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Protein

Netrin receptor UNC5C

Gene

Unc5c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 (PubMed:9126743, PubMed:9389662, PubMed:12451134). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity).By similarity3 Publications

GO - Molecular functioni

  • netrin receptor activity Source: MGI

GO - Biological processi

  • anterior/posterior axon guidance Source: MGI
  • apoptotic process Source: UniProtKB-KW
  • axon guidance Source: MGI
  • brain development Source: MGI
  • positive regulation of apoptotic process Source: MGI
  • regulation of cell migration Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-MMU-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
Rostral cerebellar malformation protein1 Publication
Gene namesi
Name:Unc5c
Synonyms:Rcm1 Publication, Unc5h31 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1095412. Unc5c.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • integral component of membrane Source: UniProtKB-KW
  • neuron projection Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
  • synapse Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Involvement in diseasei

Defects in Unc5c are the cause of rostral cerebellar malformation (Rcm). Rcm is characterized by cerebellar and midbrain defects, apparently as a result of abnormal neuronal migration.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi568Y → F: Abolishes interaction with PTPN11, leading to a increased level of phosphorylation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 40Sequence analysisAdd BLAST40
ChainiPRO_000003607641 – 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...)Sequence 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...)Sequence analysis1
Modified residuei502PhosphoserineCombined sources1
Modified residuei568Phosphotyrosine1 Publication1

Post-translational modificationi

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.1 Publication
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

Sites

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO08747.
PaxDbiO08747.
PRIDEiO08747.

PTM databases

iPTMnetiO08747.
PhosphoSitePlusiO08747.

Expressioni

Tissue specificityi

Mainly expressed in regions of differentiating neurons. Highly expressed in brain and lung. Weakly expressed in testis, ovary, spleen, thymus and bladder. Expressed at very low level in kidney, intestine and salivary gland.2 Publications

Gene expression databases

BgeeiENSMUSG00000059921.
CleanExiMM_UNC5C.
ExpressionAtlasiO08747. baseline and differential.
GenevisibleiO08747. MM.

Interactioni

Subunit structurei

Interacts with the cytoplasmic part of DCC (PubMed:10399920, PubMed:11533026). Interacts (tyrosine phosphorylated form) with PTPN11 (PubMed:11533026). Interacts (via extracellular domain) with FLRT3 (via extracellular domain) (PubMed:22405201).3 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000101843.

Structurei

3D structure databases

ProteinModelPortaliO08747.
SMRiO08747.
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
Domaini528 – 634ZU5PROSITE-ProRule annotationAdd BLAST107
Domaini850 – 929DeathAdd BLAST80

Region

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

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.
GeneTreeiENSGT00850000132260.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO08747.
KOiK07521.
OMAiVRVYCLD.
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.
IPR033772. UPA.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 1 hit.
PF17217. UPA. 1 hit.
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: O08747-1) [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 QDDEFFHELP
60 70 80 90 100
ETFPSDPPEP LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV
110 120 130 140 150
HQKDHVVDER VDETSGLIVR EVSIEISRQQ VEELFGPEDY WCQCVAWSSA
160 170 180 190 200
GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL EQEVLLQCRP PEGIPVAEVE
210 220 230 240 250
WLKNEDIIDP AEDRNFYITI DHNLIIKQAR LSDTANYTCV AKNIVAKRKS
260 270 280 290 300
TTATVIVYVN GGWSTWTEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE
310 320 330 340 350
GQSVQKIACT TLCPVDGRWT SWSKWSTCGT ECTHWRRREC TAPAPKNGGK
360 370 380 390 400
DCDGLVLQSK NCTDGLCMQA APDSDDVALY VGIVIAVTVC LAITVVVALF
410 420 430 440 450
VYRKNHRDFE SDIIDSSALN GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR
460 470 480 490 500
GPVYALHDVS DKIPMTNSPI LDPLPNLKIK VYNSSGAVTP QDDLAEFSSK
510 520 530 540 550
LSPQMTQSLL ENEALNLKNQ SLARQTDPSC TAFGTFNSLG GHLIIPNSGV
560 570 580 590 600
SLLIPAGAIP QGRVYEMYVT VHRKENMRPP MEDSQTLLTP VVSCGPPGAL
610 620 630 640 650
LTRPVILTLH HCADPSTEDW KIQLKNQAVQ GQWEDVVVVG EENFTTPCYI
660 670 680 690 700
QLDAEACHIL TENLSTYALV GQSTTKAAAK RLKLAIFGPL CCSSLEYSIR
710 720 730 740 750
VYCLDDTQDA LKEVLQLERQ MGGQLLEEPK ALHFKGSIHN LRLSIHDIAH
760 770 780 790 800
SLWKSKLLAK YQEIPFYHIW SGSQRNLHCT FTLERLSLNT VELVCKLCVR
810 820 830 840 850
QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA STITTVTGPS AFSIPLPIRQ
860 870 880 890 900
KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN
910 920 930
FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y
Length:931
Mass (Da):103,063
Last modified:July 1, 1997 - v1
Checksum:i8A5D951A4EECA179
GO
Isoform 2 (identifier: O08747-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     370-370: A → GFIYPISTEHRPQNEYGFSS

Show »
Length:950
Mass (Da):105,303
Checksum:i2074B4BCE6FEC603
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16L → I in BAC27495 (PubMed:16141072).Curated1
Sequence conflicti733H → R in BAC27495 (PubMed:16141072).Curated1
Sequence conflicti924S → Y in BAC27495 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011702370A → GFIYPISTEHRPQNEYGFSS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72634 mRNA. Translation: AAB54103.1.
AK031655 mRNA. Translation: BAC27495.1.
CCDSiCCDS17873.1. [O08747-1]
CCDS80034.1. [O08747-2]
RefSeqiNP_033498.1. NM_009472.4. [O08747-1]
UniGeneiMm.24430.

Genome annotation databases

EnsembliENSMUST00000075282; ENSMUSP00000074758; ENSMUSG00000059921. [O08747-2]
ENSMUST00000106236; ENSMUSP00000101843; ENSMUSG00000059921. [O08747-1]
ENSMUST00000142762; ENSMUSP00000118212; ENSMUSG00000059921. [O08747-2]
GeneIDi22253.
KEGGimmu:22253.
UCSCiuc008roe.2. mouse. [O08747-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72634 mRNA. Translation: AAB54103.1.
AK031655 mRNA. Translation: BAC27495.1.
CCDSiCCDS17873.1. [O08747-1]
CCDS80034.1. [O08747-2]
RefSeqiNP_033498.1. NM_009472.4. [O08747-1]
UniGeneiMm.24430.

3D structure databases

ProteinModelPortaliO08747.
SMRiO08747.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000101843.

PTM databases

iPTMnetiO08747.
PhosphoSitePlusiO08747.

Proteomic databases

MaxQBiO08747.
PaxDbiO08747.
PRIDEiO08747.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000075282; ENSMUSP00000074758; ENSMUSG00000059921. [O08747-2]
ENSMUST00000106236; ENSMUSP00000101843; ENSMUSG00000059921. [O08747-1]
ENSMUST00000142762; ENSMUSP00000118212; ENSMUSG00000059921. [O08747-2]
GeneIDi22253.
KEGGimmu:22253.
UCSCiuc008roe.2. mouse. [O08747-1]

Organism-specific databases

CTDi8633.
MGIiMGI:1095412. Unc5c.

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
GeneTreeiENSGT00850000132260.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO08747.
KOiK07521.
OMAiVRVYCLD.
TreeFamiTF316767.

Enzyme and pathway databases

ReactomeiR-MMU-418886. Netrin mediated repulsion signals.

Miscellaneous databases

ChiTaRSiUnc5c. mouse.
PROiO08747.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000059921.
CleanExiMM_UNC5C.
ExpressionAtlasiO08747. baseline and differential.
GenevisibleiO08747. MM.

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.
IPR033772. UPA.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 1 hit.
PF17217. UPA. 1 hit.
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...

Entry informationi

Entry nameiUNC5C_MOUSE
AccessioniPrimary (citable) accession number: O08747
Secondary accession number(s): Q8CD16
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: July 1, 1997
Last modified: November 30, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.