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Protein

Netrin receptor UNC5C

Gene

Unc5c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processApoptosis

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1095412 Unc5c

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

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.1 Publication

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...) 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 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 Expressed in 265 organ(s), highest expression level in ureter smooth muscle
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
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
InParanoidiO08747
KOiK07521
OMAiMHIEASN
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, 1 hit
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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PVI4E9PVI4_MOUSE
Netrin receptor UNC5C
Unc5c
876Annotation score:

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

Similar proteinsi

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
GeneTreeiENSGT00920000149006
HOGENOMiHOG000060306
HOVERGENiHBG056483
InParanoidiO08747
KOiK07521
OMAiMHIEASN
TreeFamiTF316767

Miscellaneous databases

ChiTaRSiUnc5c mouse
PROiPR:O08747
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000059921 Expressed in 265 organ(s), highest expression level in ureter smooth muscle
CleanExiMM_UNC5C
ExpressionAtlasiO08747 baseline and differential
GenevisibleiO08747 MM

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, 1 hit
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
ProtoNetiSearch...

Entry informationi

Entry nameiUNC5C_MOUSE
AccessioniPrimary (citable) accession number: O08747
Secondary accession number(s): Q8CD16
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: July 1, 1997
Last modified: September 12, 2018
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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