UNC5D_HUMAN
ID UNC5D_HUMAN Reviewed; 953 AA.
AC Q6UXZ4; Q8WYP7;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 160.
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=KIAA1777, UNC5H4 {ECO:0000303|Ref.2};
GN ORFNames=UNQ6012/PRO34692;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Nakajima D., Nakayama M., Nagase T., Ohara O.;
RT "Identification of unc5H4 gene.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INDUCTION BY DNA DAMAGE, AND FUNCTION.
RX PubMed=24691657; DOI=10.3892/mmr.2014.2100;
RA Wang H., Wu Q., Li S., Zhang B., Chi Z., Hao L.;
RT "Unc5D regulates p53-dependent apoptosis in neuroblastoma cells.";
RL Mol. Med. Report. 9:2411-2416(2014).
RN [4]
RP FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=24519068; DOI=10.1007/s13277-014-1706-6;
RA Wang H., Zhang B., Gu M., Li S., Chi Z., Hao L.;
RT "Overexpression of the dependence receptor UNC5H4 inhibits cell migration
RT and invasion, and triggers apoptosis in neuroblastoma cell.";
RL Tumor Biol. 35:5417-5425(2014).
RN [5]
RP 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 (By similarity). Plays a role in cell-cell adhesion and cell
CC guidance. Receptor for netrin involved in cell migration. Plays a role
CC in axon guidance by mediating axon repulsion of neuronal growth cones
CC in the developing nervous system upon ligand binding (By similarity).
CC May play a role in apoptosis in response to DNA damage
CC (PubMed:24691657). It also acts as a dependence receptor required for
CC apoptosis induction when not associated with netrin ligand
CC (PubMed:24519068). Mediates cell-cell adhesion via its interaction with
CC FLRT3 on an adjacent cell (By similarity).
CC {ECO:0000250|UniProtKB:Q8K1S2, ECO:0000305|PubMed:24519068,
CC ECO:0000305|PubMed:24691657}.
CC -!- SUBUNIT: Interacts (via extracellular domain) with FLRT2 (via
CC extracellular domain); the interaction is direct (By similarity).
CC Interacts (via extracellular domain) with FLRT3 (via extracellular
CC domain); the interaction is direct (PubMed:26235030). Identified in a
CC complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself
CC (PubMed:26235030). {ECO:0000250|UniProtKB:Q8K1S2,
CC ECO:0000269|PubMed:26235030}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26235030};
CC Single-pass type I membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6UXZ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UXZ4-2; Sequence=VSP_011703;
CC -!- INDUCTION: Up-regulated by p53/TP53 in response to DNA damage.
CC {ECO:0000269|PubMed:24691657}.
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.
CC {ECO:0000269|PubMed:24519068}.
CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
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DR EMBL; AB055056; BAB83663.1; -; mRNA.
DR EMBL; AY358147; AAQ88514.1; -; mRNA.
DR CCDS; CCDS6093.2; -. [Q6UXZ4-1]
DR CCDS; CCDS83279.1; -. [Q6UXZ4-2]
DR RefSeq; NP_001309747.1; NM_001322818.1. [Q6UXZ4-2]
DR RefSeq; NP_543148.2; NM_080872.3. [Q6UXZ4-1]
DR AlphaFoldDB; Q6UXZ4; -.
DR SMR; Q6UXZ4; -.
DR BioGRID; 126494; 3.
DR CORUM; Q6UXZ4; -.
DR IntAct; Q6UXZ4; 1.
DR STRING; 9606.ENSP00000385143; -.
DR GlyGen; Q6UXZ4; 4 sites.
DR iPTMnet; Q6UXZ4; -.
DR PhosphoSitePlus; Q6UXZ4; -.
DR BioMuta; UNC5D; -.
DR DMDM; 54036576; -.
DR EPD; Q6UXZ4; -.
DR MassIVE; Q6UXZ4; -.
DR PaxDb; Q6UXZ4; -.
DR PeptideAtlas; Q6UXZ4; -.
DR PRIDE; Q6UXZ4; -.
DR ProteomicsDB; 67684; -. [Q6UXZ4-1]
DR ProteomicsDB; 67685; -. [Q6UXZ4-2]
DR Antibodypedia; 23389; 135 antibodies from 27 providers.
DR DNASU; 137970; -.
DR Ensembl; ENST00000404895.7; ENSP00000385143.2; ENSG00000156687.11. [Q6UXZ4-1]
DR Ensembl; ENST00000453357.6; ENSP00000394303.2; ENSG00000156687.11. [Q6UXZ4-2]
DR GeneID; 137970; -.
DR KEGG; hsa:137970; -.
DR MANE-Select; ENST00000404895.7; ENSP00000385143.2; NM_080872.4; NP_543148.2.
DR UCSC; uc003xjr.3; human. [Q6UXZ4-1]
DR CTD; 137970; -.
DR DisGeNET; 137970; -.
DR GeneCards; UNC5D; -.
DR HGNC; HGNC:18634; UNC5D.
DR HPA; ENSG00000156687; Tissue enhanced (brain, intestine).
DR MIM; 616466; gene.
DR neXtProt; NX_Q6UXZ4; -.
DR OpenTargets; ENSG00000156687; -.
DR PharmGKB; PA38612; -.
DR VEuPathDB; HostDB:ENSG00000156687; -.
DR eggNOG; KOG1480; Eukaryota.
DR GeneTree; ENSGT00950000182815; -.
DR HOGENOM; CLU_014383_0_0_1; -.
DR InParanoid; Q6UXZ4; -.
DR OrthoDB; 334938at2759; -.
DR PhylomeDB; Q6UXZ4; -.
DR TreeFam; TF316767; -.
DR PathwayCommons; Q6UXZ4; -.
DR Reactome; R-HSA-418886; Netrin mediated repulsion signals.
DR SignaLink; Q6UXZ4; -.
DR SIGNOR; Q6UXZ4; -.
DR BioGRID-ORCS; 137970; 12 hits in 1054 CRISPR screens.
DR ChiTaRS; UNC5D; human.
DR GenomeRNAi; 137970; -.
DR Pharos; Q6UXZ4; Tbio.
DR PRO; PR:Q6UXZ4; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q6UXZ4; protein.
DR Bgee; ENSG00000156687; Expressed in ganglionic eminence and 82 other tissues.
DR ExpressionAtlas; Q6UXZ4; baseline and differential.
DR Genevisible; Q6UXZ4; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IDA:UniProtKB.
DR GO; GO:0021859; P:pyramidal neuron differentiation; IEA:Ensembl.
DR GO; GO:2001222; P:regulation of neuron migration; IEA:Ensembl.
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 Alternative splicing; Apoptosis; Cell membrane; Developmental protein;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..953
FT /note="Netrin receptor UNC5D"
FT /id="PRO_0000036079"
FT TOPO_DOM 33..379
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 380..400
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 401..953
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 54..151
FT /note="Ig-like"
FT DOMAIN 153..244
FT /note="Ig-like C2-type"
FT DOMAIN 252..306
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 308..360
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 542..682
FT /note="ZU5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 859..936
FT /note="Death"
FT REGION 91..93
FT /note="Important for interaction with FLRT2"
FT /evidence="ECO:0000250|UniProtKB:F1LW30"
FT SITE 416..417
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000305"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 75..136
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 87..134
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 180..231
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 264..301
FT /evidence="ECO:0000250"
FT DISULFID 268..305
FT /evidence="ECO:0000250"
FT DISULFID 279..291
FT /evidence="ECO:0000250"
FT DISULFID 320..354
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 324..359
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 332..344
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT VAR_SEQ 1..34
FT /note="MGRAAATAGGGGGARRWLPWLGLCFWAAGTAAAR -> MILVLVKALSDVCA
FT GTSGFLLDFSSQTSP (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_011703"
FT VARIANT 728
FT /note="R -> K (in dbSNP:rs35487923)"
FT /id="VAR_059848"
SQ SEQUENCE 953 AA; 105880 MW; 5F893B9DF746F731 CRC64;
MGRAAATAGG GGGARRWLPW LGLCFWAAGT AAARGTDNGE ALPESIPSAP GTLPHFIEEP
DDAYIIKSNP IALRCKARPA MQIFFKCNGE WVHQNEHVSE ETLDESSGLK VREVFINVTR
QQVEDFHGPE DYWCQCVAWS HLGTSKSRKA SVRIAYLRKN FEQDPQGREV PIEGMIVLHC
RPPEGVPAAE VEWLKNEEPI DSEQDENIDT RADHNLIIRQ ARLSDSGNYT CMAANIVAKR
RSLSATVVVY VNGGWSSWTE WSACNVRCGR GWQKRSRTCT NPAPLNGGAF CEGMSVQKIT
CTSLCPVDGS WEVWSEWSVC SPECEHLRIR ECTAPPPRNG GKFCEGLSQE SENCTDGLCI
LDKKPLHEIK PQSIENASDI ALYSGLGAAV VAVAVLVIGV TLYRRSQSDY GVDVIDSSAL
TGGFQTFNFK TVRQGNSLLL NSAMQPDLTV SRTYSGPICL QDPLDKELMT ESSLFNPLSD
IKVKVQSSFM VSLGVSERAE YHGKNHSRTF PHGNNHSFST MHPRNKMPYI QNLSSLPTRT
ELRTTGVFGH LGGRLVMPNT GVSLLIPHGA IPEENSWEIY MSINQGEPSL QSDGSEVLLS
PEVTCGPPDM IVTTPFALTI PHCADVSSEH WNIHLKKRTQ QGKWEEVMSV EDESTSCYCL
LDPFACHVLL DSFGTYALTG EPITDCAVKQ LKVAVFGCMS CNSLDYNLRV YCVDNTPCAF
QEVVSDERHQ GGQLLEEPKL LHFKGNTFSL QISVLDIPPF LWRIKPFTAC QEVPFSRVWC
SNRQPLHCAF SLERYTPTTT QLSCKICIRQ LKGHEQILQV QTSILESERE TITFFAQEDS
TFPAQTGPKA FKIPYSIRQR ICATFDTPNA KGKDWQMLAQ KNSINRNLSY FATQSSPSAV
ILNLWEARHQ HDGDLDSLAC ALEEIGRTHT KLSNISESQL DEADFNYSRQ NGL
