Supplementary Methods

Mutation and microdeletion screening by high resolution melting

High-throughput mutation screening of DIS3L2 exons 1-16 and HDAC4 was performed by Lightscanner high resolution melting analysis (Idaho Technology, Salt Lake City, UT). Exons 17-21 of DIS3L2 were not sequenced due to an apparent genomic duplication and consequent inability to uniquely amplify these exons. DNA samples were amplified using LightScanner mastermix under the manufacturer’s guidelines

(Idaho Technology). After PCR, samples were heated at 0.1°C/s in the Lightscanner instrument and fluorescence was collected from 60 to 95°C. Melting curves were analyzed using LightScanner software

(v2.0, Idaho Technology). Microdeletion screening across DIS3L2 was performed on paired normal- tumor samples using Lightscanner Lunaprobe SNP genotyping. Seven SNPs, ~60 Kb apart (rs2679184, rs12988522, rs4973500, rs3100586, rs3116179, rs923333 and rs2633254) were amplified in separate reactions and analyzed as above. Detailed conditions and primer/probe sequences are available on request. Variant amplicons were sequenced as described below. Direct sequencing was also performed for all exons where a common polymorphism might mask detection of a mutation by Lightscanner.

Samples with known LOH were analyzed entirely by direct sequencing, since Lightscanner detects altered melting profiles of DNA heteroduplexes and these cannot exist in hemizygous samples.

Sequencing of candidate genes

Direct sequencing of exons and flanking consensus splice signals was performed for DIS3L2, GIGYF2,

NPPC, HDAC4, TWIST2 and miR-562. PCR amplification was performed using HotStarTaq Mastermix and Q solution (Qiagen, Valencia, CA); all conditions and primers are available on request. PCR products were treated with shrimp alkaline phosphatase and exonuclease-I (New England Biolabs, Ipswich, MA) and sequenced using BigDye terminator chemistry on a 3730xl sequencer (Applied Biosystems, Foster

City, CA). Sequencing products were analyzed using Mutation Surveyor software (Softgenetics, State

College, PA).

Bisulfite sequencing of DIS3L2 promoter

Bisulfite sequencing of the DIS3L2 promoter CpG island (chr2:232,534,322-232,535,080, hg18 assembly) was performed only on tumors showing LOH across this region. Primers are available on request. DNA (1 μg) was bisulfite converted using the EpiTect Bisulfite kit (Qiagen) according to the manufacturer’s protocol. PCR amplification was carried out using HotStarTaq Mastermix and Q solution

(Qiagen, Valencia, CA). The resulting PCR products were cloned using the TOPO TA cloning system

(Invitrogen, Carlsbad, CA). Individual clones were miniprepped and sequenced using M13 reverse primer and BigDye terminator chemistry on a 3730xl sequencer (Applied Biosystems, Foster City, CA). The resulting sequences were aligned and analyzed using 4 Peaks (http://mekentosj.com) and MethTools

(http://genome.imb-jena.de/methtools/). Supplementary Table 1: Functional annotation from bioinformatics analysis of putative miR-562 targets miR-Target Gene Description Chr Expression in Association with renal cell Gene Kidney* processes/disease (Metacore pathway tool) Symbols ABCA1 ATP-binding cassette, sub-family 9 Overexpressed Renal nephritis A (ABC1), member 1

AGTR1 angiotensin II receptor, type 1 3 Overexpressed Renal atrophy, Renal fibrosis, Renal and urological disease, Renal system process

ALOX12 arachidonate 12-lipoxygenase 17 Not expressed Renal cell carcinoma

BCAM basal cell adhesion molecule 19 Not expressed Renal and urological system development and (Lutheran blood group) function C3AR1 complement component 3a 12 Under expressed Renal system process receptor 1

CASP1 caspase 1, apoptosis-related 11 Under expressed Renal necrosis, Renal and urological disease cysteine peptidase (interleukin 1, beta, convertase)

CCNE1 cyclin E1 19 Under expressed Renal cell carcinoma

CHRNB3 cholinergic receptor, nicotinic, 8 Not expressed Renal system process beta 3 COL4A3 collagen, type IV, alpha 3 2 Overexpressed Renal nephritis, Renal and urological disease, (Goodpasture antigen) Renal and urological system development and function

CTSL2 cathepsin L2 9 Overexpressed Renal and urological system development and function

CUL2 cullin 2 10 Overexpressed Renal cell carcinoma

DAB1 disabled homolog 1 (Drosophila) 1 Overexpressed Renal and urological disease

EFNB2 ephrin-B2 13 Overexpressed Renal cell carcinoma ESR1 estrogen receptor 1 6 Under expressed Renal nephritis, Renal and urological disease, Renal cell carcinoma

EYA1 eyes absent homolog 1 8 Under expressed Renal hypoplasia; overexpressed in Wilms (Drosophila) tumor

FGFR1 fibroblast growth factor receptor 8 Under expressed Renal and urological disease 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome)

GJA1 gap junction protein, alpha 1, 6 Under expressed Renal and urological system development and 43kDa function HES1 hairy and enhancer of split 1, 3 Under expressed Renal cell carcinoma (Drosophila)

KCNJ13 potassium inwardly-rectifying 2 Overexpressed Renal tubular transport, inborn errors channel, subfamily J, member 13

LAMA1 laminin, alpha 1 18 Overexpressed Renal degradation

MET met proto-oncogene (hepatocyte 7 Overexpressed Renal cell carcinoma; expressed in Wilms tumor growth factor receptor)

MUC1 mucin 1, cell surface associated 1 Under expressed Renal cell carcinoma

NFAT5 nuclear factor of activated T-cells 16 Overexpressed Renal hydronephrosis 5, tonicity-responsive NFATC3 nuclear factor of activated T- 16 Under expressed Renal hypertrophy cells, cytoplasmic, calcineurin- dependent 3

NFKB1 nuclear factor of kappa light 4 Overexpressed Renal inflammation, Renal cell carcinoma polypeptide gene enhancer in B- cells 1 (p105)

NPHS1 nephrosis 1, congenital, Finnish 19 Overexpressed Renal necrosis, Renal and urological disease; type (nephrin) An association of congenital nephrotic syndrome, Finnish type and human NPHS1 occurs (OMIM: 256300) P2RY11 purinergic receptor P2Y, G- 19 Expressed Renal system process protein coupled, 11

PCMT1 protein-L-isoaspartate (D- 6 Under expressed Renal cell carcinoma aspartate) O-methyltransferase PRKD2 protein kinase D2 19 Under expressed Renal cell carcinoma

PSEN1 presenilin 1 (Alzheimer disease 14 Under expressed Renal and urological system development and 3) function

PTGDS prostaglandin D2 synthase 9 Under expressed Renal and urological disease 21kDa (brain)

PTK2 PTK2 protein tyrosine kinase 2 8 Under expressed Renal cell carcinoma

RANBP9 RAN binding protein 9 6 Under expressed Renal and urological disease SLC7A9 solute carrier family 7 (cationic 19 Overexpressed Renal aminoaciduria; Renal tubular transport, amino acid transporter, y+ inborn errors system), member 9

TBXA2R thromboxane A2 receptor 19 Overexpressed Renal system process

TRPC6 transient receptor potential cation 11 Under expressed Renal and urological disease; An association of channel, subfamily C, member 6 focal segmental glomerulosclerosis and human TRPC6 occurs (OMIM: 603965)

UCHL1 ubiquitin carboxyl-terminal 4 Under expressed Renal cell carcinoma esterase L1 (ubiquitin thiolesterase)

*Expression information from WebGestalt, (http://bioinfo.vanderbilt.edu/webgestalt/). Expression is based on the data from the CGAP (Cancer Genome Anatomy Project) expressed sequence tag (EST) libraries and over/under-representation of individual genes in the tissue is evaluated by hypergeometric test. Gene Summary (NCBI RefSeq) Gene Ontology Annotations (http://www.geneontology.org/)

The membrane-associated protein encoded by this gene is a member of the superfamily ATP binding/ATPase activity/anion transporter of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules activity/nucleotide binding/protein binding/sterol transporter across extra- and intracellular membranes. ABC genes are divided into seven distinct activity/cholesterol metabolism/lipid metabolism/steroid subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a metabolism/transport/integral to plasma member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major membrane/membrane ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in this gene have been associated with Tangier's disease and familial high-density lipoprotein deficiency.

Angiotensin II is a potent vasopressor hormone and a primary regulator of aldosterone C-X-C chemokine receptor activity/angiotensin type II secretion. It is an important effector controlling blood pressure and volume in the receptor activity/bradykinin receptor activity/receptor cardiovascular system. It acts through at least two types of receptors. This gene encodes activity/rhodopsin-like receptor activity/G-protein signaling, the type 1 receptor which is thought to mediate the major cardiovascular effects of coupled to IP3 second messenger (phospholipase C angiotensin II. This gene may play a role in the generation of reperfusion arrhythmias activating)/circulation following restoration of blood flow to ischemic or infarcted myocardium.

Not available arachidonate 12-lipoxygenase activity/hepoxilin-epoxide hydrolase activity/iron ion binding/lipoxygenase activity/metal ion binding/oxidoreductase activity/potassium channel inhibitor activity/anti-apoptosis/arachidonic acid metabolism/c

Lutheran blood group glycoprotein is a member of the immunoglobulin superfamily and a transmembrane receptor activity/cell adhesion/signal receptor for the extracellular matrix protein, laminin. The protein contains five, N-terminus, transduction/cell surface/integral to plasma extracellular immunoglobulin domains, a single transmembrane domain, and a short, C- membrane/plasma membrane terminal cytoplasmic tail. This protein may play a role in epithelial cell cancer and in vaso- occlusion of red blood cells in sickle cell disease. Not available C3a anaphylatoxin receptor activity/complement component C3a receptor activity/phosphoinositide phospholipase C activity/receptor activity/rhodopsin-like receptor activity/G- protein coupled receptor protein signaling pathway/cell motility This gene encodes a protein which is a member of the cysteine-aspartic acid protease caspase activator activity/caspase activity/cysteine-type (caspase) family. Sequential activation of caspases plays a central role in the execution- peptidase activity/protein binding/signal transducer phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic activity/positive regulation of I-kappaB kinase/NF-kappaB processing at conserved aspartic residues to produce 2 subunits, large and small, that cascade/proteolysis/regulation of apoptosis/signal dimerize to form the active enzyme. This gene was identified by its ability to proteolytically transduction cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease.

The protein encoded by this gene belongs to the highly conserved cyclin family, whose androgen receptor binding/protein binding/transcription members are characterized by a dramatic periodicity in protein abundance through the cell coactivator activity/G1/S transition of mitotic cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct cycle/androgen receptor signaling pathway/cell cycle/cell expression and degradation patterns which contribute to the temporal coordination of each division/positive regulation of transcription, DNA- mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of dependent/regulation CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB.

Not available channel or pore class transporter activity/extracellular ligand- gated ion channel activity/ion channel activity/neurotransmitter receptor activity/nicotinic acetylcholine-activated cation-selective channel activity/ion transport/signal transducer Type IV collagen, the major structural component of basement membranes, is a extracellular matrix structural constituent/integrin multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 binding/metalloendopeptidase inhibitor activity/protein different genes, alpha 1 through alpha 6, each of which can form a triple helix structure binding/caspase activation/cell adhesion/cell proliferation/cell with 2 other subunits to form type IV collagen. This gene encodes alpha 3. In the surface receptor linked signal transduction/circulation Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein. A specific kinase phosphorylates amino acids in this same C-terminal region and the expression of this kinase is upregulated during pathogenesis. This gene is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to this syndrome are also located within the exons that encode this C-terminal region.

The protein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cathepsin L activity/proteolysis/lysosome cysteine proteinase that may play an important role in corneal physiology. This gene is expressed in colorectal and breast carcinomas but not in normal colon, mammary gland, or peritumoral tissues, suggesting a possible role for this gene in tumor processes.

Not available protein binding/G1/S transition of mitotic cell cycle/cell cycle/cell cycle arrest/induction of apoptosis by intracellular signals/negative regulation of cell proliferation/ubiquitin cycle

The laminar organization of multiple neuronal types in the cerebral cortex is required for cell differentiation/nervous system development normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related ephrin receptor binding/cell differentiation/cell-cell receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have signaling/morphogenesis/nervous system been implicated in mediating developmental events, especially in the nervous system and development/integral to plasma in erythropoiesis. Based on their structures and sequence relationships, ephrins are membrane/membrane/plasma membrane divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNB class ephrin which binds to the EPHB4 and EPHA3 receptors. This gene encodes an estrogen receptor, a ligand-activated transcription factor composed estrogen receptor activity/lipid binding/metal ion binding/nitric- of several domains important for hormone binding, DNA binding, and activation of oxide synthase regulator activity/protein binding/sequence- transcription. The protein localizes to the nucleus where it may form a homodimer or a specific DNA binding/steroid binding/steroid hormone heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual receptor activity/transcription factor activity/zinc ion binding development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded hydrolase activity/magnesium ion binding/phosphoprotein protein may play a role in the developing kidney, branchial arches, eye, and ear. Mutations phosphatase activity/protein tyrosine phosphatase of this gene have been associated with branchiootorenal dysplasia syndrome, branchiootic activity/development/metabolism/morphogenesis/regulation syndrome, and sporadic cases of congenital cataracts and ocular anterior segment of transcription, DNA-dependent/sensory perception of anomalies. A similar protein in mice can act as a transcriptional activator. sound/transcription

The protein encoded by this gene is a member of the fibroblast growth factor receptor ATP binding/fibroblast growth factor receptor activity/heparin (FGFR) family, where amino acid sequence is highly conserved between members and binding/nucleotide binding/protein binding/protein-tyrosine throughout evolution. FGFR family members differ from one another in their ligand kinase activity/receptor activity/transferase activity/MAPKKK affinities and tissue distribution. A full-length representative protein consists of an cascade/cell growth/fibroblast growth factor receptor extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome.

This gene is a member of the connexin gene family. The encoded protein is a component integral to plasma membrane/membrane/connexon channel of gap junctions, which are composed of arrays of intercellular channels that provide a activity/ion transporter activity/protein binding/signal route for the diffusion of low molecular weight materials from cell to cell. The encoded transducer activity/cell-cell signaling/gap junction protein is the major protein of gap junctions in the heart that are thought to have a crucial assembly/heart development/muscle contraction role in the synchronized contraction of the heart and in embryonic development. A related intronless pseudogene has been mapped to chromosome 5. Mutations in this gene have been associated with oculodentodigital dysplasia and heart malformations. This protein belongs to the basic helix-loop-helix family of transcription factors. It is a transcription regulator activity/nervous system transcriptional repressor of genes that require a bHLH protein for their transcription. development/regulation of transcription, DNA- dependent/nucleus/DNA binding Not available voltage-gated potassium channel complex/inward rectifier potassium channel activity/potassium ion binding/voltage- gated ion channel activity/ion transport/potassium ion transport/integral to membrane/membrane Not available extracellular matrix structural constituent/receptor binding/development/positive regulation of epithelial cell proliferation/regulation of cell adhesion/regulation of cell migration/regulation of embryonic development/basement membrane The proto-oncogene MET product is the hepatocyte growth factor receptor and encodes ATP binding/hepatocyte growth factor receptor tyrosine-kinase activity. The primary single chain precursor protein is post-translationally activity/nucleotide binding/protein binding/protein-tyrosine cleaved to produce the alpha and beta subunits, which are disulfide linked to form the kinase activity/receptor activity/transferase activity/cell mature receptor. Various mutations in the MET gene are associated with papillary renal proliferation/development/protein amino acid carcinoma. phosphorylation/signaling This gene is a member of the mucin family and encodes a membrane bound, glycosylated actin binding/hormone activity/cytoskeleton/extracellular phosphoprotein. The protein is anchored to the apical surface of many epithelia by a region/integral to membrane/integral to plasma transmembrane domain, with the degree of glycosylation varying with cell type. It also membrane/membrane includes a 20 aa variable number tandem repeat (VNTR) domain, with the number of repeats varying from 20 to 120 in different individuals. The protein serves a protective function by binding to pathogens and also functions in a cell signaling capacity. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. The product of this gene is a member of the nuclear factors of activated T cells family of RNA polymerase II transcription factor activity/protein transcription factors. Proteins belonging to this family play a central role in inducible gene binding/transcription factor activity/excretion/regulation of transcription during the immune response. This protein regulates gene expression induced transcription, DNA-dependent/signal by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, transduction/transcription from RNA polymerase II this protein exists as a homodimer and forms stable dimers with DNA elements. promoter/nucleus The product of this gene is a member of the nuclear factors of activated T cells DNA- transcription coactivator activity/transcription factor binding transcription complex. This complex consists of at least two components: a activity/inflammatory response/regulation of transcription preexisting cytosolic component that translocates to the nucleus upon T cell receptor from RNA polymerase II promoter/regulation of transcription, (TCR) stimulation and an inducible nuclear component. Other members of this family DNA-dependent/nucleus participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Not available protein binding/transcription factor activity/anti- apoptosis/antibacterial humoral response (sensu Vertebrata)/apoptosis/inflammatory response/positive regulation of transcription/regulation of transcription, DNA- dependent/signal transduction Nephrin is a kidney glomerular filtration barrier protein that is an essential component of protein binding/cell adhesion/excretion/integral to plasma the interpodocyte-spanning slit diaphragm. Mutations in the nephrin gene are associated membrane/membrane with congenital nephrotic syndrome.

The product of this gene belongs to the family of G-protein coupled receptors. This family purinergic nucleotide receptor activity, G-protein has several receptor subtypes with different pharmacological selectivity, which overlaps in coupled/receptor activity/rhodopsin-like receptor activity/G- some cases, for various adenosine and uridine nucleotides. This receptor is coupled to the protein signaling, coupled to IP3 second messenger stimulation of the phosphoinositide and adenylyl cyclase pathways and behaves as a (phospholipase C activating)/adenylate cyclase selective purinoceptor. Naturally occuring read-through transcripts, resulting from activation/defense response intergenic splicing between this gene and an immediately upstream gene (PPAN, encoding peter pan homolog), have been found. The PPAN-P2RY11 read-through mRNA is ubiquitously expressed and encodes a fusion protein that shares identity with each individual gene product. Three classes of protein carboxyl methyltransferases, distinguished by their methyl- methyltransferase activity/protein-L-isoaspartate (D- acceptor substrate specificity, have been found in prokaryotic and eukaryotic cells. The aspartate) O-methyltransferase activity/transferase type II enzyme catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to activity/protein amino acid methylation/protein the free carboxyl groups of D-aspartyl and L-isoaspartyl residues. These methyl-accepting modification/endoplasmic reticulum residues result from the spontaneous deamidation, isomerization, and racemization of normal L-aspartyl and L-asparaginyl residues and represent sites of covalent damage to aging proteins PCMT1 (EC 2.1.1.77) is a protein repair enzyme that initiates the conversion of abnormal D-aspartyl and L-isoaspartyl residues to the normal L-aspartyl form. The protein encoded by this gene belongs to the protein kinase D (PKD) family of ATP binding/diacylglycerol binding/metal ion serine/threonine protein kinases. This kinase can be activated by phorbol esters as well as binding/nucleotide binding/protein serine/threonine kinase by gastrin via the cholecystokinin B receptor (CCKBR) in gastric cancer cells. It can bind to activity/transferase activity/zinc ion binding/intracellular diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral signaling cascade/protein amino acid membrane protein exit from TGN. phosphorylation/intracellular Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in peptidase activity/protein binding/Notch receptor the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These processing/amyloid precursor protein catabolism/anti- disease-linked mutations result in increased production of the longer form of amyloid-beta apoptosis/apoptosis/cell adhesion/chromosome organization (main component of amyloid deposits found in AD brains). Presenilins are postulated to and biogenesis (sensu Eukaryota)/chromosome regulate APP processing through their effects on gamma-secretase, an enzyme that segregation/intracellular signal cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. The protein encoded by this gene is a glutathione-independent prostaglandin D synthase rough endoplasmic reticulum/binding/isomerase that catalyzes the conversion of prostaglandin H2 (PGH2) to postaglandin D2 (PGD2). activity/prostaglandin-D synthase activity/retinoid PGD2 functions as a neuromodulator as well as a trophic factor in the central nervous binding/transporter activity/fatty acid biosynthesis/lipid system. PGD2 is also involved in smooth muscle contraction/relaxation and is a potent metabolism/prostaglandin biosynthesis/regulation of inhibitor of platelet aggregation. This gene is preferentially expressed in brain. Studies with circadian sleep/wake cycle transgenic mice overexpressing this gene suggest that this gene may be also involved in the regulation of non-rapid eye movement sleep.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in ATP binding/SH2 domain binding/binding/nucleotide the focal adhesions that form between cells growing in the presence of extracellular matrix binding/protein binding/protein-tyrosine kinase constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine activity/transferase activity/integrin-mediated signaling kinases but lacks significant sequence similarity to kinases from other subfamilies. pathway/protein amino acid phosphorylation/cytoskeleton Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix.

This gene encodes a protein that binds RAN, a small GTP binding protein belonging to the protein binding/microtubule nucleation/nucleus RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The protein encoded by this gene has also been shown to interact with several other proteins, including met proto-oncogene, homeodomain interacting protein kinase 2, androgen receptor, and cyclin-dependent kinase 11. This gene encodes a protein that belongs to a family of light subunits of amino acid L-cystine transporter activity/amino acid-polyamine transporters. This protein plays a role in the high-affinity and sodium-independent transporter activity/neutral amino acid transporter transport of cystine and neutral and dibasic amino acids, and appears to function in the activity/peptide antigen binding/amino acid reabsorption of cystine in the kidney tubule. Mutations in this gene cause non-type I metabolism/neutral amino acid transport/protein complex cystinuria, a disease that leads to cystine stones in the urinary system due to impaired assembly/transport/integral to plas transport of cystine and dibasic amino acids. Not available Eicosanoid Metabolism/receptor activity/rhodopsin-like receptor activity/thromboxane A2 receptor activity/G-protein coupled receptor protein signaling pathway/muscle contraction/respiratory gaseous exchange/signal transduction/ The protein encoded by this gene forms a receptor-activated calcium channel in the cell calcium channel activity/calcium ion binding/ion channel membrane. The channel is activated by diacylglycerol and is thought to be under the activity/nonselective cation channel activity/calcium ion control of a phosphatidylinositol second messenger system. Activation of this channel transport/cation transport/integral to membrane/plasma occurs independently of protein kinase C and is not triggered by low levels of intracellular membrane calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). UCHL1 is a member of a gene family whose products hydrolyze small C-terminal adducts cysteine-type endopeptidase activity/ligase activity/omega of ubiquitin to generate the ubiquitin monomer. Expression of UCHL1 is highly specific to peptidase activity/ubiquitin binding/ubiquitin thiolesterase neurons and to cells of the diffuse neuroendocrine system and their tumors. It is present in activity/protein deubiquitination/ubiquitin-dependent protein all neurons. catabolism/cytoplasm/intracellular

*Expression information from WebGestalt, (http://bioinfo.vanderbilt.edu/webgestalt/). Expression is based on the data from the CGAP (Cancer Genome Anatomy Project) expressed sequence tag (EST) libraries and over/under-representation of individual genes in the tissue is evaluated by hypergeometric test. Location Protein Family

Plasma Membrane transporter

Plasma Membrane G-protein coupled receptor

Cytoplasm enzyme

Plasma Membrane transmembrane receptor Plasma Membrane G-protein coupled receptor

Cytoplasm peptidase

Nucleus transcription regulator

Plasma Membrane transmembrane receptor Extracellular Space structural

Cytoplasm peptidase

Nucleus enzyme

Cytoplasm signal transducer

Plasma Membrane receptor protein- tyrosine kinase Nucleus ligand-dependent nuclear receptor

Nucleus phosphatase

Plasma Membrane kinase

Plasma Membrane transporter Nucleus transcription regulator

Plasma Membrane ion channel

Extracellular Space Not available

Plasma Membrane kinase

Plasma Membrane phosphoprotein

Nucleus transcription regulator Nucleus transcription regulator

Nucleus transcription regulator

Plasma Membrane

Plasma Membrane G-protein coupled receptor

Cytoplasm enzyme Cytoplasm kinase

Plasma Membrane peptidase

Cytoplasm enzyme

Cytoplasm kinase

Nucleus Not available Plasma Membrane transporter

Plasma Membrane G-protein coupled receptor

Plasma Membrane ion channel

Cytoplasm peptidase

*Expression information from WebGestalt, (http://bioinfo.vanderbilt.edu/webgestalt/). Expression is based on the data from the CGAP (Cancer Genome Anatomy Project) expressed sequence tag (EST) libraries and over/under-representation of individual genes in the tissue is evaluated by hypergeometric test.