UNC5D_RAT
ID UNC5D_RAT Reviewed; 956 AA.
AC F1LW30;
DT 11-NOV-2015, integrated into UniProtKB/Swiss-Prot.
DT 11-NOV-2015, sequence version 4.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Netrin receptor UNC5D;
DE AltName: Full=Protein unc-5 homolog D;
DE Flags: Precursor;
GN Name=Unc5d {ECO:0000312|RGD:1309245};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|Proteomes:UP000002494};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0007744|PDB:4V2B}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-130 IN COMPLEX WITH FLRT2,
RP INTERACTION WITH FLRT2 AND FLRT3, DISULFIDE BONDS, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF TRP-89 AND HIS-91.
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).
CC -!- FUNCTION: Receptor for the netrin NTN4 that promotes neuronal cell
CC survival. Plays a role in cell-cell adhesion and cell guidance.
CC Receptor for netrin involved in cell migration. Plays a role in axon
CC guidance by mediating axon repulsion of neuronal growth cones in the
CC developing nervous system upon ligand binding. May play a role in
CC apoptosis in response to DNA damage. It also acts as a dependence
CC receptor required for apoptosis induction when not associated with
CC netrin ligand (By similarity). Mediates cell-cell adhesion via its
CC interaction with FLRT3 on an adjacent cell (By similarity).
CC {ECO:0000250|UniProtKB:Q6UXZ4, ECO:0000250|UniProtKB:Q8K1S2}.
CC -!- SUBUNIT: Interacts (via extracellular domain) with FLRT2 and FLRT3 (via
CC extracellular domain); the interaction is direct. Has higher affinity
CC for FLRT2 (PubMed:25374360). Identified in a complex with FLRT3 and
CC ADGRL3; does not interact with ADGRL3 by itself (By similarity).
CC {ECO:0000250|UniProtKB:Q8K1S2}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25374360};
CC Single-pass type I membrane protein {ECO:0000305}.
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 -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
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DR EMBL; AABR06088887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07026201; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07026202; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07026203; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07026204; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07026205; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001100789.2; NM_001107319.2.
DR PDB; 4V2B; X-ray; 2.00 A; A/B=1-161.
DR PDB; 4V2C; X-ray; 4.00 A; B/D=1-161.
DR PDB; 5FTT; X-ray; 3.40 A; A/E=32-307.
DR PDB; 5FTU; X-ray; 6.01 A; A/E/I=32-161.
DR PDBsum; 4V2B; -.
DR PDBsum; 4V2C; -.
DR PDBsum; 5FTT; -.
DR PDBsum; 5FTU; -.
DR AlphaFoldDB; F1LW30; -.
DR SMR; F1LW30; -.
DR STRING; 10116.ENSRNOP00000015879; -.
DR GlyGen; F1LW30; 2 sites.
DR PaxDb; F1LW30; -.
DR Ensembl; ENSRNOT00000111680; ENSRNOP00000077568; ENSRNOG00000011858.
DR GeneID; 306534; -.
DR KEGG; rno:306534; -.
DR CTD; 137970; -.
DR RGD; 1309245; Unc5d.
DR eggNOG; KOG1480; Eukaryota.
DR GeneTree; ENSGT00950000182815; -.
DR InParanoid; F1LW30; -.
DR OrthoDB; 334938at2759; -.
DR TreeFam; TF316767; -.
DR PRO; PR:F1LW30; -.
DR Proteomes; UP000002494; Chromosome 16.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; ISO:RGD.
DR GO; GO:0021859; P:pyramidal neuron differentiation; ISO:RGD.
DR GO; GO:2001222; P:regulation of neuron migration; ISO:RGD.
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 3D-structure; Apoptosis; Cell membrane; Developmental protein;
KW Disulfide bond; 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_0000434580"
FT TOPO_DOM 31..382
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 383..403
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 404..956
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 52..149
FT /note="Ig-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 164..242
FT /note="Ig-like C2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
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 /evidence="ECO:0000305"
FT REGION 89..91
FT /note="Important for interaction with FLRT2"
FT /evidence="ECO:0000269|PubMed:25374360"
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 DISULFID 73..134
FT /evidence="ECO:0007744|PDB:4V2B"
FT DISULFID 85..132
FT /evidence="ECO:0007744|PDB:4V2B"
FT DISULFID 178..229
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44,
FT ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 262..299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 266..303
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 277..289
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
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"
FT MUTAGEN 89
FT /note="W->N: Abolishes interaction with FLRT2; when
FT associated with T-91."
FT /evidence="ECO:0000269|PubMed:25374360"
FT MUTAGEN 91
FT /note="H->T: Abolishes interaction with FLRT2; when
FT associated with N-89."
FT /evidence="ECO:0000269|PubMed:25374360"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 69..77
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:4V2B"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 108..116
FT /evidence="ECO:0007829|PDB:4V2B"
FT HELIX 118..123
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 139..152
FT /evidence="ECO:0007829|PDB:4V2B"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 188..197
FT /evidence="ECO:0007829|PDB:5FTT"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 212..222
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 225..232
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 263..274
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:5FTT"
FT STRAND 293..301
FT /evidence="ECO:0007829|PDB:5FTT"
SQ SEQUENCE 956 AA; 106520 MW; E389EEE963CEE79E CRC64;
MGTGAADRSR GARWWLPWLG LCFWAAGAEA ARGADSGEVL 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 LLLNPAMHPD 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
CAFQEVVSDE RHQGGQLLEE PKLLHFKGNT FSLQISVLDI PPFLWRIKPF TACQEVPFSR
VWSSNRQPLH CAFSLERYTP TTTQLSCKIC IRQLKGHEQI LQVQTSILES ERETITFFAQ
EDSTFPAQTG PKAFKIPYSI RQRICATFDT PNAKGKDWQM LAQKNSINRN LSYFATQSSP
SAVILNLWEA RHQQDGDLDS LACALEEIGR THTKLSNITE PQLDDTDFNY SRQNGL
