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   24-JAN-2024, entry version 152.
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   GlyCosmos; Q8K1S2; 4 sites, No reported glycans.
DR   GlyGen; Q8K1S2; 4 sites.
DR   PhosphoSitePlus; Q8K1S2; -.
DR   SwissPalm; Q8K1S2; -.
DR   MaxQB; Q8K1S2; -.
DR   PaxDb; 10090-ENSMUSP00000128521; -.
DR   ProteomicsDB; 275384; -.
DR   Antibodypedia; 23389; 150 antibodies from 27 providers.
DR   DNASU; 210801; -.
DR   Ensembl; ENSMUST00000168630.4; ENSMUSP00000128521.3; ENSMUSG00000063626.7.
DR   GeneID; 210801; -.
DR   KEGG; mmu:210801; -.
DR   UCSC; uc009liz.2; mouse.
DR   AGR; MGI:2389364; -.
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; TTQLCCT; -.
DR   OrthoDB; 2971005at2759; -.
DR   PhylomeDB; Q8K1S2; -.
DR   TreeFam; TF316767; -.
DR   BioGRID-ORCS; 210801; 0 hits in 77 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 135 other cell types or tissues.
DR   ExpressionAtlas; Q8K1S2; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
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; 2.60.220.30; -; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 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; NETRIN RECEPTOR UNC5; 1.
DR   PANTHER; PTHR12582:SF5; NETRIN RECEPTOR UNC5D; 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   PRINTS; PR01705; TSP1REPEAT.
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; DEATH domain; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 2.
DR   SUPFAM; SSF82895; TSP-1 type 1 repeat; 2.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   PROSITE; PS50092; TSP1; 2.
DR   PROSITE; PS51145; ZU5; 1.
DR   Genevisible; Q8K1S2; MM.
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
//