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Protein

Netrin receptor UNC5D

Gene

Unc5d

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for the netrin NTN4 that promotes neuronal cell survival (PubMed:21216843). Plays a role in cell-cell adhesion and cell guidance. Receptor for netrin involved in cell migration (By similarity). Plays a role in the regulation of neuronal cell migration in the developing brain via its interaction with FLRT2 (PubMed:21673655). Plays a role in axon guidance by mediating axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (PubMed:21673655). May play a role in apoptosis in response to DNA damage. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates cell-cell adhesion via its interaction with FLRT3 on an adjacent cell (PubMed:26235030).By similarityCurated3 Publications

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • axon guidance Source: MGI
  • cell-cell adhesion Source: MGI
  • pyramidal neuron differentiation Source: MGI
  • regulation of neuron migration Source: MGI
  • signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Apoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Netrin receptor UNC5D
Alternative name(s):
Protein unc-5 homolog 4
Protein unc-5 homolog D
Gene namesi
Name:Unc5d
Synonyms:Unc5h4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:2389364. Unc5d.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 382352ExtracellularSequence analysisAdd
BLAST
Transmembranei383 – 40321HelicalSequence analysisAdd
BLAST
Topological domaini404 – 956553CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice are viable, appear healthy, and do not display any obvious behavorial defects. Cortical neurons from mutant mice display impaired axon growth cone collapse in response to Flrt2 and a tendency towards accelerated radial migration in the developing brain.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030Sequence analysisAdd
BLAST
Chaini31 – 956926Netrin receptor UNC5DPRO_0000036080Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi73 ↔ 134By similarity
Disulfide bondi85 ↔ 132By similarity
Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence analysis
Disulfide bondi178 ↔ 229By similarity
Glycosylationi226 – 2261N-linked (GlcNAc...)Sequence analysis
Disulfide bondi262 ↔ 299By similarity
Disulfide bondi266 ↔ 303By similarity
Disulfide bondi277 ↔ 289By similarity
Disulfide bondi318 ↔ 352By similarity
Disulfide bondi322 ↔ 357By similarity
Disulfide bondi330 ↔ 342By similarity
Glycosylationi351 – 3511N-linked (GlcNAc...)Sequence analysis
Glycosylationi379 – 3791N-linked (GlcNAc...)Sequence analysis

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei419 – 4202Cleavage; by caspase-3Curated

Site

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei419 – 4202Cleavage; by caspase-3Curated

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ8K1S2.
PaxDbiQ8K1S2.
PRIDEiQ8K1S2.

PTM databases

PhosphoSiteiQ8K1S2.

Expressioni

Tissue specificityi

Detected in multipolar cells in the brain subventricular zone (at protein level) (PubMed:18547816). Detected in embryonic brain neocortex, especially in the subventricular zone (PubMed:21673655). Detected in multipolar cells in the brain subventricular zone (PubMed:18547816). Detected in brain neocortex from young pups, especially in the somatosensory cortex (PubMed:21216843). Expressed in developing limb and mammary gland (PubMed:12351186).4 Publications

Gene expression databases

BgeeiQ8K1S2.
CleanExiMM_UNC5D.
GenevisibleiQ8K1S2. MM.

Interactioni

Subunit structurei

Interacts (via extracellular domain) with FLRT2 and FLRT3 (via extracellular domain); the interaction is direct (PubMed:19492039, PubMed:21673655, PubMed:25374360, PubMed:26235030). Has higher affinity for FLRT2 (PubMed:25374360). Identified in a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself (PubMed:26235030).4 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000128521.

Structurei

3D structure databases

ProteinModelPortaliQ8K1S2.
SMRiQ8K1S2. Positions 50-362, 548-940.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini52 – 14998Ig-likeAdd
BLAST
Domaini151 – 24292Ig-like C2-typeAdd
BLAST
Domaini250 – 30455TSP type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini306 – 35853TSP type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini543 – 648106ZU5PROSITE-ProRule annotationAdd
BLAST
Domaini862 – 93978DeathAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni89 – 913Important for interaction with FLRT2By similarity

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.
GeneTreeiENSGT00820000127004.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ8K1S2.
KOiK07521.
OMAiINQGEPS.
OrthoDBiEOG7BGHJX.
PhylomeDBiQ8K1S2.
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.
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.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
[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]

Sequencei

Sequence statusi: Complete.

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

Q8K1S2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTGAADGSR GARRWLPWLG LFFWAAGAAA ARGADGSEIL PDSIPSAPGT
60 70 80 90 100
LPHFIEEPED AYIIKSNPIA LRCKARPAMQ IFFKCNGEWV HQNEHVSEES
110 120 130 140 150
LDESSGLKVR EVFINVTRQQ VEDFHGPEDY WCQCVAWSHL GTSKSRKASV
160 170 180 190 200
RIAYLRKNFE QDPQGREVPI EGMIVLHCRP PEGVPAAEVE WLKNEEPIDS
210 220 230 240 250
EQDENIDTRA DHNLIIRQAR LSDSGNYTCM AANIVAKRRS LSATVVVYVN
260 270 280 290 300
GGWSSWTEWS ACNVRCGRGW QKRSRTCTNP APLNGGAFCE GMSVQKITCT
310 320 330 340 350
ALCPVDGSWE VWSEWSVCSP ECEHLRIREC TAPPPRNGGK FCEGLSQESE
360 370 380 390 400
NCTDGLCILD KKPLHEIKPQ RWSRRGIENA SDIALYSGLG AAVVAVAVLV
410 420 430 440 450
IGVTLYRRSH SDYGVDVIDS SALTGGFQTF NFKTVRQGNS LLLNPAMQPD
460 470 480 490 500
LTVSRTYSGP ICLQDPLDKE LMTESSLFNP LSDIKVKVQS SFMVSLGVSE
510 520 530 540 550
RAEYHGKNHS GTFPHGNNRG FSTIHPRNKT PYIQNLSSLP TRTELRTTGV
560 570 580 590 600
FGHLGGRLVM PNTGVSLLIP HGAIPEENSW EIYMSINQGE PSLQSDGSEV
610 620 630 640 650
LLSPEVTCGP PDMLVTTPFA LTIPHCADVS SEHWNIHLKK RTQQGKWEEV
660 670 680 690 700
MSVEDESTSC YCLLDPFACH VLLDSFGTYA LTGEPITDCA VKQLKVAVFG
710 720 730 740 750
CMSCNSLDYN LRVYCVDNTP CAFQEVISDE RHQGGQLLEE PKLLHFKGNT
760 770 780 790 800
FSLQVSVLDI PPFLWRIKPF TACQEVPFSR VWSSNRQPLH CAFSLERYTP
810 820 830 840 850
TTTQLSCKIC IRQLKGHEQI LQVQTSILES ERETITFFAQ EDSTFPAQTG
860 870 880 890 900
PKAFKIPYSI RQRICATFDT PNAKGKDWQM LAQKNSINRN LSYFATQSSP
910 920 930 940 950
SAVILNLWEA RHQQDGDLDS LACALEEIGR THTKLSNITE PQIDDADFNY

SRQNGL
Length:956
Mass (Da):106,352
Last modified:October 1, 2002 - v1
Checksum:iDFDF07839C10C68D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ487854 mRNA. Translation: CAD32252.1.
BC137615 mRNA. Translation: AAI37616.1.
CCDSiCCDS40314.1.
RefSeqiNP_694775.1. NM_153135.3.
UniGeneiMm.248433.

Genome annotation databases

EnsembliENSMUST00000168630; ENSMUSP00000128521; ENSMUSG00000063626.
GeneIDi210801.
KEGGimmu:210801.
UCSCiuc009liz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ487854 mRNA. Translation: CAD32252.1.
BC137615 mRNA. Translation: AAI37616.1.
CCDSiCCDS40314.1.
RefSeqiNP_694775.1. NM_153135.3.
UniGeneiMm.248433.

3D structure databases

ProteinModelPortaliQ8K1S2.
SMRiQ8K1S2. Positions 50-362, 548-940.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000128521.

PTM databases

PhosphoSiteiQ8K1S2.

Proteomic databases

MaxQBiQ8K1S2.
PaxDbiQ8K1S2.
PRIDEiQ8K1S2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000168630; ENSMUSP00000128521; ENSMUSG00000063626.
GeneIDi210801.
KEGGimmu:210801.
UCSCiuc009liz.2. mouse.

Organism-specific databases

CTDi137970.
MGIiMGI:2389364. Unc5d.

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
GeneTreeiENSGT00820000127004.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ8K1S2.
KOiK07521.
OMAiINQGEPS.
OrthoDBiEOG7BGHJX.
PhylomeDBiQ8K1S2.
TreeFamiTF316767.

Miscellaneous databases

ChiTaRSiUnc5d. mouse.
NextBioi373061.
PROiQ8K1S2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8K1S2.
CleanExiMM_UNC5D.
GenevisibleiQ8K1S2. 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.
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.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
[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 of three mouse Unc5 genes and their expression patterns at mid-gestation."
    Engelkamp D.
    Mech. Dev. 118:191-197(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  2. "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].
    Tissue: Testis.
  3. "The cortical subventricular zone-specific molecule Svet1 is part of the nuclear RNA coded by the putative netrin receptor gene Unc5d and is expressed in multipolar migrating cells."
    Sasaki S., Tabata H., Tachikawa K., Nakajima K.
    Mol. Cell. Neurosci. 38:474-483(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "Unc5B interacts with FLRT3 and Rnd1 to modulate cell adhesion in Xenopus embryos."
    Karaulanov E., Boettcher R.T., Stannek P., Wu W., Rau M., Ogata S., Cho K.W.Y., Niehrs C.
    PLoS ONE 4:E5742-E5742(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLRT3.
  5. "Laminar and areal expression of unc5d and its role in cortical cell survival."
    Takemoto M., Hattori Y., Zhao H., Sato H., Tamada A., Sasaki S., Nakajima K., Yamamoto N.
    Cereb. Cortex 21:1925-1934(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. Cited for: DISRUPTION PHENOTYPE, INTERACTION WITH FLRT3, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. "FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development."
    Seiradake E., del Toro D., Nagel D., Cop F., Haertl R., Ruff T., Seyit-Bremer G., Harlos K., Border E.C., Acker-Palmer A., Jones E.Y., Klein R.
    Neuron 84:370-385(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLRT2 AND FLRT3.
  8. "Structural basis of latrophilin-FLRT-UNC5 interaction in cell adhesion."
    Lu Y.C., Nazarko O.V., Sando R. III, Salzman G.S., Suedhof T.C., Arac D.
    Structure 23:1678-1691(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FLRT3, SUBUNIT, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiUNC5D_MOUSE
AccessioniPrimary (citable) accession number: Q8K1S2
Secondary accession number(s): B9EHC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 1, 2002
Last modified: January 20, 2016
This is version 106 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.