UNC5D_MOUSE
ID UNC5D_MOUSE Reviewed; 956 AA.
AC Q8K1S2; B9EHC0;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Netrin receptor UNC5D;
DE AltName: Full=Protein unc-5 homolog 4;
DE AltName: Full=Protein unc-5 homolog D;
DE Flags: Precursor;
GN Name=Unc5d; Synonyms=Unc5h4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12351186; DOI=10.1016/s0925-4773(02)00248-4;
RA Engelkamp D.;
RT "Cloning of three mouse Unc5 genes and their expression patterns at mid-
RT gestation.";
RL Mech. Dev. 118:191-197(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=18547816; DOI=10.1016/j.mcn.2008.04.002;
RA Sasaki S., Tabata H., Tachikawa K., Nakajima K.;
RT "The cortical subventricular zone-specific molecule Svet1 is part of the
RT nuclear RNA coded by the putative netrin receptor gene Unc5d and is
RT expressed in multipolar migrating cells.";
RL Mol. Cell. Neurosci. 38:474-483(2008).
RN [4]
RP INTERACTION WITH FLRT3.
RX PubMed=19492039; DOI=10.1371/journal.pone.0005742;
RA Karaulanov E., Boettcher R.T., Stannek P., Wu W., Rau M., Ogata S.,
RA Cho K.W.Y., Niehrs C.;
RT "Unc5B interacts with FLRT3 and Rnd1 to modulate cell adhesion in Xenopus
RT embryos.";
RL PLoS ONE 4:E5742-E5742(2009).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21216843; DOI=10.1093/cercor/bhq265;
RA Takemoto M., Hattori Y., Zhao H., Sato H., Tamada A., Sasaki S.,
RA Nakajima K., Yamamoto N.;
RT "Laminar and areal expression of unc5d and its role in cortical cell
RT survival.";
RL Cereb. Cortex 21:1925-1934(2011).
RN [6]
RP DISRUPTION PHENOTYPE, INTERACTION WITH FLRT3, FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21673655; DOI=10.1038/emboj.2011.189;
RA Yamagishi S., Hampel F., Hata K., Del Toro D., Schwark M., Kvachnina E.,
RA Bastmeyer M., Yamashita T., Tarabykin V., Klein R., Egea J.;
RT "FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive
RT neurons.";
RL EMBO J. 30:2920-2933(2011).
RN [7]
RP INTERACTION WITH FLRT2 AND FLRT3.
RX PubMed=25374360; DOI=10.1016/j.neuron.2014.10.008;
RA Seiradake E., del Toro D., Nagel D., Cop F., Haertl R., Ruff T.,
RA Seyit-Bremer G., Harlos K., Border E.C., Acker-Palmer A., Jones E.Y.,
RA Klein R.;
RT "FLRT structure: balancing repulsion and cell adhesion in cortical and
RT vascular development.";
RL Neuron 84:370-385(2014).
RN [8]
RP FUNCTION, INTERACTION WITH FLRT3, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=26235030; DOI=10.1016/j.str.2015.06.024;
RA Lu Y.C., Nazarko O.V., Sando R. III, Salzman G.S., Suedhof T.C., Arac D.;
RT "Structural basis of latrophilin-FLRT-UNC5 interaction in cell adhesion.";
RL Structure 23:1678-1691(2015).
CC -!- FUNCTION: Receptor for the netrin NTN4 that promotes neuronal cell
CC survival (PubMed:21216843). Plays a role in cell-cell adhesion and cell
CC guidance. Receptor for netrin involved in cell migration (By
CC similarity). Plays a role in the regulation of neuronal cell migration
CC in the developing brain via its interaction with FLRT2
CC (PubMed:21673655). Plays a role in axon guidance by mediating axon
CC repulsion of neuronal growth cones in the developing nervous system
CC upon ligand binding (PubMed:21673655). May play a role in apoptosis in
CC response to DNA damage. It also acts as a dependence receptor required
CC for apoptosis induction when not associated with netrin ligand (By
CC similarity). Mediates cell-cell adhesion via its interaction with FLRT3
CC on an adjacent cell (PubMed:26235030). {ECO:0000250|UniProtKB:Q6UXZ4,
CC ECO:0000269|PubMed:21216843, ECO:0000269|PubMed:21673655,
CC ECO:0000269|PubMed:26235030, ECO:0000305}.
CC -!- SUBUNIT: Interacts (via extracellular domain) with FLRT2 and FLRT3 (via
CC extracellular domain); the interaction is direct (PubMed:19492039,
CC PubMed:21673655, PubMed:25374360, PubMed:26235030). Has higher affinity
CC for FLRT2 (PubMed:25374360). Identified in a complex with FLRT3 and
CC ADGRL3; does not interact with ADGRL3 by itself (PubMed:26235030).
CC {ECO:0000269|PubMed:19492039, ECO:0000269|PubMed:21673655,
CC ECO:0000269|PubMed:25374360, ECO:0000269|PubMed:26235030}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21216843,
CC ECO:0000269|PubMed:21673655, ECO:0000269|PubMed:26235030}; Single-pass
CC type I membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in multipolar cells in the brain
CC subventricular zone (at protein level) (PubMed:18547816). Detected in
CC embryonic brain neocortex, especially in the subventricular zone
CC (PubMed:21673655). Detected in multipolar cells in the brain
CC subventricular zone (PubMed:18547816). Detected in brain neocortex from
CC young pups, especially in the somatosensory cortex (PubMed:21216843).
CC Expressed in developing limb and mammary gland (PubMed:12351186).
CC {ECO:0000269|PubMed:12351186, ECO:0000269|PubMed:18547816,
CC ECO:0000269|PubMed:21216843, ECO:0000269|PubMed:21673655}.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The cleavage
CC does not take place when the receptor is associated with netrin ligand.
CC Its cleavage by caspases is required to induce apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:Q6UXZ4}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are viable, appear
CC healthy, and do not display any obvious behavorial defects. Cortical
CC neurons from mutant mice display impaired axon growth cone collapse in
CC response to Flrt2 and a tendency towards accelerated radial migration
CC in the developing brain. {ECO:0000269|PubMed:21673655}.
CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
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DR EMBL; AJ487854; CAD32252.1; -; mRNA.
DR EMBL; BC137615; AAI37616.1; -; mRNA.
DR CCDS; CCDS40314.1; -.
DR RefSeq; NP_694775.1; NM_153135.3.
DR AlphaFoldDB; Q8K1S2; -.
DR SMR; Q8K1S2; -.
DR BioGRID; 229183; 4.
DR IntAct; Q8K1S2; 1.
DR STRING; 10090.ENSMUSP00000128521; -.
DR GlyGen; Q8K1S2; 4 sites.
DR PhosphoSitePlus; Q8K1S2; -.
DR MaxQB; Q8K1S2; -.
DR PaxDb; Q8K1S2; -.
DR PRIDE; Q8K1S2; -.
DR ProteomicsDB; 275384; -.
DR Antibodypedia; 23389; 135 antibodies from 27 providers.
DR DNASU; 210801; -.
DR Ensembl; ENSMUST00000168630; ENSMUSP00000128521; ENSMUSG00000063626.
DR GeneID; 210801; -.
DR KEGG; mmu:210801; -.
DR UCSC; uc009liz.2; mouse.
DR CTD; 137970; -.
DR MGI; MGI:2389364; Unc5d.
DR VEuPathDB; HostDB:ENSMUSG00000063626; -.
DR eggNOG; KOG1480; Eukaryota.
DR GeneTree; ENSGT00950000182815; -.
DR HOGENOM; CLU_014383_0_0_1; -.
DR InParanoid; Q8K1S2; -.
DR OMA; XLRKNFE; -.
DR OrthoDB; 334938at2759; -.
DR PhylomeDB; Q8K1S2; -.
DR TreeFam; TF316767; -.
DR BioGRID-ORCS; 210801; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Unc5d; mouse.
DR PRO; PR:Q8K1S2; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8K1S2; protein.
DR Bgee; ENSMUSG00000063626; Expressed in cortical layer IV and 134 other tissues.
DR ExpressionAtlas; Q8K1S2; baseline and differential.
DR Genevisible; Q8K1S2; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005042; F:netrin receptor activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; IGI:MGI.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; ISO:MGI.
DR GO; GO:0021859; P:pyramidal neuron differentiation; IDA:MGI.
DR GO; GO:2001222; P:regulation of neuron migration; IGI:MGI.
DR CDD; cd08801; Death_UNC5D; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 2.20.100.10; -; 2.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR037936; UNC5.
DR InterPro; IPR042058; UNC5D_Death.
DR InterPro; IPR033772; UPA.
DR InterPro; IPR000906; ZU5_dom.
DR PANTHER; PTHR12582; PTHR12582; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF00090; TSP_1; 2.
DR Pfam; PF17217; UPA; 1.
DR Pfam; PF00791; ZU5; 1.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00209; TSP1; 2.
DR SMART; SM00218; ZU5; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF82895; SSF82895; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS50092; TSP1; 2.
DR PROSITE; PS51145; ZU5; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell membrane; Developmental protein; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..956
FT /note="Netrin receptor UNC5D"
FT /id="PRO_0000036080"
FT TOPO_DOM 31..382
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 383..403
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 404..956
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 52..149
FT /note="Ig-like"
FT DOMAIN 151..242
FT /note="Ig-like C2-type"
FT DOMAIN 250..304
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 306..358
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 545..685
FT /note="ZU5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 862..939
FT /note="Death"
FT REGION 89..91
FT /note="Important for interaction with FLRT2"
FT /evidence="ECO:0000250|UniProtKB:F1LW30"
FT SITE 419..420
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000305"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 73..134
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 85..132
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 178..229
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 262..299
FT /evidence="ECO:0000250"
FT DISULFID 266..303
FT /evidence="ECO:0000250"
FT DISULFID 277..289
FT /evidence="ECO:0000250"
FT DISULFID 318..352
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 322..357
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 330..342
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
SQ SEQUENCE 956 AA; 106352 MW; DFDF07839C10C68D CRC64;
MGTGAADGSR GARRWLPWLG LFFWAAGAAA ARGADGSEIL PDSIPSAPGT LPHFIEEPED
AYIIKSNPIA LRCKARPAMQ IFFKCNGEWV HQNEHVSEES LDESSGLKVR EVFINVTRQQ
VEDFHGPEDY WCQCVAWSHL GTSKSRKASV RIAYLRKNFE QDPQGREVPI EGMIVLHCRP
PEGVPAAEVE WLKNEEPIDS EQDENIDTRA DHNLIIRQAR LSDSGNYTCM AANIVAKRRS
LSATVVVYVN GGWSSWTEWS ACNVRCGRGW QKRSRTCTNP APLNGGAFCE GMSVQKITCT
ALCPVDGSWE VWSEWSVCSP ECEHLRIREC TAPPPRNGGK FCEGLSQESE NCTDGLCILD
KKPLHEIKPQ RWSRRGIENA SDIALYSGLG AAVVAVAVLV IGVTLYRRSH SDYGVDVIDS
SALTGGFQTF NFKTVRQGNS LLLNPAMQPD LTVSRTYSGP ICLQDPLDKE LMTESSLFNP
LSDIKVKVQS SFMVSLGVSE RAEYHGKNHS GTFPHGNNRG FSTIHPRNKT PYIQNLSSLP
TRTELRTTGV FGHLGGRLVM PNTGVSLLIP HGAIPEENSW EIYMSINQGE PSLQSDGSEV
LLSPEVTCGP PDMLVTTPFA LTIPHCADVS SEHWNIHLKK RTQQGKWEEV MSVEDESTSC
YCLLDPFACH VLLDSFGTYA LTGEPITDCA VKQLKVAVFG CMSCNSLDYN LRVYCVDNTP
CAFQEVISDE RHQGGQLLEE PKLLHFKGNT FSLQVSVLDI PPFLWRIKPF TACQEVPFSR
VWSSNRQPLH CAFSLERYTP TTTQLSCKIC IRQLKGHEQI LQVQTSILES ERETITFFAQ
EDSTFPAQTG PKAFKIPYSI RQRICATFDT PNAKGKDWQM LAQKNSINRN LSYFATQSSP
SAVILNLWEA RHQQDGDLDS LACALEEIGR THTKLSNITE PQIDDADFNY SRQNGL
