UNC5C_RAT
ID UNC5C_RAT Reviewed; 931 AA.
AC Q761X5;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 118.
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 {ECO:0000303|PubMed:15010202};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DISEASE.
RX PubMed=15010202; DOI=10.1016/j.molbrainres.2003.12.003;
RA Kuramoto T., Kuwamura M., Serikawa T.;
RT "Rat neurological mutations cerebellar vermis defect and hobble are caused
RT by mutations in the netrin-1 receptor gene Unc5h3.";
RL Brain Res. Mol. Brain Res. 122:103-108(2004).
RN [2]
RP FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=11387206; DOI=10.1093/emboj/20.11.2715;
RA Llambi F., Causeret F., Bloch-Gallego E., Mehlen P.;
RT "Netrin-1 acts as a survival factor via its receptors UNC5H and DCC.";
RL EMBO J. 20:2715-2722(2001).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=22405201; DOI=10.1016/j.neuron.2012.01.018;
RA O'Sullivan M.L., de Wit J., Savas J.N., Comoletti D., Otto-Hitt S.,
RA Yates J.R. III, Ghosh A.;
RT "FLRT proteins are endogenous latrophilin ligands and regulate excitatory
RT synapse development.";
RL Neuron 73:903-910(2012).
CC -!- FUNCTION: Receptor for netrin required for axon guidance (By
CC similarity). Mediates axon repulsion of neuronal growth cones in the
CC developing nervous system upon ligand binding (By similarity).
CC NTN1/Netrin-1 binding might cause dissociation of UNC5C from
CC polymerized TUBB3 in microtubules and thereby lead to increased
CC microtubule dynamics and axon repulsion (By similarity). Axon repulsion
CC in growth cones may also be caused by its association with DCC that may
CC trigger signaling for repulsion (By similarity). Might also collaborate
CC with DSCAM in NTN1-mediated axon repulsion independently of DCC (By
CC similarity). Also involved in corticospinal tract axon guidance
CC independently of DCC (By similarity). Involved in dorsal root ganglion
CC axon projection towards the spinal cord (By similarity). It also acts
CC as a dependence receptor required for apoptosis induction when not
CC associated with netrin ligand (PubMed:11387206).
CC {ECO:0000250|UniProtKB:O08747, ECO:0000250|UniProtKB:O95185,
CC ECO:0000269|PubMed:11387206}.
CC -!- SUBUNIT: Interacts with DCC (via cytoplasmic domain) (By similarity).
CC Interacts (tyrosine phosphorylated form) with PTPN11 (By similarity).
CC Interacts (via extracellular domain) with FLRT3 (via extracellular
CC domain) (By similarity). Interacts (via Ig-like C2-type domain) with
CC DSCAM (via extracellular domain) (By similarity). Interacts (via death
CC domain) with DAPK1 (By similarity). Interacts (via cytoplasmic domain)
CC with TUBB3; this interaction is decreased by NTN1/Netrin-1 (By
CC similarity). {ECO:0000250|UniProtKB:O08747,
CC ECO:0000250|UniProtKB:O95185}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O08747};
CC Single-pass type I membrane protein {ECO:0000255}. Cell surface
CC {ECO:0000250|UniProtKB:O95185}. Synapse, synaptosome
CC {ECO:0000269|PubMed:22405201}. Cell projection, axon
CC {ECO:0000250|UniProtKB:O08747}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:O08747}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:O08747}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:O08747}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:O08747}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level)
CC (PubMed:22405201). Mainly expressed in brain. Also expressed in kidney.
CC Not expressed in developing or adult lung.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The cleavage
CC does not take place when the receptor is associated with netrin ligand.
CC Its cleavage by caspases is required to induce apoptosis.
CC {ECO:0000269|PubMed:11387206}.
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 netrin-
CC dependent. {ECO:0000250|UniProtKB:O08747}.
CC -!- DISEASE: Note=Defects in Unc5c are the cause of cerebellar vermis
CC defect (cvd) and hobble (hob) phenotypes. Cvd and hob rats exhibit
CC cerebellar and midbrain defects, possibly as a result of abnormal
CC neuronal migration, and exhibit laminar structure abnormalities in the
CC fused cerebellar hemispheres and ectopic cerebellar tissues in the
CC cerebello-pontine junction. {ECO:0000269|PubMed:15010202}.
CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
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DR EMBL; AB118026; BAD05181.1; -; mRNA.
DR RefSeq; NP_955439.1; NM_199407.1.
DR AlphaFoldDB; Q761X5; -.
DR SMR; Q761X5; -.
DR STRING; 10116.ENSRNOP00000050380; -.
DR GlyGen; Q761X5; 2 sites.
DR iPTMnet; Q761X5; -.
DR PhosphoSitePlus; Q761X5; -.
DR jPOST; Q761X5; -.
DR PaxDb; Q761X5; -.
DR GeneID; 362049; -.
DR KEGG; rno:362049; -.
DR CTD; 8633; -.
DR RGD; 735109; Unc5c.
DR eggNOG; KOG1480; Eukaryota.
DR InParanoid; Q761X5; -.
DR OrthoDB; 334938at2759; -.
DR PhylomeDB; Q761X5; -.
DR PRO; PR:Q761X5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005042; F:netrin receptor activity; ISO:RGD.
DR GO; GO:0005043; F:netrin receptor activity involved in chemorepulsion; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0015631; F:tubulin binding; ISO:RGD.
DR GO; GO:0033564; P:anterior/posterior axon guidance; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0061643; P:chemorepulsion of axon; ISS:UniProtKB.
DR GO; GO:1990791; P:dorsal root ganglion development; ISS:UniProtKB.
DR GO; GO:0038007; P:netrin-activated signaling pathway; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030334; P:regulation of cell migration; ISO:RGD.
DR CDD; cd08799; Death_UNC5C; 1.
DR Gene3D; 1.10.533.10; -; 1.
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; IPR042154; Death_UNC5C.
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; 1.
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 1: Evidence at protein level;
KW Apoptosis; Cell membrane; Cell projection; Developmental protein;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Synapse;
KW Synaptosome; Transmembrane; Transmembrane helix.
FT SIGNAL 1..40
FT /evidence="ECO:0000255"
FT CHAIN 41..931
FT /note="Netrin receptor UNC5C"
FT /id="PRO_0000036077"
FT TOPO_DOM 41..380
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..931
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 62..159
FT /note="Ig-like"
FT DOMAIN 161..256
FT /note="Ig-like C2-type"
FT DOMAIN 260..314
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 316..368
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 530..673
FT /note="ZU5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 850..929
FT /note="Death"
FT REGION 402..931
FT /note="Required for netrin-mediated axon repulsion of
FT neuronal growth cones"
FT /evidence="ECO:0000250|UniProtKB:O08747"
FT REGION 694..712
FT /note="Interaction with DCC"
FT /evidence="ECO:0000250|UniProtKB:O08747"
FT SITE 415..416
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000305|PubMed:11387206"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 568
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O08747"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 83..144
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 95..142
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 188..239
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 272..309
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 276..313
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 287..299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 328..362
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 332..367
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 340..352
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
SQ SEQUENCE 931 AA; 103135 MW; 25B183A97BCB8401 CRC64;
MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDDFFHELP ETFPSDPPEP
LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV HQKDHVVDER VDETSGLIVR
EVSIEISRQQ VEELFGPEDY WCQCVAWSSA GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL
EQEVLLQCRP PEGIPMAEVE WLKNEDIIDP VEDRNFYITI DHNLIIKQAR LSDTANYTCV
AKNIVAKRKS TTATVIVYVN GGWSTWAEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE
GQSVQKIACT TLCPVDGRWT SWSKWSTCGT ECTHWRRREC TAPAPKNGGK DCDGLVLQSK
NCTDGLCMQA APDSDDVALY VGIVIAVTVC LAITVVVALF VYRKNHRDFE SNIIDSSALN
GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR GPVYALHDVS DKIPMTNSPI LDPLPNLKIK
VYNSSGAVTP QDDLAEFSSK LSPQMTQSLL ENEALNLKNQ SLARQTDPSC TAFGTFNSLG
GHLIIPNSGV SLLIPAGAIP QGRVYEMYVT VHRKENMRPP MEDSQTLLTP VVSCGPPGAL
LTRPVILTLH HCADPNTEDW KIQLKNQAVQ GQWEDVVVVG EENFTTPCYI QLDAEACHIL
TENLSTYALV GQSTTKAAAK RLKLAIFGPL CCSSLEYSIR VYCLDDTQDA LKEVLQLERQ
MGGQLLEEPK ALHFKGSIHN LRLSIHDITH SLWKSKLLAK YQEIPFYHIW SGSQRNLHCT
FTLERLSLNT VELVCKLCVR QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA STITTVTGPS
AFSIPLPIRQ KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN
FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y
