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Protein

Netrin receptor UNC5C

Gene

UNC5C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. Also involved in corticospinal tract axon guidances independently of DCC. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand.By similarity

Miscellaneous

Down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers.1 Publication

GO - Molecular functioni

  • netrin receptor activity Source: ProtInc

GO - Biological processi

  • anterior/posterior axon guidance Source: Ensembl
  • apoptotic process Source: UniProtKB-KW
  • axon guidance Source: ProtInc
  • brain development Source: ProtInc
  • positive regulation of apoptotic process Source: Ensembl
  • regulation of cell migration Source: Ensembl

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-418886 Netrin mediated repulsion signals
SIGNORiO95185

Names & Taxonomyi

Protein namesi
Recommended name:
Netrin receptor UNC5C
Alternative name(s):
Protein unc-5 homolog 3
Protein unc-5 homolog C
Gene namesi
Name:UNC5C
Synonyms:UNC5H3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000182168.14
HGNCiHGNC:12569 UNC5C
MIMi603610 gene
neXtProtiNX_O95185

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini41 – 380ExtracellularSequence analysisAdd BLAST340
Transmembranei381 – 401HelicalSequence analysisAdd BLAST21
Topological domaini402 – 931CytoplasmicSequence analysisAdd BLAST530

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi8633
OpenTargetsiENSG00000182168
PharmGKBiPA37206

Polymorphism and mutation databases

BioMutaiUNC5C

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 40Sequence analysisAdd BLAST40
ChainiPRO_000003607541 – 931Netrin receptor UNC5CAdd BLAST891

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi83 ↔ 144By similarity
Disulfide bondi95 ↔ 142By similarity
Disulfide bondi188 ↔ 239By similarity
Glycosylationi236N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi272 ↔ 309By similarity
Disulfide bondi276 ↔ 313By similarity
Disulfide bondi287 ↔ 299By similarity
Disulfide bondi328 ↔ 362By similarity
Disulfide bondi332 ↔ 367By similarity
Disulfide bondi340 ↔ 352By similarity
Glycosylationi361N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei502PhosphoserineBy similarity1
Modified residuei568PhosphotyrosineBy similarity1

Post-translational modificationi

Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis.By similarity
Phosphorylated on different cytoplasmic tyrosine residues. Phosphorylation of Tyr-568 leads to an interaction with PTPN11 phosphatase, suggesting that its activity is regulated by phosphorylation/dephosphorylation. Tyrosine phosphorylation is netrin-dependent.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei415 – 416Cleavage; by caspase-3By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO95185
PeptideAtlasiO95185
PRIDEiO95185
ProteomicsDBi50694
50695 [O95185-2]

PTM databases

iPTMnetiO95185
PhosphoSitePlusiO95185

Expressioni

Tissue specificityi

Mainly expressed in brain. Also expressed in kidney. Not expressed in developing or adult lung.1 Publication

Gene expression databases

BgeeiENSG00000182168
CleanExiHS_UNC5C
ExpressionAtlasiO95185 baseline and differential
GenevisibleiO95185 HS

Interactioni

Subunit structurei

Interacts with the cytoplasmic part of DCC. Interacts (tyrosine phosphorylated form) with PTPN11. Interacts (via extracellular domain) with FLRT3 (via extracellular domain) (By similarity).By similarity

Protein-protein interaction databases

BioGridi114186, 4 interactors
DIPiDIP-46276N
IntActiO95185, 2 interactors
STRINGi9606.ENSP00000406022

Structurei

3D structure databases

ProteinModelPortaliO95185
SMRiO95185
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 159Ig-likeAdd BLAST98
Domaini161 – 256Ig-like C2-typeAdd BLAST96
Domaini260 – 314TSP type-1 1PROSITE-ProRule annotationAdd BLAST55
Domaini316 – 368TSP type-1 2PROSITE-ProRule annotationAdd BLAST53
Domaini530 – 673ZU5PROSITE-ProRule annotationAdd BLAST144
Domaini850 – 929DeathAdd BLAST80

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni694 – 712Interaction with DCCBy similarityAdd BLAST19

Sequence similaritiesi

Belongs to the unc-5 family.Curated

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1480 Eukaryota
ENOG410XRS6 LUCA
GeneTreeiENSGT00920000149006
HOGENOMiHOG000060306
HOVERGENiHBG056483
InParanoidiO95185
KOiK07521
OMAiMHIEASN
OrthoDBiEOG091G040Q
PhylomeDBiO95185
TreeFamiTF316767

Family and domain databases

Gene3Di2.20.100.10, 2 hits
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
IPR037936 UNC5
IPR033772 UPA
IPR000906 ZU5_dom
PANTHERiPTHR12582 PTHR12582, 1 hit
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF07679 I-set, 1 hit
PF00090 TSP_1, 2 hits
PF17217 UPA, 1 hit
PF00791 ZU5, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00409 IG, 1 hit
SM00408 IGc2, 1 hit
SM00209 TSP1, 2 hits
SM00218 ZU5, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48726 SSF48726, 2 hits
SSF82895 SSF82895, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS50092 TSP1, 2 hits
PS51145 ZU5, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95185-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDDFFHELP
60 70 80 90 100
ETFPSDPPEP LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV
110 120 130 140 150
HQKDHIVDER VDETSGLIVR EVSIEISRQQ VEELFGPEDY WCQCVAWSSA
160 170 180 190 200
GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL EQEVLLQCRP PEGIPVAEVE
210 220 230 240 250
WLKNEDIIDP VEDRNFYITI DHNLIIKQAR LSDTANYTCV AKNIVAKRKS
260 270 280 290 300
TTATVIVYVN GGWSTWTEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE
310 320 330 340 350
GQSVQKIACT TLCPVDGRWT PWSKWSTCGT ECTHWRRREC TAPAPKNGGK
360 370 380 390 400
DCDGLVLQSK NCTDGLCMQT APDSDDVALY VGIVIAVIVC LAISVVVALF
410 420 430 440 450
VYRKNHRDFE SDIIDSSALN GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR
460 470 480 490 500
GPVYALHDVS DKIPMTNSPI LDPLPNLKIK VYNTSGAVTP QDDLSEFTSK
510 520 530 540 550
LSPQMTQSLL ENEALSLKNQ SLARQTDPSC TAFGSFNSLG GHLIVPNSGV
560 570 580 590 600
SLLIPAGAIP QGRVYEMYVT VHRKETMRPP MDDSQTLLTP VVSCGPPGAL
610 620 630 640 650
LTRPVVLTMH HCADPNTEDW KILLKNQAAQ GQWEDVVVVG EENFTTPCYI
660 670 680 690 700
QLDAEACHIL TENLSTYALV GHSTTKAAAK RLKLAIFGPL CCSSLEYSIR
710 720 730 740 750
VYCLDDTQDA LKEILHLERQ MGGQLLEEPK ALHFKGSTHN LRLSIHDIAH
760 770 780 790 800
SLWKSKLLAK YQEIPFYHVW SGSQRNLHCT FTLERFSLNT VELVCKLCVR
810 820 830 840 850
QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA NTITTVTGPS AFSIPLPIRQ
860 870 880 890 900
KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN
910 920 930
FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y
Length:931
Mass (Da):103,146
Last modified:May 5, 2009 - v2
Checksum:i98A95995129532A7
GO
Isoform 2 (identifier: O95185-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     370-370: T → SFIYPISTEQRTQNEYGFSS
     579-931: Missing.

Show »
Length:597
Mass (Da):66,079
Checksum:i994086225416B9A2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti219T → I in AAH41156 (PubMed:15489334).Curated1
Sequence conflicti489T → S in AAC67491 (PubMed:9782087).Curated1
Sequence conflicti651Q → K in AAC67491 (PubMed:9782087).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01973137G → V. Corresponds to variant dbSNP:rs2306715Ensembl.1
Natural variantiVAR_019732721M → T1 PublicationCorresponds to variant dbSNP:rs2289043Ensembl.1
Natural variantiVAR_055327841A → T. Corresponds to variant dbSNP:rs34585936Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011700370T → SFIYPISTEQRTQNEYGFSS in isoform 2. 1 Publication1
Alternative sequenceiVSP_011701579 – 931Missing in isoform 2. 1 PublicationAdd BLAST353

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF055634 mRNA Translation: AAC67491.1
AC098584 Genomic DNA No translation available.
AC105395 Genomic DNA No translation available.
AC106881 Genomic DNA No translation available.
BC041156 mRNA Translation: AAH41156.1
CCDSiCCDS3643.1 [O95185-1]
RefSeqiNP_003719.3, NM_003728.3 [O95185-1]
UniGeneiHs.388565

Genome annotation databases

EnsembliENST00000453304; ENSP00000406022; ENSG00000182168 [O95185-1]
ENST00000506749; ENSP00000426153; ENSG00000182168 [O95185-2]
GeneIDi8633
KEGGihsa:8633
UCSCiuc003hto.4 human [O95185-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUNC5C_HUMAN
AccessioniPrimary (citable) accession number: O95185
Secondary accession number(s): Q8IUT0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: May 5, 2009
Last modified: June 20, 2018
This is version 152 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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