Tables Index Receptor proteins 1337 Ligand-gated ion channels 1337 Receptors with intrinsic enzyme function 1339 Receptor tyrosine kinases (RTKs) 1339 Receptor serine/threonine kinases 1341 Receptor tyrosine phosphatases 1342 Receptor-linked guanylyl cyclases 1342 G-protein coupled receptors (GPCRs) 1343 Cytokine receptors (Jak/STAT-coupled) 1353 TNF receptor superfamily 1354 IL-1/toll-like receptors 1355 Other cell surface receptors 1356 Plexins 1356 LDL receptor family 1357 Nuclear receptors 1357 Membrane transport proteins 1359 Channel proteins 1359 Sodium-channels 1359 Potassium channels 1360 Voltage-dependent Ca2+-channels 1363 Chloride 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 ATPases (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 Integrins 1389 Selectins 1390 Syndecans 1391 Immunoglobulin superfamily 1391 1334 Enzymes 1393 Oxidoreductases 1393 Cyclooxygenases (EC 1.14.99.1) 1393 Lipoxygenases (EC 1.13.11.-) 1393 Nitric oxide synthases (NOS; EC 1.14.13.39) 1393 Cytochrome P450 monooxygenases (EC 1.14.-) 1394 Amino acid hydroxylases (NOS; EC 1.14.16.-) 1396 Transferases 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 (casein kinase 1) 1400 CMGC group (containing Cdk, MAPK, GSK3, Clk families) 1401 RGC group (Receptor Guanylyl Cyclases; Guanylyl Cyclases) 1402 STE Group (homologues of yeast Sterile-7, -11, -20 kinases; MAP kinase cascades) 1402 TKL group (Tyrosine kinase-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 Hydrolases 1413 GTPases 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 Phosphodiesterases (EC 3.1.4.17) 1424 Phospholipases 1425 Lyases 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 Aspartic acid peptidases 1433 Cysteine proteases 1434 Metallopeptidases 1437 Serine proteases 1442 Threonine peptidases 1447 Decarboxylases (EC 4.1.1.-) 1447 Isomerases 1448 Prostanoid synthases (EC 5.3.99.-) 1448 Transcription factors 1449 Superclass: basic domains 1449 Leucine zipper factots (bZIP) 1449 Helix-loop-helix factors (bHLH) 1450 Helix-loop-helix/leucine zipper factors (bHLH-ZIP) 1452 NF-1 1453 RF-X 1453 Helix-span-helix factors (bHSH) 1453 Zinc-coordinating DNA-binding domains 1453 Cys4 zinc finger 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 p53 1463 MADS-box 1463 TATA-binding-proteins 1464 HMG 1464 Heteromeric CCAAT factors 1464 Grainyhead 1464 Cold-shock domain factors 1465 Runt 1465 Other transcription 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 signal transduction 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 (enzymes, 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/ steroids), 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 cytoplasm 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 neurotransmitters. 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-, glycine- 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.