ID UNC5C_HUMAN Reviewed; 931 AA. AC O95185; Q8IUT0; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 12-SEP-2018, entry version 153. DE RecName: Full=Netrin receptor UNC5C; DE AltName: Full=Protein unc-5 homolog 3; DE AltName: Full=Protein unc-5 homolog C; DE Flags: Precursor; GN Name=UNC5C; Synonyms=UNC5H3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND RP VARIANT THR-721. RC TISSUE=Brain; RX PubMed=9782087; DOI=10.1006/geno.1998.5425; RA Ackerman S.L., Knowles B.B.; RT "Cloning and mapping of the UNC5C gene to human chromosome 4q21-q23."; RL Genomics 52:205-208(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP DOWN-REGULATION IN CANCER. RX PubMed=12655055; DOI=10.1073/pnas.0738063100; RA Thiebault K., Mazelin L., Pays L., Llambi F., Joly M.-O., RA Scoazec J.-Y., Saurin J.-C., Romeo G., Mehlen P.; RT "The netrin-1 receptors UNC5H are putative tumor suppressors RT controlling cell death commitment."; RL Proc. Natl. Acad. Sci. U.S.A. 100:4173-4178(2003). CC -!- FUNCTION: Receptor for netrin required for axon guidance. Mediates CC axon repulsion of neuronal growth cones in the developing nervous CC system upon ligand binding. Axon repulsion in growth cones may be CC caused by its association with DCC that may trigger signaling for CC repulsion. Also involved in corticospinal tract axon guidances CC independently of DCC. It also acts as a dependence receptor CC required for apoptosis induction when not associated with netrin CC ligand. {ECO:0000250|UniProtKB:O08747}. CC -!- SUBUNIT: Interacts with the cytoplasmic part of DCC. Interacts CC (tyrosine phosphorylated form) with PTPN11. Interacts (via CC extracellular domain) with FLRT3 (via extracellular domain) (By CC similarity). {ECO:0000250|UniProtKB:O08747}. CC -!- SUBCELLULAR LOCATION: Cell membrane CC {ECO:0000250|UniProtKB:O08747}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:O08747}. Cell junction, synapse, CC synaptosome {ECO:0000250|UniProtKB:Q761X5}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95185-1; Sequence=Displayed; CC Name=2; CC IsoId=O95185-2; Sequence=VSP_011700, VSP_011701; CC -!- TISSUE SPECIFICITY: Mainly expressed in brain. Also expressed in CC kidney. Not expressed in developing or adult lung. CC {ECO:0000269|PubMed:9782087}. CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The CC cleavage does not take place when the receptor is associated with CC netrin ligand. Its cleavage by caspases is required to induce CC apoptosis. {ECO:0000250|UniProtKB:Q761X5}. CC -!- PTM: Phosphorylated on different cytoplasmic tyrosine residues. CC Phosphorylation of Tyr-568 leads to an interaction with PTPN11 CC phosphatase, suggesting that its activity is regulated by CC phosphorylation/dephosphorylation. Tyrosine phosphorylation is CC netrin-dependent. {ECO:0000250|UniProtKB:O08747}. CC -!- MISCELLANEOUS: Down-regulated in multiple cancers including CC colorectal, breast, ovary, uterus, stomach, lung, or kidney CC cancers. {ECO:0000269|PubMed:12655055}. CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF055634; AAC67491.1; -; mRNA. DR EMBL; AC098584; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC105395; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC106881; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC041156; AAH41156.1; -; mRNA. DR CCDS; CCDS3643.1; -. [O95185-1] DR RefSeq; NP_003719.3; NM_003728.3. [O95185-1] DR UniGene; Hs.388565; -. DR ProteinModelPortal; O95185; -. DR SMR; O95185; -. DR BioGrid; 114186; 4. DR DIP; DIP-46276N; -. DR IntAct; O95185; 2. DR STRING; 9606.ENSP00000406022; -. DR iPTMnet; O95185; -. DR PhosphoSitePlus; O95185; -. DR BioMuta; UNC5C; -. DR PaxDb; O95185; -. DR PeptideAtlas; O95185; -. DR PRIDE; O95185; -. DR ProteomicsDB; 50694; -. DR ProteomicsDB; 50695; -. [O95185-2] DR Ensembl; ENST00000453304; ENSP00000406022; ENSG00000182168. [O95185-1] DR Ensembl; ENST00000506749; ENSP00000426153; ENSG00000182168. [O95185-2] DR GeneID; 8633; -. DR KEGG; hsa:8633; -. DR UCSC; uc003hto.4; human. [O95185-1] DR CTD; 8633; -. DR DisGeNET; 8633; -. DR EuPathDB; HostDB:ENSG00000182168.14; -. DR GeneCards; UNC5C; -. DR H-InvDB; HIX0024552; -. DR HGNC; HGNC:12569; UNC5C. DR MIM; 603610; gene. DR neXtProt; NX_O95185; -. DR OpenTargets; ENSG00000182168; -. DR PharmGKB; PA37206; -. DR eggNOG; KOG1480; Eukaryota. DR eggNOG; ENOG410XRS6; LUCA. DR GeneTree; ENSGT00920000149006; -. DR HOGENOM; HOG000060306; -. DR HOVERGEN; HBG056483; -. DR InParanoid; O95185; -. DR KO; K07521; -. DR OMA; MHIEASN; -. DR OrthoDB; EOG091G040Q; -. DR PhylomeDB; O95185; -. DR TreeFam; TF316767; -. DR Reactome; R-HSA-418886; Netrin mediated repulsion signals. DR SIGNOR; O95185; -. DR ChiTaRS; UNC5C; human. DR GeneWiki; UNC5C; -. DR GenomeRNAi; 8633; -. DR PRO; PR:O95185; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; ENSG00000182168; Expressed in 159 organ(s), highest expression level in lung. DR CleanEx; HS_UNC5C; -. DR ExpressionAtlas; O95185; baseline and differential. DR Genevisible; O95185; HS. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-KW. DR GO; GO:0005042; F:netrin receptor activity; TAS:ProtInc. DR GO; GO:0033564; P:anterior/posterior axon guidance; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0007411; P:axon guidance; TAS:ProtInc. DR GO; GO:0007420; P:brain development; TAS:ProtInc. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl. DR Gene3D; 2.20.100.10; -; 2. DR Gene3D; 2.60.40.10; -; 2. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR000884; TSP1_rpt. DR InterPro; IPR036383; TSP1_rpt_sf. DR InterPro; IPR037936; UNC5. DR InterPro; IPR033772; UPA. DR InterPro; IPR000906; ZU5_dom. DR PANTHER; PTHR12582; PTHR12582; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF07679; I-set; 1. DR Pfam; PF00090; TSP_1; 2. DR Pfam; PF17217; UPA; 1. DR Pfam; PF00791; ZU5; 1. DR SMART; SM00005; DEATH; 1. DR SMART; SM00409; IG; 1. DR SMART; SM00408; IGc2; 1. DR SMART; SM00209; TSP1; 2. DR SMART; SM00218; ZU5; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF48726; SSF48726; 2. DR SUPFAM; SSF82895; SSF82895; 2. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS50092; TSP1; 2. DR PROSITE; PS51145; ZU5; 1. PE 2: Evidence at transcript level; KW Alternative splicing; Apoptosis; Cell junction; Cell membrane; KW Complete proteome; Developmental protein; Disulfide bond; KW Glycoprotein; Immunoglobulin domain; Membrane; Phosphoprotein; KW Polymorphism; Receptor; Reference proteome; Repeat; Signal; Synapse; KW Synaptosome; Transmembrane; Transmembrane helix. FT SIGNAL 1 40 {ECO:0000255}. FT CHAIN 41 931 Netrin receptor UNC5C. FT /FTId=PRO_0000036075. FT TOPO_DOM 41 380 Extracellular. {ECO:0000255}. FT TRANSMEM 381 401 Helical. {ECO:0000255}. FT TOPO_DOM 402 931 Cytoplasmic. {ECO:0000255}. FT DOMAIN 62 159 Ig-like. FT DOMAIN 161 256 Ig-like C2-type. FT DOMAIN 260 314 TSP type-1 1. {ECO:0000255|PROSITE- FT ProRule:PRU00210}. FT DOMAIN 316 368 TSP type-1 2. {ECO:0000255|PROSITE- FT ProRule:PRU00210}. FT DOMAIN 530 673 ZU5. {ECO:0000255|PROSITE- FT ProRule:PRU00485}. FT DOMAIN 850 929 Death. FT REGION 694 712 Interaction with DCC. {ECO:0000250}. FT SITE 415 416 Cleavage; by caspase-3. FT {ECO:0000250|UniProtKB:Q761X5}. FT MOD_RES 502 502 Phosphoserine. FT {ECO:0000250|UniProtKB:O08747}. FT MOD_RES 568 568 Phosphotyrosine. FT {ECO:0000250|UniProtKB:O08747}. FT CARBOHYD 236 236 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 361 361 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 83 144 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 95 142 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 188 239 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 272 309 {ECO:0000250}. FT DISULFID 276 313 {ECO:0000250}. FT DISULFID 287 299 {ECO:0000250}. FT DISULFID 328 362 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 332 367 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 340 352 {ECO:0000250|UniProtKB:Q6ZN44}. FT VAR_SEQ 370 370 T -> SFIYPISTEQRTQNEYGFSS (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_011700. FT VAR_SEQ 579 931 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_011701. FT VARIANT 37 37 G -> V (in dbSNP:rs2306715). FT /FTId=VAR_019731. FT VARIANT 721 721 M -> T (in dbSNP:rs2289043). FT {ECO:0000269|PubMed:9782087}. FT /FTId=VAR_019732. FT VARIANT 841 841 A -> T (in dbSNP:rs34585936). FT /FTId=VAR_055327. FT CONFLICT 219 219 T -> I (in Ref. 3; AAH41156). FT {ECO:0000305}. FT CONFLICT 489 489 T -> S (in Ref. 1; AAC67491). FT {ECO:0000305}. FT CONFLICT 651 651 Q -> K (in Ref. 1; AAC67491). FT {ECO:0000305}. SQ SEQUENCE 931 AA; 103146 MW; 98A95995129532A7 CRC64; MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDDFFHELP ETFPSDPPEP LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV HQKDHIVDER VDETSGLIVR EVSIEISRQQ VEELFGPEDY WCQCVAWSSA GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL EQEVLLQCRP PEGIPVAEVE WLKNEDIIDP VEDRNFYITI DHNLIIKQAR LSDTANYTCV AKNIVAKRKS TTATVIVYVN GGWSTWTEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE GQSVQKIACT TLCPVDGRWT PWSKWSTCGT ECTHWRRREC TAPAPKNGGK DCDGLVLQSK NCTDGLCMQT APDSDDVALY VGIVIAVIVC LAISVVVALF VYRKNHRDFE SDIIDSSALN GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR GPVYALHDVS DKIPMTNSPI LDPLPNLKIK VYNTSGAVTP QDDLSEFTSK LSPQMTQSLL ENEALSLKNQ SLARQTDPSC TAFGSFNSLG GHLIVPNSGV SLLIPAGAIP QGRVYEMYVT VHRKETMRPP MDDSQTLLTP VVSCGPPGAL LTRPVVLTMH HCADPNTEDW KILLKNQAAQ GQWEDVVVVG EENFTTPCYI QLDAEACHIL TENLSTYALV GHSTTKAAAK RLKLAIFGPL CCSSLEYSIR VYCLDDTQDA LKEILHLERQ MGGQLLEEPK ALHFKGSTHN LRLSIHDIAH SLWKSKLLAK YQEIPFYHVW SGSQRNLHCT FTLERFSLNT VELVCKLCVR QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA NTITTVTGPS AFSIPLPIRQ KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y //