (B lymphocyte kinase) Brk (breast tumor kinase; PTK6) Fgr (Gardner-Rasheed sarcoma virus oncogene) Fyn (related to Fgr and Yes) Hck (hemopoietic cell kinase; Bmk) (lymphocyte protein tyrosine kinase) Lyn (JTK8) Src Yes (yamaguchi 73 sarcoma virus oncogene) Frk (Fyn-related kinase; Gtk; Lyk; Rak) Srm Syk (Spleen tyrosine kinase) Syk (p72Syk) Zap70 (ζ-chain associated protein kinase) Tec (Tyrosine kinase expressed in hepatocellular carcinoma) Btk (Bruton’s tyrosine kinase) Itk (IL-2 inducible T-cell kinase; Tsk) Tec Txx Bmx (bone marrow kinase, X-linked; Etk)

SH2 Domain Proteins SH2 domain proteins are characterized by the presence a particular protein by tyrosine kinases and tyrosine of a Src homology 2 domain (SH2 domain) which phosphatases can therefore determine the interaction of consists of about 100 amino acids and has the ability the phosphorylated tyrosine and an SH2 domain- to bind to a phosphorylated tyrosine residue. The containing protein (Schlessinger, Lemmon (2003) regulation of the phosphorylation of tyrosine residue in Science STKE 191:RE12) (▶tyrosine kinases).

SH2 Domain Proteins

Name Alternate names/symbols aliases Other domains/functions

Adaptors Nck1 NCK, NCKalpha, MGC12668, Nck 3 x SH3 Nck2 GRB4, NCKbeta, NCK-2, Grb4, NCKbeta 3 x SH3 Crk CRKII, Crko, Crk-I, Crk-II, Crk3, Crkol, CrkIII, Crk-III 2 x SH3 Crkl Crk-like, Crkol, 1110025F07Rik 2 x SH3 Grb2 ASH, Grb3-3, EGFRBP-GRB2, Ash 2 x SH3 Grap MGC64880, P38, GRAP2, GRID, GRPL, 8430435N19Rik 2 x SH3 Enzymes 1409

SH2 Domain Proteins (Continued)

Name Alternate names/symbols aliases Other domains/functions

Gads Grbx, Mona, GRB2L, GRBLG, Grf40, GRAP-2, GRID, Gads 2 x SH3 SLAP SLA1, SLAP2, SLA, Slap, Slap-1 1 x SH3 SLAP2 SLAP-2, SLA-2, FLJ21992, MGC49845, C20orf156, 1 x SH3 LOC284948, , SLAP2, A930009E21Rik

Scaffolds Shc1 SHC, SHCA, SHC-1, p52SHC, p66SHC, FLJ26504, Shc, 1 x PTB p66, ShcA Shc2 SLI, SCK, SHCB, Sli, ShcB, 6720466E06 1 x PTB Shc3 NSHC, SHCC, N-Shc, Rai, ShcC 1 x PTB Shc4 MGC34023, RaLP, SHCD, Gm685, 9930029B02Rik, 1 x PTB 6230417E10Rik BLNK Ly57, SLP65, BLNK-s, SLP-65, B-cell linker, BCA, Bca, BASH, BLNK, Ly-57, Lyw-57 MIST CLNK, MIST SLNK Linker protein, SH2 linker protein related to BLNK, 4933424C13Rik, MGC118336 SLP76 SLP-76, LCP2 1 x SAM SH2D5 LOC400745, BC036961 1 x PTB Kinases Fes FPS, c-FES, c-fes 1 x FCH, 1 x Y kinase Fer TYK3, c-FER, p94-FER, Fer, Fert, C330004K0Rik 1 x FCH, 1 x Y kinase Src ASV, SRC1, c-src, p60-Src 1 x SH3, 1 x Y kinase Csk CYL 1 x SH3, 1 x Y kinase Matk LSK, CHK, CTK, HYL, HHYLTK, MGC1708, MGC2101, 1 x SH3, 1 x Y kinase DKFZp43N1212, Ntk Fgr SRC2, c-, p55c-fgr 1 x SH3, 1 x Y kinase Fyn SLK, SYN, MGC45350 1 x SH3, 1 x Y kinase Yes Yes, C-Yes, c-yes, P61-YES, HST441, YES1 1 x SH3, 1 x Y kinase Hck JTK9, Bmk, Hck-1, MGC18625 1 x SH3, 1 x Y kinase Lck LSK, Hck-3, p56 1 x SH3, 1 x Y kinase Lyn JTK8, Hck-2 1 x SH3, 1 x Y kinase Blk MGC10442 1 x SH3, 1 x Y kinase Frk GTK, RAK, PTK5, BSK, BSK/YK 1 x SH3, 1 x Y kinase Brk PTK6, BRK, Sik, tks, Tksk 1 x SH3, 1 x Y kinase Srms SRM, C20orf148, dJ697K14.1, srm, A230069J08Rik 1 x SH3, 1 x Y kinase Zap70 70, TZK, Srk, 70 kDa, TZK, ZAP-70 1 x Y kinase Syk – 1 x Y kinase Abl1 ABL, JTK7, p150, c-ABL, Abl, E430008G22Rik 1 x SH3, 1 x Y kinase Abl2 ARG, ABLL, Arg, Abll 1 x SH3, 1 x Y kinase Btk AT, ATK, BPK, XLA, IMD1, AGMX1, PSCTK1, xid, AI528679 1 x PH, 1 x BTK, 1 x SH3, 1 x Y kinase Tec PSCTK4 1 x PH, 1 x BTK, 1 x SH3, 1 x Y kinase Itk EMT, LYK, PSCTK2, Emt, Tsk, Tcsk 1 x PH, 1 x BTK, 1 x SH3, 1 x Y kinase Bmx ETK, PSCTK2, PSCTK3, Etk, Etk/Bmx 1 x PH, 1 x BTK, 1 x SH3, 1 x Y kinase Txk RLK, TKL, BTKL, PSCTK5, PTK4, Rlk, Btkl 1 x SH3, 1 x Y Kinase JAK1 Jak1A, Jak1B, Jak-1, MGC37919, C130039L05Rik 1 x FERM, 1 x Y kinase JAK2 Jak-2, Fd17, AI504024 1 x FERM, 1 x Y kinase JAK3 JAK-3, JAKL, LJAK, L-JAK 1 x FERM, 1 x Y kinase Tyk2 JTK1 1 x FERM, 1 x Y kinase

Signal regulation SH2D1A DSHP, LYP, SAP, XLP, EBVS, IMD5, XLPD, MTCP1 SH2D1B EAT-2, EAT2 SOCS1 JAB, CIS1, SSI1, TIP3, CISH1, Cish1, SSI-1, SOCS-1, 1 x SOCS SOCS1, Cish7 1410 Enzymes

SH2 Domain Proteins (Continued)

Name Alternate names/symbols aliases Other domains/functions

SOCS2 CIS2, SSI2, Cish2, SSI-2, SOCS-2, STATI2, hg, JAB, 1 x SOCS 8030460M17 SOCS3 CIS3, Cish3, SSI-3, SOCS-3, MGC71791, EF-10 1 x SOCS CISH CIS, G18, SOCS, CIS-1, Cis, F17, F23, CIS1 1 x SOCS SOCS4 SOCS7, CIS4, STAT4, SSI4, DKFZp686J1568, SOCS7, 1 x SOCS 3110032M18Rik SOCS5 CIS6, CISH6, Cish5, SOCS-5, KIAA0671, 1810018L08Rik 1 x SOCS SOCS6 CIS4, SSI4, Cish4, SOCS4, STAI4, STAT4, STATI4, 1 x SOCS HSPC060, Cis4SOCS-4, 5830401B18Rik SOCS7 NAP4, NAP-4, SOCS4, SOCS-7, Nap4, 2310063P06Rik 1 x SOCS Shb RP11-3J10.8 Shd LOC56961 She LOC126669, LOC214547, 9430022A14 Shf Hypothetical protein BC007586, Shf, SHB like adaptor, LOC435684 SH2D2A VRAP, TSAD, TSAd, F2771, Lad, RIBP, Ribp HSH2D FLJ14886, HSH2, ALX, Alx, Hsh2 SH2D4A SH2A, FLJ20967, 2210402M20Rik SH2D4B FLJ41984, CAI14998, A430109M18Rik Grb7 – 1 x RA, 1 x PH Grb10 RSS, IRBP, MEG1, GRB-IR, KIAA0207, Meg1, 1 x RA, 1 x PH 5730571D09Rik Grb14 – 1 x RA, 1 x PH APS Aps 1 x PH Lnk – 1xPH SH2B SH2-B, DKFZP547G1110, Irip, SH2-Bb 1 x PH DAPP1 BAM32, DKFZp667E0716, Bam32 1 x PH BRDG1 STAP-1, AI586015 1 x PH BKS STAP2, FLJ20234, AWO49765 1 x PH SH3BP2 CRPM, RES4-23, CRBM, 3BP2 1 x PH

Phosphotases PTPN6 HCP, HCPH, SHP-1, HPTP1C, PTP-1C, SHP-1L, SH-PTP1, 1 x phosphatase me, hcp, Hcph, Ptp1C, motheaten PTPN11 CFC, NS1, SHP2, SHP-2, BPTP3, PTP2C, PTP-1D, SH- 1 x phosphatase PTP2, SH-PTP3, MGC14433, PRO184, Syp, Shp2, PTP1D, PTP2C, SAP-2, 2700084A17Rik

Transcription STAT1 ISGF-3, STAT91, 2010005J02Rik 1 x TA STAT2 P113, ISGF-3, STAT113, MGC59816, 1600010G07Rik 1 x TA STAT3 APRF, FLJ20882, MGC16063, Aprf, 1110034C02Rik 1 x TA STAT4 – 1xTA STAT5 MGF, STAT5, Stat5 1 x TA STAT6 STAT6B, STAT6C, D12S1644, IL-4-STAT 1 x TA Ubiquitination Cbl CBL2, c-CBL, RNF55, Cas-Br-M, cbl, 4732447J05Rik 1 x 4H, 1 x EF, 1 x RING, 1 x UBA Cblb RNF56 1 x 4H, 1 x EF, 1 x RING, 1 x UBA Cblc CBL-3, CBL-SL, 1 x 4H, 1 x EF, 1 x RING RNF57, Cbl3, 2310076I21Rik, 2310079L19Rik Phospholipoid second messenger signaling PIK3R3 P85G, PIK3R3, p55-GAMMA, p55pik PIK3R1 P85A, PIK3R1, GRB1, PI3K, p50alpha, p85alpha, 1 x SH3, 1 x RhoGAP C530050K14 PIK3R2 P85B, PIK3R2 1 x SH3, 1 x RhoGAP Enzymes 1411

SH2 Domain Proteins (Continued)

Name Alternate names/symbols aliases Other domains/functions

PLCγ1 PLC1, PLC148, PLC-II, Plc-1, Plcg-1, Plc-gamma1, Cded 2 x PH, 1 x SH3, 1xC2 PLCγ2 PLC-IV, Plcg-2, MGC38590 2 x PH, 1 x SH3, 1xC2 SHIP INPP5D, HCK, MGC104855, SHIP, SIP-145, hp51CN, 145 1 x phosphatase kDa, s-SHIP SHIP2 INPPL1, 51C, SHIP2 1 x phosphatase, 1 x SAM

Cytoskeletal regulation TenC1 C1-TEN, KIAA1075, C1TEN, TNS2, C1-ten 1 x C1, 1 x PTB TNS3 TEM6, FLJ13732, TENS1, H_NH04123.2, Tem6, Tensin3, 1 x PTB Tens1, F830010I22Rik TNS4 CTEN, FLJ14950, AU016405, 9930017A07Rik 1 x PTB TNS1 TNS, TENSIN, PRO0929, DKFZP434G162, 1 x PTB Tensin, Tns1200014E20Rik, 1110018I21rik remodeling Supt6h SPT6, SPT6H, emb-5, KIAA0162 1 x CSZ, 1 x S1

Small GTPase signaling RASA1 RASA, GAP, RASGAP, p120GAP, PKWS, CMAVM, Gap, 1 x SH3, 1 x PH, Rasa, RasGAP, MGC7759 1 x C2, 1 x RasGAP SH2D3A NSP1, N/A 1 x RasGEF SH2D3C NSP3, CHAT, 1 x RasGEF Pro34088, Chat, Nsp3, Shep1 BCAR3 SH2D3B, NSP2, KIAA0554, AND-34 1 x RasGEF Rin1 – 1 x VSP9, 1 x RA Rin2 RASSF4, 2010003K16Rik, 4632403N06Rik 1 x VSP9, 1 x RA Rin3 FLJ22439, DKFZp762H1613, 6430500K07 1 x VSP9, 1 x RA Vav1 VAV, Vav 1 x CH, 1 x RhoGEF, 1 x PH, 1 x C1, 2 x SH3 Vav2 VAV-2, 2810040F13Rik 1 x CH, 1 x RhoGEF, 1 x PH, 1 x C1, 2 x SH3 Vav3 VAV-3, MGC27838, Aa30094I06Rik 1 x CH, 1 x RhoGEF, 1 x PH, 1 x C1, 2 x SH3 Chn1 RHOGAP2, n-chimerin, chimerin, 1700112L09Rik, 1 x C1, 1 x RhoGAP 2900046J01Rik, ARHGP2 Chn2 ARHGAP3, beta chimerin, chimerin2, 1700026N20Rik, 1 x C1, 1 x RhoGAP Chimerin (chimaerin) 2, Bch, ARHGAP2

SH3, Src Homology 3; PTB, Phosphotyrosine binding domain; RA, Ras Association; RING, Ring domain; SAM Sterile Alpha Motif; RhoGAP, RhoGEF; Y Kinase, Tyrosine Kinase; CH Calponin homology; FCH, Fes/Cip4 homology domain; SOCS, Suppressor of Cytokine Signaling; PH, Pleckstrin Homology; 4H, four helix bundle; UBA associated domain

PTB Domain Proteins Phosphotyrosine-binding domain (PTB) containing (Schlessinger, Lemmon (2003) Science STKE 191: proteins bind to mostly phosphorylated, but in RE12) (▶tyrosine kinases). some cases also unphosphorylated, tyrosine residues

PTB Domain Proteins

Name Aliases Other domains

Mint1 Apba1, Lin-10, X11 2 x PDZ Mint 2 Apba2, X11L 2 x PDZ Mint3 Apba3, X11L2 2 x PDZ 1412 Enzymes

PTB Domain Proteins (Continued)

Name Aliases Other domains

Apbb1 Fe65, Rir 1 x WW Apbb2 Fe65L1 1 x WW Apbb3 Fe65L2 1 x WW

RabGAP1 GAPCenA 1 x RabGAP RabGAP1L HHL 1 x RabGAP

FAM43A FLJ20701 CCM2 Tbc1D4

Eps8 1 x SH3, 2 x PH Eps8L1 1 x SH3 Eps8L2 1 x SH3 Eps8L3 1 x SH3

Dok1 p62 1 x PH Dok2 P56, Frip 1 x PH Dok3 1xPH Dok4 1xPH Dok5 1xPH Dok6 1xPH Dok7 1xPH

Irs1 Hirs-1 1 x PH Irs2 1xPH Irs4 1xPH Frs2 SNT Frs3

Appl1 1xPH Appl2 1xPH Jip1 JNK-interacting protein 1, MAPK8IP1 1 x SH3 Jip2 JNK-interacting protein 2, MAPK8IP2 1 x SH3

Tensin1 Tensin2 Tensin3 TEM6 Tensin4 CTEN 1 x SH2

RGS12 1 x RGS

SHC1 1 x SH2 SHC2 1 x SH2 SHC3 1 x SH2 SHC4 1 x SH2

Anks1 Anks1L

Numb NumbL CAG3A, CTG3a Enzymes 1413

PTB Domain Proteins (Continued)

Name Aliases Other domains

Dab1 Dab2 DOC-2

Gulp1 CED6 ARH Capon NOS1AP

Transglutaminases (EC 2.3.2.13)

Gene Name Aliases

F13A1 factor XIIIa, protein-glutamine gamma- glutamyltransferase A chain TGM1 Transglutaminase 1, transglutaminase K, protein-glutamine-γ-glutamyltransferase TGASE, TGK, LI, LI1, ICR2 TGM2 Transglutaminase 2, tissue transglutaminase, protein- TGC glutamine-γ-glutamyltransferase TGM3 Transglutaminase 3, TGE transglutaminase E, protein- glutamine-γ-glutamyltransferase TGM4 Transglutaminase 4, prostate transglutaminase TGP TGM5 Transglutaminase 5, transglutaminase X TGX TGM6 Transglutaminase 6, transglutaminase Y TGM3L, TGY TGM7 Transglutaminase 7, transglutaminase Z TGMZ

Hydrolases GTPases Heterotrimeric G-proteins Heterotrimeric G-proteins couple seven transmembrane possesses structural and functional homologies to other receptors (G-protein coupled receptors; GPCR) to members of the guanine nucleotide binding proteins various effectors, such as enzymes and ion channels. superfamily. The β- and γ-subunits of heterotrimeric G-protein regulated effectors produce intracellular G-proteins form an non-dissociable complex and signals, that result in specific cellular responses. represent a functional unit. The functional properties G-protein functions are highly diverse, and the cellular of a heterotrimeric G-protein are primarily defined response to the activation of a GPCR depends on the by the identity of its α-subunit. Both, the α-subunit pattern of G-protein subtypes activated through the and the β/γ-complex can regulate effectors like in- receptor. The diversity of G-proteins is due to their ward rectifier K+-channels (GIRKs), voltage-dependent composition of different α-, β-and γ-subunits, each of Ca2+-channels (VDCC), adenylyl cyclases (AC) or them being a product of a different gene. The α-subunit C β-isoforms (PLC-β).

Heterotrimeric G-proteins

Name Gene symbol Expression Effectors

α-subunits

Gαs class

Gαs GNAS Ubiquitous (AC) ↑ Gαolf GNAL Olfactory epithelium, brain AC ↑ Gαi/o class Gαi1 GNAI1 Widely distributed AC↓, GIRK1-4 (Kir3.1-3.4) ↑ Gαi2 GNAI2 Ubiquitous AC↓, GIRK1-4 (Kir3.1-3.4) ↑ 1414 Enzymes

Heterotrimeric G-proteins (Continued)

Name Gene symbol Expression Effectors

Gαi3 GNAI3 Widely distributed AC↓, GIRK1-4 (Kir3.1-3.4) ↑ Gαo GNAO Neuronal, neuroendocrine N-,P/Q-,R-type VDCC (Cav2.1-2.3) ↓, GIRK ↑ Gαz GNAZ Neuronal, platelets AC↓,? Gαgust GNAG Taste cells, brush cells ? Gαt-r GNAT1 Retinal rods, taste cells cGMP PDE ↑ Gαt-c GNAT2 Retinal cones cGMP PDE ↑ Gαq/11 class Gαq GNAQ Ubiquitous PLC-β ↑ Gα11 GNA11 Almost ubiquitous PLC-β ↑ Gα14 GNA14 Kidney, lung, spleen PLC-β ↑ Gα15/16 GNA15 Hematopoietic cells PLC-β ↑ Gα12/13 class Gα12 GNA12 Ubiquitous ? Gα13 GNA13 Ubiquitous ? β-subunits

β1 GNB1 Widely, retinal rods Adenylyl cyclase type I ↓ ↑ β2 GNB2 Widely distributed Adenylyl cyclase types II, IV β β β β ↑ β3 GNB3 Widely, retinal cones - ( 3> 2> 1) ↑ β4 (GNB4) Widely distributed GIRK1-4 (Kir3.1-3.4) ↑ β5 GNB5 Mainly brain Receptor kinases (GRK 2 and 3) ↑ Phosphoinositide 3 kinase β,γ↑

N,P/Q-,R-type VDCC (Cav2.1-2.3) ↓ γ-subunits Phosphoinositide 3 kinase β, γ ↑

γ1, γrod GNGT1 Retinal rods, brain N-,P/Q-,R-type VDCC (Cav2.1–2.3) ↓ γ14, γcone, γ8 GNGT2 Retinal cones, brain Adenylyl cyclase type I ↓ γ2, γ6 GNG2 Widely Adenylyl cyclase type II, IV ↑ γ3 GNG3 Brain, blood Phospholipase c-β (β3>β2>β1) ↑ γ4 GNG4 Brain and other tissues GIRK 1-4 (kir3.1–3.4) ↑ γ5 GNG5 Widely Phospholipase A2 ↑ γ7 GNG7 Widely Receptor kinases (GRK 2 and 3) ↑ γ10 GNG10 Widely γ11 GNG11 Widely γ12 GNG12 γ13 GNG13 Taste buds

RGS Proteins Regulators of G-protein signaling (RGS) proteins play an RGS protein accelerate the deactivation of G-proteins important role in GPCR signal transduction. RGS resulting in the reduction of GPCR signaling. Some RGS proteins contain a conserved RGS box, which is often proteins also have an effector function and transmit accompanied by other signaling regulatory elements. signals.

RGS Proteins

Name G-protein interaction Expression A- or RZ-subfamily

RGS19 (GAIP) Gi,Gq Ubiquitous, low in brain

RGS17 Gi (Gzα) (RGS-Z2) Enzymes 1415

RGS Proteins (Continued)

Name G-protein interaction Expression

RGS20 Gi (Gzα) Brain (RGS-Z1)

B- or R4-subfamily

RGS4 Gi,Gq Brain, heart RGS1 Gi,Gq B-lymphocytes, lung

RGS2 Gq»Gi Ubiquitous (GOS8)

RGS3 Gi,Gq Ubiquitous RGS5 Gi,Gq Ubiquitous RGS8 Gi Brain RGS13 ND Lung

RGS16 Gi,Gq Retina, pituitary, liver, ubiquitous? RGS18 Gi,Gq C- or -subfamily

RGS9 Gi Retina, neurons RGS6 Gi (Goα) Brain RGS7 Gi (Goα >Giα2 >Giα1) Brain, B-cells RGS11 Gi (Goα) Brain D- or R12-subfamily

RGS12 Gi Lung, brain, spleen, testis

RGS10 Gi Brain RGS14 Gi Brain, spleen, lung E- or RA-subfamily Axin ND Ubiquitous, greatest in thymus, testis Axil ND Lung, thymus F- or GEF-subfamily

p115-RhoGEF G13 Ubiquitous, leukocytes PDZ-RhoGEF G12/13 Ubiquitous, low in liver, lung, colon LARG G12/13 H- or SNX-subfamily

SNX13 Gs (RGS-PX1) SNX14 ND SNX25 ND

D-AKAP2 D-AKAP2 ND Ubiquitous, greatest in testis

Small GTPases The small GTP-binding proteins (small GTPases) consist cell functions and to mediate other regulatory influences. of more than 100 proteins. This superfamily is divided Due totheir important function, small GTPases are targets into five families, Ras, Rho, , Arf and (Takai et al. of a variety of regulators which either promote the (2001) Physiol Rev 81:153–208; Wennerberg et al. exchange of GDP for GTP (guanine nucleotide exchange (2005) J Cell Sci 118:843–846). All small GTPases have factors (GEFs) or which stimulate the rate of GTP in common that they function as molecular switches by hydrolysis of the small GTPase (the GTPase activating cycling between an active (GTP-bound) and an inactive proteins (GAPs) (Bos et al. (2007) Cell 129:865–877) (GDP-bound) state. This pivotal regulatory mechanism (▶small GTPases). allows small GTPases to initiate and terminate specific 1416 Enzymes

Small GTPases

Protein Synonyms Effectors

Ras family Ha-Ras H-Ras, Harvey Raf1, PI-3-K., RalGDS ras Ki-Ras K-Ras, Kirsten Raf1, PI-3-K., RalGDS ras N-Ras p21 Ras, neuro- Raf1, RasGRP2 blastoma ras

R-Ras1 R-Ras Raf1, B-Raf, RalGDS, PLCε, PI-3-K. p110α R-Ras2 TC21 PI-3-K. M-Ras Mras, R-Ras3 Raf, PI-3-K.

RalA PLD, PLC-δ1, RalBP1 RalB

Rap1A Krev1, SMGP21 Raf1, B-Raf, RGS14, RalGDS Rap1B K-REV Raf1, B-Raf, RGS14, RalGDS Rap2A RPIP8, RalGDS, RGS14, Rlf Rap2B RPIP8, RalGDS, RGS14, Rlf

Rit RIBB, Rit1, Roc1 Rin RIBA, Rit2, Roc2

Rad Rrad Rem1 Ges Rem2 Rem-2 Gem

Rheb mTOR

κB-Ras1 κB-Ras2 KBRAS2

Rhes Dex-Ras AGS1, RASD1 Gαi, CAPON, Nck-2

NOEY2 Rig

Rho family RhoA RHOH12 ROCK I/II, PRK, mDia1/2, Citron RhoB RHOH6 ROCK I/II, PRK, mDia1/2 RhoC RHOH9 ROCK I/II, PRK, mDia1/2, FHOD1

Rnd1 Rho6 Socius Rho7, RhoN Rapostlin, pragmin Rho8, RhoE ROCK I, p190RhoGAP, socius RhoF Rif, Afr2 mDia2 RhoD RhoM, RhoH81 mDia3

Rac1 TC-25 PAK1-3, MEKK, p67phox, POSH, Sra1, IRSp53 Rac2 RacB PAK1-3 PAK1-3 RhoG ELMO, kinectin Enzymes 1417

Small GTPases (Continued)

Protein Synonyms Effectors

Cdc42 G25K PAK, WASP, ACK, PAR-6, NCK, IRSp53 TC10 RhoQ PAK, IQGAP1, WASP, ACK TCL RhoJ PAK, WASP RhoU Wrch-1, CDC42L1 RhoV Chp, WRCH2 PAK, WASP RhoH TTF

RhoBTB1 RhoBTB2 DBC2

RhoT1 Miro1 RhoT2 Miro2

ARF family Arf1 Arf2 Arf3 Arf4 Arf5 Arf6 Arl1 Arf-like protein 1 Arl2 Arf-like protein 2 Arl3 Arf-like protein 3 Arl4A Arf-like protein 4A Arl4C LAK, Arl7, Arf-like protein 4C Arl4D Arf-like protein 4D Arl5A Arf-like protein 5A Arl5B Arl8, Arf-like protein 5B Arl5C Arl12, Arf-like protein 5C Arl6 ARF4L, Arf-like protein 6 Arl58A Arl10b, Gie2, Arf-like protein 8A Arl58B Arl10c, Gie1, Arf-like protein 8B Arl9 Arf-like protein 9 Arl10 Arm1, Arf-like pro- tein 10 Arl11 ArltS1, Arf-like protein 11 Arl13A Arf-like protein 13A Arl13B Arl2l1, Arf-like protein 13B Arl14 Arf7, Arf-like protein 14 Arl15 Arfrp2, Arf-like protein 15 Arl16 Arf-like protein 16 1418 Enzymes

Small GTPases (Continued)

Protein Synonyms Effectors

Ran family Ran1

Rab family Rab1A Ypt1, Gtbp Rab1B Rab2A Rab2B Rab3A Rab3B Rab3C Rab3D Gov, D2-2, Rab1b, Rad3d Rab4A Rab4B Rab5A Rab5B Rab5C RabL, Rab5CL Rab6A Rab6B Rab6C WTH3 Rab7A Rab7B Rab8A MEL Rab8B Rab9A Rab9B Rab9L Rab10 Rab11A YL8 Rab11B H-YPT3 Rab12 Rab13 Rab14 FBP Rab15 Rab17 Rab18 Rab19 Rab19B Rab20 Rab21 Rab22A Rab22B Rab31 Rab23 HSPC137 Rab24 Rab25 CATX-8 Rab26 Rab27A Ram Rab27B Rab28 Rab30 Rab31 Rab32 Rab33A RabS10 Rab33B Rab34 Rah, Rab39 Enzymes 1419

Small GTPases (Continued)

Protein Synonyms Effectors

Rab35 Ray, H-ray, Rab1C Rab36 Rab37 Rab38 NY-MEL-1 Rab39A Rab39B Rab40A Rar2A, Rar-2 Rab40B Rar, SEC4L Rab40C Rar3, RarL, RasL8C Rab41 Rab43 Rab42 Rab7L1 RabL4 RayL RasEF Rab45

GTPase Activating Proteins (GAPs)

Protein Synonyms Specificity

RhoGAPs p50RhoGAP ARHGAP1, Cdc42GAP Cdc42 > Rac1, RhoA BPGAP1 ARHGAP8 Cdc42 > RhoA

Bcr Rac1 > Cdc42, Rac2 Abr Cdc42, Rac1, Rac2

GRIT Cdc42, RhoA > Rac1 hCdGAP Cdc42, Rac1, RhoA

ARAP1 ARAP2 Centaurin δ1, PARX ARAP3 Centaurin δ2, DRAG1 RhoA > Cdc42, Rac1

srGAP3 MEGAP, WRP, ARHGAP14 Rac1 > Cdc42 Pn5 ARHGAP4, C7, ChOGAP4 RLIP76 RIP, RIP1, RALBP1 Cdc42 > Rac1

DLC-1 p122-RhoGAP, ARHGAP7, STARD12 RhoA > Cdc42 DLC-2 STARD13, GT650 RhoA > Cdc42

α1-Chimaerin Rac1

RICH-1 ARHGAP17, NADRIN Cdc42, Rac1 RICH-2 Cdc42, Rac2

Oligophrenin-1 OPN1 Cdc42, Rac1, RhoA Graf-2 ARHGAP10 Cdc42, RhoA

GMIP RhoA PARG1 ARHGAP29 Cdc42, Rac1, RhoA 1420 Enzymes

GTPase Activating Proteins (GAPs) (Continued)

Protein Synonyms Specificity

ArhGAP9 10c Cdc42, Rac1 > RhoA ArhGAP12 ND Arhgap15 Rac1

Myosin-IXb RhoA

ArhGAP10 GRAF2, ARHGAP21 Cdc42 > RhoA, Rac1

MgcRacGAP RacGAP1 Rac1, Cdc42, RhoA

FilGAP Cdc42, Rac1 p73RhoGAP ND

ArhGAP6 RhoGAPX-1 RhoA

OCRL-1 INPP5F Rac1

p190-B ARHGAP5 RhoA > Rac1, Cdc42

Ras GAPs p120RasGAP Rasa1 H-Ras, N-Ras, R-Ras, R-Ras2, R-Ras3, Rab5

Neurofibromin NF1-GAP, NF-1, WSS H-Ras, N-Ras, K-Ras, R-Ras, R-Ras2, R-Ras3

Syn GAP H-Ras,

GAP1m Rasa2 H-Ras, R-Ras, R-Ras2, R-Ras3 RASAL1 H-Ras, Rap1 CAPRI H-Ras, Rap1 GAP1IP4BP R-Ras GAP, Rasa3

DAB2IP H-Ras, K-Ras, R-Ras, R-Ras2

Tsc1 Rheb Tsc2 Rheb Plexin B1 R-Ras

Rap1GAP1 Rap1 Rap1GAP2 Rap1

ArfGAPs ArfGAP1 Arf1GAP Arf1, Arf2, Arf3, Arf5 ArfGAP3 Arf1-5

Git1 Cat-1, p95-APP1, p95Cat Arf1, Arf3, Arf5, Arf6 Git2 APAP2, Cat-2, Cyr1, p95-APP2 Arf1, Arf3, Arf5, Arf6

ASAP1 Centaurin-β4, Shog1, DDEF1 Arf1, Arf5 ASAP2 PAPα, PAG3 Arf1, Arf5 ASAP3 UPLC

ACAP1 Centaurin-β1 ACAP2 Centaurin-β2 ACAP3 Centaurin-β5 Enzymes 1421

GTPase Activating Proteins (GAPs) (Continued)

Protein Synonyms Specificity

ARAP1 Centaurin-δ2 Arf1, Arf5, Arf6 ARAP2 Centaurin-δ1 ARAP3 DRAG1

AGAP1 Centaurin-γ2, PIKE-A AGAP2 Centaurin-γ1, PIKE AGAP3 Centaurin-γ3, MRIP-1

Centaurin-α1 GC1L, p42IP4 Centaurin-α2

Arfd1 RNF46, Trim23

Hrb HIV rev-binding protein, Rip Hrb2 HIV rev-binding protein2, Rip-2

RabGAPs TBC1D1 TBC, TBC1, KIAA1108 TBC1D2 PARIS1, TBC1D2A TBC1D2B KIAA1055 TBC1D3 TBC1D3A, DKFZp434P2235, PRC17 TBC1D3B PRC17 TBC1D3C MGC44903 TBC1D3D TBC1D3E TBC1D3F TBC1D3G TBC1D3H TBC1D3I TBC1D3P1 TBC1D3P2 TBC1D4 KIAA0603, AS160 Rab8A, Rab10, Rab14 TBC1D5 KIAA0210 TBC1D6 FLJ22474, GRTP1 TBC1D7 dJ257A7.3, FLJ32666 TBC1D8 HBLP1, VRP, AD3 TBC1D8B FLJ20298 TBC1D9 KIAA0882, MDR1 TBC1D9B KIAA0676 TBC1D10A TBC1D10, EPI64 TBC1D10B DKFZp434P1750 TBC1D10C FLJ00332, carabin TBC1D11 GAPCenA, RabGAP1 TBC1D12 KIAA0608 TBC1D13 FLJ10743 TBC1D14 KIAA1322 TBC1D15 FLJ12085, DKFZp761D0223 TBC1D16 MGC25062, FLJ20748 TBC1D17 FLJ12168 TBC1D18 HHL, KIAA0471, RABGAP1L TBC1D19 FLJ11082 TBC1D20 C20orf140 TBC1D21 MGC34741 1422 Enzymes

GTPase Activating Proteins (GAPs) (Continued)

Protein Synonyms Specificity

TBC1D22A C22orf4 TBC1D22B C6orf197, FLJ20337, dJ744I24.2 TBC1D23 FLJ11046 TBC1D24 KIAA1171 TBC1D25 OATL1

Guanine Nucleotide Exchange Factors (GEFs)

Protein Synonyms Substrates

Rho GEFs p190-RhoGEF GEF-H1 ARHGEF2, LFP40, P40 RhoA Lbc AKAP13 RhoA p114-RhoGEF ARHGEF18 RhoA PDZ-RhoGEF ARHGEF11, GTRAP48 RhoA p115-RhoGEF ARHGEF1 RhoA LARG ARHGEF12 RhoA

Net1 ARHGEF8 RhoA Xpln RhoA, RhoB

Itsn2 Intersectin2, SWAP Cdc42 Itsn1 Intersectin1, SH3P17 Cdc42

AAH26778 BAA91741 AAH42606

Tim ARHGEF5 RhoA WGEF NGEF/ephexin RhoA, Rac1, Cdc42 Vsm-Rho-GEF RhoA SGEF RhoG Neuroblasto- ma

AAH33666

XP294019 Ect2 RhoA

RasGRF1 CDC25 Rac1 RasGRF2 Rac1

KIAA0294 ARHGEF10 KIAA1626 p164-RhoGEF ARHGEF17, TEM4 RhoA Abr RhoA, Rac1, Cdc42 Bcr RhoA, Rac1, Cdc42 Enzymes 1423

Guanine Nucleotide Exchange Factors (GEFs) (Continued)

Protein Synonyms Substrates

Sos2 Rac1 Sos1 Rac1 Farp2/Frg FIR, Cdc42 PLEKHC3 CDEP/Farp1 PLEKHC2 RhoA

KIAA1362 BAC85128

Fdg3 Cdc42 Fdg1 Cdc42 Frabin FGD4, FRABP Cdc42 Fdg2 Cdc42

KIAA1909 BAB15765 Scambio RhoA, RhoC

p63RhoGEF RhoA Trio C RhoA Duet Kalirin, TRAD Duo Rac1 Trio N RhoG, Rac1 Dbl MCF2 RhoA, RhoB, RhoC, RhoG, Cdc42 Dbs MCF2L, ARHGEF14, OST KIAA0861 MCF2L2

Obscurin

XP376334 Tuba Cdc42

XP027307 XP05127 hClg/ Cdc42 BAB15719

P-Rex2 Rac1 P-Rex1 Rac1 BAB71009 hPEM-2 ARHGEF9, Cdc42 collybistin Asef ARHGEF4, STM6 Rac1

Tiam1 STEF Rac1, Rac2, Rac3 Tiam2 Rac1 α-Pix ARHGEF6, Cool-2 Rac1, Cdc42 β-Pix ARHGEF7, PIXβ Rac1, Cdc42

Vav1 RhoA, Rac1, RhoG, Cdc42 Vav3 RhoA, Rac1, RhoG, Cdc42 Vav2 RhoA, Rac1, RhoG, Cdc42 Alsin Rac1 1424 Enzymes

Guanine Nucleotide Exchange Factors (GEFs) (Continued)

Protein Synonyms Substrates

Ras GEFs Sos1 Ras-Gef1 H-Ras, N-Ras, K-Ras, R-Ras2, R-Ras3, Rac1 Sos2 Ras-Gef2 H-Ras

Ras GFR1 CDC25, GNRP, Grf1, GRF55, p190, p190-A, H-Ras, K-Ras, N-Ras, R-Ras, R-Ras2, R-Ras3, Rasgrp3 Rac1 Ras GFR2 Gfr2 H-Ras, Rac1

Ras GRP1 CalDAG-GEFII H-Ras, N-Ras, R-Ras, R-Ras2, R-Ras3 Ras GRP2 CalDAG-GEFI, CDC25L N-Ras, K-Ras, R-Ras, R-Ras2, Rap1A, Rap2A Ras GRP3 CalDAG-GEFIII H-Ras, R-Ras, R-Ras2, R-Ras3, Rap1A, Rap2B Ras GRP4 H-Ras

Ral GDS Ral GEF, Rgds, RGF RalA, RalB Rgl1 RalA, RalB Rgl2 Rlf RalA, RalB Rgl3 RalA, RalB

And34 BCAR2 R-Ras

Epac1 cAMPGEF1, RapGEF3 Rap1, Rap2 Epac2 cAMPGEF2, CGEF2 Rap1, Rap2

PDZ-Gef1 Ra-GEF, Rap-GEF, Rap-GEP Rap1, Rap2 PDZ-Gef2 Rapgef6, Ra-gef2 Rap1, Rap2

Arf GEFs BIG1 Arfgef1, BFA-inhibited GEF1 BIG2 Arfgef2, BFA-inhibited GEF2

Pscd1 ARNO2, CLM1, CTH-1, cytohesin-1 Pscd2 ARNO, CLM2, CTH-2, cytohesin-2, Sec7 Pscd3 ARNO3, cytohesin-3, Grp1 Arf1, Arf6 and others Pscd4 ARNO4, cytohesin-4

GBF1 Golgi, BFA resistance factor Arf5

EFA6 Psd, TYL Arf6

Rab GEFs Rin1 Rab5 Rin2 RASSF4 Rin3 Rabex-5 Rabgef1 Rab5

Phosphodiester Hydrolases Phosphodiesterases (EC 3.1.4.17) Cyclic nucleotide phosphodiesterases control the cellu- properties, expression levels and intracellular localiza- lar levels of the second messengers cAMP and cGMP tion (Bender, Beavo (2006) Pharmacol Rev 58:488– by catalyzing their transformation in the inactive 520; Omori, Kotera (2007) Circ Res 100:309–327) products AMP and GMP. The known PDE family (▶phosphodiesterases). members are characterized by their regulation, kinetic Enzymes 1425

Name Gene Previous symbols, Protein length Substrate(s) Expression aliases (AAs) PDE 1A PDE1A CaM-PDE 556 cGMP > cAMP Ubiquitous PDE 1B PDE1B PDES1B, Aop2 535 cGMP > cAMP Brain PDE 1C PDE1C Hcam3 654 cGMP = cAMP Brain, olfactory epithelium PDE 2A PDE2A 941 cGMP = cAMP Adrenal cortex, brain, heart PDE 3A PDE3A CGI-PDE 1141 cGMP = cAMP Heart, smooth muscle, platelet PDE 3B PDE3B 799 cAMP Brain, smooth muscle, submand. gl. PDE 4A PDE4A DPDE2, dunce 610 cAMP Ubiquitous PDE 4B PDE4B DPDE4 721 cAMP Ubiquitous PDE 4C PDE4C DPDE1 712 cAMP ? PDE 4D PDE4D DPDE3 673 cAMP Ubiquitous PDE 5A PDE5A 875 cGMP Smooth muscle PDE 6A, rod, α PDE6A PDEA 860 cGMP Rods PDE 6B, rod, β PDE6B PDEB, CSNB3 856 cGMP Rods PDE6C,cone,α PDE6C 858 cGMP Cones PDE 6D, rod, δ PDE6D 150 cGMP Rods PDE 6G, rod, γ PDE6G PDEG 83 (cGMP) Rods PDE6H,cone,γ PDE6H 87 (cGMP) Cones PDE 7A PDE7A HCP1 482 cAMP Brain, skeletal muscle, immune cells PDE 7B PDE7B 446 cAMP Pancreas, brain, heart PDE 8A PDE8A 823 cAMP Brain PDE 8B PDE8B cAMP Thyroid PDE 9A PDE9A 534 cGMP Brain, prostate PDE 10° PDE10A 779 cAMP > cGMP Brain PDE 11A PDE11A 490 cGMP, cAMP Adrenal gland, pituitary, prostate

Phospholipases Phospholipases are a group of enzymes which are able to head group, and ▶ cleaves on the other cleave like phosphoglycerides or sphin- side of the phosphodiester bond releasing phosphatidic gomyelin into fatty acids and other lipophilic sub- acid and an alcohol. Sphingomyelin is cleaved by the stances. Phospholipases which cleave phosphoglycerides enzyme ▶sphingomyelinase into ceramide, consisting are divided into four types depending on the site of of sphingosine and a fatty acid, and phosphocholine. cleavage. ▶Phospholipases A1 and ▶Phospholipases A2 The products of most phospholipases are important cleave [s2] the ester bonds that link fatty acids to the sn-1 cellular signaling molecules, and the activity of phos- and sn-2 positions of the phosphoglycerides, respectively. pholipases therefore is subject of complex regulation ▶Phospholipase C cleaves the phosphate thereby (▶phospholipases; ▶lisophospholipids). releasing diacyl glycerol and a phosphate-containing

Phospholipases

Name Gene Previous symbols, Protein length Substrate(s) aliases (AAs)

Phospholipase A2 (PLA2) (EC 3.1.1.-) PLA1 PLA1A ps-PLA1 456 Phospholipids PLA2, group IB PLA2G1B PLA2, PPLA2, PLA2A 146 Phospholipids PLA2, group IIA PLA2G2A PLA2B, PLA2L 68 Phospholipids PLA2, group IID PLA2G2D sPLA2S 144 Phospholipids PLA2G2E 142 Phospholipids PLA2G2F 168 Phospholipids 1426 Enzymes

Phospholipases (Continued)

Name Gene Previous symbols, Protein length Substrate(s) aliases (AAs)

PLA2, group III PLA2G3 GIII-SPLA2 509 Phospholipids PLA2, group IVA PLA2G4A PLA2G4, cPLA2-α 748 Phospholipids PLA2, group IVB PLA2G4B cPLA2-β 1012 Phospholipids PLA2, group IVC PLA2G4C cPLA2-γ 541 Phospholipids/lysophospholi- pids

PLA2, group V PLA2G5 138 Phospholipids PLA2, group VI PLA2G6 iPLA2 806 Phospholipids PLA2, group VII PLA2G7 PAFAH, LDL-PLA2 441 Platelet activating factor PLA2, group X PLA2G10 GXPLA2 155 Phospholipids PLA2, group XIIa PLA2G12A 189 Phospholipids PLA2, group XIII PLA2G13 Phospholipase C (PLC) (EC 3.1.4.11)

PLCβ1 PLCB1 KIAA0581 1173 PIP2 PLCβ2 PLCB2 1181 PIP2 PLCβ3 PLCB3 1234 PIP2 PLCβ4 PLCB4 1175 PIP2 PLCδ1 PLCD1 756 Phosphoinositides

PLCδ3 PLCD3 789 PIP2 PLCδ4 PLCD4 762 PIP2 PLCD5 PLCε1 PLCE1 KIAA1516, PLCE 2303 Phosphoinositides PLCγ1 PLCG1 PLC1 1290 Phosphoinositides PLCγ2 PLCG2 1252 Phosphoinositides

Phospholipase D (PLD) (EC 3.1.4.4) PLD1 PLD1 1047 Phosphatidylcholine PLD2 PLD2 933 Phosphatidylcholine PLD3 PLD3 HU-K4 490 Phosphatidylcholine PLD4 PLD4 506 Phosphatidylcholine

Sphingomyelinases (EC 3.1.4.12) Neutral sphingomyelinase SMPD2 nSMase 423 Sphingomyelin, Lyso-PAF type 1 Neutral sphingomyelinase SMPD3 NSMASE2 655 Sphingomyelin type 2 Neutral sphingomyelinase SMPD4 827 Sphingomyelin type 3 Acidic sphingomyelinase SMPD1 ASM 629 Sphingomyelin Alkaline sphingomyelinase ENPP7 alk-Smase 458 Sphingomyelin, palmitoyl lyso-phosphocholine

Lyases Phosphatases Non-Protein Phosphatases Non-Protein Phosphatases

Gene Name Aliases, previous symbols

Inositol phosphatases INPP1 Inositol polyphosphate-1-phosphatase INPP3 Inositol polyphosphate-3-phosphatase INPP4A Inositol polyphosphate-4-phosphatase, type I, 107 kDa INPP4 Enzymes 1427

Non-Protein Phosphatases (Continued)

Gene Name Aliases, previous symbols

INPP4B Inositol polyphosphate-4-phosphatase, type II, 105 kDa INPP5A Inositol polyphosphate-5-phosphatase, 40 kDa 5PTASE INPP5B Inositol polyphosphate-5-phosphatase, 75 kDa INPP5C Inositol polyphosphate-5-phosphatase, 120 kDa INPP5D Inositol polyphosphate-5-phosphatase, 145 kDa SHIP, hp51CN INPP5E Inositol polyphosphate-5-phosphatase, 72 kDa PPI5PIV INPP5F Inositol polyphosphate-5-phosphatase F SAC2, hSac2

Inositol monophosphatases IMPA1 Inositol(myo)-1(or 4)-monophosphatase 1 IMPA IMPA2 Inositol(myo)-1(or 4)-monophosphatase 2

Sphingosine-1-phosphate phosphatases SGPP1 Sphingosine-1-phosphate phosphatase 1 SGPP2 Sphingosine-1-phosphate phosphotase 2 SPP2 Phosphatidic acid phosphatases PPAP2A Phosphatidic type 2A PAP-2a PPAP2B Phosphatidic acid phosphatase type 2B PAP-2b PPAP2C Phosphatidic acid phosphatase type 2C PAP-2c

Nudix motif phosphatases NUDT1 7,8-Dihydro-8-oxoguanine MTH1 NUDT2 Bis (5Υ-nucleosyl)-tetraphosphatase APAH1, Ap4Aase NUDT3 Diphosphoinositol polyphosphate phosphohydrolase 1 DIPP NUDT4 Diphosphoinositol polyphosphate phosphohydrolase 2 DIPP2, DIPP2alpha, DIPP2beta NUDT5 ADP-sugar hYSAH1, YSA1H NUDT6 gfg-1, bFGF, FGF-2, FGF-AS NUDT7 NUDT8 Nucleoside diphosphate phosphatase NUDT9 ADP-ribose pyrophosphatase ADPR-PPase NUDT10 Diphosphoinositol polyphosphate phosphohydrolase 3α DIPP3α NUDT11 Diphosphoinositol polyphosphate phosphohydrolase 3β DIPP3β NUDT12 Peroxisomal NADH pyrophosphatase NUDT13 NUDT14 Uridine diphosphate glucose pyrophosphatase UGPP NUDT15 7,8-Dihydro-8-oxoguanine triphosphatase MTH2 NUDT16 Nucleoside diphosphate phosphatase NUDT17 NUDT18 NUDT19 RP2 NUDT21 Cleavage and polyadenylation specificity factor 5 CFIM25, CPSF5 NUDT22

Acid phosphatases ACP1 Acid phosphatase 1, soluble ACP2 Acid phosphatase 2, lysosomal ACP5 Acid phosphatase 5, tartrate resistant ACP6 Acid phosphatase 6, lysophosphatidic LPAP, ACPL1 ACPP Acid phosphatase, prostate ACP3, ACP-3 ACPT Acid phosphatase, testicular

Alkaline phosphatases ALPI , intestinal ALPL Alkaline phosphatase, liver/bone/kidney HOPS, TNSALP ALPP Alkaline phosphatase, placental (Regan isozyme) ALPPL2 Alkaline phosphatase, placental-like 2 1428 Enzymes

Non-Protein Phosphatases (Continued)

Gene Name Aliases, previous symbols

Acylphosphatases ACYP1 1, erythrocyte (common) type ACYP2 Acylphosphatase 2, muscle type

Protein Phosphatases Protein phosphatases are enzymes which catalyze the in three main families, tyrosine-specific phospha- dephosphorylation of their protein substrates, thus, tases, serine/threonine-specific phosphatases, and dual reversing the reaction performed by protein kinases. specificity phosphatases, which can dephosphory- Based on the phosphorylated amino acid which is late phospho-tyrosine, -serine and -threonine (▶protein dephosphorylated, protein phosphatases are divided phosphatases).

Protein Serine/Threonine Phosphatases (EC 3.1.3.16)

Gene Protein Aliases, previous symbols type 1 (catalytic subunit) PPP1CA , α isoform PPP1A PPP1CB Protein phosphatase 1, β isoform PPP1CC Protein phosphatase 1, γ isoform

Protein phosphatase type 1 (regulatory subunit) PPP1R1A Protein phosphatase 1, subunit 1A PPP1R1B Protein phosphatase 1, subunit 1B DARPP-32 PPP1R1C Protein phosphatase 1, subunit 1C Inhibitor-1-like PPP1R2 Protein phosphatase 1, subunit 2 IPP2 PPP1R3A Protein phosphatase 1, subunit 3A PPP1R3 PPP1R3B Protein phosphatase 1, subunit 3B GL, PPP1R4 PPP1R3C Protein phosphatase 1, subunit 3C PPP1R5 PPP1R3D Protein phosphatase 1, subunit 3D PPP1R3E Protein phosphatase 1, subunit 3E FLJ00089 PPP1R3F Protein phosphatase 1, subunit 3F Hb2E PPP1R3G Protein phosphatase 1, subunit 3G PPP1R7 Protein phosphatase 1, subunit 7 sds22 PPP1R8 Protein phosphatase 1, subunit 8 ard-1, NIPP-1, ARD1 PPP1R9A Protein phosphatase 1, subunit 9A Neurabin-I PPP1R9B Protein phosphatase 1, subunit 9B PPP1R6, PPP1R9 PPP1R10 Protein phosphatase 1, subunit 10 PNUTS, FB19 PPP1R11 Protein phosphatase 1, subunit 11 HCGV, Tctex5, TCTE5 PPP1R12A Protein phosphatase 1, subunit 12A MBS, MYPT1 PPP1R12B Protein phosphatase 1, subunit 12B MYPT2 PPP1R12C Protein phosphatase 1, subunit 12C p84 PPP1R13B Protein phosphatase 1, subunit 13B p53BP2-like, p85, ASPP1 PPP1R13L Protein phosphatase 1, subunit 13 like RAI, IASPP PPP1R14A Protein phosphatase 1, subunit 14A CPI-17, PPP1INL PPP1R14B Protein phosphatase 1, subunit 14B SOM172, PNG, PLCB3N PPP1R14C Protein phosphatase 1, subunit 14C CPI17-like, NY-BR-81 PPP1R14D Protein phosphatase 1, subunit 14D CPI17-like PPP1R15A Protein phosphatase 1, subunit 15A GADD34 PPP1R15B Protein phosphatase 1, subunit 15B PPP1R16A Protein phosphatase 1, subunit 16A PPP1R16B Protein phosphatase 1, subunit 16B TIMAP, ANKRD4 Enzymes 1429

Protein Serine/Threonine Phosphatases (EC 3.1.3.16) (Continued)

Gene Protein Aliases, previous symbols

Protein phosphatase type 2 (catalytic subunit) PPP2CA , α isoform PPP2CB Protein phosphatase 2, β isoform Protein phosphatase type 2 (regulatory subunit) PPP2R1A Protein phosphatase 2, A, α isoform PR65A PPP2R1B Protein phosphatase 2, A, β isoform PR65B PPP2R2A Protein phosphatase 2, B, α isoform PR52A, PR55A, B55A PPP2R2B Protein phosphatase 2, B, β isoform PR55-BETA, PR52B, SCA12 PPP2R2C Protein phosphatase 2, B, γ isoform PR52, IMYPNO, PR55G PPP2R2D Protein phosphatase 2, B, δ isoform MDS026 PPP2R3A Protein phosphatase 2, B’, α PPP2R3 PPP2R3B Protein phosphatase 2, B’, β PPP2R3LY, PPP2R3L PPP2R3C Protein phosphatase 2, B’, γ G4-1, G5PR PPP2R4 Protein phosphatase 2A activator 4 PTPA, PR53 PPP2R5A Protein phosphatase 2, B’, α isoform PR61A, B56A PPP2R5B Protein phosphatase 2, B’, β isoform FLJ35411, B56B, PR61B PPP2R5C Protein phosphatase 2, B’, β isoform B56G, PR61G PPP2R5D Protein phosphatase 2, B’, δ isoform B56D PPP2R5E Protein phosphatase 2, B’, ε isoform

Protein phosphatase type 3 (catalytic subunit) PPP3CA Protein phosphatase 3, α isoform Aα-subunit, CNA1, CCN1, PPP2B, CALN PPP3CB Protein phosphatase 3, β isoform Calcineurin Aβ-subunit, CALNB PPP3CC protein phosphatase 3, γ isoform Calcineurin Aγ-subunit Protein phosphatase type 3 (regulatory subunit) PPP3R1 Protein phosphatase 3, B,α isoform Calcineurin B B1-subunit, CALNB1, CNB, CNB1 PPP3R2 Protein phosphatase 3, B, β isoform Calcineurin B B2-subunit, PPP3RL

Protein phosphatase type 4–6 and others PPP4C Protein phosphatase 4, catalytic subunit PP4, PPH3 PPP4R1 Protein phosphatase 4, regulatory subunit 1 PP4R1 PPP4R2 Protein phosphatase 4, regulatory subunit 2 PPP5C Protein phosphatase 5, catalytic subunit PP5, PPP5 PPP6C Protein phosphatase 6, catalytic subunit PPEF1 Protein phosphatase, EF-hand domain 1 PP7 PPEF2 Protein phosphatase, EF-hand domain 2

Protein Tyrosine Phosphatases

Gene Protein Alias, synonyms

Transmembrane tyrosine phosphatases PTPRA Receptor tyrosine-protein phosphatase α RPTPα PTPRB Receptor tyrosine-protein phosphatase β RPTPβ PTPRC CD45 CD45, LCA PTPRD Receptor tyrosine-protein phosphatase δ RPTPδ PTPRE Receptor tyrosine-protein phosphatase ε RPTPε PTPRF Receptor tyrosine-protein phosphatase F LAR PTPRG Receptor tyrosine-protein phosphatase γ RPTPγ PTPRH Receptor tyrosine-protein phosphatase H SAP1 PTPRJ Receptor tyrosine-protein phosphatase η DEP1, CD148, RPTPη PTPRK Receptor tyrosine-protein phosphatase κ RPTPκ PTPRM Receptor tyrosine-protein phosphatase μ RPTPμ 1430 Enzymes

Protein Tyrosine Phosphatases (Continued)

Gene Protein Alias, synonyms

PTPRN Receptor tyrosine-protein phosphatase N IA-2, Islet cell antigen 512 PTPRN2 Receptor tyrosine-protein phosphatase N2 PTPRP, RPTPπ, IA-2β, phogrin, GLEPP1/PTP-U2/PTPROτ PTPRO Receptor tyrosine-protein phosphatase O isoforms A/B/C PTPRQ Receptor tyrosine-protein phosphatase Q PTPS31 PTPRR Receptor tyrosine-protein phosphatase R PTP-SL, PCPTP, PTPBR7, PC12-PTP1 PTPRS Receptor tyrosine-protein phosphatase S RPTPσ PTPRT Receptor tyrosine-protein phosphatase T RPTPρ PTPRU Receptor tyrosine-protein phosphatase U PTPJ/PTP-U1/PTPRomicron isoforms 1/2/3 PTPRV OST-PTP PTPRZ RPTPζ

Nonreceptor tyrosine phosphatases (EC 3.1.3.48) PTPN1 Protein-tyrosine phosphatase 1B PTP1B PTPN2 T-cell protein-tyrosine phosphatase TCPTP, MPTP, PTP-S PTPN3 Protein-tyrosine phosphatase H1 PTPH1 PTPN4 Protein-tyrosine phosphatase MEG1 PTP-MEG1, TEP PTPN5 Protein-tyrosine phosphatase -enriched STEP PTPN6 Protein-tyrosine phosphatase 1C SHP1, PTP1C, SH-PTP1, HCP PTPN7 Protein-tyrosine phosphatase LC-PTP HePTP, LCPTP PTPN9 Protein-tyrosine phosphatase MEG2 PTP-MEG2 PTPN11 Protein-tyrosine phosphatase 2C SHP2, SH-PTP2, Syp, PTP1D, PTP2C, SH-PTP3 PTPN12 Protein-tyrosine phosphatase G1 PTP-PEST, PTP-P19, PTPG1) PTPN13 Protein-tyrosine phosphatase 1E PTP-BAS, FAP-1, PTP1E, RIP, PTPL1, PTP-BL PTPN14 Protein-tyrosine phosphatase pez PTP36, PEZ, PTPD2 PTPN18 Brain-derived phosphatase PTP-HSCF, PTP20, BDP PTPN20 TypPTP PTPN21 Protein-tyrosine phosphatase D1 PTPD1, PTP2E, PTP-RL10 PTPN22 Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP LYP, PEP PTPN23 His domain-containing protein tyrosine phosphatase HD-PTP, HDPTP, PTP-TD14

Dual Specificity Phosphatases (PSP) or VH1-Like

Gene Protein Alias, synonyms MAP kinase phosphatases (PTyr, PThr) (EC 3.1.3.48/16) DUSP1 MAP kinase phosphatase 1 MKP-1, 3CH134, PTPN10, erp, CL100/HVH1 DUSP2 Dual specificity protein phosphatase PAC-1 PAC-1 Dual specificity protein phosphatase VHR VHR DUSP4 Mitogen-activated protein kinase phosphatase 2 MKP-2, hVH2/TYP1 DUSP5 Dual specificity protein phosphatase hVH3 hVH3/B23 DUSP6 MAP kinase phosphatase 3 PYST1, MKP-3/rVH6 DUSP7 Dual specificity protein phosphatase PYST2 PYST2, B59, MKP-X DUSP8 Dual specificity protein phosphatase hVH-5 hVH5, M3/6, HB5 DUSP9 MAP kinase phosphatase 4 MKP-4, Pyst3 DUSP10 MAP kinase phosphatase 5 MKP-5 DUSP16 MAP kinase phosphatase 7 MKP-7, MKP-M

Atypical dual specificity phosphatases (PTyr, PThr, mRNA) DUSP3 VHR, T-DSP11 DUSP11 Phosphatase that interacts with RNA/RNP complex 1 PIR1 Enzymes 1431

Dual Specificity Phosphatases (PSP) or VH1-Like (Continued)

Gene Protein Alias, synonyms

DUSP12 Dual specificity tyrosine phosphatase YVH1 HYVH1, GKAP, LMW-DSP4 DUSP13 Testis- and skeletal-muscle-specific DSP BEDP DUSP14 MAP kinase phosphatase 6 MKP6, MKP-L DUSP15 Vaccinia virus VH1-related dual-specific protein phosphatase Y VHY DUSP18 Low molecular weight dual specificity phosphatase 20 DUSP20, LMW-DSP20 DUSP19 Stress-activated protein kinase pathway-regulating phosphatase 1 DUSP17, SKRP1, LDP-2, TS- DSP1 DUSP21 Low molecular weight dual specificity phosphatase 21 LMW-DSP21 DUSP22 JNK-stimulatory phosphatase-1 VXH, MKPX, JSP1, LMW-DSP2, TS-DSP2, JKAP DUSP23 Low molecular mass dual specificity phosphatase 3 MOSP DUSP24 MGC1136 DUSP25 VHZ, LMW-DSP3 DUSP26 Low-molecular-mass dual-specificity phosphatase 4 VHP DUSP27b DUPD1, FMDSP EPM2A Laforin RNGTT mRNA-capping enzyme

Slingshots (PSer) SSH1 SSH1, slingshot 1 SSH2 SSH2, slingshot 2 SSH3 SSH3, slingshot 3 PRLs (PTyr) PTP4A1 Protein-tyrosine phosphatase 4a1 PRL-1 PTP4A2 Protein-tyrosine phosphatase 4a2 PRL-2, OV-1 PTP4A3 Protein-tyrosine phosphatase 4a3 PRL-3

CDC14s (PSer, PThr) CDC14A CDC14A CDC14B CDC14B CDKN3 KAP PTP9Q22 PTP9Q22

PTEN (phosphatase and tensin homolog) (D3-phosphoinositides) PTEN Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual- PTEN, MMAC1, TEP1 specificity protein phosphatase TPIP TPIPα, TPTE and PTEN homolo- gous TPTE PTEN-like, PTEN2 TNS Tensin TENC1 C1 domain-containing phosphatase and tensin homolog C1-TEN, TENC1

Myotubularins (PI(3)P) MTM1 Myotubularin MTMR1 Myotubularin-related protein 1 MTMR1 MTMR2 Myotubularin-related protein 2 MTMR2 MTMR3 Myotubularin-related protein 3 MTMR3, FYVE-DSP1 MTMR4 Myotubularin-related protein 4 MTMR4, FYVE-DSP2 MTMR5 Myotubularin-related protein 5 MTMR1, SFB1 MTMR6 Myotubularin-related protein 6 MTMR6 MTMR7 Myotubularin-related protein 7 MTMR7 MTMR8 Myotubularin-related protein 8 MTMR8 MTMR9 Myotubularin-related protein 9 MTMR9, LIP-STYX MTMR10 Myotubularin-related protein 10 MTMR10 MTMR11 Myotubularin-related protein 11 MTMR11CRA α/β MTMR12 Myotubularin-related protein 12 MTMR12, 3-PAP 1432 Enzymes

Dual Specificity Phosphatases (PSP) or VH1-Like (Continued)

Gene Protein Alias, synonyms

MTMR13 Myotubularin-related protein 13 MTMR13, SBF2, CMT4B2 MTMR14 Myotubularin-related protein 14 FLJ22075, hJumpy, hEDTP MTMR15 Myotubularin-related protein 15 Class II Cys-based PTPases (PTyr) ACP1 LMPTP, low Mr PTP, LMWPTP, BHPTP

Class III Cys-based PTPases (PTyr, PThr) CDC25A CDC25A CDC25B CDC25B CDC25C CDC25C Asp-based PTPases (PTyr, PSer?) EYA1 Eyes absent homolog 1 Eya1 EYA2 Eyes absent homolog 2 Eya2 EYA3 Eyes absent homolog 3 Eya3 EYA4 Eyes absent homolog 4 Eya4

Cyclases Adenylyl Cyclases (EC 4.6.1.1) Adenylyl cyclases catalyze the conversion of ATP to cyclases are characterized by their expression pat- pyrophosphate and cAMP, an important second mes- tern and their individual mode of regulation by G- senger which regulates cellular functions by binding to protein α- and βγ-subunits, Ca2+ or phosphorylation cyclic nucleotide-gated ion channels, cAMP-dependent (▶adenylyl cyclases). protein kinases and other effector molecules. Adenylyl

Name Gene Previous sym- Protein Substrate Expression Regulation bols, aliases length (AAs) (s)

AC1 ADCY1 AC1 1119 ATP Brain, adrenal gland Gαs↑, Ca/CaM↑, Forskolin↑, Gβγ↓,Gαi/o↓

AC2 ADCY2 HBAC2, 1091) ATP Brain Gαs↑, PKC↑,Gβγ↑ KIAA1060, AC2

AC3 ADCY3 AC3 1144 ATP Brain, olfactory epithelium Gαs↑,Gαi/o↓, Forskolin↑ AC4 ADCY4 AC4 1077 ATP Ubiquitous Gαs↑, Forskolin↑,Gβγ↑ 2+ AC5 ADCY5 AC5 1261 ATP Brain, heart, adrenal Gαs↑, Forskolin↑,Ca ↓, gland Gαi/o↓ AC6 ADCY6 AC6 1168 ATP Heart, liver, kidney, brain Gαs↑, Forskolin↑,Gαi/o↓, PKC↓, PKA↓

AC7 ADCY7 KIAA0037, AC7 1080 ATP Ubiquitous Gαs↑, Forskolin↑,Gβγ↑ 2+ AC8 ADCY8 ADCY3, HBAC1, 1251 ATP Brain, lung, pancreas Gαs↑, Forskolin↑,Ca ↑, AC8 Gαi/o↓ AC9 ADCY9 AC9 1353 ATP Cochlea, heart, brain, Gαs↑ skeletal muscle

Guanylyl Cyclases (EC 4.6.1.2.) Guanylyl cyclases catalyze the formation of pyrophos- can be divided in two subgroups, the so-called soluble phate and cGMP from GTP. The intracellular messen- guanylyl cyclases (sGC) which are activated by nitric ger cGMP regulates cellular functions by acting on oxide and in the membraneous guanylyl cyclases which cyclic nucleotide-gated ion channels, cGMP-dependent are enzyme-linked receptors (see “Receptor-linked protein kinases or phosphodiesterases. Guanylyl cyclases guanylyl cyclases”)(▶guanylyl cyclases). Enzymes 1433

Name Gene Previous symbols, aliases Protein length (AAs) Substrate(s)

Soluble guanylyl cyclases

Guanylyl cyclase 1, soluble, α2 GUCY1A2 GUC1A2, GC-SA2 732 GTP

Guanylyl cyclase 1, soluble, α3 (α1) GUCY1A3 GC-SA3, GC-S-α1 690 GTP Guanylyl cyclase 1, soluble, β2 GUCY1B2 GC-SB2 617 GTP Guanylyl cyclase 1, soluble, β3 (β1) GUCYB3 GC-SB3, GC-S-β1 646 GTP Membranous guanylyl cyclases (s. 1.2.4)

Peptidases Peptidases or proteases are one of the largest enzyme aspartic acid or cysteine residue in their active centre are families and are involved in multiple cellular and called serine, threonine, aspartic acid or cysteine biological functions. Proteases are divided in at least proteases. The so-called metalloproteinases (metallo- five classes depending on the mechanism of . peptidases) bind metal ion such as Zn2+ or Ca2+ in their Peptidases which carry an important serine, threonine, (▶non-viral proteases; ▶viral proteases).

Aspartic Acid Peptidases

Peptidase Gene

Pepsin family Pepsin A PGA3 Gastricsin PGC Memapsin-2 BACE1 Chymosin CYMP Rennin REN D CTSD Cathepsin E CTSE Memapsin-1 BACE2 Napsin A NAPSA Mername-AA034 peptidase (deduced from nucleotide sequence by MEROPS) Pepsin A5 (Homo sapiens) PGA5 Napsin B pseudogene (napsin B pseudogene) NAPSB

Retropepsin family Mouse mammary tumor virus retropepsin Human endogenous retrovirus K retropepsin Human endogenous retrovirus K retropepsin Rabbit endogenous retrovirus S71-related human endogenous retropepsin RTVL-H-like putative peptidase Human endogenous retrovirus retropepsin homologue 1 Human endogenous retrovirus retropepsin homologue 2 Subfamily A2A non-peptidase homologues

Presenilin family Presenilin 1 PSEN1 Presenilin 2 PSEN2 Impas 1 peptidase HM13 Impas 4 peptidase Impas 2 peptidase Impas 5 peptidase Impas 3 peptidase 1434 Enzymes

Cysteine Proteases

Peptidase Gene

Papain family CTSL2 CTSZ -like peptidase 2 CTSLL2 Cathepsin L-like peptidase 3 CTSLL3 CTSF Cathepsin L CTSL CTSS CTSO CTSK CTSW CTSH CTSB Dipeptidyl-peptidase I CTSC Tubulointerstitial nephritis antigen TINAG Tubulointerstitial nephritis antigen-related protein LCN7

Calpain family -1 CAPN1 Calpain-2 CAPN2 Calpain-3 CAPN3 Calpain-9 CAPN9 Calpain-8 Calpain-7 CAPN7 Calpain-15 SOLH Calpain-5 CAPN5 Calpain-11 CAPN11 Calpain-12 CAPN12 Calpain-10 CAPN10 Calpain-13 CAPN13 Calpain-14 CAPN14 Calpamodulin (calpamodulin) CAPN6

Ubiquitin C-terminal family Ubiquitinyl hydrolase-L1 UCHL1 Ubiquitinyl hydrolase-L3 UCHL3 Ubiquitinyl hydrolase-BAP1 (KIAA0272 protein) BAP1 Ubiquitinyl hydrolase-UCH37 UCHL5

Legumain family Legumain (plant alpha form) Legumain LGMN Glycosylphosphatidylinositol:protein transamidase PIGK

Caspase family Caspase-1 CASP1 Caspase-3 CASP3 Caspase-7 CASP7 Caspase-6 CASP6 Caspase-2 CASP2 Caspase-4 CASP4 Caspase-5 CASP5 Caspase-8 CASP8 Caspase-9 CASP9 Caspase-10 CASP10 Caspase-14 CASP14 MALT1 Enzymes 1435

Cysteine Proteases (Continued)

Peptidase Gene

Mername-AA143 peptidase Mername-AA186 peptidase Putative caspase (Homo sapiens) FLIP protein (casper) CFLAR Mername-AA142 protein

Pyroglutamyl peptidase I family Pyroglutamyl-peptidase I (chordate) PGPEP1 Mername-AA073 peptidase Ubiquitin-specific protease family Ubiquitin-specific peptidase 5 USP5 Ubiquitin-specific peptidase 6 USP6 Ubiquitin-specific peptidase 4 (ubiquitin carboxy-terminal hydrolase UNP) USP4 Ubiquitin-specific peptidase 8 (KIAA0055 protein) USP8 Ubiquitin-specific peptidase 13 USP13 Ubiquitin-specific peptidase 2 USP2 Ubiquitin-specific peptidase 11 USP11 Ubiquitin-specific peptidase 14 USP14 Ubiquitin-specific peptidase 7 (ubiquitin carboxyl-terminal hydrolase HAUSP) USP7 Ubiquitin-specific peptidase 9X USP9X Ubiquitin-specific peptidase 10 (KIAA0190 protein) USP10 Ubiquitin-specific USP1 Ubiquitin-specific peptidase 12 USP12 Ubiquitin-specific peptidase 16 USP16 Ubiquitin-specific peptidase 15 USP15 Ubiquitin-specific peptidase 17 USP17 Ubiquitin-specific peptidase 19 USP19 Ubiquitin-specific peptidase 20 USP20 Ubiquitin-specific peptidase 3 USP3 Ubiquitin-specific peptidase 9Y USP9Y Ubiquitin-specific peptidase 18 USP18 Ubiquitin-specific peptidase 21 USP21 Ubiquitin-specific peptidase 22 USP22 Ubiquitin-specific peptidase 33 USP33 Ubiquitin-specific peptidase 29 USP29 Ubiquitin-specific peptidase 25 USP25 Ubiquitin-specific peptidase 36 USP36 Ubiquitin-specific peptidase 32 USP32 Ubiquitin-specific peptidase 26 (human-type) USP26 Ubiquitin-specific peptidase 24 USP24 Ubiquitin-specific peptidase 42 USP42 Ubiquitin-specific peptidase 46 USP46 Ubiquitin-specific peptidase 37 USP37 Ubiquitin-specific peptidase 28 USP28 Ubiquitin-specific peptidase 47 USP47 Ubiquitin-specific peptidase 38 USP38 Ubiquitin-specific peptidase 44 USP44 Ubiquitin-specific peptidase 50 USP50 Ubiquitin-specific peptidase 35 USP35 Ubiquitin-specific peptidase 30 USP30 Mername-AA091 peptidase Ubiquitin-specific peptidase 45 USP45 Ubiquitin-specific peptidase 51 USP51 Ubiquitin-specific peptidase 34 USP34 Ubiquitin-specific peptidase 48 USP48 Ubiquitin-specific peptidase 40 USP40 1436 Enzymes

Cysteine Proteases (Continued)

Peptidase Gene

Ubiquitin-specific peptidase 41 USP41 Ubiquitin-specific peptidase 31 USP31 Mername-AA129 peptidase Ubiquitin-specific peptidase 49 USP49 Mername-AA187 peptidase USP27X USP17-like peptidase Ubiquitin-specific peptidase 54 USP54 Ubiquitin-specific peptidase 53 USP53 Ubiquitin-specific endopeptidase 39 [misleading] USP39 Mername-AA090 non-peptidase homologue Ubiquitin-specific peptidase 43 [misleading] USP43 Ubiquitin-specific peptidase 52 [misleading] USP52 Mername-AA088 peptidase USP8P NEK2 pseudogene (deduced from nucleotide sequence by MEROPS) NEK2P

γ-Glutamyl hydrolase family Gamma-glutamyl hydrolase GGH Guanine 5Υ-monophosphate synthetase GMPS Carbamoyl-phosphate synthase (Homo sapiens) (CPS1 protein) Dihydro-orotase (N-terminal unit) (Homo sapiens) CAD

Amidophosphoribosyltransferase precursor PPAT Glutamine-fructose-6-phosphate transaminase 1 (glucosamine-fructose-6-phosphate aminotransferase) GFPT1 Glutamine:fructose-6-phosphate amidotransferase GFPT2 Mername-AA144 protein Asparagine synthetase ASNS

Hedgehog family Sonic hedgehog protein SHH Indian hedgehog protein IHH Desert hedgehog protein DHH

Ulp1 endopeptidase family SENP1 peptidase SENP1 SENP3 peptidase SENP3 SENP6 peptidase SENP6 SENP2 peptidase SENP2 SENP5 peptidase SENP5 SENP7 peptidase SENP7 SENP8 peptidase SENP8 SENP4 peptidase family Separase ESPL1 Aut2 peptidase family -2 ATG4A Autophagin-1 ATG4B Autophagin-3 ATG4C Autophagin-4 ATG4D Pfpl endopeptidase family DJ-1 putative peptidase PARK7 Mername-AA100 peptidase Mername-AA101 non-peptidase homologue KIAA0361 protein (Homo sapiens) PFAS FLJ34283 protein (Homo sapiens) Cezanne deubiquitinylating peptidase family Enzymes 1437

Cysteine Proteases (Continued)

Peptidase Gene

Cezanne deubiquitinylating peptidase ZA20D1 Cezanne-2 peptidase C15orf16 alpha-induced protein 3 TNFAIP3 TRABID protein ZRANB1 Otubain-1 OTUB1 Otubain-2 OTUB2 CylD protein CYLD Secernin 1 SCRN1 Secernin 2 (SCRN2 protein) SCRN2 Secernin 3 (SCRN3 protein) SCRN3 UfSP1 peptidase UfSP2 peptidase

Metallopeptidases

Peptidase Gene N ANPEP Aminopeptidase A ENPEP Leukotriene A4 hydrolase (LTA4H protein) LTA4H Pyroglutamyl-peptidase II TRHDE Cytosol alanyl aminopeptidase NPEPPS Cystinyl aminopeptidase LNPEP RNPEP Aminopeptidase PILS Mername-AA050 peptidase RNPEPL1 Leukocyte-derived arginine aminopeptidase Laeverin Aminopeptidase O Tata binding protein associated factor TAF2

Metallo- Angiotensin-converting enzyme peptidase unit 1 ACE Angiotensin-converting enzyme peptidase unit 2 ACE Angiotensin-converting enzyme 2 ACE2 Mername-AA153 protein

Thimet Thimet THOP1 Neurolysin NLN Mitochondrial intermediate peptidase MIPEP Mername-AA154 protein Leishmanolysin-2 LMLN Matrix-metallopeptidases Matrix metallopeptidase-1 (interstitial collagenase) MMP1 Matrix metallopeptidase-8 (neutrophil collagenase) MMP8 Matrix metallopeptidase-2 (gelatinase A) MMP2 Matrix metallopeptidase-9 (gelatinase B) MMP9 Matrix metallopeptidase-3 (stromelysin 1) MMP3 Matrix metallopeptidase-10 (stromelysin 2) MMP10 Matrix metallopeptidase-11 (stromelysin 3) MMP11 Matrix metallopeptidase-7 (matrilysin 1) MMP7 Matrix metallopeptidase-12 (metalloelastase) MMP12 Matrix metallopeptidase-13 (collagenase 3) MMP13 1438 Enzymes

Metallopeptidases (Continued)

Peptidase Gene

Membrane-type matrix metallopeptidase-1 MMP14 Membrane-type matrix metallopeptidase-2 MMP15 Membrane-type matrix metallopeptidase-3 MMP16 Membrane-type matrix metallopeptidase-4 MMP17 Matrix metallopeptidase-20 MMP20 Matrix metallopeptidase-19 MMP19 Matrix metallopeptidase-23B MMP23B Membrane-type matrix metallopeptidase-5 MMP24 Membrane-type matrix metallopeptidase-6 MMP25 Matrix metallopeptidase-21 MMP21 Matrix metallopeptidase-22 MMP27 Matrix metallopeptidase-26 (matrilysin 2) MMP26 Matrix metallopeptidase-28 MMP28 Matrix metallopeptidase-23A MMP23A Macrophage homologue Mername-AA156 protein Matrix metallopeptidase-like 1 MMPL1

ADAM metallo- Meprin alpha subunit (alpha) MEP1A Meprin beta subunit (beta) MEP1B Procollagen C-peptidase BMP1 Mammalian tolloid-like 1 protein TLL1 Mammalian tolloid-like 2 protein TLL2 ADAMTS9 peptidase ADAMTS9 ADAMTS14 peptidase ADAMTS14 ADAMTS15 peptidase ADAMTS15 ADAMTS16 peptidase ADAMTS16 ADAMTS17 peptidase ADAMTS17 ADAMTS18 peptidase ADAMTS18 ADAMTS19 peptidase ADAMTS19 ADAM1 peptidase ADAM1 ADAM8 peptidase ADAM8 ADAM9 peptidase ADAM9 ADAM10 peptidase ADAM10 ADAM12 peptidase ADAM12 Adamalysin-19 ADAM19 ADAM15 peptidase ADAM15 ADAM17 peptidase ADAM17 ADAM20 peptidase ADAM20 ADAMDEC1 peptidase ADAMDEC1 ADAMTS3 peptidase ADAMTS3 ADAMTS4 peptidase ADAMTS4 ADAMTS1 peptidase ADAMTS1 ADAM28 peptidase (human-type) ADAM28 ADAMTS5 peptidase ADAMTS5 ADAMTS8 peptidase ADAMTS8 ADAMTS6 peptidase ADAMTS6 ADAMTS7 peptidase ADAMTS7 ADAM30 peptidase ADAM30 ADAM21 peptidase (Homo sapiens) (ADAM 21 protein) ADAM21 ADAMTS10 peptidase ADAMTS10 ADAMTS12 peptidase ADAMTS12 ADAMTS13 peptidase ADAMTS13 Enzymes 1439

Metallopeptidases (Continued)

Peptidase Gene

ADAM33 peptidase ADAM33 Ovastacin ASTL ADAMTS20 peptidase (Homo sapiens) ADAMTS20 Procollagen I N-peptidase ADAMTS2 ADAM2 protein (ADAM 2 protein) ADAM2 ADAM6 protein ADAM6 protein ADAM6 protein ADAM7 protein (GP-83 glycoprotein) ADAM7 ADAM18 protein ADAM18 ADAM32 protein ADAM32 ADAM3A protein (human-type) (ADAM 3A protein) ADAM3A ADAM3B protein (human-type) (ADAM 3B protein) ADAM3B ADAM11 protein (ADAM 11 protein) ADAM11 ADAM22 protein (ADAM 22 protein) ADAM22 ADAM23 protein (ADAM 23 protein) ADAM23 ADAM29 protein ADAM29 Protein similar to ADAM21 peptidase preproprotein (Homo sapiens) Mername AA-225 peptidase homologue (Homo sapiens) family Neprilysin MME Endothelin-converting enzyme 1 ECE1 Endothelin-converting enzyme 2 ECE2 DINE peptidase ECEL1 Neprilysin-2 MELL1 Kell blood-group protein KEL PHEX peptidase PHEX

Carboxypeptidase A family A1 CPA1 CPA2 CPB1 Carboxypeptidase N CPN1 CPE CPM CPB2 Carboxypeptidase A3 CPA3 Metallocarboxypeptidase D peptidase unit 1 (peptidase unit 1) CPD Metallocarboxypeptidase Z CPZ Metallocarboxypeptidase D peptidase unit 2 (peptidase unit 2) CPD Carboxypeptidase A4 CPA4 CPA6 Carboxypeptidase A5 CPA5 Metallocarboxypeptidase O CPO Mername-AA216 hypothetical peptidase Mername-AA213 putative peptidase AGBL3 Hypothetical protein flj14442 (Homo sapiens) and similar AGBL4 Mername-AA217 hypothetical peptidase AGTPBP1 A430081C19RIK (Mus musculus)-type protein AGBL2 Hetallocarboxypeptidase D non-peptidase unit (peptidase unit 3) CPD -enhancer binding protein 1 AEBP1 Carboxypeptidase-like protein X1 CPXM Cytosolic carboxypeptidase CPXM2 1440 Enzymes

Metallopeptidases (Continued)

Peptidase Gene

Pitrilysin family Insulysin IDE Mitochondrial processing peptidase beta-subunit (beta) PMPCB Nardilysin NRD1 Eupitrilysin (MP1 protein) PITRM1 Mitochondrial processing peptidase non-peptidase alpha subunit (alpha) PMPCA Ubiquinol-cytochrome c reductase core protein I (ubiquinol-cytochrome c reductase core protein 1) UQCRC1 Ubiquinol-cytochrome c reductase core protein II (ubiquinol-cytochrome c reductase core protein 2) UQCRC2 Mername-AA158 protein Mitochondrial processing peptidase beta subunit domain 2 (beta) PMPCB Ubiquinol-cytochrome c reductase core 2 (ubiquinol-cytochrome c reductase UQCRC1 core protein 1) Insulysin unit 2 IDE Nardilysin unit 2 NRD1 Insulysin unit 3 (Homo sapiens) (IDE protein) IDE

Leucyl aminopeptidase family () LAP3 Mername-AA040 peptidase Mername-AA014 peptidase NPEPL1

Aminopeptidase I DNPEP

Membrane family DPEP1 Membrane-bound dipeptidase-2 DPEP2 Membrane-bound dipeptidase-3 DPEP3 Glutamate carboxypeptidase dipeptidase II CNDP2 Carnosine dipeptidase I CNDP1 Mername-AA218 hypothetical peptidase Mername-AA161 protein ACY1L2 Aminoacylase (aminoacylase-1) ACY1

O-sialoglycoprotein peptidase Kae1 putative peptidase OSGEP Mername-AA018 peptidase OSGEPL1

Methionyl aminopeptidases 1 METAP1 Methionyl aminopeptidase 2 METAP2 Aminopeptidase P2 XPNPEP2 Xaa-Pro dipeptidase () PEPD Aminopeptidase P1 XPNPEP1 Aminopeptidase P homologue Mername-AA021 peptidase MAP1D Mername-AA020 peptidase homologue Proliferation-association protein 1 PA2G4 Chromatin-specific transcription 140 kDa subunit SUPT16H Proliferation-associated protein 1-like (Homo sapiens X) Mername AA-226 peptidase homologue (Homo sapiens) Mername AA-227 peptidase homologue (Homo sapiens)

Aminopeptidase Y family Glutamate carboxypeptidase II FOLH1 NAALADASE L peptidase NAALADL1 Enzymes 1441

Metallopeptidases (Continued)

Peptidase Gene

Glutamate carboxypeptidase III NAALAD2 Plasma glutamate carboxypeptidase (hematopoietic lineage switch 2) Mername-AA103 peptidase QPCTL Transferrin receptor protein (transferrin receptor) TFRC Transferrin receptor 2 protein (transferrin receptor 2) TFR2 Glutaminyl cyclase QPCT Glutamate carboxypeptidase II (Homo sapiens)-like protein NAALADL2 Nicalin NCLN

β-aspartyl dipeptidase family Dihydro-orotase () CAD Dihydropyrimidinase DPYS Dihydropyrimidinase related protein-1 CRMP1 Dihydropyrimidinase related protein-2 DPYSL2 Dihydropyrimidinase related protein-3 DPYSL3 Dihydropyrimidinase related protein-4 DPYSL4 Dihydropyrimidinase related protein-5 DPYSL5 Hypothetical protein like 5730457F11RIK 1300019j08rik protein Guanine GDA

FtsH endopeptidase family i-AAA peptidase YME1L1 Paraplegin SPG7 Afg3-like protein 2 AFG3L2 Afg3-like protein 1 AFG3L1 Mername-AA024 peptidase

Cytophagalysin family Pappalysin-1 PAPPA Pappalysin-2 PAPPA2 Ste24 endopeptidase family Farnesylated-protein converting enzyme 1 ZMPSTE24 Metalloprotease-related protein-1 OMA1

Dipeptidyl-peptidase III family Dipeptidyl-peptidase III DPP3 Mername-AA163 protein Mername-AA164 protein S2P peptidase family S2P peptidase MBTPS2 Poh1 peptidase PSMD14 Jab1/MPN domain metalloenzyme COPS5 Mername-AA165 peptidase Mername-AA166 peptidase CXorf53 Mername-AA167 peptidase MYSM1 AMSH deubiquitinating peptidase STAMBP Putative peptidase (Homo sapiens ) Mername-AA168 protein EIF3S3 COP9 signalosome subunit 6 COPS6 26S proteasome non-ATPase regulatory subunit 7 PSMD7 Eukaryotic translation initiation factor 3 subunit 5 EIF3S5 IFP38 peptidase homologue EIF3S5 Atp23 peptidase 1442 Enzymes

Serine Proteases

Peptidase Gene

Chymotrysin family B, human-type GZMB Testisin PRSS21 beta TPSAB1 Tryptase beta (2) TPSB2 -related peptidase 5 KLK5 Corin CORIN Kallikrein-related peptidase 12 KLK12 DESC1 peptidase TMPRSS11E Tryptase gamma 1 TPSG1 Kallikrein-related peptidase 14 KLK14 Hyaluronan-binding peptidase (HGF activator-like protein) HABP2 Transmembrane peptidase, serine 4 TMPRSS4 Adrenal secretory serine peptidase TMPRSS11D Tryptase delta 1 (Homo sapiens) TPSD1 -3 TMPRSS7 Marapsin PRSS27 Tryptase homologue 2 (Homo sapiens) PRSS33 Tryptase homologue 3 (Homo sapiens) Transmembrane peptidase, serine 3 TMPRSS3 Kallikrein-related peptidase 15 KLK15 Mername-AA031 peptidase serine peptidase long-form TMPRSS13 Mername-AA038 peptidase Mername-AA128 peptidase (deduced from ESTs by MEROPS) Mername-AA204 peptidase Cationic trypsin (Homo sapiens-type) (1 (cationic)) PRSS1 ELA2 Mannan-binding lectin-associated serine peptidase-3 MASP1 CTSG () PRTN3 GZMA Granzyme M GZMM (human-type) CMA1 Tryptase alpha (1) TPSAB1 Granzyme K GZMK Granzyme H GZMH B CTRB1 ELA1 Pancreatic endopeptidase E (A) ELA3A Pancreatic elastase II (IIA) PRSS7 CTRC Prostasin PRSS8 Kallikrein hK1 KLK1 Kallikrein-related peptidase 2 KLK2 Kallikrein-related peptidase 3 KLK3 Mesotrypsin PRSS3 Complement component C1r-like peptidase C1RL Complement DF Complement component activated C1r C1R Complement component activated C1s C1S Complement component C2a C2 BF Enzymes 1443

Serine Proteases (Continued)

Peptidase Gene

Mannan-binding lectin-associated serine peptidase 1 MASP1 IF Pancreatic endopeptidase E form B (B) ELA3B Pancreatic elastase II form B (Homo sapiens) (IIB) ELA1 Coagulation factor XIIa F12 KLKB1 Coagulation factor Xia F11 Coagulation factor Ixa F9 Coagulation factor VIIa F7 Coagulation factor Xa F10 Thrombin F2 (activated) PROC ACR HPN Hepatocyte growth factor activator HGFAC Mannan-binding lectin-associated serine peptidase 2 MASP2 u- PLAU t-Plasminogen activator PLAT PLG Kallikrein-related peptidase 6 (Homo sapiens) KLK6 Neurotrypsin PRSS12 Kallikrein-related peptidase 8 KLK8 Kallikrein-related peptidase 10 KLK10 Epitheliasin TMPRSS2 Kallikrein-related peptidase 4 KLK4 Prosemin PRSS22 Chymopasin CTRL Kallikrein-related peptidase 11 KLK11 Trypsin-2 (human-type) (II) PRSS2 HtrA1 peptidase PRSS11 HtrA2 peptidase PRSS25 HtrA3 peptidase HTRA3 HtrA4 peptidase HTRA4 Tysnd1 peptidase TYSND1 LOC144757 peptidase (Homo sapiens) and similar (protein sequence extended by use of MEROPS EST TMPRSS12 alignment) HAT-like putative peptidase 2 TMPRSS11A Trypsin C Mername-AA175 peptidase Kallikrein-related peptidase 7 KLK7 Matriptase ST14 Kallikrein-related peptidase 13 KLK13 Kallikrein-related peptidase 9 KLK9 Matriptase-2 TMPRSS6 Umbelical vein peptidase PRSS23 LCLP peptidase (LCLP (N-terminus)) Spinesin TMPRSS5 Marapsin-2 Complement factor D-like putative peptidase PRSSL1 Mername-AA180 peptidase OVCH2 Mername-AA181 peptidase TMPRSS11F Mername-AA182 peptidase OVCH1 Epidermis-specific SP-like putative peptidase Testis serine peptidase 5 Testis serine peptidase 1 1444 Enzymes

Serine Proteases (Continued)

Peptidase Gene

Polyserase-IA (unit 1) (unit 1) TMPRSS9 Polyserase-IA (unit 2) (unit 2) TMPRSS9 Testis serine peptidase 2 (human-type) Hypothetical acrosin-like peptidase (Homo sapiens) Mername-AA221 putative peptidase TMPRSS11B Polyserase-3 (unit 1) Polyserase-3 (unit 2) Peptidase similar to tryptophan/ Polyserase-2 (unit 1) Polyserase-2 (unit 2) Polyserase-2 (unit 3) Secreted trypsin-like serine peptidase homologue (deduced from nucleotide sequence by MEROPS) Ppolyserase-1A (unit 3) (unit 3) TMPRSS9 Azurocidin (azurocidin) AZU1 Haptoglobin-1 (haptoglobin-2) HP Haptoglobin-related protein (haptoglobin-related protein) HPR Macrophage-stimulating protein (macrophage-stimulating protein) MST1 Hepatocyte growth factor (hepatocyte growth factor) HGF Hepatocyte growth factor-like protein homologue (hepatocyte growth factor-like protein homologue) MST1 Protein Z (protein Z) PROZ TESP1 protein (deduced from nucleotide sequence by MEROPS) LOC136242 gene product (protein sequence amended by use of MEROPS EST alignment) Mername-AA199 Testis-specific protein TSP50 Dj223e3.1 protein (Homo sapiens) PRSS35 DKFZp586H2123-like protein Apolipoprotein LPA psi-KLK1 pseudogene (Homo sapiens) KLKP1 Tryptase pseudogene I Tryptase pseudogene II Tryptase pseudogene III

Subtilisin family -like peptidase (Pneumocystis carinii) 9 PCSK9 Site-1 peptidase (KIAA0091 protein) MBTPS1 FURIN PCSK1 PCSK2 Proprotein convertase 4 PCSK4 PACE4 proprotein convertase PCSK6 Proprotein convertase 5 PCSK5 Proprotein convertase 7 PCSK7 Tripeptidyl-peptidase II TPP2

Prolyl oligopeptidase family Prolyl oligopeptidase PREP Dipeptidyl-peptidase IV (eukaryote) DPP4 Acylaminoacyl-peptidase APEH Fibroblast activation protein alpha subunit FAP PREPL A protein PREPL Dipeptidyl-peptidase 8 DPP8 Dipeptidyl-peptidase 9 (R26984_1 protein) DPP9 FLJ1 putative peptidase C13orf6 Mername-AA194 putative peptidase C19orf27 Mername-AA195 putative peptidase Enzymes 1445

Serine Proteases (Continued)

Peptidase Gene

Mername-AA196 putative peptidase C20orf22 Mername-AA197 putative peptidase C9orf77 C14orf29 protein C14orf29 Hypothetical protein ABHD10 Hypothetical /lipase/ Protein bat5 BAT5 Hypothetical protein flj40219 Hypothetical protein flj37464 Hypothetical protein flj33678 Hypothetical protein flj90714 (Homo sapiens) C13orf6 Dipeptidylpeptidase homologue DPP6 (DPP6 protein) DPP6 Dipeptidylpeptidase homologue DPP10 DPP10 Protein similar to open reading frame 135 (Mus musculus) C20orf135 Kynurenine AFMID Thyroglobulin precursor (thyroglobulin) TG ACHE BCHE D1 Liver carboxylesterase CES1 CES3 Carboxylesterase 2 CES2 Bile salt-dependent lipase CEL Carboxylesterase-related protein CES4 3 NLGN3 Neuroligin 4, X-linked NLGN4X Neuroligin 4, Y-linked NLGN4Y Esterase D (Homo sapiens) ESD Arylacetamide deacetylase AADAC KIAA1363-like protein AADACL1 Hormone-sensitive lipase LIPE Neuroligin 1 NLGN1 Neuroligin 2 NLGN2

Serine PPGB Vitellogenic carboxypeptidase-like protein (WUGSC:H_RG113D17.1 protein) CPVL RISC peptidase SCPEP1 D-Ala-D-Ala carboxypeptidase B family LACT-1 peptidase LACTB

Clp endopeptidase family Peptidase Clp (type 3) CLPP

Ion protease family PIM1 peptidase PRSS15 Mername-AA102 peptidase

Signal peptidase I family Signalase (eukaryote) 18 kDa component (18 kDa) SEC11L1 Signalase (eukaryote) 21 kDa component SEC11L3 Mitochondrial inner membrane peptidase 2 IMMP2L Mitochondrial (metazoa) Mername AA-228 putative peptidase (Homo sapiens)

Lysosomal Pro-Xaa carboxypeptidase PRCP Dipeptidyl-peptidase II DPP7 Thymus-specific serine peptidase PRSS16 1446 Enzymes

Serine Proteases (Continued)

Peptidase Gene

Epoxide hydrolase-like putative peptidase ABHD8 Loc328574-like protein SERHL Abhydrolase domain-containing protein 4 ABHD4 Epoxide hydrolase (epoxide hydrolase) EPHX1 Mesoderm specific transcript protein MEST Cytosolic epoxide hydrolase EPHX2 Similar to hypothetical protein FLJ22408 ABHD7 CGI-58 putative peptidase ABHD5 Williams-Beuren syndrome critical region protein 21 epoxide hydrolase ABHD11 Epoxide hydrolase ABHD6 Hypothetical protein flj22408 (epoxide hydrolase) ABHD9 Monoglyceride lipase MGLL Hypothetical protein ABHD14A Valacyclovir hydrolase BPHL Ccg1-interacting factor b Protein phosphatase methylesterase 1 NDRG4 protein NDRG4 NDRG3 protein NDRG3 Mername AA-229 peptidase homologue (Homo sapiens) NDRG1 C-terminal processing peptidase family Interphotoreceptor retinoid-binding protein, unit 1 RBP3 Interphotoreceptor retinoid-binding protein, unit 2 RBP3

Tripeptidyl-peptidase I TPP1

Rhomboid family Rhomboid-like protein 2 RHBDL2 Rhomboid-like protein 1 RHBDL1 Ventrhoid RHBDL4 Rhomboid-like protein 5 RHBDF1 protein RHBDF1 Peptidase homologue similar to hypothetical protein FLJ22341 RHBDL6 Rhomboid-like protein 7 RHBDL7

Nucleoporin 145 NUP98 NUp 36 protein

Lactoferrin (unit 1) LTF Lactotransferrin precursor, domain 2 (unit 2) LTF Serotransferrin precursor (domain 1) (unit 1) TF domain 1 (unit 1) MFI2 Serotransferrin precursor (domain 2) (unit 2) TF Melanotransferrin domain 2 (unit 2) MFI2

EGF-like module containing mucin-like -like 2 EMR2 CD97 antigen CD97 EGF-like module containing mucin-like hormone receptor-like 3 EMR3 EGF-like module containing mucin-like hormone receptor-like 1 (Homo sapiens) EMR1 EGF-like module containing mucin-like hormone receptor-like 4 EMR4 Cadherin EGF LAG seven-pass G-type receptor 2 precursor (Homo sapiens) CELSR2 PIDD auto-processing protein unit 1 PIDD auto-processing protein unit 2 Enzymes 1447

Threonine Peptidases

Peptidase Gene

Proteasome family Proteasome catalytic subunit 1 PSMB6 Proteasome catalytic subunit 2 PSMB7 Proteasome catalytic subunit 3 PSMB5 Proteasome catalytic subunit 1i PSMB9 Proteasome catalytic subunit 2i PSMB10 Proteasome catalytic subunit 3i PSMB8 RIKEN cDNA 5830406J20 Protein serine kinase c17 Proteasome subunit alpha 6 PSMA6 Proteasome subunit alpha 2 PSMA2 Proteasome subunit alpha 4 PSMA4 Proteasome subunit alpha 7 (XAPC7) PSMA7 Proteasome subunit alpha 7 Proteasome subunit alpha 5 PSMA5 Proteasome subunit alpha 1 PSMA1 Proteasome subunit alpha 3 PSMA3 2410072d24rik protein (mouse) PSMA8 Proteasome subunit beta 3 PSMB3 Proteasome subunit beta 2 PSMB2 Proteasome subunit beta 1 PSMB1 Proteasome subunit beta 1 Proteasome subunit beta 4 PSMB4 Mername AA-230 peptidase homologue

Glycosylasparaginase precursor AGA Ioaspartyl dipeptidase (threonine type) ASRGL1

Taspase-1 TASP1 γ-Glutamyltransferase family Gamma-glutamyltransferase 5 GGTLA1 Gamma-glutamyltransferase 1 GGT1 Gamma-glutamyltransferase 2 GGT2 Gamma-glutamyltransferase-like protein 4 GGTL4 Gamma-glutamyltransferase-like protein 3 GGTL3 Similar to gamma-glutamyltransferase 1 precursor Similar to gamma-glutamyltransferase 1 precursor Mername-AA211 putative peptidase Gamma-glutamyl transpeptidase homologue

Decarboxylases (EC 4.1.1.-)

Name Gene Protein length (AA) Product

S-adenosylmethionine AMD1 334 (5-deoxy-5-adenosyl) (3-aminopropyl)-methylsulfonium decarboxylase L-arginine decarboxylase ADC 460 Agmatin Aromatic-L-amino-acid DDC 480 Dopamine, 5-hydroxytryptamine decarboxylase (DOPA-decarboxylase) Glutamate decarboxylase 1 GAD1 594 GABA Histidine decarboxylase HDC 662 Histamine Ornithine decarboxylase ODC1 461 Putrescine Phosphatidylserine decarboxylase PISD 408 Phosphatidyl-ethanolamine 1448 Enzymes

Isomerases Prostanoid synthases (EC 5.3.99.-)

Name Gene Protein length (AA) Expression

Prostaglandin-D2 synthase PTGDS 190 Brain, kidney, leukocytes Prostaglandin-E synthase PTGES 152 Widely Prostaglandin-E synthase 2 (mPGES-2) PTGES2 377 Widely Prostaglandin-E synthase 3 (cPGES) PTGES3 160 Widely PTGIS 500 Widely Thromboxane-A synthase TBXAS1 533 Platelets, lung, kidney, immune cells Transcription Factors

Transcription factors are able to bind to DNA and to transcription factors contains DNA-binding motifs enhance or repress the transcription of genes by which contain one or more zinc atoms as structural RNA polymerase. Often, transcription factors recruit components. These zinc-coordinated DNA-binding other proteins, and they can themselves be regulated motifs are commonly called zinc fingers. The zinc by ligands, phosphorylation, or the interaction with atom is bound by either four cysteine residues or by a other co-regulatory proteins or other transcription combination of two cysteine and two histidine factors. Transcription factors are grouped into residues. Transcription factors whose DNA-binding different classes depending on their DNA-binding domain is constructed from two α-helices connected domain (TRANSFAC; ▶http://www.gene-regulation. by a short extended chain of amino acids constitute com). Transcription factors with the characteristic the helix-turn-helix family of transcription factors. A leucine zipper and helix-loop-helix (HLH) motifs are completely different strategy to interact with DNA the major members of the superfamily of basic has evolved in the group of β-scaffold factors in domain transcription factors which typically act as which a two-stranded β-sheet binds to the major homo- or heterodimers. Another important group of groove of DNA.

Superclass: Basic Domains Leucine Zipper Factors (bZIP)

AP-1(-like) components AP-1(-like) components, Jun XBP1 X box-binding protein 1 JUN Transcription factor ap-1 JUNB Transcription factor jun-b JUND Transcription factor jun-d AP-1(-like) components, Fos FOS Proto-oncogene protein c-fos FOSB Protein FosB FOSL1 Fos-like antigen 1 (FRA-1) FOSL2 Fos-like antigen 2 (FRA-2) ATF3, LRF1 Activating transcription factor 3 JDP2 2 BATF ATF-like basic leucine zipper transcriptional factor AP-1(-like) components, Maf cMAF, MAF Transcription factor Maf MAFA Transcription factor MAFA MAFB Transcription factor MAFB MAFF Transcription factor MAFF MAFG Transcription factor MAFG MAFK Transcription factor MAFK NRL Neural retina-specific leucine zipper protein AP-1(-like) components, NF-E2 NFE2 Nuclear factor erythroid 2 NFE2L1 Nuclear factor erythroid 2-related factor 1 NFE2L2, NRF2 Nuclear factor erythroid 2-related factor 2 1450 Transcription Factors

Leucine Zipper Factors (bZIP) (Continued)

NFE2L3 Nuclear factor erythroid 2-related factor 3 BACH1 BTB and CNC homology transcription regulator 1 (BACH 1) BACH2 BTB and CNC homology transcription regulator 1 (BACH 1) AP-1(-like) components, CRE-BP/ATF ATF1 Activating transcription factor 1 ATF2, CREBP1 Activating transcription factor 2 ATF3, LRF1 Activating transcription factor 3 ATF4, CREB2 Activating transcription factor 4 ATF4A Activating transcription factor 4A ATF4B Activating transcription factor 4B ATF5 Activating transcription factor 5 ATF6 Activating transcription factor 5 ATF7, ATFA Activating transcription factor 7 ATFF Activating transcription factor, other eukaryote CREB5, CREBPA cAMP -binding protein 5

CREB CREB1 cAMP response element-binding protein 1 CREB3 cAMP response element-binding protein 3 CREB3L1 cAMP response element-binding protein 3-like 1 CREB3L2 cAMP response element-binding protein 3-like 2 CREB3L3 cAMP response element-binding protein 3-like 3 CREM cAMP response element modulator

C/EBP-like factors CEBPA CCAAT/enhancer binding protein (C/EBP), alpha CEBPB CCAAT/enhancer binding protein (C/EBP), beta CEBPG CCAAT/enhancer binding protein (C/EBP), gamma CEBPD CCAAT/enhancer binding protein (C/EBP), delta CEBPE CCAAT/enhancer binding protein (C/EBP), epsilon CEBPN CCAAT/enhancer binding protein (C/EBP), invertebrate DDIT3 GADD153; DNA damage-inducible transcript 3

bZIP/PAR DBP Albumin D box-binding protein HLF Hepatic leukemia factor TEF Thyrotrophic embryonic factor NFIL3 E4BP4; nuclear factor, regulated

ZIP only GCF, C2orf3 GC-rich sequence DNA-binding factor

Helix-Loop-Helix Factors (bHLH)

Ubiquitous (class A) factors TCF3 (E2A) Transcription factor 3 TCF4 (ITF2) Transcription factor 4 TCF12 (HEB) Transcription factor 12

Myogenic transcription factors MYOD (MYF3) Myogenic factor 3 MYOG (MYF4) Myogenic factor 4 MYF5 Myogenic factor 5 MYF6 (herculin) Myogenic factor 6 MYODF Myogenic factor, other eukaryote FIGLA Factor in the germline alpha Transcription Factors 1451

Helix-Loop-Helix Factors (bHLH) (Continued)

Achaete-Scute ASCL1 (ASH1) Achaete-scute complex protein 1 ASCL2 (ASH2) Achaete-scute complex protein 2 ASCL3 Achaete-scute complex protein 3 ASCL4 Achaete-scute complex protein 4 ASCL5 Achaete-scute complex protein 5

Tal/Twist/Atonal/Hen Lymphoid factors TAL1 T-cell acute lymphocytic leukemia protein 1 TAL2 T-cell acute lymphocytic leukemia protein 2 Mesodermal Twist-like factors TWIST1 Twist 1 (SCS) TWIST2 Twist 2 (Dermo1) TCF15 Transcription factor 15 HAND1 (eHand) Heart-and neural crest derivatives-expressed protein 1 HAND2 (dHand) Heart-and neural crest derivatives-expressed protein 2 MSC Musculin (activated B-cell factor-1) PTF1A Pancreas-specific transcription factor 1a HEN NHLH1 Nescient helix-loop-helix protein-1 (HEN1, NSCL1) NHLH2 Nescient helix-loop-helix protein-2 (HEN2, NSCL2) Mesp MESP1 Mesoderm posterior-1 MESP2 Mesoderm posterior-2 MSGN1 Mesogenin 1 Atonal NEUROD1 Neurogenic differentiation factor 1 NEUROD2 Neurogenic differentiation factor 2 NEUROD4 ATOH3, MATH3; neurogenic differentiation factor 4 NEUROD5 ATOH6, neurogenic differentiation factor 5 NEUROD6 ATOH2, MATH2; neurogenic differentiation factor 6 NEUROG1 Neurogenin 1 NEUROG2 Neurogenin 2 NEUROG3 Neurogenin 3 ATOH1 Atonal protein 1 ATOH7 Atonal protein 7 ATOH8 Atonal protein 8 BHLHB1 Class B basic helix-loop-helix protein 1 BHLHB6 Class B basic helix-loop-helix protein 6 BHLHB7 Class B basic helix-loop-helix protein 7 BHLHB8, MIST1 Class B basic helix-loop-helix protein 8 Pancreatic factors BHLHB4 Class B basic helix-loop-helix protein 4 BHLHB5 Class B basic helix-loop-helix protein 5

Hairy, Hairy/E(SPL) HES1 Hairy and enhancer of split 1 HES2 Hairy and enhancer of split 2 HES3 Hairy and enhancer of split 3 HES4 Hairy and enhancer of split 4 HES5 Hairy and enhancer of split 5 HES6 Hairy and enhancer of split 6 HES7 Hairy and enhancer of split 7 HEY1 Hairy and enhancer of split related with YRPW motif -1 HEY2 Hairy and enhancer of split related with YRPW motif –2 BHLHB2, DEC1 BHLHB3, DEC1 Class B basic helix-loop-helix protein 2 1452 Transcription Factors

Helix-Loop-Helix Factors (bHLH) (Continued)

BHLHB3, DEC2 Class B basic helix-loop-helix protein 3 TCFL5, CHA Transcription factor-like 5

Factors with PAS domain AHR Aryl hydrocarbon receptor AHRR, AHH Aryl hydrocarbon receptor HIF1A Hypoxia-inducible factor 1 alpha HIF2A, EPAS1 Hypoxia-inducible factor 2 alpha HIF3A Hypoxia-inducible factor 3 alpha HIF1B, ARNT Hypoxia-inducible factor 1 beta NPAS1 Neuronal PAS domain-containing protein 1 NPAS2 Neuronal PAS domain-containing protein 2 NPAS3 Neuronal PAS domain-containing protein 3 NPAS4 Neuronal PAS domain-containing protein 4 CLOCK Circadian locomotor output cycles kaput protein ARNTL, BMAL1 Aryl hydrocarbon receptor nuclear translocator-like protein 1 ARNTL2, BMAL2 Aryl hydrocarbon receptor nuclear translocator-like protein 2 SIM Single-minded NCOA coactivator

HLH domain only ID1 Inhibitor of DNA binding 1, dominant negative helix-loop-helix protein ID2 Inhibitor of DNA binding 2, dominant negative helix-loop-helix protein ID2B Inhibitor of DNA binding 2B, dominant negative helix-loop-helix protein ID3 Inhibitor of DNA binding 3, dominant negative helix-loop-helix protein ID4 Inhibitor of DNA binding 4, dominant negative helix-loop-helix protein EBF1, OLF1 Early B-cell factor 1 EBF2, COE2 Early B-cell factor 2 EBF3, COE3 Early B-cell factor 3 EBF4, COE4 Early B-cell factor 4

Helix-Loop-Helix/Leucine Zipper Factors (bHLH-ZIP)

Ubiquitous bHLH-ZIP factors TFE3 TFE3 Transcription factor E3-related TFEB Transcription factor EB TFEC Transcription factor EC MITF -associated transcription factor USF USF1 Upstream stimulatory factor-1 USF2 Upstream stimulatory factor-2 SREBP SREBP1 Sterol regulatory element-binding transcription factor 1 SREBP2 Sterol regulatory element-binding transcription factor 2 AP-4 TFAP4 Transcription factor AP-4 Cell cycle controlling factors, MYC Myc proto-oncogene protein NMYC, MYCN N-myc proto-oncogene protein LMYC, MYCL L-myc proto-oncogene protein BMYC, MYCB Brain expressed myelocytomatosis oncogene SMYC, MYCS myc-Like oncogene Transcription Factors 1453

Helix-Loop-Helix/Leucine Zipper Factors (bHLH-ZIP) (Continued)

Cell cycle controlling factors, Mad/Max MAX Max protein MLX MAX-like protein X MXD1 MAD1; MAX dimerization protein-1 MXD3 MAD3; MAX dimerization protein-3 MXD4 MAD4; MAX dimerization protein-4 MXI1 MAX-interactor 1 MNT ROX; MAX-binding protein

NF-1

NFIA /A NFIB Nuclear factor I/B NFIC Nuclear factor I/C NFIX Nuclear factor I/X

RF-X

RFX1 Regulatory factor X 1 RFX2 Regulatory factor X 2 RFX3 Regulatory factor X 3 RFX4 Regulatory factor X 4 RFX5 Regulatory factor X 5

Helix-Span-Helix Factors (bHSH)

TFAP2A Transcription factor AP-2 alpha TFAP2B Transcription factor AP-2 beta TFAP2C Transcription factor AP-2 gamma TFAP2D Transcription factor AP-2 delta TFAP2E Transcription factor AP-2 epsilon

Zinc-Coordinating DNA-Binding Domains Cys4 Zinc Finger of Nuclear Type

Thyroid hormone-like NR1A1, THRA Nuclear receptor, subfamily 1, group A, member 1 NR1A2, THRB Nuclear receptor, subfamily 1, group A, member 2 NR1B1, RARA Nuclear receptor, subfamily 1, group B, member 1 NR1B2, RARB Nuclear receptor, subfamily 1, group B, member 2 NR1B3, RARG Nuclear receptor, subfamily 1, group B, member 3 NR1C1, PPARA Nuclear receptor, subfamily 1, group C, member 1 NR1C2, PPARD Nuclear receptor, subfamily 1, group C, member 2 NR1C3, PPARG Nuclear receptor, subfamily 1, group C, member 3 NR1D1 Nuclear receptor, subfamily 1, group D, member 1 NR1D2 Nuclear receptor, subfamily 1, group D, member 2 NR1F1, RORA Nuclear receptor, subfamily 1, group F, member 1 NR1F2, RORB Nuclear receptor, subfamily 1, group F, member 2 NR1F3, RORC Nuclear receptor, subfamily 1, group F, member 3 NR1H2, LXRB Nuclear receptor, subfamily 1, group H, member 2 NR1H3, LXRA Nuclear receptor, subfamily 1, group H, member 3 NR1H4, FXR Nuclear receptor, subfamily 1, group H, member 4 NR1H5, FXRB Nuclear receptor, subfamily 1, group H, member 5 1454 Transcription Factors

Cys4 Zinc Finger of Nuclear Type (Continued)

NR1I1, VDR Nuclear receptor, subfamily 1, group I, member 1 NR1I2, PXR Nuclear receptor, subfamily 1, group I, member 2 NR1I3, CAR Nuclear receptor, subfamily 1, group I, member 3

Hepatocyte nuclear factor 4-like NR2A1, HNF4A Nuclear receptor, subfamily 2, group A, member 1 NR2A2, HNF4G Nuclear receptor, subfamily 2, group A, member 2 NR2A3, HNF4B Nuclear receptor, subfamily 2, group A, member 3 NR2B1, RXRA Nuclear receptor, subfamily 2, group B, member 1 NR2B2, RXRB Nuclear receptor, subfamily 2, group B, member 2 NR2B3, RXRG Nuclear receptor, subfamily 2, group B, member 3 NR2C1, TR2 Nuclear receptor, subfamily 2, group C, member 1 NR2C2, TR4 Nuclear receptor, subfamily 2, group C, member 2 NR2E1, TLX Nuclear receptor, subfamily 2, group E, member 1 NR2E3, PNR Nuclear receptor, subfamily 2, group E, member 3 NR2F1, TFCOUP1, nuclear receptor, subfamily 2, group F, member 1 NR2F2 TFCOUP2, nuclear receptor, subfamily 2, group F, member 2 NR2F5, SVP46 Nuclear receptor, subfamily 2, group F, member 5 NR2F6, EAR2 Nuclear receptor, subfamily 2, group F, member 6

Estrogen-like NR3A1, ESR1 Nuclear receptor, subfamily 3, group A, member 1 NR3A2, ESR2 Nuclear receptor, subfamily 3, group A, member 2 NR3B1, ESRRA Nuclear receptor, subfamily 3, group B, member 1 NR3B2, ESRRB Nuclear receptor, subfamily 3, group B, member 2 NR3B3, ESRRG Nuclear receptor, subfamily 3, group B, member 3 NR3C1, GR Nuclear receptor, subfamily 3, group C, member 1 NR3C2, MR Nuclear receptor, subfamily 3, group C, member 2 NR3C3, PGR Nuclear receptor, subfamily 3, group C, member 3 NR3C4, AR Nuclear receptor, subfamily 3, group C, member 4 Nerve growth factor IB-like NR4A1, HMR Nuclear receptor, subfamily 4, group A, member 1 NR4A2, NURR1 Nuclear receptor, subfamily 4, group A, member 2 NR4A3, NOR1 Nuclear receptor, subfamily 4, group A, member 3 NR4N Nuclear receptor, subfamily 4, invertebrate Fushi tarazu-F1-like NR5A1, SF1 Nuclear receptor, subfamily 5, group A, member 1 NR5A2, FTF Nuclear receptor, subfamily 5, group A, member 2

Germ cell nuclear factor NR6A1, GCNF Nuclear receptor, subfamily 6, group A, member 1

DAX 1-like NR0B1, DAX1 Nuclear receptor, subfamily 0, group B, member 1 NR0B2, SHP Nuclear receptor, subfamily 0, group B, member 2

Diverse Cys4 Zinc Fingers

GATA-factors GATA1 GATA-binding protein 1 GATA2 GATA-binding protein 2 GATA3 GATA-binding protein 3 GATA4 GATA-binding protein 4 GATA5 GATA-binding protein 5 GATA6 GATA-binding protein 6 Transcription Factors 1455

Diverse Cys4 Zinc Fingers (Continued)

Trithorax MLL1 Myeloid/lymphoid or mixed-lineage leukemia protein 1 MLL2, ALR Myeloid/lymphoid or mixed-lineage leukemia protein 2 MLL3 Myeloid/lymphoid or mixed-lineage leukemia protein 3 MLL5 Myeloid/lymphoid or mixed-lineage leukemia protein 5

Cys2His2 Zinc Finger Domain

Ubiquitous factors GTF3A General transcription factor IIIA Sp1 Sp2 Sp3 Sp4 SP5 Transcription factor Sp5 SP6 Transcription factor Sp6 Sp7 Sp8 SP9 Transcription factor Sp9 YY1 Transcription factor YY1 YY21 Transcription factor YY2 Developmental/cell cycle regulators Egr/Krox EGR1 Early growth response protein 1 EGR2 Early growth response protein 2 EGR3 Early growth response protein 3 EGR4 Early growth response protein 4 Krueppel-like KLF1 Krueppel-like factor 1 KLF2 Krueppel-like factor 2 KLF3 Krueppel-like factor 3 Krueppel-like factor 4 KLF5 Krueppel-like factor 5 KLF6 Krueppel-like factor 6 KLF7 Krueppel-like factor 7 KLF8 Krueppel-like factor 8 KLF9 Krueppel-like factor 9 KLF10 Krueppel-like factor 10 KLF11 Krueppel-like factor 11 KLF12 Krueppel-like factor 12 KLF13 Krueppel-like factor 13 KLF14 Krueppel-like factor 14 KLF15 Krueppel-like factor 15 KLF16 Krueppel-like factor 16 KLF17 Krueppel-like factor 17 OSR1, ODD Odd-skipped 1 OSR2 Odd-skipped 2 OVOL1 Ovo-like 1 OVOL2 Ovo-like 2 SNAI1 Snail 1 SNAI1L1 Snail 1-like 1 SNAI2, SLUG Snail 2 SNAI3 Snail 3 1456 Transcription Factors

Cys2His2 Zinc Finger Domain (Continued)

SCRT1 Scratch 1 SCRT2 Scratch 2 EVI1 Ecotropic virus integration site 1 protein IKZF1, ZNFN1A1 IKAROS family zinc finger protein 1 (ikaros) IKZF2, ZNFN1A2 IKAROS family zinc finger protein 2 (helios) IKZF3, ZNFN1A3 IKAROS family zinc finger protein 3 (aiolos) IKZF4, ZNFN1A4 IKAROS family zinc finger protein 4 (eos) IKZF5, ZNFN1A5 IKAROS family zinc finger protein 5 (pegasus) MZF1, ZNF42 Myeloid zinc finger protein 1 REST RE1-silencing transcription factor GFI1 Growth factor independent 1 ZIC1 Zinc finger protein ZIC 1 ZIC2 Zinc finger protein ZIC 2 ZIC3 Zinc finger protein ZIC 3 ZIC4 Zinc finger protein ZIC 4 ZIC5 Zinc finger protein ZIC 5 KRABA1 KRAB domain-containing zinc finger protein 1 KRABA2 KRAB domain-containing zinc finger protein 2 ZKSCAN1 KRAB and SCAN domains-containing zinc finger protein 1 ZKSCAN2 KRAB and SCAN domains-containing zinc finger protein 2 ZKSCAN3 KRAB and SCAN domains-containing zinc finger protein 3 ZKSCAN4 KRAB and SCAN domains-containing zinc finger protein 4 ZKSCAN5 KRAB and SCAN domains-containing zinc finger protein 5 SCAND1 SCAN domain-containing zinc finger protein 1 SCAND2 SCAN domain-containing zinc finger protein 2 GLI-like GLI Zinc finger protein GLI GLIS1 Zinc finger protein GLIS1 GLIS2 Zinc finger protein GLIS2 GLIS3 Zinc finger protein GLIS3 WT1 Wilms tumor protein 1 WT21 Wilms tumor protein 2 Others TSHZ1 Teashirt zinc finger 1 TSHZ2 Teashirt zinc finger homeobox 2 TSHZ3 Teashirt zinc finger homeobox 3

Large factors with NF-6B-like binding properties HIVEP1 Human immunodeficiency virus type I enhancer-binding protein 1 HIVEP2 Human immunodeficiency virus type I enhancer-binding protein 2

Superclass: Helix-Turn-Helix Homeo Domain

Homeo domain only AbdB HOXA9 Homeobox protein HoxA9 HOXB9 Homeobox protein HoxB9 HOXC9 Homeobox protein HoxC9 HOXD9 Homeobox protein HoxD9 HOXA10 Homeobox protein HoxA10 HOXC10 Homeobox protein HoxC10 HOXD10 Homeobox protein HoxD10 Transcription Factors 1457

Homeo Domain (Continued)

HOXA11 Homeobox protein HoxA11 HOXC11 Homeobox protein HoxC11 HOXD11 Homeobox protein HoxD11 HOXC12 Homeobox protein HoxC12 HOXD12 Homeobox protein HoxD12 HOXA13 Homeobox protein HoxA13 HOXC13 Homeobox protein HoxC13 HOXD13 Homeobox protein HoxD13 ZEB1 (ZFHX1a) Zinc finger homeobox protein 1 ZEB2 (ZFHX1b) Zinc finger homeobox protein 2 Antp HOXA1 Homeobox protein HoxA1 HOXB1 Homeobox protein HoxB1 HOXD1 Homeobox protein HoxD1 HOXA2 Homeobox protein HoxA2 HOXB2 Homeobox protein HoxB2 HOXA3 Homeobox protein HoxA3 HOXB3 Homeobox protein HoxB3 HOXD3 Homeobox protein HoxD3 HOXA4 Homeobox protein HoxA4 HOXB4 Homeobox protein HoxB4 HOXC4 Homeobox protein HoxC4 HOXD4 Homeobox protein HoxD4 HOXA5 Homeobox protein HoxA5 HOXB5 Homeobox protein HoxB5 HOXC5 Homeobox protein HoxC5 HOXA6 Homeobox protein HoxA6 HOXB6 Homeobox protein HoxB6 HOXC6 Homeobox protein HoxC6 HOXA7 Homeobox protein HoxA7 HOXB7 Homeobox protein HoxB7 HOXB8 Homeobox protein HoxB8 HOXC8 Homeobox protein HoxC8 HOXD8 Homeobox protein HoxD8 NKX1 Homeobox protein Nkx-1 IPF1, PDX1 Insulin factor 1 Cad CDX1 Homeobox protein CDX1 CDX2 Homeobox protein CDX2 CDX4 Homeobox protein CDX4 Cut CUTL1 Homeobox protein cut-like1 CUTL2 Homeobox protein cut-like2 Dll DLX1 Homeobox protein DLX1 DLX2 Homeobox protein DLX2 DLX3 Homeobox protein DLX3 DLX4 Homeobox protein DLX4 DLX5 Homeobox protein DLX5 DLX6 Homeobox protein DLX6 Ems EMX1 Homeobox protein EMX1 EMX2 Homeobox protein EMX2 VAX1 Homeobox protein ventral anterior-1 VAX2 Homeobox protein ventral anterior-2 1458 Transcription Factors

Homeo Domain (Continued)

En EN1 Homeobox protein -1 EN2 Homeobox protein engrailed-2 Eve Homeobox even-skipped homolog protein-1 EVX2 Homeobox even-skipped homolog protein-2 GBX1 Homeobox protein GBX-1 GBX2 Homeobox protein GBX-2 HLXB9, HB9 Homeobox protein HB9 MEOX1 Homeobox protein MOX-1 MEOX2 Homeobox protein MOX-2 Prd ARX Homeobox protein aristaless-related ALX1, CART1 Homeobox protein aristaless-like 1 ALX3 Homeobox protein aristaless-like 3 ALX4 Homeobox protein aristaless-like 4 GSC Homeobox protein goosecoid GSCL Homeobox protein goosecoid-like OTX1 Homeobox protein OTX1 OTX2 Homeobox protein OTX2 PROP1 Homeobox protein prophet of Pit-1 PRRX1, PMX1 Paired mesoderm homeobox protein PHOX2, PMX2 Paired mesoderm homeobox protein 2 SHOX Short stature homeobox protein SHOX2 Short stature homeobox protein 2 RAX, RX Retina and anterior neural fold homeobox protein RAXL Retina and anterior neural fold homeobox-like protein VSX1 Visual system homeobox protein 1 VSX2, CHX10 Visual system homeobox protein 2 CRX Cone-rod homeobox protein HD-ZIP HD-ZIP Homeobox-leucine zipper protein H2.0 HLX1 Homeobox protein HLX1 TLX1, HOX11 T-cell leukemia homeobox protein-1 TLX2 T-cell leukemia homeobox protein-2 TLX3 T-cell leukemia homeobox protein-3 HNF1 TCF1, HNF1A Transcription factor 1, hepatocyte nuclear factor 1-alpha TCF2, HNF1B Transcription factor 2, hepatocyte nuclear factor 1-beta Msh MSX1 Homeobox protein MSX1 MSX2 Homeobox protein MSX2 NK-2 NKX2-1, TITF1 Homeobox protein Nkx-2.1 NKX2-2 Homeobox protein Nkx-2.2 NKX2-3 Homeobox protein Nkx-2.3 NKX2-4 Homeobox protein Nkx-2.4 NKX2-5 Homeobox protein Nkx-2.5 NKX2-6 Homeobox protein Nkx-2.6 NKX2-8 Homeobox protein Nkx-2.8 NKX3-1 Homeobox protein Nkx-3.1 NKX3-2, BAPX1 Homeobox protein Nkx-3.2 NKX5, HMX Homeobox protein Nkx-5 NKX6-1 Homeobox protein Nkx-6.1 NKX6-2 Homeobox protein Nkx-6.2 Transcription Factors 1459

Homeo Domain (Continued)

NKX6-3 Homeobox protein Nkx-6.3 LBX1 Homeobox protein LBX1 LBX2 Homeobox protein LBX2 XANF HESX1 Homeobox protein expressed in ES cells 1 PBC PBX1 Pre-B-cell leukemia transcription factor1 PBX2 Pre-B-cell leukemia transcription factor2 PBX3 Pre-B-cell leukemia transcription factor3 PBX4 Pre-B-cell leukemia transcription factor4 Not assigned PITX1 Paired-like homeodomain transcription factor 1 PITX2 Paired-like homeodomain transcription factor 2 PITX3 Paired-like homeodomain transcription factor 3 MATA1 Mating-type protein A1 MATA2 Mating-type protein A2 PHO2 Regulatory protein PHO2 HHEX, PRH Homeobox protein HEX BARHL1 BarH-like1 BARHL2 BarH-like2 BARX1 BarH-like homeobox1 BARX2 BarH-like homeobox2

POU domain factors POU1F, PIT1 POU domain transcription factor, class 1 POU2F1, OTF1 POU domain transcription factor, class 2,1 POU2F2, OTF2 POU domain transcription factor, class 2,2 POU2F3, OCT11 POU domain transcription factor, class 2,3 POU3F1, OTF6 POU domain transcription factor, class 3,1 POU3F2, OTF7 POU domain transcription factor, class 3,2 POU3F3, OTF8 POU domain transcription factor, class 3,3 POU3F4, OTF9 POU domain transcription factor, class 3,4 POU4F1, BRN3a POU domain transcription factor, class 4,1 POU4F2, BRN3b POU domain transcription factor, class 4,2 POU4F3, BRN3c POU domain transcription factor, class 4,3 POU5F1 POU domain transcription factor, class 5,1 POU5F2 POU domain transcription factor, class 5,2 POU6F1 POU domain transcription factor, class 6,1 POU6F2 POU domain transcription factor, class 6,2

Homeo domain with LIM region ISL1 Insulin gene enhancer protein ISL1 ISL2 Insulin gene enhancer protein ISL2 LMX1A LIM homeobox transcription factor 1A LMX1B LIM homeobox transcription factor 1B LHX1 LIM homeobox protein 1 LHX2 LIM homeobox protein 2 LHX3 LIM homeobox protein 3 LHX4 LIM homeobox protein 4 LHX5 LIM homeobox protein 5 LHX6 LIM homeobox protein 6 LHX7 LIM homeobox protein 7 LHX8 LIM homeobox protein 8 LIM-only transcription (co-)factors CSRP1 Cysteine and glycine-rich protein-1 CSRP2 Cysteine and glycine-rich protein-2 CSRP3 Cysteine and glycine-rich protein-3 1460 Transcription Factors

Homeo Domain (Continued)

Homeo domain plus zinc finger motifs ATBF1 AT-binding transcription factor 1 ZFHX2 Zinc finger homeobox protein 2 ZFHX4 Zinc finger homeobox protein 4

Paired Box

Paired plus homeo domain PAX3 Paired box protein 3 PAX4 Paired box protein 4 PAX6 Paired box protein 6 PAX7 Paired box protein 7

Paired domain only PAX1 Paired box protein 1 PAX2 Paired box protein 2 PAX5 Paired box protein 5 PAX8 Paired box protein 8 PAX9 Paired box protein 9

Fork Head/Winged Helix

Developmental regulators FOXA2, HNF3B Forkhead box protein A2, hepatocyte nuclear factor 3-beta FOXC1 Forkhead box protein C1 FOXC2 Forkhead box protein C2 FOXG Forkhead box protein G FOXN1 Forkhead box protein N1 FOXN2 Forkhead box protein N2 FOXN3 Forkhead box protein N3 FOXN4 Forkhead box protein N4

Tissue-specific regulators FOXA1, HNF3A Forkhead box protein A1, hepatocyte nuclear factor 3-alpha FOXA3, HNF3G Forkhead box protein A3, hepatocyte nuclear factor 3-gamma FOXJ1 Forkhead box protein J1 Cell cycle-controlling factors E2F transcription factor 1 E2F transcription factor 2 E2F transcription factor 3 E2F transcription factor 4 E2F transcription factor 5 E2F6 E2F transcription factor 6 E2F7 E2F transcription factor 7 E2F8 E2F transcription factor 8 DP TFDP1 Transcription factor Dp-1 TFDP2 Transcription factor Dp-2 TFDP3 Transcription factor Dp-3 Transcription Factors 1461

Fork Head/Winged Helix (Continued)

Other regulators FOXB1 Forkhead box protein B1 FOXB2 Forkhead box protein B2 FOXD1 Forkhead box protein D1 FOXD2 Forkhead box protein D2 FOXD3 Forkhead box protein D3 FOXD4 Forkhead box protein D4 FOXE1 Forkhead box protein E1 FOXE2 Forkhead box protein E2 FOXE3 Forkhead box protein E3 FOXF1 Forkhead box protein F1 FOXF2 Forkhead box protein F2 FOXH Forkhead box protein H FOXI1 Forkhead box protein I1 FOXI2 Forkhead box protein I2 FOXJ2 Forkhead box protein J2 FOXJ3 Forkhead box protein J3 FOXK1 Forkhead box protein K1 FOXK2 Forkhead box protein K2 FOXL1 Forkhead box protein L1 FOXL2 Forkhead box protein L2 FOXM Forkhead box protein M FOXO1 FOXO3 Forkhead box protein O3 FOXO4 Forkhead box protein O4 FOXP1 Forkhead box protein P1 FOXP2 Forkhead box protein P2 FOXP3 Forkhead box protein P3 FOXP4 Forkhead box protein P4 OXQ, HFH1 Forkhead box protein Q FOXR1 Forkhead box protein, R1 FOXR2 Forkhead box protein, R2 FKHL18 Forkhead-like 18 protein

Heat Shock Factors

HSF1 Heat shock transcription factor 1 HSF2 Heat shock transcription factor 2 HSF3 Heat shock transcription factor 3 HSF4 Heat shock transcription factor 4 HSFN Heat shock transcription factor, invertebrate HSFF Heat shock transcription factor, other eukaryote

Tryptophan Clusters

Myb Myb-factors MYB Proto-oncogene protein MYBL myb-Related protein MYBP myb Proto-oncogene protein, plant 1462 Transcription Factors

Tryptophan Clusters (Continued)

Myb-like factors SNAPC1 snRNA-activating protein complex subunit 1 SNAPC2 snRNA-activating protein complex subunit 2 SNAPC3 snRNA-activating protein complex subunit 3 SNAPC4 snRNA-activating protein complex subunit 4 BAS1 Myb-like DNA-binding protein BAS1 REB1 Myb-like DNA-binding protein REB1 RAP1 Myb-like DNA-binding protein RAP1

Ets-type ELF1 E74-like factor 1 ELF2 E74-like factor 2 ELF3 E74-like factor 3 ELF4 E74-like factor 4 ELF5 E74-like factor 5 ELK1 ETS domain-containing protein Elk-1 ELK3 ETS domain-containing protein Elk-3 (SRF accessory protein 2) ELK4, SAP1 ETS domain-containing protein Elk-4 (SRF accessory protein 1) ETV1 ETS translocation variant 1 ETV2, ER71 ETS translocation variant 2 ETV3 ETS translocation variant 3 ETV4 ETS translocation variant 4 ETV5 ETS translocation variant 5 ETV6 ETS translocation variant 6 ETV7 ETS translocation variant 7 ERF ETS domain-containing transcription factor ERF ETS1, pnt c-ets Proto-oncogene protein ETS2 c-ets Proto-oncogene protein ERG Transcriptional regulator ERG FLI1 Friend leukemia integration 1 transcription factor FEV ETS oncogene family protein FEV SPI1 Transcription factor PU.1 SPIB Transcription factor Spi-B SPIC Transcription factor Spi-C GABPA GA-binding protein transcription factor, alpha SPDEF SAM pointed domain-containing ETS transcription factor

Interferon-regulating factors IRF1 Interferon regulatory factor 1 IRF2 Interferon regulatory factor 2 IRF3 Interferon regulatory factor 3 IRF4 Interferon regulatory factor 4 IRF5 Interferon regulatory factor 5 IRF6 Interferon regulatory factor 6 IRF7 Interferon regulatory factor 7 IRF8 Interferon regulatory factor 8 IRF9, ISGF3G Interferon regulatory factor 9

TEA Domain

TEA TEAD1 TEA domain family member 1 TEAD2 TEA domain family member 2 TEAD3 TEA domain family member 3 TEAD4 TEA domain family member 4 Transcription Factors 1463

Beta-Scaffold Factors with Minor Groove Contacts RHR (Rel Homology Region)

Rel/ankyrin NFKB1 Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 NFKB2 Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 RELA Transcription factor p65 RELB Transcription factor RelB REL c-Rel proto-oncogene protein

Ankyrin only NFKBIA Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha NFKBIB Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta NFKBIE Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon NFKBIL1 Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 1 NFKBIL2 Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2 BCL3 B-cell CLL/lymphoma protein 3 GABPB GA-binding protein transcription factor, beta

NF-AT NFATC1 Nuclear factor of activated T-cells, cyclasmic, calcineurin-dependent-1 NFATC2 Nuclear factor of activated T-cells, cyclasmic, calcineurin-dependent-2 NFATC3 Nuclear factor of activated T-cells, cyclasmic, calcineurin-dependent-3 NFATC4 Nuclear factor of activated T-cells, cyclasmic, calcineurin-dependent-4

STAT

STAT STAT1 Signal transducer and activator of transcription-1 STAT2 Signal transducer and activator of transcription-2 STAT3 Signal transducer and activator of transcription-3 STAT4 Signal transducer and activator of transcription-4 STAT5A Signal transducer and activator of transcription-5A STAT5B Signal transducer and activator of transcription-5B STAT6 Signal transducer and activator of transcription-6

p53

p53 TP53, P53 Tumor protein p53

MADS-Box

Regulators of differentiation, MEF-2 MEF2A MADS-box transcription enhancer factor 2A MEF2B MADS-box transcription enhancer factor 2B MEF2C MADS-box transcription enhancer factor 2C MEF2D MADS-box transcription enhancer factor 2D Responders to external signals SRF 1464 Transcription Factors

TATA-Binding-Proteins

TBP TBP Transcription initiation factor TFIID TATA-box-binding protein

HMG

SOX SRY Sex-determining region Y protein (SOX group A) SOX1 Transcription factor SOX1 Transcription factor SOX2 SOX3 Transcription factor SOX3 SOX4 Transcription factor SOX4 SOX5 Transcription factor SOX5 SOX6 Transcription factor SOX6 SOX7 Transcription factor SOX7 SOX8 Transcription factor SOX8 SOX9 Transcription factor SOX9 SOX10 Transcription factor SOX10 SOX11 Transcription factor SOX11 SOX12 Transcription factor SOX12 SOX13 Transcription factor SOX13 SOX14 Transcription factor SOX14 SOX15 Transcription factor SOX15 SOX17 Transcription factor SOX17 SOX18 Transcription factor SOX18 SOX21 Transcription factor SOX21 SOX30 Transcription factor SOX30

TCF-1 LEF1 Lymphoid enhancer-binding factor 1 TCF7 Transcription factor 7 TCF7L1 Transcription factor 7-like 1 TCF7L2 Transcription factor 7-like 2

HMG2-related SSRP1 Structure-specific recognition protein 1

UBF UBTF Upstream-binding transcription factor

Heteromeric CCAAT Factors

Heteromeric CCAAT factors NFYA Nuclear transcription factor Y, alpha NFYB Nuclear transcription factor Y, beta NFYC Nuclear transcription factor Y, gamma

Grainyhead

Grainyhead TFCP2 Transcription factor CP2 and related proteins Transcription Factors 1465

Cold-Shock Domain Factors

Csd DbpA-like CSDA, ZONAB Cold shock domain protein A YB-1/DbpB-like YBX1, NSEP1 Y-box-binding protein 1 FRG Y2-like YBX2 Y-box-binding protein 2

Runt

Runt RUNX1, AML1 Runt-related transcription factor 1 RUNX2, AML3 Runt-related transcription factor 2 RUNX3, AML2 Runt-related transcription factor 3

Other Transcription Factors HMGI(Y) HMGI(Y)

HMGA1 High mobility group AT-hook protein 1 HMGA1L1 High mobility group AT-hook protein 1L1 HMGA1L2 High mobility group AT-hook protein 1L2 HMGA1L3 High mobility group AT-hook protein 1L3 HMGA1L5 High mobility group AT-hook protein 1L5 HMGA1L6 High mobility group AT-hook protein 1L6 HMGA1L7 High mobility group AT-hook protein 1L7 HMGA2 High mobility group AT-hook protein 2

Pocket Domain

Rb RB1 Retinoblastoma 1 RBL Retinoblastoma-like

CBP EP300, CREBBP E1A/CREB-binding protein List of Established Drugs

List of Established Drugs

Drug Group/Class Link

Abacavir Reverse transcriptase Inhibitor ▶Antiviral agents Abarelix GnRH- ▶GnRH Abatacept Soluble CTLA4 construct ▶Immunology Abciximab GPIIb/IIIa-inhibitor ▶Anti-platelet drugs Acarbose Alpha-glucosidase inhibitor ▶Oral antidiabetic drugs ▶Diabetes mellitus Acebutolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Aceclofenac Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶Non-steroidal antiinflammatory drugs Acetaminophen Analgetic/Antipyretic drug ▶Analgesics Acetazolamide Carbonic anhydrase inhibitor ▶ Acetylsalicylic acid Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶Non steroidal antiinflammatory drugs Aciclovir/Acyclovir Antiviral drug ▶Antiviral drugs Acitretin Retinoid ▶Retinoids Adalimumab anti-TNFα-antibody ▶Immune defense Adenosine Nucleoside ▶Purinergic system ▶Antiarrhythmic drugs Adrenaline Adrenoceptor agonist ▶Beta-adrenergic system (Epinephrin) ▶Alpha-adrenergic system Ajmalin Antiarrhythmic drug ▶Antiarrhyrthmic drugs Albuterol Beta-adrenergic agonist ▶Beta-adrenergic system Alefacept Soluble LFA-3 construct ▶Immunology Alemtuzumab anti-CD52 antibody ▶antineoplastic agents Alendronate Biphosphonate ▶Bone metabolism Aliskiren Renin-Inhibitor ▶Renin–Angiotensin–Aldosteron System Alfentanil Opioid, Analgesic ▶Opioid system ▶Analgesics Alfuzosin Alpha-adrenergic antagonist ▶Alpha-adrenergic system Alprenolol Beta-adrenergic antagonist ▶Beta-adrenergic system Allopurinol Anti-gout drug ▶Anti-gout drugs Alprazolam Benzodiazepine ▶Benzodiazepines Alteplase (t-PA) Fibrinolytic ▶Fibrinolytics Amantadine Anti-Parkinson drug ▶Anti-Parkinson drugs ▶Antiviral drugs antagonist ▶ Amikacin Aminoglycoside (antibacterial drug) ▶Aminoglycosides 1468 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Amiloride Potassium-sparing ▶Diuretics ▶Epithelial sodium channels Amiodarone Antiarrhythmic drug ▶Antiarrhyrthmic drugs Non-selective monoamine reuptake inhibitor (NSMRI) ▶Antidepressants ▶Neurotransmitter transporter Amlodipine Dihydropyridine ▶ blockers ▶Voltage-dependent calcium channels Amoxicillin Beta-lactam antibiotic ▶Beta-lactam antibiotics Amphetamine Indirect sympathomimetic ▶Psychostimmulants Amphotericin B Polyene ▶Antifungal drugs Ampicillin Beta-lactam antibiotic ▶Beta-lactam antibiotics Amprenavir Viral protease inhibitor ▶Antiviral drugs ▶Viral proteases Amrinone PDE-inhibitor ▶Phosphodiesterases Anakinra Recombinant IL-1-receptor antagonist ▶Cytokines Anastrozole Aromatase inhibitior ▶Aromatase Anidulafungine Antifungal drugs ▶Antifungal drugs Apomorphine agonist, Emetic ▶Emesis Aprepitant NK1 receptor antagonist ▶Emesis Argatroban Thrombin-inhibitor ▶Anticoagulants Aripiprazole Atypical neuroleptic ▶Antipsychotic drugs Atazanavir Viral protease inhibitor ▶Antiviral drugs ▶Viral proteases Atenolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Atipamezole Alpha-adrenergic antagonist ▶Alpha-adrenergic system Atorvastatin HMG-CoA-Reductase inhibitor (statin) ▶HMG-CoA-Reductase inhibitors (statin) Atosiban antagonist ▶Vasopressin/Oxytocin Atovaquone Antimalarial agent ▶Antiprotozoal drugs Atracurium Neuromuscular blocking drug ▶Nicotinic receptors Atropine Muscarinic antagonist (parasympatholytic) ▶Muscarinic receptors Auranofin Antirheumatoid drugs ▶Gold compounds 5-Azacytidine DNA methylation inhibitor ▶Epigenetics Azathioprine Immunosuppressant, Antineoplastic drugs ▶Immunosuppressants ▶Antineoplastic drugs Azithromycin Macrolide (antibacterial drugs) ▶Ribosomal protein synthesis inhibitors Aztreonam Beta-lactam antibiotic ▶Beta-lactam antibiotics Baclofen Muscle relaxant ▶GABAergic system Basiliximab Anti-IL-2-receptor antibody ▶Immune system ▶Cytokines Beclomethason- Glucocorticoid ▶Glucocorticoids Diproprionat Benazepril ACE inhibitor ▶ACE inhibitors ▶Renin–angiotensin–aldosterone system Bendamustine Alkylating agent ▶Antineoplasts agents Benperidole Butyrophenone ▶Antipsychotic drugs Benserazid Dopa decarboxylase inhibitor ▶Anti-Parkinson drugs Benzbromarone Uricosuric agent ▶Anti-gout drugs Betamethason Glucocorticoid ▶Glucocorticoids Betaxolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Bethanechol Muscarinic receptor agonist (parasympathomimetic) ▶Muscarinic receptors Anti-VEGF antibody ▶Angiogenesis List of Established Drugs 1469

List of Established Drugs (Continued)

Drug Group/Class Link

Bezafibrate Fibrate ▶Fibrates

Bicuculline GABAA-receptor antagonist ▶GABAergic system Biperiden Anticholinergic agent ▶Anti-Parkinson drugs ▶Muscarinic receptors Bisoprolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Bivalirudin Hirudin analogon ▶Anticoagulants Bleomycin Antineoplastic agent ▶Antineoplastic agents Bortezomib Proteasome inhibitor ▶Ubiquitin/Proteasome system Endothelin receptor antagonist ▶Endothelins Botulinum toxin Toxin ▶Bacterial toxins Bromazepam Benzodiazepine ▶Benzodiazepines Dopamine receptor agonist ▶Dopamine system Brotizolam Benzodiazepine ▶Benzodiazepines Budesonide Glucocorticoid ▶Glucocorticoids Bumetanide Loop diuretic ▶Diuretics Bupivacaine Local anaesthetic ▶Local anesthetics ▶Votage-dependent sodium channels Bupranolol Beta-adrenergic antagonist ▶Beta-adrenergic system Buprenorphine Opioid, Analgesic ▶Opioid system ▶Analgesics Bupropion Antidepressant ▶Antidepressants Buspirone Serotonin receptor agonist ▶Serotoninergic system Buserelin GnRH receptor antagonist ▶GnRH Busulphan Alkylating agent ▶Antineoplastic agents Butorphanol Opioid, Analgesic ▶Opioid system, analgesics Butylscopolamin Muscarinic receptor antagonist (parasympatholytic) ▶Muscarinic receptors Caffeine PDE inhibitor/ antagonist ▶Phosphodiesterases Calcitonin Hormone ▶Bone metabolism Calcitriol Vitamin D metabolite ▶Bone metabolism Candesartan Angiotensin receptor antagonist ▶Renin–angiotensin–aldosterone system Capecitabine Antimetabolite ▶Antineoplastic agents Capsaicin TRP channel activator ▶Nociceptive system ACE inhibitor ▶ACE inhibitors ▶Renin–angiotensin–aldosterone system Carbachol Muscarinic receptor agonist (parasympatholytic) ▶Muscarinic receptors Carbamazepine Antiepileptic drug ▶Antiepileptic drugs Carbetocin Oxytocin receptor agonist ▶Vasopressin/Oxytocin Carbidopa Anti-Parkinson drug ▶Anti-Parkinson drugs Carbimazole Antithyroid drug ▶Antithyroid drugs Carboplatin Antineoplastic agent ▶Antineoplastic agents Carmustin Alkylating agent ▶Antineoplastic agents Carteolol Beta-adrenergic antagonist ▶Beta-adrenergic system Carvedilol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Cefachlor Cephalosporin ▶Beta-lactam antibiotics Cefadroxil Cephalosporin ▶Beta-lactam antibiotics Cefazolin Cephalosporin ▶Beta-lactam antibiotics Cefepime Cephalosporin ▶Beta-lactam antibiotics Cefixime Cephalosporin ▶Beta-lactam antibiotics Cefotaxime Cephalosporin ▶Beta-lactam antibiotics Cefotetan Cephalosporin ▶Beta-lactam antibiotics Ceftazidime Cephalosporin ▶Beta-lactam antibiotics Ceftriaxone Cephalosporin ▶Beta-lactam antibiotics 1470 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Cefuroxime Cephalosporin ▶Beta-lactam antibiotics Celecoxib Antiinflammatory agent ▶Cyclooxygenases ▶Non-steroidal antiinflammatory drugs Celiprolol Beta-adrenergic antagonist ▶Beta-adrenergic system Cephalexin Cephalosporin ▶Beta-lactam antibiotics Cetirizine antagonist ▶Histaminergic system, Allergy Anti-EGFR antibody ▶Receptor tyrosine kinases ▶Growth factors Chlorambucil Alkylating agent ▶Antineoplastic agents Chlordiazepoxide Benzodiazepine ▶Benzodiazepines Chloroquine Antimalarial drug ▶Antiprotozoal drugs Chlorpheniramine Histamine receptor antagonist ▶Histaminergic system Chlorpromazine Phenothiazine ▶Antipsychotic drugs Chlorprothixene Thioxanthene ▶Antipsychotic drugs Chlorthalidone Thiazide ▶Diuretics Cholestyramine Anion exchange resin ▶Lipid-lowering drugs Ciclesonide Glucocorticoid ▶Glucocorticoids Ciclopirox Hydroxypyridone ▶Antifungal drugs Cidofovir Antiviral drug ▶Antiviral drugs Beta-lactamase inhibitor ▶Beta-lactam antibiotics Cilazapril ACE-inhibitor ▶ACE inhibitors Cilostazol PDE-inhibitor ▶Phosphodiesterases Cimetidine Histamine receptor antagonist ▶Histaminergic system Cinacalcet Ca2+ sensing ▶Ca2+-sensing receptor Ciprofloxacin Quinolone ▶Quinolones Cisapride Serotonin receptor agonist ▶Serotoninergic system Cisplatin Antineoplastic agent ▶Antineoplastic agents Citalopram Selective serotonine reuptake inhibitor (SSRI) ▶Antidepressants ▶Neurotransmitter transporters Clarithromycin Macrolide (antibacterial drugs) ▶Ribosomal protein synthesis inhibitors Clavulanate Beta lactamase inhibitor ▶Beta-lactam antibiotics Clemastine Histamine receptor antagonist ▶Histaminergic system Clenbuterol Beta-adrenergic agonist ▶Beta-adrenergic system Clindamycin Antibacterial agent ▶Ribosomal protein synthesis inhibitors Clobazam Benzodiazepine ▶Benzodiazepines Clofibrate Fibrate ▶Fibrates Clomiphene antagonist ▶Sex steroid receptors Clomipramine Non-selective monoamine reuptake inhibitor (NSMRI) ▶Antidepressants ▶Neurotransmitter transporters Clonazepam Benzodiazepine ▶Benzodiazepines Clonidine Alpha-adrenergic agonist ▶Alpha-adrenergic system Clopidogrel Thienopyridine ▶Anti-platelet drugs Clorazepate Benzodiazepine ▶Benzodiazepines Clotrimazole Antifungal drugs ▶Antifungal drugss Clozapine Atypical neuroleptic ▶Antipsychotic drugs ▶Neurotransmitter transporters Cocaine Psychostimulant ▶Psychostimulants ▶Drug addiction dependence Codeine Opioid ▶Opioid systems Colchicine Anti-gout drug ▶Anti-gout drugs ▶Cytoskeleton Colestipol Anion exchange resin ▶Lipid-lowering drugs List of Established Drugs 1471

List of Established Drugs (Continued)

Drug Group/Class Link

Conivaptan antagonist ▶Vasopressin Cortisone-Acetat Glucocorticoid ▶Glucocorticoids Cromoglycate Cromone ▶Allergy (Cromoglycin) Cyclophosphamide Alkylating agent ▶Antineoplastic agents Cyclosporine Immunosuppressive agent ▶Immunosuppressive agents Cyproterone antagonist ▶Sex steroid receptors Cytarabine Antimetabolite ▶Antineoplastic agents Dabigatranetexilat Thrombin-Inhibitor ▶Anticoagulants Daclizumab Anti-IL-2-receptor antibody ▶Immune system ▶Cytokines Danaparoid Glycosaminoglycans ▶Anticoagulants Dapsone Antibacterial drug ▶Antibacterial drugs/antiprozotoal drugs Darifenacin Muscarinic receptor antagonist ▶Muscarinic receptors Darunavir Viral protease inhibitor ▶Antiviral drugs ▶Viral proteases Endothelin receptor antagonist ▶Endothelins Tyrosine kinase inhibitor ▶Tyrosine kinases Daunorubicin Anthracycline ▶Antineoplastic agents Decitabine Antimetabolite ▶Antineoplastic agents Delavirdine Reverse transcriptase inhibitor ▶Antiviral agents Desirudin Hirudin-analog ▶Anticoagulants Desloratadine Histamine receptor antagonist ▶Histaminergic system Desmopressin Vasopressin receptor agonist ▶Vasopressin/Oxytocin Desonide Glucocorticoid ▶Glucocorticoids Glucocorticoid ▶Glucocorticoids Diamorphin (Heroin) Opioid ▶Opioid system ▶Drug addiction/dependence Diazepam Benzodiazepine ▶Benzodiazepines Diazoxide Vasorelaxant ▶ATP-dependent potassium channels Diclofenac Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶Non-steroidal antiinflammatory drugs Dicloxacillin Beta-lactam antibiotic ▶Beta-lactam antibiotics Didanosine Reverse transcriptase inhibitor ▶Antiviral drugs Digitoxin Cardiac glycoside ▶Cardiac glycosides Digoxin Cardiac glycoside ▶Cardiac glycosides Diltiazem Benzothiazepine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Dimenhydrinate Histamine receptor antagonist ▶Histaminergic system Diphenhydramine Histamine receptor antagonist ▶Histaminergic system Disopyramide Antiarrhythmic drugs ▶Antiarrhyrthmic drugs Dizocilpine NMDA-receptor antagonist blocker ▶Glutamate receptors Dobutamine Beta agonist ▶Beta adrenergic system Docetaxel Taxane ▶Antineoplastic agents ▶Cytoskeleton Dofetilide Antiarrhythmic drug ▶Antiarrhythmic drugs ▶Potassium channels Dolasetron Antiemetic drug, Serotonin receptor antagonist ▶Emesis ▶Serotoninergic system 1472 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Donepezil Acetylcholinesterase inhibitor ▶Acetylcholinesterase Doxazosin Alpha-adrenergic antagonist ▶Alpha-adrenergic system Doxepin Non-selective monoamine reuptake inhibitor (NSMRI) ▶Antidepressants ▶Neurotransmitter transporters Doxorubicin Anthracycline ▶Antineoplastic agents Doxycycline Tetracycline ▶Ribosomal protein synthesis inhibitors Dronabinol agonist ▶Cannabinoid receptors Dutasteride 5α-reductase inhibitor ▶Sex steroid receptors Eculizumab Complement-inhibitor ▶Immune defense, Allergy Edrophonium Acetylcholinesterase inhibitor ▶Acetylcholinesterase Efalizumab Anti-LFA-1 antibody ▶Immune defense Efavirenz Reverse transcriptase inhibitor ▶Antiviral agents Eflornithine Antitrypanosomal drug ▶Antiprotozoal drugs Enalapril ACE inhibitor ▶ACE inhibitors ▶Renin–angiotensin–aldosterone- system Enalaprilat ACE inhibitor ▶ACE inhibitors ▶Renin–angiotensin–aldosterone system Endostatin Angiogenesis inhibitor ▶Angiogenesis Enflurane General anaesthetics ▶General anaesthetics Enfuvirtide Virus entry inhibitor ▶Antiviral drugs Enoxaparin Low-molecular-weight heparin ▶Anticoagulants Enfuvirtide HIV fusion inhibitor ▶Antiviral agents Entacapone COMT-inhibitor ▶Anti-Parkinson drugs ▶Catechol-O-methyltransferase Entecavir Nucleosid analog ▶Antiviral drugs Ephedrine Epinephrine (Adrena- Adrenoceptor agonist ▶Beta-adrenergic system lin) ▶alpha-adrenergic system Epirubicin Anthracycline ▶Antineoplastic agents Eplerenone Aldosterone receptor antagonist ▶Antihypertensive agents/Blood pressure control Epoetin alpha Hematopoietic growth factor ▶Hematopoietic growth factors Eprosartan Angiotensin receptor antagonist ▶Renin–angiotensin– aldosterone-system Eptifibatide GPIIb/IIIa inhibitor ▶Antiplatelet drugs Ergometrine Ergot alkaloid ▶Ergot alkaloids Ergotamine Ergot alkaloid ▶Ergot alkaloids Anti-EGF receptor antibody ▶Growth factor Erythromycin Macrolide (Antibacterial drug) ▶Ribosomal protein synthesis inhibitors Esmolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Estradiol Estrogen receptor agonist ▶Sex steroid receptors Etanercept Soluble TNF receptor construct ▶Immune system Ethacrynic acid loop diuretic ▶Diuretics Ethambutol Antituberculotic agent ▶Antituberculotic drugs Ethinylesteradiol Estrogen receptor agonist ▶Sex steroid receptors Ethosuximide Antiepileptic drugs ▶Antiepileptic drugs Etodolac Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶Non-steroidal antiinflammatory List of Established Drugs 1473

List of Established Drugs (Continued)

Drug Group/Class Link

Etoposide Antineoplastic agent ▶Antineoplastic agents Etravirine Reverse transcriptase inhibitor ▶Antiviral drugs Etretinate Retinoid ▶Retinoids Immunosuppressant ▶Immunosuppressive agents Exemestane Aromatase inhibitor ▶Aromatase GLP-1-receptor agonist ▶Diabetes mellitus Ezetimib Cholesterol absorption inhibitor. ▶Lipid-lowering drugs Famotidine Histamine receptor antagonist ▶Histaminergic system Felbamate Antiepileptic drugs ▶Antiepileptic drugs Felodipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Fenoterol Beta-adrenergic agonist ▶Beta-adrenergic system Fentanyl Opioid, Analgesic ▶Opioid system ▶Analgesics Fexofenadine Histamine receptor antagonist ▶Histaminergic system, Allergy Hematopoietic growth factor ▶Hematopoietic growth factors Finasteride Antiandrogen ▶Sex steroid receptors Fingolimod (FTY720) S1P receptor agonist ▶Lysophospholipids, Immunosuppressants Flecainide Antiarrhythmic drug ▶Antiarrhyrthmic drugs Fluconazole Azole ▶Antifungal drugs Fludarabine Antimetabolite ▶Antineoplastic agents Fludrocortisone Glucocorticoid ▶Glucocorticoids ▶Gluco/Mineralocorticoid receptors Flumazenil Benzodiazepine ▶Benzodiazepines Flunisolid-Acetonid Glucocorticoid ▶Glucocorticoids Flunitrazepam Benzodiazepine ▶Benzodiazepines 5-Fluorouracil Antimetabolite ▶Antineoplastic agents Fluoxetine Selective serotonine reuptake inhibitor (SSRI) ▶Antidepressants ▶Neurotransmitter transporters Fluphenazine Phenothiazine ▶Antipsychotic drugs Flupenthixol Thioxanthene ▶Antipsychotic drugs Flurazepam Benzodiazepine ▶Benzodiazepines Fluspirilen Antipsychotic drug ▶Antipsychotic drugs Fluticasone Glucocorticoid ▶Glucocorticoids Flurbiprofen Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶NSAID ▶Cycloxygenase Flutamide Androgen receptor antagonist ▶Sex steroid receptors Fluvastatin HMG-CoA-Reductase inhibitor (Statin) ▶HMG-CoA-Reductase inhibitors (Statin) Fluvoxamine Selective serotonine reuptake inhibitor (SSRI) ▶Antidepressants ▶Neurotransmitter transporters Fomivirsen Oligonucleotide against CMV gene ▶Antiviral drugs Fondaparinux Synthetic pentasaccharide ▶Anticoagulants Formoterol Beta-adrenergic agonist ▶Beta-adrenergic system Formestane Aromatase inhibitor ▶Aromatase ACE inhibitor ▶ACE inhibitors Frovatriptan Serotonin receptor agonist ▶Serotoninergic system Fulvestrant Estrogen receptor antagonist ▶Sex steroid receptors Furosemide Loop diuretic ▶Diuretics Gabapentin Antiepileptic drug ▶Antiepileptic drugs 1474 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Gallamine Neuromuscular blocking drug ▶Nicotinic receptors Gallopamil Phenylalkylamine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Ganciclovir Antiviral drug ▶Antiviral drugs Ganirelix GnRh receptor antagonist Gatifloxacin Quinolone ▶Quinolones ▶Growth factor inhibitor Gemcitabine Antimetabolite ▶Antineoplastic agents Gemfibrozil Fibrate ▶Fibrates Gentamicin Aminoglycoside (Antibacterial drug) ▶Ribosomal protein synthesis inhibitor Glibenclamide Sulphonylurea ▶ATP-dependent potassium channels ▶Oral antidiabetic drugs Glimepiride Sulphonylurea ▶ATP-dependent potassium channels ▶Oral antidiabetic drugs Glipizide Sulphonylurea ▶ATP-dependent potassium channels ▶Oral antidiabetic drugs Glyburide Sulphonylurea ▶ATP-dependent potassium channels ▶Oral antidiabetic drugs Glyceryltrinitrate Organic nitrate ▶Guanylyl cyclases Granisetron Antiemetic drug, Serotonin receptor antagonist ▶Emesis ▶Serotoninergic system Grepafloxacin Quinolone ▶Quinolones Griseofulvin Antifungal drug ▶Antifungal drugs Haloperidol Butyrophenone ▶Antipsychotic drugs Halothane General anesthetics ▶General anaesthetics Heparin Anticoagulant ▶Anticoagulants Human-Insulin Antidiabetic drug ▶Insulin receptors ▶Diabetes mellitus Hydralazine Vasodilator ▶Antihypertensive agents Hydrochlorthiazide Thiazide ▶Diuretics Hydroxychloroquine Antimalarial drug ▶Antiprotozoal drugs Hydroxyurea Antineoplastic agent ▶Antineoplastic agents Ibandronate Bisphosphonate ▶Bone metabolism Ibritumomab Anti-CD20 antibody ▶Antineoplastic agents Ibuprofen Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶NSAID Idarubicin Anthracycline ▶Antineoplastic agents Ifosfamide Alkylating agent ▶Antineoplastic agents IL-2 Cytokine ▶Cytokines Iloprost Prostacycline analog ▶Prostanoids (STI 571) Tyrosine kinase inhibitor ▶Tyrosine kinases Imidapril ACE-inhibitor ▶ACE inhibitors Imipenem Beta-lactam antibiotic ▶Beta-lactam antibiotics Imipramine Non-selective monoamine reuptake inhibitor (NSMRI) ▶Antidepressants ▶Neurotransmitter transporters Imiquomid Toll-like receptor activator ▶Immune defense List of Established Drugs 1475

List of Established Drugs (Continued)

Drug Group/Class Link

Indinavir Protease inhibitor ▶Antiviral drugs ▶Viral proteases Indomethacin Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶Non-steroidal antiinflammatory drugs Infliximab Anti-TNFαantibody ▶Humanized monoclonal antibodies ▶Immune defense Insulin Antidiabetic drug ▶Insulin receptors ▶Diabetes mellitus Insulin analog ▶Insulin receptors ▶Diabetes mellitus Insulin analog ▶Insulin receptors ▶Diabetes mellitus Insulin analog ▶Insulin receptors ▶Diabetes mellitus Insulin analog ▶Insulin receptors ▶Diabetes mellitus Insulin analog ▶Insulin receptors ▶Diabetes mellitus Interferon alpha Immunomodulator ▶Interferons ▶Cytokines Interferon beta Immunomodulator ▶Interferons ▶Cytokines Immunomodulator ▶Interferons ▶Cytokines Ipratropium Muscarinic receptor antagonist (Parasympatholytic) ▶Muscarinic receptors Irbesartan Angiotensin receptor antagonist ▶Renin–angiotensin–aldosterone system Irinotecan Topoisomerase-I-inhibitor ▶Antineoplastic agents Isoflurane General anaesthetics ▶General anaesthetics Isoniazid Antituberculotic agent ▶Antituberculotic agents Isoprenaline Adrenoceptor agonist ▶Beta-adrenergic system/ alpha-adrenergic system Isoproterenol Adrenoceptor agonist ▶Beta-adrenergic system/ alpha-adrenergic system Isosorbide dinitrate Organic nitrate ▶Guanylyl cyclases Isosorbidmononitrate Organic nitrate ▶Guanylyl cyclases Isradipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Itraconazole Azole ▶Antifungal drugs Ivabradine HCN channel inhibitor ▶Cyclic nucleotide gated cation channels Ivermectin Antiparasitic agent ▶Antiparasitic agents Ketamine NMDA receptor antagonist, Channel blocker ▶General anaesthetics ▶NMDA-receptor ▶Psychomimetic drugs Ketoconazole Azole ▶Antifungal drugs Ketoprofen Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶NSAID Ketorolac Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase 1476 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Lacidipine Dihydropyridine ▶Calcium channel blockers Lactulose Laxative ▶Laxatives Lamivudine Reverse transcriptase inhibitor ▶Antiviral agents Lamotrigine Antiepileptic drug ▶Antiepileptic drugs Lansoprazole Proton pump inhibitor ▶Proton pump inhibitors Tyrosine kinase inhibitor ▶Tyrosine kinases Latanoprost PGF2α analog ▶Prostanoids L-dopa Anti-Parkinson drug ▶Anti-Parkinson drugs Lenalidomide Angiogenesis inhibitor ▶Angiogenesis Hematopoietic growth factor ▶Hematopoietic growth factors Lepirudin Hirudin-analog ▶Anticoagulants Lercandipine Dihydropyridine ▶Calcium channel blockers Letrozole Aromatase inhibitior ▶Aromatase Levetiracetam Antiepileptic drug ▶Antiepileptic drugs Levodopa Anti-Parkinson drug ▶Anti-Parkinson drugs Levofloxacin Quinolone ▶Quinolones Levomepromazine Phenothiazine ▶Antipsychotic drugs Levomethadon Opioid ▶Opioid system Lidocaine Local anaesthetic, Antiarrhythmic drug ▶Local anaesthetics ▶Antiarrhythmic drugs ▶Votage-dependent sodium channels Linezolide Oxazolidinone ▶Antibacterial drugs Lisinopril ACE inhibitor ▶ACE inhibitors ▶Renin–angiotensin–aldosterone system Lisuride Dopamine receptor agonist ▶Dopamine system Lithium Mood stabilizer ▶Mood stabilizer Loperamide Opioid ▶Opioid system Lopinavir Viral protease inhibitor ▶Antiviral drugs ▶Viral proteases Loratadine Histamine receptor antagonist ▶Histaminergic system, Allergy Lorazepam Benzodiazepine ▶Benzodiazepines Lormetazepam Benzodiazepine ▶Benzodiazepines Losartan Angiotensin receptor antagonist ▶Renin–angiotensin– aldosterone-system Lovastatin HMG-CoA-reductase inhibitor (Statin) ▶HMG-CoA-reductase inhibitors (Statin) Lubiprostone activator ▶Cl− channels Lumiracoxib COX2-inhibitor ▶Cyclooxygenases Lysergic acid Serotonin receptor agonist ▶Psychomimetic drugs diethylamide Madipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Maraviroc CCR5 receptor antagonist ▶Antiviral drugs ▶ Mebendazole Anthelmintic drug ▶Antimalarial drugs ▶Antiprotozoal drugs Medazepam Benzodiazepine ▶Benzodiazepines Medroxyprogesterone agonist ▶Sex steroid receptors Mefloquine Antimalarial drug ▶Antiprotozoal drugs Melarsoprol Antiprotozoal drug ▶Antiprotozoal drugs List of Established Drugs 1477

List of Established Drugs (Continued)

Drug Group/Class Link

Meloxicam Analgetic/Antipyretic/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶NSAID Melperone Butyrophenone ▶Antipsychotic drugs Melphalan Alkylating agent ▶Antineoplastic agents Memantine NMDA receptor antagonist ▶Ionotropic glutamate receptors Meperidine Opioid, Analgesic ▶Opioid system, analgesics Mercaptopurine Antimetabolite ▶Antineoplastic agents Meropenem Beta-lactam antibiotic ▶Beta-lactam antibiotics Mescaline Psychotomimetic drug ▶Psychotomimetic drugs Metamizol Analgetic/Antipyretic drug ▶Analgesics Biguanide ▶Oral antidiabetic drugs ▶Diabetes mellitus Methadone Opioid ▶Opioid system Methotrexate Antimetabolite ▶Antineoplastic agents Methylphenidate Indirect sympathomimetic ▶Psychostimulants Methylprednisolone Glucocorticoid ▶Glucocorticoids Methysergide Serotonin receptor antagonist ▶Serotoninergic system Metixene Muscarinic receptor antagonist ▶Anti-Parkinson drugs ▶Muscarinic receptors Serotonin receptor antagonist ▶Serotoninergic system Metoprolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Metronidazole Antibacterial agent, Antiprozotoal agent ▶Antiprozotoal drugs Mexiletine Antiarrhythmic drugs ▶Antiarrhyrthmic drugs Mianserin Antidepressant ▶Antidepressants Midazolam Benzodiazepine ▶Benzodiazepines Mifepristone (RU 486) Progesterone receptor antagonist ▶Sex steroid receptors Miglitol Alpha-glucosidase inhibitor ▶Oral antidiabetic drugs Milrinone PDE-inhibitor ▶Phosphodiesterases Tetracycline ▶Ribosomal protein synthesis inhibitor Mirtazapine Antidepressants ▶Antidepressants Misoprostol Prostaglandin derivative ▶Prostanoids Mivacurium Neuromuscular blocking drug ▶Nicotinic receptors

Moclobemide MAOA-inhibitor ▶Antidepressants Moexipril ACE inhibitor ▶ACE inhibitors Hematopoietic growth factor ▶Hematopoietic growth factors Molsidomine NO-donator ▶Guanylyl cyclases antagonist ▶Leukotrienes Morphine Opiate, Analgesics ▶Opioid system ▶Analgsics Moxifloxacin Quinolone ▶Quinolones Moxonidine Alpha-adrenergic agonist ▶Alpha-adrenergic system Muromonab Anti-T-cell receptor antibody ▶Cytokines Mycophenolate Immunosuppressant ▶Immunosuppressants Mycophenolate- Immunosuppressant ▶Immunosuppressants Mofetil Na-Aurothiomalate Antirheumatoid drugs ▶Gold compounds Nabumetone Analgetic-, Antipyretic-, Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶NSAID Nadifloxacin Quinolone ▶Quinolones Nadolol Beta-adrenergic antagonist ▶Beta-adrenergic system Naftifine Allylamine ▶Antifungal drugs 1478 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Nalbuphine Opioid, Analgesic ▶Opioid system ▶Analgesics Nalmefene antagonist ▶Opioid system Naloxone Opioid receptor antagonist ▶Opioid system Nandrolon- Anabolic ▶Sex steroid receptors Decanoate Naproxen Analgetic-, Antipyretic-, Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶NSAID Naratriptan Serotonin receptor agonist ▶Serotoninergic system Natalizumab Anti-α4 integrin antibody ▶Integrins Nateglinide Meglitinide ▶Oral antidiabetic drugs Nebivolol β-adrenergic antagonist ▶β-adrenergic receptors Nedocromil Cromone ▶Allergy Nelarabine Antimetabolite ▶Antineoplastic agents Nelfinavir Viral protease inhibitor ▶Antiviral drugs ▶Viral proteases Neomycin Aminoglycoside (Antibacterial drug) ▶Ribosomal protein synthesis inhibitor Neostigmine Acetylcholinesterase inhibitor ▶Acetylcholinesterase Nevirapine Reverse transcriptase inhibitor ▶Antiviral agents Nicardipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Nicotine Nicotinic receptor agonist ▶Nicotinic receptors Nicotinic acid Lipid lowering drug, Vitamin ▶Lipid lowering drugs Nifedipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Tyrosine Kinase inhibitor ▶Tyrosine Kinases Nilvadipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Nisoldipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Nitrazepam Benzodiazepine ▶Benzodiazepines Nitrendipine Dihydropyridine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Nitrofurantoin Antimicrobial agent ▶Antimicrobial drugs Nitroglycerin Organic nitrate ▶Guanylyl cyclases Nitroprussidnatrium NO-donator ▶Guanylyl cyclases Noradrenalin Adrenoceptor agonist ▶Beta-adrenergic system ▶alpha-adrenergic system Norethisteron-Acetat Estrogen receptor agonist ▶Sex steroid receptors Nortriptyline Non-selective monoamine reuptake inhibitor (NSMRI) ▶Antidepressants ▶Neurotransmitter transporters Nystatin Antifungal agent ▶Antifungal agents Octreotide agonist ▶Somatostatin Ofloxacin Quinolone ▶Quinolones Olanzapine Atypical neuroleptic ▶Antipsychotic drugs Olmesartan Angiotensin receptor antagonist ▶Renin–angiotensin–aldosteron system Omalizumab Anti-IgE antibody ▶Allergy List of Established Drugs 1479

List of Established Drugs (Continued)

Drug Group/Class Link

Omeprazole Proton pump inhibitor ▶Proton pump inhibitors Ondansetron Antiemetic drug, Serotonin receptor antagonist ▶Emesis ▶Serotoninergic system Orlistat Lipase inhibitor ▶Anti- drugs Oseltamivir Neuraminidase inhibitor ▶Antiviral drugs Oxacilin Beta-lactam antibiotic ▶Beta-lactam antibiotics Oxazepam Benzodiazepine ▶Benzodiazepines Oxaliplatin Antineoplastic agent ▶Antineoplastic agent Oxcarbazepine Antiepileptic drug ▶Antiepileptic drugs Oxprenolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Oxybutynin Muscarinic receptor antagonist ▶Muscarinic receptors Oximetazoline Alpha-adrenergic agonist ▶Alpha-adrenergic system Oxytocin Hormone Paclitaxel Taxane ▶Antineoplastic agents ▶Cytoskeleton Recombinant growth factor ▶Growth factors Palivizumab Anti-RSV antibody ▶Antiviral drugs Paliperidone Atypical neuroleptic ▶Antipsychotic drugs Palonosetron Serotonin receptor antagonist ▶Emesis ▶Serotoninergic system Pancuronium Neuromuscular blocking drug ▶Nicotinic receptors Receptor tyrosine kinase blocking antibody ▶Growth factors Pantoprazol Proton pump inhibitor ▶Proton pump inhibitors Paracetamol (Acet- Analgetic-/Antipyretic drug ▶Analgesics aminophen) Parathion Acetylcholinesterase inhibitor ▶Acetylcholinesterase Parecoxib COX-2 inhibitor ▶Cyclooxygenases Paroxetine Selective serotonin reuptake inhibitor (SSRI) ▶Antidepressants ▶Neurotransmitter transporters VEGF receptor antagonist ▶Angiogenesis Penicillin Beta-lactam antibiotic ▶Beta-lactam antibiotics Pergolid Dopamine receptor agonist ▶Dopamine system Perphenazine Phenothiazine ▶Antipsychotic drugs Pentazocine Opioid, Analgesic ▶Opioid system, Analgesics Pentostatin Antimetabolite ▶Antineoplastic agents Perindopril ACE inhibitor ▶ACE inhibitors Phencyclidine NMDA receptor antagonist, Channel blocker ▶General anesthetics ▶NMDA-receptor ▶Psychomimetic drugs Pethidine Opioid/analgesic ▶Opioid system ▶Analgesics Phenobarbital Barbiturate ▶Antiepileptic drugs Phenprocoumon Coumarinderivative ▶Anticoagulants ▶ Phenylephrine Alpha-adrenergic agonist ▶Alpha-adrenergic system Phenytoin Antiepileptic drug ▶Antiepileptic drugs Physostigmine Acetylcholinesterase inhibitor ▶Acetylcholinesterase Pilocarpine Muscarinic agonist (Parasympathomimetic) ▶Muscarinic receptors Pimecrolimus Immunosuppressant ▶Immunosuppressive agents Pimozide Neuroleptic ▶Antipsychotic drugs Pindolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Pioglitazone Thiazolidinedione ▶Oral antidiabetic drugs ▶Diabetes mellitus Pipamperon Butyrophenone ▶Antipsychotic drugs Piretanide Loop diuretic ▶Diuretics 1480 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Piroxicam Analgetic-/Antipyretic-/Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶NSAID Pizotifen Serotonin receptor antagonist ▶Serotoninergic system Plerixafor CXCR4 receptor antagonist ▶Antiviral drugs ▶Chemokines Posaconazole Azole ▶Antifungal drugs Pramipexole Dopamine receptor agonist ▶Dopamine system ▶Anti-Parkinson drugs Pravastatin HMG-CoA-reductase inhibitor (statin) ▶HMG-CoA-Reductase inhibitors (statin) Prazepam Benzodiazepine ▶Benzodiazepines Praziquantel Anthelmintic agent ▶Anthelmintic agents Alpha-adrenergic antagonist ▶Alpha-adrenergic system Prednisolone Glucocorticoid ▶Glucocorticoids Prednisone Glucocorticoid ▶Glucocorticoids Pregabaline Antiepileptic drug ▶Antiepileptic drugs Prilocaine Local anesthetic ▶Local anesthetics ▶Votage-dependent sodium channels Primaquine Antimalarial drug ▶Antiprotozoal drugs Probenecid Uricosuric agent ▶Anti-gout drugs Procainamide Local anaesthetic ▶Local anaesthetics Proguanil Antimalarial drug ▶Antiprotozoal drugs Promazine Phenothiazine ▶Antipsychotic drugs Promethazine Histamine receptor antagonist ▶Histaminergic system Propofol Anaesthetic ▶General anaesthetics ▶GABAergic system Propranolol Beta-adrenergic antagonist (β-blocker) ▶Beta-adrenergic system Pyridostigmine Acetylcholinesterase inhibitor ▶Acetylcholinesterase Pyrimethamin Antiprozotoal drug ▶Antiprozotoal drugs Quetiapine Atypical neuroleptic ▶Antipsychotic drugs Quinapril ACE inhibitor ▶ACE inhibitors Quinidine Antiarrhythmic drugs ▶Antiarrhyrthmic drugs Quinine Antimalarial drug ▶Antiprotozoal drugs Rabeprazole Proton pump inhibitor ▶Proton pump inhibitors Racecadotril inhibitor ▶Opioid system Raloxifene Selective estrogen receptor modulator (SERM) ▶Selective estrogen receptor modulators (SERM) Raltegravir Integrase inhibitor ▶Antiviral drugs agonist ▶Sleep Ramipril ACE inhibitor ▶ACE inhibitors ▶Renin–angiotensin–aldosterone system Receptor tyrosine kinase blocking antibody ▶Growth factors Ranitidine Histamine receptor antagonist ▶Histaminergic system Rapacuronium Neuromuscular blocking drug ▶Nicotinic receptors Rasagiline MAO-B inhibitor ▶Anti-Parkinson drugs Reboxetine Selective noradrenaline reuptake inhibitor (SNRI) ▶Antidepressants Remifentanil Opioid, Analgesic ▶Opioid system ▶Analgesics Repaglinide Meglitinide ▶ATP-dependent potassium channels ▶Oral antidiabetic drugs Reteplase Fibrinolytic ▶Fibrinolytics List of Established Drugs 1481

List of Established Drugs (Continued)

Drug Group/Class Link

Ribavirin Antiviral agent ▶Antiviral drugs Rifabutin Antituberculotic agent ▶Antituberculotic drugs Rifampin Antituberculotic agent ▶Antituberculotic drugs Rimonabant Cannabinoid receptor antagonist ▶Anti-obesity drugs, ▶Endocannabinoids Risedronate Bisphosphonate ▶Bone metabolism Atypical neuroleptic ▶Antipsychotic drugs Ritonavir Viral protease inhibitor ▶Antiviral drugs ▶Viral proteases Rituximab Anti-CD20 antibody ▶Antineoplastic Agents Rivastgmine Acetylcholinesterase inhibitor ▶Acetylcholinesterase Rizatriptan Serotonin receptor agonist ▶Serotoninergic system Rofecoxib Antiinflammatory agent ▶Cyclooxygenases ▶Non-steroidal antiinflammatory drugs Rolipram PDE-inhibitor ▶Phosphodiesterases Ropinirole Dopamine receptor agonist ▶Dopamine system Ropivacain Local anaesthetic ▶Local anaesthetics Thiazolidinedione ▶Oral antidiabetic drugs ▶Diabetes mellitus Rosuvastatin HMG-CoA-reductase Inhibitor ▶HMG-CoA-reductase inhibitors Rotigotine Dopamine receptor agonist ▶Dopaminergic system Roxithromycin Macrolide (Antibacterial drugs) ▶Ribosomal protein synthesis inhibitors Salbutamol Beta-adrenergic agonist ▶Beta-adrenergic system Salmeterol Beta-adrenergic agonist ▶Beta-adrenergic system Saquinavir Viral protease inhibitor ▶Antiviral drugs ▶Viral proteases Hematopoietic growth factor ▶Hematopoietic growth factors Scopolamine Muscarinic receptor antagonist (Parasympatholytic) ▶Muscarinic receptors

Selegiline MAOB-inhibitor ▶Anti-Parkinson drugs Sertindol Atypical neuroleptic ▶Antipsychotic drugs Sertraline Selective serotonine reuptake inhibitor (SSRI) ▶Antidepressants ▶Neurotransmitter transporters Sibutramine Reuptake inhibitor ▶Antidepressants ▶Appetite control ▶Anti-obesity drugs Sildenafil PDE-inhibitor ▶Phosphodiesterases Simvastatin HMG-CoA-reductase inhibitor (statin) ▶HMG-CoA-reductase inhibitors (statin) (Rapamy- Immunosuppressant ▶Immunosuppressive agents cin) Sitagliptin DPP4 inhibitor ▶Diabetes mellitus Sitaxentane Endothelin receptor Antagonist ▶Endothelins Solifenacin Muscarinic receptor antagonist ▶Muscarinic receptors Spironolactone Aldosterone receptor antagonist ▶Gluco-Mineralocorticoid receptors ▶Renin–angiotensin–aldosterone system Kinase inhibitor ▶Tyrosine kinases Sotalol Antiarrhythmic drug, Beta adrenergic receptor antagonist ▶Antiarrhythmic drugs adrenergic receptor antagonists ▶Beta Sparfloxacine Quinolone ▶Quinolones Spirapril ACE inhibitor ▶ACE inhibitors Stavudine Reverse transcriptase inhibitor ▶Antiviral agents 1482 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Streptokinase Fibrinolytic ▶Fibrinolytics Streptomycin Aminoglycoside (Antibacterial drug) ▶Ribosomal protein synthesis inhibitor Strophantine Cardiac glycoside ▶Cardiac glycosides Strychnine antagonist ▶Glycine receptors Sufentanil Opioid, Analgesic ▶Opioid system ▶Analgesics Sulfamethoxazole Sulfonamide ▶Sufonamides Sulfasalazine Antiinflammatory drug ▶Non-steroidal antiinflammatory drugs Sulfipyrazone Uricosuric agent ▶Anti-gout drugs Sulfisoxazole Sulfonamide ▶Sulfonamides Sulindac Analgetic-, Antipyretic-, Antiinflammatory drug ▶Analgesics ▶Cycloxygenase ▶NSAID Sulpirid Atypical neuroleptic ▶Antipsychotic drugs Sumatriptan Serotonin receptor agonist ▶Serotoninergic system ▶Analgesics Tyrosine kinase inhibitor ▶Tyrosine kinases Suxamethonium Nicotine receptor agonist ▶Nicotinic receptors Tacrine Acetylcholinesterase inhibitor ▶Acetylcholinesterase Tacrolimus (FK 506) Immunosuppressant ▶Immunosuppressive agents Tadalafil PDE-inhibitor ▶Phosphodiesterases Talinolol Beta-adrenergic antagonist ▶Beta-adrenergic system Tamoxifen Selective estrogen receptor modulator (SERM) ▶Selective estrogen receptor modulators (SERM) Tamsulosin Alpha-adrenergic antagonist ▶Alpha-adrenergic system Tegaserod Serotonin receptor agonist ▶Serotoninergic system Telbivudine Reverse transcriptase inhibitor ▶Antiviral agents Telithromycin Ketolid ▶Antibacterial agents Telmisartane Angiotensin receptor antagonist ▶Renin–angiotensin–aldosterone system Temazepam Benzodiazepine ▶Benzodiazepines mTOR inhibitor ▶Antineoplastic agents Tenecteplase Fibrinolytic ▶Fibrinolytics Terazosin Alpha-adrenergic antagonist ▶Alpha-adrenergic system Terbinafin Allylamine ▶Antifungal drugs Terbutaline Beta-adrenergic agonist ▶Beta-adrenergic system Hormone analoque ▶Bone metabolism Testosteron-Propio- Androgen receptor agonist ▶Sex steroid receptors nat Tetracaine Local anaesthetic ▶Local anaesthetics ▶Votage-dependent sodium channels Tetracycline Tetracycline ▶Ribosomal protein synthesis inhibitors Thalidomide Angiogenesis inhibitor ▶Angiogenesis Theophylline PDE inhibitor, Adenosine receptor antagonist ▶Phosphodiesterases Thiamazol Antithyroid drug ▶Antithyroid drugs Thiethylperazine Phenothiazine ▶Antipsychotic drugs Thioguanine Antimetabolite ▶Antineoplastic agents Thiopental Barbiturate ▶General Anaesthetics Thioridazine Phenothiazine ▶Antipsychotic drugs Thiotepa Alkylating agent ▶Antineoplastic agents List of Established Drugs 1483

List of Established Drugs (Continued)

Drug Group/Class Link

Tiagabine Antiepileptic drug ▶Antiepileptic drugs Ticlopidine Thienopyridine ▶Antiplatelet drugs Tilidin Opioid, Analgesic ▶Opioid system ▶Analgesics Timolol Beta-adrenergic antagonist ▶Beta-adrenergic system Tiotropiumbromide Muscarinic receptor antagonist ▶Muscarinic receptors Tipranavir Vitral protease inhibitor ▶Viral proteases ▶Antiviral drugs Tirofiban GPIIb/IIIa inhibitor ▶Antiplatelet drugs Tobramycin Aminoglycoside (Antibacterial drug) ▶Ribosomal protein synthesis inhibitors Tocainide Antiarrhythmic drugs ▶Antiarrhyrthmic drugs Tolbutamide Sulphonylurea ▶ATP-dependent potassium channels ▶Oral antidiabetic drugs Tolcapone COMT-inhibitor ▶Anti-Parkinson drugs ▶Catechol-O-methyltransferase Tolterodine Muscarinic receptor antagonist ▶Muscarinic receptors Topiramate Antiepileptic drug ▶Antiepileptic drugs Topotecan Topoisomerase-I-inhibitor ▶Antineoplastic agents Torasemide Loop diuretic ▶Diuretics Toremifene Selective estrogen receptor modulator (SERM) ▶Selective estrogen receptor modulators (SERM) Tramadol Opioid, Analgesic ▶Opioid system ▶Analgesics Trandolapril ACE inhibitor ▶ACE inhibitors ▶Renin–angiotensin– aldosterone-system Receptor tyrosine kinase blocking antibody ▶Growth factors Trazodone Antidepressant ▶Antidepressants Triamterene Potassium-sparing diuretic ▶Diuretics ▶Epithelial sodium channels Triazolam Benzodiazepine ▶Benzodiazepines Trimethoprim Antibacterial agent ▶Antibacterial agents Trimipramin Non-selective monoamine reuptake inhibitor (NSMRI) ▶Antidepressants ▶Neurotransmitter transporters Tropicamide Muscarinic antagonist (Parasympatholytic) ▶Muscarinic receptors Tropisetron Antiemetic drug, Serotonin receptor antagonist ▶Emesis ▶Serotoninergic system Trovafloxacine Quinolone ▶Quinolones Tubocurarin Neuromuscular blocking agent ▶Nicotinic receptors Urapidil Alpha-adrenergic antagonist ▶Alpha-adrenergic system Fibrinolytic ▶Fibrinolytics Valacyclovir Antiviral drug ▶Antiviral drugs Valproic acid Antiepileptic drug ▶Antiepileptic drugs Valsartan Angiotensin receptor antagonist ▶Renin–angiotensin–aldosterone system Vancomycin Antibacterial agent ▶Antibacterial agents Vardenafil PDE-inhibitor ▶Phosphodiesterases Varenicline Nicotinic agonist ▶Nicotinic receptors Venronium Neuromuscular blocking agent ▶Nicotinic receptors Venlafaxine Selective noradrenaline, Serotonine reuptake inhibitor ▶Antidepressants (SSRNI) ▶Neurotransmitter transporters 1484 List of Established Drugs

List of Established Drugs (Continued)

Drug Group/Class Link

Verapamil Phenylalkylamine ▶Calcium channel blockers ▶Voltage-dependent calcium channels Vidagliptine DPPIV inhibitor ▶Diabetes mellitus Vigabatrin Antiepileptic drug ▶Antiepileptic drugs Vinblastine Vinca alkaloid ▶Antineoplastic agents ▶Cytoskeleton Vincristine Vinca alkaloid ▶Antineoplastic agents ▶Cytoskeleton Vindesine Vinca alkaloid ▶Antineoplastic agents ▶Cytoskeleton Warfarin Coumarinderivative ▶Anticoagulants ▶Vitamin K Ximelagatran Thrombin inhibitor ▶Anticoagulants Xipamide Thiazide ▶Diuretics Xylometazoline Alpha-adrenergic antagonist ▶Alpha-adrenergic system Yohimbine Alpha-adrenergic antagonist ▶Alpha-adrenergic system Leukotriene receptor antagonist ▶Leukotrienes Zalcitabine Reverse transcriptase inhibitor ▶Antiviral agents Zaleplon Sedative ▶GABAergic system Zanamivir Neuraminidase inhibitor ▶Antiviral drugs Zaprinast PDE-inhibitor ▶Phosphodiesterases Ziconotide Analgetic ▶Calcium channel blocker Zidovudine Reverse transcriptase inhibitor ▶Antiviral agents 5-Lipoxygenase inhibitor ▶Leukotrienes Ziprasidone Atypical neuroleptic ▶Antipsychotic drugs Zoledronate Biphosphonate ▶Bone metabolism Zolmitriptan Serotonin receptor agonist ▶Serotoninergic system Zolpidem Sedative ▶GABAergic system Zopiclone Sedative ▶GABAergic system List of Entries

Essays are shown in blue

2DE Adipokines 14-3-3σ A Kinase Anchoring Proteins (AKAPs) Adipose Tissue ABC-proteins Adrenal Gland ABC Transporters Adrenaline ABPs Adrenergic Receptor Absence Epilepsy α-Adrenergic Receptors Absorption α-Adrenergic System Abstinence Syndrome β-Adrenergic System Abused Drugs Adrenoceptor Acadesine β-Adrenoceptor System ACE Inhibitors α-Adrenoceptors ACE2 Adrenomedullin Acetyl β-methylcholinesterase Adverse/Unwanted Reactions Acetylcholine Affective Disorders Acetylcholine Hydrolase Affinity Acetylcholinesterase Age-related Macular Degeneration (AMD) Acetylthiocholinesterase Agonist Acetyltransferase Agouti-related Protein (AgRP) N-Acetyltransferases Ah Receptor α1-Acid Glycoprotein AIDS Acidosis Airway Hyperresponsiveness ACPD Airway Surface Liquid ACTH AKAPs Actin AKT Actin Binding Proteins Alcohol Actin Filaments Alcohol Dehydrogenase Action Potential Aldehyde Dehydrogenase Activated Partial Thromboplastin Time Aldosterone Activator Protein-1 Aldosterone Receptor Active Site AlF4– Active Transport Alkaloid Active Transporters Alkylating Agents Activins Alkylation Acute Phase Reactants Allele Acyl-CoA Allergen Acyl-CoA Synthetase Allergy Adaptive Immunity Allodynia Adaptor Proteins Alloimmunity Addiction Allostatic State Addison's Disease Allosteric Modulators Additive Interaction Allylamines Adenosine ALS Adenosine Receptors Adenoviruses Alzheimer’s Disease Adenylate Cyclase Ames Test Adenylyl Cyclases Amiloride ADH Amiloride-sensitive Na+ Channel ADHD γ-Aminobutyric Acid (GABA) Adhesion Molecules Aminoglycosides Adipocyte Aminopeptidase Adipocytokines AMP, Cyclic 1486 List of Entries

AMP-activated Protein Kinase Anticoagulants AMPA Receptors Anticonvulsants Amphetamine Antidepressant Drugs Amphipathic Antidiabetic Drugs AMPK Antidiabetic Drugs other than Insulin Amyloid Antidiarrhoeal Agents Aβ Amyloid Antidiuretic Hormone Amyloid Precursor Protein Antidysrhythmic Drugs Amyotrophic Lateral Sclerosis (ALS) Anti-emetic Drugs Anabolic Steroids Antiepileptic Drugs Anaesthetics Antiestrogen Analeptics Antifibrinolytic Drugs Analgesia Antifungal Drugs Analgesics Antigen Analogous Proteins Antigen Presentation Anandamide Antigen-presenting Cells Anaphase Promoting Complex (APC) Antigen Receptors Anaphylactic Shock Anti-gout Drugs Anchoring Protein Antihistamines Andersen's Syndrome Antihypertensive Drugs Androgen Anti-inflammatory Drugs Androgen Receptor Anti-integrins Anemia, Macrocytic Hyperchromic Antimalarial Drugs Angel Dust Antimetabolic Agents Angina Pectoris Antimetabolites Angiogenesis and Vascular Antimicrobial Agents Angioplasty Antimode Antimycotic Drugs Angiotensin Converting Enzyme Antineoplastic Agents Angiotensin Converting Enzyme-2 (ACE2) Anti-obesity Drugs Angiotensin II Receptor-like 1 Antioncogene Angiotensin Receptors Angiotensinogen Antiparasitic Drugs Anion Exchange Resin Anti-Parkinson Drugs Ankyrin Repeat αα-2 Antiplasmin Antiplatelet Drugs Anomalous Rectifiers Antiprogestins Anorexigenic Antiproliferative Agents Antacids Antiprotozoal Drugs Antagonist Antipsychotic Drugs Anterograde Amnesia Antipyretic Agents Anthelminthic Drugs Antiretroviral Agents Anthracyclins Antirheumatoid Drugs Anthraquinones Antisense DNA Antiarrhythmic Drugs Antisense Oligonucleotides Antiarrhythmic Drugs Class I Antithyroid Drugs Antiarrhythmic Drugs Class II Antitrypanosomal Drugs Antiarrhythmic Drugs Class III Antituberculosis Drugs Antiarrhythmic Drugs Class IV Antitumor Drugs Antibiotic Resistance Antitussive Drugs Antibiotics Antiviral Drugs Antibodies Anxiety Antibodies to Cyclic-citrullinated Anxiolytics (Anti-CCPs) APCs Antibody-dependent Cellular Cytotoxicity (ADCC) Apelins and the Anticancer Drugs Apical Membrane List of Entries 1487

APJ Receptor Autoreactive Lymphocytes Autoreceptor Apoptosis Autosomal Dominant Hypocalcemia (ADH) Apoptotic Executioner Apoptotic Initiator Caspases Axon Appetite Axon Reflex Appetite Control Axonal Guidance Aptamers Axonal Membrane aPTT Azole Aquaporins B-Leukotriene Aquaretic Agents B Lymphocyte Arachidonic Acid BAC Area Postrema Back Propagation Area under the Curve Bacterial Toxins L-Arginine Bacteriophage Arginine Vasopressin Barbiturates Aromatase Baroreceptor Reflex Aromatase Inhibitor β Barrel Arousal Bartter’s Syndrome Array Basal Activity Arrestins Basal Ganglia Arrhythmias Basement Membrane Arrhythmogenic Right Ventricular Dysplasia/ Basophils Cardiomyopathy Bax Arteriogenesis Bazedoxifene Arteriosclerosis Bcl-2 Arylhydrocarbon Receptor Bcl-x L-Ascorbic Acid BCR-ABL Fusion Protein ASF Family of Transporters BCRP Asn-linked BDNF ASON Behavioral State Aspartyl Proteinases Benign Familial Neonatal Convulsions Aspirin Benzoapyrene Aspirin-like Drugs, Benzodiazepine Receptor Agonists Asthma Benzodiazepines Astrocytes Benzothiazepines Atherogenesis Benzoylcholinesterase Beri-Beri Atherosclerotic Plaques BH Domain Atopy Biased Agonism ATP Bicuculline ATP-binding Cassette Transporter Superfamily BID ATP-dependent K+ Channels Biguanide ATP-powered Pump Bile Acids ATP-regulated K+ Channel Bile Salts ATP-sensitive K+ Channel Bimodal Distribution Atrial Fibrillation Bioavailability Atrial Natriuretic Peptide Biochip Attention Deficit Hyperactivity Disorder Biocomputing AUC Biogenic Amines Autacoid Autoantigen Biological Medicines Autocrine Biological Therapeutics Autoimmune Disease Biologicals Autonomic Nervous System Biologics Autophagy Biomarker 1488 List of Entries

Biopterin Calcilytics Biotin Calcimimetics BiP Calcineurin Bipolar Disorder Calcitonin Bisphosphonates Calcitonin Gene Related Peptide Bistability Calmodulin Bisubstrate Analogs BKCa Channel Blastocyst cAMP β-Blockers cAMP-GEFs Blood–brain Barrier Camptothecins Blood Clotting Cancer, Molecular Mechanisms of Therapy Blood Pressure Control Cannabinoid Receptors Blood Pressure Lowering Drugs Cannabinoids Blood Products Cannabis BMPs Capsaicin Body Mass Index (BMI) Capsaicin-sensitive Primary Afferent Neurons Bombesin-like Peptides Capsid Bone Metabolism CaR Bone Morphogenetic Proteins Carbon Monoxide Botulinum Toxin Carbon Oxide Botulism Carbonic Anhydrase Bradykinesia Carboxypeptidase Bradykinin Brain Derived Neurotrophic Factor Cardiac Glycosides Brain Natriuretic Peptide Cardiac IK1 Cariporide Bremelanotide Carotinoids Bronchial Asthma CART Btk Caspases Butyrophenones Cataplexy Catecholaminergic Polymorphic Ventricular C2 Domain Tachycardia (CPVT) C Kinase Catecholamines C-reactive Protein Catechol-O-Methyltransferase Ca2+-ATPase Ca2+-binding Proteins Cationic Proteins Ca2+ Channel Causalgia Ca2+ Channel Antagonists Caveolae Ca2+ Channel Blockers CCK Ca2+-dependent Adhesion Protein Plakoglobin CD26 Ca2+-dependent Cysteine Proteases CDK Ca2+-induced Ca2+ Release CDR Ca2+ Receptor β-cell Ca2+ Release Channel Cell Adhesion Molecules Ca2+-sensing Receptor Cell-cycle Arrest Ca2+ Sparks Cell Cycle Checkpoints Ca2+ Spikes Cell Cycle Control Ca2+ Transient Cell Division Cycle Ca2+ Waves Cell Multiplication Cachexia Cell Proliferation Cachexin Cellular Immmunity Cadherins Central Core Disease (CCD) Cadherins/Catenins Central Diabetes Insipidus cADP-ribose Central Tolerance Calbindins Centrosome List of Entries 1489

Cephalosporins CO CFTR Coactivator and Corepressors cGMP Coagulation/Thrombosis cGMP Kinase Coatomer cGMP-regulated Phosphodiesterases Cocaine- and Amphetamine-regulated Transcript CGRP (CART) Chagas Disease Co-chaperone Channelopathies Co-dominant Chaperones Coenzyme Q10 ChE Cogenital Nephrogenic Diabetes Insipidus Cheese Reaction Collagen Chemical Chaperone Colony-stimulating Factors Chemical Library Combinatorial Chemistry Chemical Neurotransmission Compartment Chemoattractant Receptors Competitive Antagonists Chemokine Receptors Chemokines Complement-type Repeat Chemoreceptor Trigger Zone Complex Disease Chemotaxis Compound Libraries Chemotherapy Compound Optimization Cholecystokinin Computational Biology Cholegraphic Contrast Agents Computerized Tomography Cholera Toxin COMT Cholesterol Conditioned Place Preference Cholesteryl Ester Transfer Protein (CETP) Conditioned Withdrawal Cholinergic Transmission Conditioning Cholinesterase Congenital Long QT Syndrome Cholinesterase Inhibitor Conjugative Plasmids Chorionic Gonadotropin Conjugative Transposon Choroideremia Conotoxins Chromatin Contact Inhibition Chromosomal Translocations Contraceptives Chromosome Segregation Contraction/Contracture Contrast Media Chronic Bronchitis Convulsant Drugs Chronic Obstructive Pulmonary Disease Convulsions Chylomicron Factor Chylomicron Remnants COPI Vesicle Chymase COPII Vesicle Chymotrypsin-like Proteinases Coregulators Circadian Clock Co- Circadian Rhythms Cortico-medullary Solute Gradient Circumventricular Organs Corticosteroids Cl– Channels and Cl–/H+ Exchangers Corticosterone Clathrin Corticotropin Clathrin-coated Pits Corticotropin Releasing Hormone Clathrin-coated Vesicle Co-stimulation CLC Costimulatory Molecules Clearance Cotransmission Clinical Trials Cough Clock Coumarins Clonal Selection COX-1 Clostridial Neurotoxins COX-2 Clostridium Botulinum Toxin COXIBs Clotting CpG Dinucleotide Motif CNTF CRAC Channels 1490 List of Entries

Crack Cytotoxic Agents Craving Cytotoxic T-cells CREB Danaparoid (Heparinoid) Cre/loxP Databank CRH Database Crk (Chicken Tumor Virus Regulator Kinase) and Death Receptors Cromones Death Domain Superfamily Cross-packaging Defensins Cross Talk Delayed-rectifier K+ Channels Cross Tolerance Delayed Type Hypersensitivity Reaction Crosslinks Dendritic Cells CSFs Dependence CTLs Depolarisation Curare Depolarization-induced Ca2+ Release Current-voltage Relationship (I-V) Depression Cushing’s Syndrome Dermatomycoses Cyclic Adenosine Monophosphate (Cyclic AMP; Dermatophytes cAMP) Descending Inhibitory Pathway Cyclic AMP- and Cylic GMP-dependent Protein Desensitised State Kinases Desensitization Cyclic AMP-binding Guanine Nucleotide Exchange Desmoplakin Factors Deubiquitinating Enzymes (DUBs) Cyclic-AMP Response Element Binding Protein Dexamethasone Cyclic GMP-dependent Protein Kinase DHPR Cyclic GMP-regulated Phosphodiesterases Diabesity Cyclic Guanosine Monophosphate (Cyclic GMP; Diabetes Insipidus cGMP) Diabetes Mellitus Cyclic Nucleotide-binding Domain Diacylglycerol Cyclic Nucleotide Phosphodiesterases Cyclic Nucleotide-regulated Cation Channels DICR Cyclic Nucleotides Differential Display Cyclin Differentiation Factors Cyclin-dependent Kinases Digitalis Cyclooxygenase-2 (Expression in the Kidney) Cyclooxygenases Dihydropyridine Receptor Cyclosporin A (R)-(+)-N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl-β- Cysteine Endopeptidases alanine) Cysteine Proteinases L-Dihydroxyphenylalanine Cysteinyl Leukotriene 4-Dihydroxyphenylethylamine Cystic Fibrosis Dimeric Transcription Factors Cytochalasins Dioxins Cytochrome P450 Dipeptidase Cytochrome P450 2C9 Dipeptidylpeptidase Cytochrome P450 2C19 Dipeptidylpeptidase IV Cytochrome P450 2D6 Direct Thrombin Inhibitors Cytochrome P450 Induction Discharge of Neurons Cytochrome P450 Isozymes Disease-modifying Anti-rheumatic Drugs (DMARDs) Cytochrome P450 Mono- Dissociation Constant Cytokeratin Dissociative Anesthetic Cytokine Receptors Distribution of Drugs Cytokines Diuretics Cytokinesis DNA Fragmentation Cytomegalovirus CMV DNA Methylation Cytoplasmic Tyrosine Kinases DNA Replication Cytoskeleton DNA Response Elements Cytostatic Drugs DNA Vaccination and Genetic Vaccination List of Entries 1491

Docking Protein Emesis Domain Emphysema L-DOPA/Levodopa ENaC Dopa Decarboxylase N-End Rule Dopamine System Endocannabinoids Dopamine-β-hydroxylase Endocytosis Dopaminergic Neurotoxicity Endogenous Antipyresis Dose Endogenous Opioid Peptides Dose-response Curves Endometriosis Double Stranded RNA Endopeptidase Downregulation Endoplasmic Reticulum (ER) Drotrecogin α (Recombinant Human Activated Endorphins Protein C) Endosome Drug Abuse Endothelial Cells Drug Addiction/Dependence (EL) Drug Discovery Endothelial Nitric Oxide Synthase (eNOS) Drug–Drug Interaction Endothelin Converting Enzyme Drug Efficacy Endothelins Drug Interactions Endothelium Endothelium-derived Relaxing Factor (EDRF) Drug Receptor Theory Endotoxin Drug Reinforcement Energy Balance Drug–Receptor Interaction Enkephalin Dubin–Johnson Syndrome Entamoeba Histolytica Dynamic Programming Envelope (Viral) Dyskinesias Eosinophil Dyslipidemia Epacs Dysrhythmias Eph Receptor Tyrosine Kinase E3 EC50 (EGF) ECE Epidermal Growth Factor (EGF) Receptor Family Ecogenetics Epidermal Growth Factor Receptor 2 (ErbB2) Ecstasy Epidural (Space) Ectodermin Epilepsy Ectonucleotidase Epinephrine ED50 Episodic Ataxia/Myokymia Edema Episome Edg Receptors Epithelial Ca2+ Channel EEG Epithelial Mesenchymal Transition (EMT) EF-hand Epithelial Na+ Channel Effector Epitope Efferent Function of Sensory Nerves EPS Efficacy EPSP EGF ER ER/Golgi Intermediate Compartment (ERGIC) Elastase-like Proteinases ERAD Electrochemical Driving Force ErbB Receptor Family Electroencephalogram (EEG) Erectile Dysfunction Electromyogram (EMG) ERGIC Electro-oculogram (EOG) Ergot Alkaloids Electrophilic ERT Electrospray Ionization Mass Spectrometry (ESI-MS) Erythropoietin Elimination Half-life ESI-MS Elimination of Drugs EST EM-800 Estrogen Receptor Embryonic Liver Fodrin (ELF) Estrogen Replacement Therapy (ERT) 1492 List of Entries

Estrogens Follicle-stimulating Hormone (FSH, Follitrophin) Ethanol Force Fields/Molecular Mechanics Ethyl Alcohol Forskolin Euglycaemia FoxO1a Eukaryotic Expression Cassette Frizzled Excitability Frontal Cortex Excitation–contraction Coupling FSH Excitatory Amino Acids Functional Genomics Excitotoxicity Functional Magnetic Resonance Imaging (fMRI) Exenatide Fungi Exocytosis Fungicidal Effect Exogenous Pyrogens Fungistasis Exon Funicular Myelitis Furin Exportins Furin-like Protease Extended Amygdala Fyn Extracellular Calcium-sensing Receptor (CaSR) FYVE Domain Extracellular Matrix (ECM) Fz Receptors Extrapyramidal Side Effects G-actin Extrasynaptic Receptors G-Proteins F-actin GABA Fab Fragments GABAA Receptors Factor IIa GABAB Receptors FAD GABAergic System Familial Alzheimer's Disease Gaddum Familial Hypocalciuric Hypercalcemia (FHH) Galanin Fanconi-Bickel Syndrome Galanin Receptors Farnesyl Inhibitors (FTIs) Galanin-like Peptide (GALP) FAS Ligand (FasL) GAPs FAT10 Gasotransmitters Fatty Acid Transporters Gastric H,K-ATPase Favism Gastric Inhibitory Peptide (GIP) Fc Receptor Gastrin Fever Gastrin Releasing Peptide Fibrates Gastroesophageal Reflux Disease (GERD) A-fibres Gating Fibrin G-CSF Fibrinogen GDIs Fibrinolytics GEFs Fibroblast Growth Factors Gene Activity Profile Filamin Gene Array First-order Kinetics Gene Chip First-pass (Presystemic) Metabolism Analysis FK506 Gene Gun FKBP12 Gene Products Flare Gene Promoter Flavin Adenine Dinucleotide (FAD) Gene Therapy Flavin Mononucleotide (FMN) Gene-therapy Vectors Flp/FRT Gene Transfer Fluorescence in situ Hybridization (FISH) Gene Transfer Mechanisms (Bacteria) Fluoride General Anaesthetics Fluoroquinolones General Transcription Factors FMN Genetic Polymorphism Foam Cells Genome-wide Association Study (GWA Study) Folate Genomics Folic Acid Genotype List of Entries 1493

Gephyrin G-protein-coupled Receptor Kinases (GRKs) GERD G-protein-coupled Receptors GH G-proteins and Wnt Signaling Ghrelin Granulocyte-CSF (G-CSF) Giardia lamblia Granulocyte-macrophage-CSF (GM-CSF) GIP Graves' Disease GIRK Grb-2 Gitelman’s Syndrome GRKs Glial Cells Growth Glibenclamide Growth Factors Glomerular Filtration Rate Growth Hormone GLP-1 Growth Hormone Release-inhibiting Factor Glucagon GSK3 Glucagon-like Peptide-1 (GLP-1) GTPase Activating Proteins (GAPs) GTPases Glucocorticoid Resistance Guanine Nucleotide Dissociation Inhibitors (GDIs) Glucocorticoids Guanine Nucleotide Exchange Factors (GEFs) Glucocorticoids, Inhalable Guanylyl Cyclase Glucocorticosteroids Gyrase Gluco-mineralocorticoid Receptors Haemostasis Half-life/Elimination Half-life (t1/2 or t1/2β) Glucose Transport Facilitators (GLUT) Hamartoma Syndromes Glucose Transporters Haplotype Glucose/Galactose Malabsorption (GGM) Hashish α-Glucosidase HCN GLUT HCV GLUT2 HDL GLUT4 Heat Shock Protein (HSP) Glutamate Glutamate Receptors Helicobacter Pylori γ-Glutamyl-transpeptidase Helix Bundle Glycine Helix-loop-helix Motif Glycine Receptors Helper T Cells Glycogen Synthase Kinase 3 Hemangioblast Glycopeptide Antibiotics Hematopoiesis Glycoprotein IIb/IIIa Receptor Antagonists Hematopoietic Growth Factors Glycoproteins Heme Glycosaminoglycan Hemodialysis Glycosides, Cardiac Hemofiltration Glycosylation Hemostasis Glycosylphosphatidyinositol Anchor (GPI Anchor) Hemozoin Glycylcyclines Heparin Sulfate Proteoglycans Glypiation GM-CSF Hepatitis GM2-gangliosidosis Hepatitis C GMP, Cyclic Heptahelical Domain GnRH Heptahelical Receptors Gold Compounds HERG-channels Golgi Apparatus Heterologous Desensitization Gonadorelin Heterologous Expression System Gonadotropin-releasing Factor/Hormone (GnRH) Heterotrimeric G-Proteins Gonadotropins Hidden Markov Model Gout High-density Lipoprotein (HDL) GPCRs High-throughput Screening GPI Anchor High-voltage-activated Ca2+Channels GPR30 Hill Analysis 1494 List of Entries

Hippocampus Hypoaldosteronism Hirudin Hypocretins Histamine Hypoglycaemia Histamine and Emesis Hypogonadotropic Hypogonadism Histaminergic System Hypokalemia Histone Hypomethylating Agents Histone Acetyl Transferases (HAT) Hyposensitization Histone Hypotension Histone Deacetylases Hypothalamus Histone Methylation Hypothalamus–Pituitary–Adrenal (HPA) Axis Histone Phosphorylation Hypothyroidism Histone Tails Hypoxia HIV IC50 Values HMG Box Idiopathic Hypercalciuria HMG CoA-Reductase Idiosyncratic Reactions HMG-CoA-Reductase Inhibitors IGF Homologous Desensitization IKK Complex (IKK Family) Homologous Proteins IKr Homologous Recombination Imidazoline Receptor Homology Modeling Immediate Early Genes Hormonal Contraceptives Immune Complexes Hormone Replacement Therapy (HRT) Immune Defense HPA Axis Immune System HRT Immunity Hsp Immunoglobulins (Immunoglobulin Superfamily) Hsp70 Immunomodulators HSV Immunophillins 5-HT Immunosuppressive Agents Human Leucocyte Antigens (HLA) IMPDH Humanized Monoclonal Antibodies Humoral Immunity In Silico Biology HVA Ca2+ Channels Inclusion Cell Disease Hybridization Incretin Hormones 6-Hydroxydopamine Inducible (Immunological) Nitric Oxide Synthase Hydroxypyridones (iNOS) 11β-Hydroxysteroid Dehydrogenase Type II Inflammation 5-Hydroxytryptamine (5HT) Inflammatory Caspases Hyoscine (Scopolamine) Inflammatory Disorders Hyperactivity Disorder Influenza Hyperaldosteronism Infrared Spectroscopy Hyperalgesia Innate Immunity Hypercholesterolemia Inorganic Phosphate Transporters iNOS Hyperglycaemia Inositol Hyperinsulinemic Hypoglycemia of Infancy (HI) Inositol 1,4,5-trisphosphate Receptors Hyperkalemia Insomnia Hyperlipidaemia/Hyperlipoproteinaemia Insulin Hyperplasia Insulin Desensitization Hyperpolarization-activated and Cyclic Nucleotide- Insulin Receptor gated Channels (HCN) Insulin Resistance Hyperpyrexia Insulin Secretagogues Hypersensitivity Insulin-like Growth Factor Hypertension Integrase Hyperthyroidism Integrin, α 4β 1 Hyperuricemia Integrin, α 4β 7 Hypnotic Integrin, α IIbβ 3 List of Entries 1495

Integrin, α vβ 3 K+ Homeostasis Integrin, α vβ 5 koff Integrins Kainate Receptor Integron , Lysyl-Bradykinin Interactions Kallikrein Interfacial Inhibitors KCNQ-Channels Interferon Stimulated Gene 15 KCOs Interferons KDEL Receptor Interleukin-1 (IL-1) KELL Blood Group Antigen Interleukin-2 (IL-2) Ki Values Interleukin-4 (IL-4) Kinase Interleukin-5 (IL-5) Kinase Domain Kinase Inhibitors Intermediate Filaments Intermediate-density Lipoprotein (IDL) Kir Channels Intermittent Claudication Knockout Mice Internalization Kringle Domains International Normalized Ratio (INR) K+-Sparing Diuretics Intima Kvβ -Subunits Intracellular Transport Kv-Channels Intrathecal Application KvLQT1-Channels Intrathecal Space Kynurenine Pathway Intrinsic Efficacy L-NAME Intron β-Lactam Antibiotics Inverse Agonist β-Lactamases Inward Rectification Lateral Hypothalamic Area Inward Rectifier K+ Channels Laxatives Iodide LCAT Iodine LD50 Ion Channels LDL-Cholesterol Ionic Contrast Media LDL-Receptors Ionotropic Glutamate Receptors Lead Ionotropic Receptors (Channel-linked) Lead Discovery by NMR IP3 Receptors Lecithin-Cholesterol Acyltransferase IPC Leonardo IPSP (Inhibitory Postsynaptic Potential) Leptin IRAG Lethal Dose IRAK Family Leucin Zipper Iron Chelator Leukotrienes Irreversible Antagonists Levodopa Irritable Bowel Syndrome (IBS) Lewy Bodies Isaacs’ Syndrome LH-RH Agonist Ischemic Preconditioning (IPC) Liddle's Syndrome Ischemic Stroke Ligand Isopeptide Bond Ligand-Gated Ion Channels Isoprenoid Limbic System Isoprenylation Linkage Disequilibrium (LD) ITAM Lipid-lowering Drugs Itch JAK-STAT Pathway Lipid Modifications JNKs Lipid Phosphate Phosphohydrolases KATP Channel Lipid Rafts KNDP Channel Lipid Transfer Proteins K+ Channel Openers Lipidation K Channels Lipopolysaccharide KD Lipoprotein Lipase 1496 List of Entries

Lipoprotein Metabolism Maturity-Onset Diabetes of the Young (MODY) Lipoproteins MCH Liposomes MCR 5-Lipoxygenase MDMA Lipoxygenases MDR-ABC Transporters Lithocholic Acid Mechanism-based Inhibition Local Anaesthetics Meglitinide-related Compounds Locus Melanin-concentrating Hormone Locus Ceruleus Melanocortins Long-Chain Fatty Acids Melanocyte-stimulating Hormone Long-QT Syndromes Melatonin Long-Term Depression Membrane Signal Transduction Long-Term Potentiation Membrane Transport Protein Loop Diuretics Menaquinones-n Low-density-lipoprotein-cholesterol Ménière's Disease Low-density Lipoprotein Receptor Gene Family Mesangial Cells Low-density Lipoprotein Receptor-related Proteins Mesolimbic System/Reward System Low Molecular Mass GTPases Metabolic Syndrome Low Voltage-activated (LVA) Ca2+ Channels Metabotropic Glutamate Receptors LPL LPS Metalloprote(in)ases LRP Methicillin-resistant Staphylococci LRP5 and LRP6 N-Methyl D-aspartate Receptors LTD Methylating Agents LTP 3,4-Methylenedioxymeth-Amphetamine Luteinizing Hormone 2-Methyl-6-(phenylethynyl) Pyridine Lymphangiogenesis 1-Methyl-4-Phenylpyridium Lymphocytes 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Methylxanthines Acetylation of Histones MHC Lysipressin MIC Lysolipid Mediators Michaelis–Menten Kinetics Lysophosphatidic Acid Microarray Lysophosphatidylcholine Microarray Hybridization Lysophospholipids Microarray Technology Lysosphingolipids and Lysoglycerophospholipids Microbial Resistance to Drugs M-Channels Microfilaments Macrolides Microtubule Macrophage Microtubule Associated Proteins Macula Densa Mineralcorticoids Major Histocompatibility Complex (MHC) Mineralocorticoid Receptor (MR) Malaria Minimal Inhibitory Concentration Malignant Hyperthermia (MH) MinK Malignant MirP Subunits Malignant Tumor Mitochondrial Permeability Transition Pore Mannose 6-Phosphate Receptor Mitogen MAO Mitogen-activated Protein Kinase MAP Mitosis MAP Kinase Cascades Mixed Agonists/Antagonists MAPK Mixed Function Oxygenase Marijuana MLCK Marimastat MLCP Mast Cells MMPs Matrix Metalloproteinases Molecular Cancer Therapeutics Matrix-assisted Laser Desorption/Ionization Mass Molecular Dynamics Spectrometry Molecular Dynamics Simulation List of Entries 1497

Molecular Modeling NANC Transmission/Mediators Molecular Simulation Narcolepsy Monoamine Oxidases Narcotics Monoamine Oxidases and their Inhibitors Natriuretic Drugs Monoclonal Antibody Natriuretic Peptides Monocytes Natural Killer Cells Nausea Monophasic Preparations NCX Monoxide NDP-dependent K+ Channel Mood Disorders Necrosis Mood Elevators NEP Mood-stabilising Drugs Nephrogenic Diabetes Insipidus Morbus Alzheimer Neprilysin Morphogens Nerve Growth Factor Morpholines Neuraminidase Inhibitors Motilin Neuraxis Motion Sickness Neuregulin Motor Proteins Neurodegeneration MPEP Neurokinin A MPP+ Neuroleptic-like Malignant Syndrome MPTP Neuroleptics mRNA Neuromedin B MRP MS/MS Neuromedin U mTOR, replaces FRAP, RAFT, RAPT or SEP in Neuromodulators mammals Neuromuscular Blocking Agents Mucolipin Neuromuscular Junction Multidrug Resistance Neuronal Cell Death Multidrug Resistance Gene Neuronal Cell Deterioration Multiple Sclerosis Neuronal Nitric Oxide Synthase Muscarinic Acetylcholine Receptors Neuronal Secretion Muscarinic Receptors Neuropathic Pain Muscle Relaxants Neuropeptide FF Muscle Type Nicotinic Receptors Neuropeptide Y Myasthenia Gravis Myelin Basic Protein Neuropilins Myelosuppression Neurosteroids Myocardial Infarction Neurotensin/Neuromedin N Myosin Light Chain Kinase Neurotransmitter Transporters Myosin Phosphatase (MLCP) Neurotransmitters Myotonia Myristoylation Neurotrophin N-Myristoylation Neutral Antagonist Na+/Ca2+ Antiporter Neutral Endopeptidase Na+/Ca2+ Exchanger Neutropenia Na+/Ca2+ Exchangers Neutrophils Na+ Channel NF-κB NaCl Cotransporter NF-IL6 Na+-dependent Glucose Cotransporter NFAT Family of Transcription Factors Na+-dependent Glucose Cotransporter NGF Na+/H+ Exchangers NHE Na+- and K+ activated Adenosine 5′-Triphosphatase Na+/K+-ATPase Nicotinic Acetylcholine Receptor Na+ K+ 2Cl– Cotransporter Nicotinic Receptors Na+-Proton Exchanger Nigrostriatal Tract/Pathway NADPH-diaphorase Nitrates 1498 List of Entries

Nitrergic Nerve Nucleic Acid Vaccination Nitrergic Transmission Nucleophilic Nitric Oxide Nucleosome Nitric Oxide Synthase (NOS) Nucleus Accumbens N-nitro-L-arginine Methyl Ester Obesity Nitrogen Mustards OCT Nitrosourea Derivatives Oedema Nitrovasodilators Oestrogens NK Cells Off-resin Analysis NK Receptors (Neurokinins Receptors) Olfactory Epithelium NMDA Olfactory Receptors NMDA Receptor Oligonucleotide NMR Oligopeptidase NMR-Screening Omega Peptidase NO On-resin Analysis NO Donator Oncogenes NO Synthases Oncogenesis Nociceptin/Orphanin FQ Ontology Nociception Open Reading Frame Nociceptive Transducers Opiates Nociceptors Opioid Receptors Nodes of Ranvier σ-Opioid Receptors Non-adrenergic Non-cholinergic (NANC) Opioid Systems Transmission/Mediators Opium Non-competitive Antagonism Orai Proteins Non-competitive Inhibition Oral Anticoagulants Nonionic Contrast Media Oral Blood Glucose Lowering Drugs Non-neuronal Monoamine Transporters Oral Contraceptives Non-opioid Analgesics Oral Hypoglycaemic Agents Non-rapid Eye Movement (NREM) Sleep Orexigenic Nonreceptor Tyrosine Kinases Non-selective Cation Channels Organic Cations Non-selective Monoamine Reuptake Inhibitor Organic Nitrates Non-Specific ChE Organophosphates Non-steroidal Anti-inflammatory Drugs ORL-1 Non-steroidal Anti-rheumatic Drugs Orphan G-protein-coupled Receptors Non-viral Peptidases Orphan Nuclear Receptors Noradrenaline Transporter Orphan Receptors Norepinephrine/Noradrenalin Orphan Serpentine Receptors Normoglycaemia OrphaninFQ/Nociceptin NOS Osmotic Laxatives NPA Motif Osteoarthritis NPY Osteoblast NPY3-36 Osteoclast NSAIDs Osteocyte NSAR Osteoporosis NSF Osteotropic Hormones NSMRI Ototoxicity Ntn-Hydrolase Oxazolidinones Nuclear Factor Kappa B Oxidase, Mixed Function Nuclear Factor of Activated T Cells Cytosolic NFATc Nuclear Localization Signal Oxytocin Nuclear Pore Complex P1 Receptors Nuclear Receptor Regulation of Hepatic Cytochrome p53 P450 Enzymes p70S6 Kinase Nuclear Receptors P450 Induction List of Entries 1499

P450 Mono-oxygenase System Phagocyte/Phagocytosis P-type ATPase(s) Pharmacodynamics PACAP Pharmacogenetics PAF Pharmacogenomics PAG Pain and Nociception Pharmacological Barriers Pain Pharmacological Chaperone Palmitoylation Pharmacophore Modelling PAMPs Pharmocodynamic Tolerance Pancreatic β-cell Phase I and Phase II Metabolism Pancreatic Poylpeptide Phase Shift Phenothiazines Parasite Parasympathetic Nervous System Phenylalkylamines Parasympatholytics PHHI Parasympathomimetics PHLPP Parathyroid Hormone Phorbol Esters Paraventricular Nucleus Phosphatase Parkin Phosphate Transferring Enzyme Inhibitors Parkinson's Disease Phosphatidic Acid Partial Agonists Phosphatidylinositide Kinases Parvalbumin Phosphatidylinositol PAS Domain Phosphatidylinositol 4,5-bisphosphate Passive Diffusion Phosphatidylinositol 3-kinase Patch-Clamp Method Phosphatidylinositol Kinases PC: Proconvertase Phosphatidylinositol Phophate PCI Phosphatodylinositol PDE Phosphodiesterases PDGF Phosphoinositol Kinases PDZ Domain Phospholipases PEG Phospholipid Pellagra Phospholipid Kinases Pemphigus Blistering Disease Phospholipid Phosphatases Penicillin Phosphorylation Penicillin Binding Protein Phosphotyrosine-binding Domains Pentasaccharide Photoaging Peptide Mass Fingerprint Phthalate Esters Peptide YY Phylloquinones Peptidoglycans Physical Dependence Peptidyl Transferase Center PI Response Peptidyl-Dipeptidase PIAS PER1 PIAS Proteins Percutaneous Coronary Intervention PIC1 (PML Interacting Protein 1) Periaqueductal Grey Picornaviruses Pericytes Picrotoxin Peripheral Nerve PI3-Kinase Peripheral Neuropathy PIP Peroxisome Proliferator-Activated Receptors PIP2 Peroxynitrite Pituitary Adenylyl Cyclase-Activating Polypeptide Pertussis Toxin PKA PEST Sequences PKB/Akt PGI2 PKC P-Glycoprotein PKD2 PH Domain Placebo Effect PH-Sensing Receptors Placebo Response Phage Placenta Growth Factor 1500 List of Entries

Planar Cell Polarity Pathway Protein Folding Problem Plaque Protein Kinase Plasma Binding Protein Kinase A Plasma ChE Protein Kinase C Plasma Lipid Transfer Proteins Protein Kinase Inhibitors Plasmid Protein Phosphatases α2-Plasmin Inhibitor Protein Sorting Plasmin(ogen) Protein Trafficking and Quality Control Platelet-activating Factor Protein Transport Platelet Aggregation Inhibitors Protein Tyrosine Kinases Platelet-derived Growth Factor Receptor Proteinase-activated Receptors Platelet Inhibitors Proteinases Platelets 14-3-3 Proteins Platinum Complexes Proteolytic Enzymes Pleckstrin Homology Domain Proteome Plexins Proteomics PMF Proteosomal Degradation Polyamines Prothrombin Time Polyenes Protocadherins Polyethylene Glycol Protocidal Drugs Polymorphism Proton Pump Inhibitors and Acid Pump Polypeptide Chain Binding Proteins Antagonists POMC Proton-Sensing GPCRs Poor Metabolizer Phenotype Proto-oncogene Population Pharmacokinetics PRRs Positron Emission Tomography PSD-95 Post-translational Modification Pseudocholinesterase Potassium Channels Pseudogene Potassium Competitive Acid Blockers P-Site Ligands PP Psoralens PPAR Psychedelic Hallucinogen PPCs Psycho Energizers PR Psychomotor Stimulant Drugs Psychostimulants Preintegration Complex Psychotogenic Prenylation Psychotomimetic Drugs Prepro-opiomelanocortin PT Primary Hemostasis PTB Domain Primary Hyperparathyroidism PTEN Prodrug PTM Progesterone Receptor Pulmonary Emphysema Progestins Pulmonary Hypertension Programmed Cell Death Purinergic System Prolactin Purinoceptor PXR Propionylcholinesterase Pyknosis Prostacyclin Pyramidal Cell Prostaglandin H2 Synthase Pyrexia Prostaglandins Pyrogenic Cytokines Prostanoids PYY3–36 Protamine Sulfate QA/QC Control Metrics Protease-activated Receptors QT Prolongation Proteases Quantification of Drug Effect Proteasome Quantitative PCR Protein Degradation Quinolinic Acid Protein Folding Quinolones List of Entries 1501

RAAS Retinoblastoma (Rb) Gene Rab-GTPases Retinoic Acid Radiocontrast Agents Retinoic Acid Receptors Radioiodine Retinoid-resistance Radiomimetics Raf Retinoids RAGE Retinol Rapamycin Analogs Retinyl Esters Raphe Nuclei Retrograde Messenger Rapid Eye Movement Sleep Retroviruses Ras Protein Reuptake Transporter Raynaud's Phenomenon Reverse Complementary Oligonucleotides Rb Gene Reverse Mode Reactive Oxygen Species Reverse Pharmacology Rebound Insomnia Reverse Transcription Receptor for Advanced Glycation End Products Reward (Pathways) Receptor Occupancy Reye's Syndrome Receptor Protein RGS Protein Receptor Reserve Rhabdomyolysis Receptor Serine/Threonine Kinases Rheumatoid Arthritis Receptor Subtype Rheumatoid Factor Receptor Tyrosine Kinases Rho Receptors Rho-kinase Recombinant Protein Rectification Ribosomal Protein Synthesis Inhibitors 5α-Reductase Ribosome-targeting Antibiotics Reelin Ribozymes Reentrant Arrhythmia Rigidity Regulated Secretion RING Regulation of Gene Expression RNA Editing Regulation of Ingestive Behaviour RNA Interference (RNAi) – siRNA Regulation of mRNA Synthesis RNA Polymerase Regulation of Smooth Muscle Contractility RNA Polymerase III Promoter Regulators of G-protein Signalling RNA Polymerase Inhibitors Regulatory Myosin Light Chain II RNAi Regulatory Regions RNAses Regulatory T-cells RTK Reinstatement RT-PCR RXR Rel/NF-κB Rel Proteins Ryk/Derailed Relative Potency S6K1 Relaxin S-Prenylation REM Sleep S100 Proteins Renal Glucosuria S-Acylation Renin–Angiotensin–Aldosterone System S-adenosyl-L-methionine Repolarization Salicylate Resiniferatoxin SAM Resistance Plasmid SAR Respiratory Burst SARA Restenosis Resting Potential SAR-by-NMR Resting Tremor Sarcolemma Restless Leg Syndrome Sarcoplasmic Reticulum Retinal SARMs Retinitis Pigmentosa Saxitoxin 1502 List of Entries

Scaffold Single Nucleotide Polymorphism Scaffolding Proteins Sinus Rhythm Scatchard Plot siRNAs Scavenger Receptors Skeletal Metabolism/Turnover Schild Analysis Skinned Fiber Schizophrenia Skp1/Cul1/F-Box Protein Complex Second Messenger Sleep Secretase Sleep Apnea Secretory Pathway Sleep Continuity Sedatives Sleep (Onset) Latency Seizure Sleep Quality Selectins Sleep Stages Selective Androgen Receptor Modulator Sleeping Sickness (African) Selective Estrogen Receptor Downregulator Slow Wave Activity Selective Estrogen Receptor Modulators Slow Wave Sleep Selective Noradrenaline Reuptake Inhibitors Smad Selective Progesterone Receptors Modulators Small G Proteins Selective Serotonine Reuptake Inhibitors Small GTPases Selective Sex Steroid Receptor Modulators Smooth Muscle Tone Regulation Self Tolerance SMURF Sema Domain SNAPs Semaphorins SNARE Proteins Senescence SNF1 Complex Au2 (Fungi) Sensitization SNPs Sensory Nerves SNRIs Sentrin SOCS Septicemia SOD Sequence Contig Solid Phase Synthesis Sequence Profile Sequence-specific Transcription Factors Solute Carrier Sequential Preparations SERCA Somatostatin Serine-hydroxymethyltransferase Somatotropin Release Inhibitory Factor Serine Proteinases SOS Serine/Threonine Kinase Spermidine SERM Spermine Serotonin Sphingosine Kinases Serotoninergic System Sphingosine-1-phosphate Serpentine Receptors Sphingosylphosphorylcholine Serum Sickness Spike-ins Seven Transmembrane Helix Receptors Spindle Assembly Checkpoint Sex Steroid Receptors: Androgen Receptor, Estrogen Splice Variant Receptors, Progesterone Receptor Splicing SGLT Sporotrichosis SH2, Domains SPRM SH3 Domain SR Shaker-Channels Src Gene Shine-Dalgarno Interaction Src-homology 2 Domain SIADH Src-homology 3 Domain Sialic Acid Src Kinase Sialin SRP Signal Peptidases SSRIs Signal Recognition Particle SST14 Signal Transducer and Activator of Transcription SST28 Simple Diffusion STAT Simulated Annealing State-dependent Block List of Entries 1503

Statins T Cell Anergy Status Asthmaticus T Cell Antigen Receptor Steroid Receptors T Cell Receptors Steroids T-cells Sterol Transporters Tachykinins and their Receptors STIM Tachyphylaxis Stimulant Drugs Tacrolimus Store-operated Ca2+ Entry Tandem Mass Spectrometry Tardive Dyskinesia Stress Target of Rapamycin Encoded by: TOR1 and TOR2 Stress Proteins in Yeast Structural Bioinformatics Targeted Cancer Therapy Structural Genomics Taste Receptors Strychnine TATA Box STX Taxanes Substance K TCR Substance P TDM Substance Use Disorders Temporal Lobe Substantia Gelatinosa Tendinitis Substantia Nigra Teratogen Sulfonylurea Receptor Testosterone Sulfonylureas Tetanus Sulfotransferase Tethered Ligand SUMO Tetracycline SUMOylation Δ9-Tetrahydrocannabinol (THC) Superantigen 3′,5′,3,5-L-Tetraiodothyronine Supercoils Tetramer Superfamily Tetrodotoxin Superoxide TF Superoxide Dismutase Tg Suprachiasmatic Nucleus TGF-β Receptor Signaling Pathway Supraventricular Tachycardia TH SUR Thalamocortical Synchronisation Surrogate Ligand THC Susceptibility Therapeutic Drug Monitoring Swiss-Prot Thiamin SxxK Acyl Transferases Thiazide Diuretics SxxK Free-standing Penicillin-binding Protein Thiazolidinedione SxxK β-lactamases Thienopyridines SxxK PBP Fusions Thionamides Sympatholytic Drugs Thiopurine S-methyltransferase Sympathomimetic Drugs Thioxanthene Synapse Threading Synaptic Plasticity Thrifty Gene Hypothesis Synaptic Transmission Thrombin Synaptic Vesicle Neurotransmitter Transporters Thrombin Receptors Synaptic Vesicles Thrombocytopenia Synaptotagmin Thrombolysis Syndecans Thrombopoietin Synergistic Interaction Thrombosis Systems Biology Thromboxane Systolic and Diastolic Blood Pressure and Pulse Thrombus Pressure Thymoleptics t1/2 or t1/2β Thymus T3 Thyroglobuline T4 Thyroid Autonomy 1504 List of Entries

Thyroid Peroxidase Trimodal Distribution Thyrotoxicosis Tripeptidyl-peptidase Thyroxine Tropism TIMP Troponin TIR Domain TRP Channels Tissue Factor TRPM4 Tissue-specific Agonists/Antagonists TRPM7 Tissue-type Plasminogen Activator TRPM8 T- (Ile-Ser-Bradykinin) TRPV1 TKIs TRPV4 TLR TRPV5 and TRPV6 T-lymphocytes True ChE TNF Trypsin TNF Receptor Associated Factors Trypsin-like Proteinases TNF Receptor Superfamily TSH Receptor Tocolytics T-tubule Tolerance TTX Tolerance and Desensitization Tubulin Toll-like Receptors α and β Tubulin Tonic-clonic Convulsions Tumor Necrosis Factor Topoisomerase Tumor Suppressor Genes Topotecan TUNEL TOR Signalling Turing Machine Torsade de Pointes Twitch/Tetanus Total Sleep Time Two-dimensional Gel Electrophoresis Toxicogenomics Two Metal Sites Trace Amines L-Type Ca2+ Channel TRAF Type I Allergic Reaction Trafficking Type I Transmembrane Proteins Tranquilizers Type II Allergic Reaction Transactivation Type II Transmembrane Proteins Transcription Factor Type III Allergic Reaction Transcriptional Coactivators Type IV Allergic Reaction Transcriptional Regulation Typical Antipsychotic Drugs: Neuroleptic Drugs Transcriptome Tyrosine Hydroxylase Transcriptome Analysis Tyrosine Kinase Inhibitors Transduction Tyrosine Kinases Transfection Tyrosine Phosphatases Transforming Growth Factor-Beta Tyrosylprotein Kinase Transforming Oncogenes Tyrphostins Transgene Ubiquinone Transgenic Animal Models Ubiquitin-Dependent Protein Degradation Transient Receptor Potential Ubiquitin/Proteasome Transition State Ubl1 Translation Inhibitors UDP-Glucuronyl Transferase Translocon Ultrarapid Metabolizer Transmembrane Signaling Unstable Angina Transport ATPase Unwanted Effects Transporter UPR Transposon Uptake Transporter Transverse Tubule Urate Triazenes Urea Transporter Trichomonas Vaginalis Uric Acid Tricyclic Antidepressants Uricostatic Drug Triiodothyronine Uricosuric Drug 3′,5,3-L-Triiodothyronine List of Entries 1505

Urographic Contrast Agents Urokinase-Type Plasminogen Activator Vitamin K Urotensin VLCS Urticaria VLDL UT1 VMAT V-type ATPase Voltage-dependent Ca2+ Channels Vaccination Voltage-dependent Inactivation VAChT Voltage-dependent Na+ Channels Vacuolar-type Proton Translocating ATPase Voltage-gated K+ Channels Vanilloid Receptor Voltage-gated Na+ Channel Varizella Zoster Virus Voltage Sensor Vascular Endothelial Growth Factor Vomiting, Act of Vasoactive Intestinal Peptide von Willebrand Factor Vasoconstrictor vWf Vasodilator VZV Vasopeptidase Inhibitors Wall Peptidoglycan Inhibitors Vasopressin/Oxytocin Water Channel Vasorelaxant Watson-Crick Base Pairing Vav Weight-loss Therapies VEGF Wernicke's Syndrome/Encephalopathy Venus Flytrap Module Wheal Very Long-chain Acyl-CoA Synthetase Wheezing Very Low-density Lipoprotein Wingless Vesicle Withdrawal Vesicular Acetylcholine Transporter Wnt Signaling Vesicular Transporters Wnts and Development VFT Domain Wortmannin VGAT/VIAAT WW Domain VGLUT Xanthine Oxidase Vinca Alkaloids Xanthines VIP Xenobiotic VIPomas X-linked Nephrogenic Diabetes Insipidus Viral Proteases X-ray Contrast Agents Viral Vectors X-ray Contrast Agents and Molecular Imaging Virostatics Y-27632 Virus-like Particle YAC Zellweger Syndrome Vitamin B1 Zero-Order Kinetic Vitamin B2 ZES Vitamin B6 Zinc Finger Vitamin B12 Zollinger-Ellison Syndrome Zona Glomerulosa Vitamin D Zymogen