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Protein

Netrin receptor UNC5C

Gene

UNC5C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

  • netrin receptor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-HSA-418886. Netrin mediated repulsion signals.

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

HGNCiHGNC:12569. UNC5C.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Cell junctionsynapsesynaptosome By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini41 – 380340ExtracellularSequence analysisAdd
BLAST
Transmembranei381 – 40121HelicalSequence analysisAdd
BLAST
Topological domaini402 – 931530CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37206.

Polymorphism and mutation databases

BioMutaiUNC5C.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4040Sequence analysisAdd
BLAST
Chaini41 – 931891Netrin receptor UNC5CPRO_0000036075Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi83 ↔ 144By similarity
Disulfide bondi95 ↔ 142By similarity
Disulfide bondi188 ↔ 239By similarity
Glycosylationi236 – 2361N-linked (GlcNAc...)Sequence analysis
Disulfide bondi272 ↔ 309By similarity
Disulfide bondi276 ↔ 313By similarity
Disulfide bondi287 ↔ 299By similarity
Disulfide bondi328 ↔ 362By similarity
Disulfide bondi332 ↔ 367By similarity
Disulfide bondi340 ↔ 352By similarity
Glycosylationi361 – 3611N-linked (GlcNAc...)Sequence analysis
Modified residuei502 – 5021PhosphoserineBy similarity
Modified residuei568 – 5681PhosphotyrosineBy similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei415 – 4162Cleavage; by caspase-3By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO95185.
PRIDEiO95185.

PTM databases

PhosphoSiteiO95185.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO95185.
CleanExiHS_UNC5C.
ExpressionAtlasiO95185. baseline and differential.
GenevisibleiO95185. HS.

Organism-specific databases

HPAiCAB025086.
HPA012086.

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 interactions.
DIPiDIP-46276N.
IntActiO95185. 1 interaction.
STRINGi9606.ENSP00000406022.

Structurei

3D structure databases

ProteinModelPortaliO95185.
SMRiO95185. Positions 61-367, 528-928.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 15998Ig-likeAdd
BLAST
Domaini161 – 25696Ig-like C2-typeAdd
BLAST
Domaini260 – 31455TSP type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini316 – 36853TSP type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini528 – 634107ZU5PROSITE-ProRule annotationAdd
BLAST
Domaini850 – 92980DeathAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni694 – 71219Interaction with DCCBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the unc-5 family.Curated
Contains 1 death domain.Curated
Contains 2 TSP type-1 domains.PROSITE-ProRule annotation
Contains 1 ZU5 domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
GeneTreeiENSGT00840000129679.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO95185.
KOiK07521.
OMAiVRVYCLD.
OrthoDBiEOG7BGHJX.
PhylomeDBiO95185.
TreeFamiTF316767.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR000884. TSP1_rpt.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 1 hit.
SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
SM00218. ZU5. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48726. SSF48726. 2 hits.
SSF82895. SSF82895. 2 hits.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti219 – 2191T → I in AAH41156 (PubMed:15489334).Curated
Sequence conflicti489 – 4891T → S in AAC67491 (PubMed:9782087).Curated
Sequence conflicti651 – 6511Q → K in AAC67491 (PubMed:9782087).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti37 – 371G → V.
Corresponds to variant rs2306715 [ dbSNP | Ensembl ].
VAR_019731
Natural varianti721 – 7211M → T.1 Publication
Corresponds to variant rs2289043 [ dbSNP | Ensembl ].
VAR_019732
Natural varianti841 – 8411A → T.
Corresponds to variant rs34585936 [ dbSNP | Ensembl ].
VAR_055327

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei370 – 3701T → SFIYPISTEQRTQNEYGFSS in isoform 2. 1 PublicationVSP_011700
Alternative sequencei579 – 931353Missing in isoform 2. 1 PublicationVSP_011701Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliO95185.
SMRiO95185. Positions 61-367, 528-928.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114186. 4 interactions.
DIPiDIP-46276N.
IntActiO95185. 1 interaction.
STRINGi9606.ENSP00000406022.

PTM databases

PhosphoSiteiO95185.

Polymorphism and mutation databases

BioMutaiUNC5C.

Proteomic databases

PaxDbiO95185.
PRIDEiO95185.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8633.
GeneCardsiUNC5C.
H-InvDBHIX0024552.
HGNCiHGNC:12569. UNC5C.
HPAiCAB025086.
HPA012086.
MIMi603610. gene.
neXtProtiNX_O95185.
PharmGKBiPA37206.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
GeneTreeiENSGT00840000129679.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO95185.
KOiK07521.
OMAiVRVYCLD.
OrthoDBiEOG7BGHJX.
PhylomeDBiO95185.
TreeFamiTF316767.

Enzyme and pathway databases

ReactomeiR-HSA-418886. Netrin mediated repulsion signals.

Miscellaneous databases

ChiTaRSiUNC5C. human.
GeneWikiiUNC5C.
GenomeRNAii8633.
NextBioi32363.
PROiO95185.
SOURCEiSearch...

Gene expression databases

BgeeiO95185.
CleanExiHS_UNC5C.
ExpressionAtlasiO95185. baseline and differential.
GenevisibleiO95185. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR000884. TSP1_rpt.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 1 hit.
SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
SM00218. ZU5. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48726. SSF48726. 2 hits.
SSF82895. SSF82895. 2 hits.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and mapping of the UNC5C gene to human chromosome 4q21-q23."
    Ackerman S.L., Knowles B.B.
    Genomics 52:205-208(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT THR-721.
    Tissue: Brain.
  2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Lung.
  4. "The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment."
    Thiebault K., Mazelin L., Pays L., Llambi F., Joly M.-O., Scoazec J.-Y., Saurin J.-C., Romeo G., Mehlen P.
    Proc. Natl. Acad. Sci. U.S.A. 100:4173-4178(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOWN-REGULATION IN CANCER.

Entry informationi

Entry nameiUNC5C_HUMAN
AccessioniPrimary (citable) accession number: O95185
Secondary accession number(s): Q8IUT0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: May 5, 2009
Last modified: May 11, 2016
This is version 136 of the entry and version 2 of the sequence. [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

Miscellaneous

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.