UNC5A_MOUSE
ID UNC5A_MOUSE Reviewed; 898 AA.
AC Q8K1S4; Q6PEF7; Q80T71;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Netrin receptor UNC5A;
DE AltName: Full=Protein unc-5 homolog 1;
DE AltName: Full=Protein unc-5 homolog A;
DE Flags: Precursor;
GN Name=Unc5a; Synonyms=Kiaa1976, Unc5h1;
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] (ISOFORM 1), 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] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP INTERACTION WITH FLRT3.
RX PubMed=22405201; DOI=10.1016/j.neuron.2012.01.018;
RA O'Sullivan M.L., de Wit J., Savas J.N., Comoletti D., Otto-Hitt S.,
RA Yates J.R. III, Ghosh A.;
RT "FLRT proteins are endogenous latrophilin ligands and regulate excitatory
RT synapse development.";
RL Neuron 73:903-910(2012).
RN [5]
RP INTERACTION WITH FLRT2.
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 netrin required for axon guidance. Functions in
CC the netrin signaling pathway and promotes neurite outgrowth in response
CC to NTN1. Mediates axon repulsion of neuronal growth cones in the
CC developing nervous system in response to netrin. Axon repulsion in
CC growth cones may be mediated by its association with DCC that may
CC trigger signaling for repulsion. It also acts as a dependence receptor
CC required for apoptosis induction when not associated with netrin
CC ligand. {ECO:0000250|UniProtKB:O08721}.
CC -!- SUBUNIT: Homodimer and homooligomer. Interacts with the cytoplasmic
CC part of DCC. Interacts with MAGED1. Interacts with PRKCABP, possibly
CC mediating some interaction with PKC (By similarity). Interacts (via
CC extracellular domain) with FLRT2 (via extracellular domain)
CC (PubMed:25374360). Interacts (via extracellular domain) with FLRT3 (via
CC extracellular domain) (PubMed:22405201). {ECO:0000250|UniProtKB:O08721,
CC ECO:0000269|PubMed:22405201, ECO:0000269|PubMed:25374360}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O08721};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:O08721}.
CC Membrane raft {ECO:0000250|UniProtKB:O08721}. Cell projection, neuron
CC projection {ECO:0000250|UniProtKB:O08721}. Note=The interaction with
CC PRKCABP regulates its surface expression and leads to its removal from
CC the surface of neurons and growth cones.
CC {ECO:0000250|UniProtKB:O08721}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8K1S4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K1S4-2; Sequence=VSP_011697;
CC Name=3;
CC IsoId=Q8K1S4-3; Sequence=VSP_011696;
CC -!- TISSUE SPECIFICITY: Restricted to central nervous system.
CC {ECO:0000269|PubMed:12351186}.
CC -!- DOMAIN: The ZU5 domain mediates the interaction with MAGED1, which
CC participates in the induction of apoptosis.
CC {ECO:0000250|UniProtKB:O08721}.
CC -!- PTM: Phosphorylated on cytoplasmic tyrosine residues (By similarity).
CC Phosphorylated by PKC in vitro (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:O08721}.
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:0000250|UniProtKB:O08721}.
CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65857.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ487852; CAD32250.1; -; mRNA.
DR EMBL; AK122575; BAC65857.1; ALT_INIT; mRNA.
DR EMBL; BC058084; AAH58084.1; -; mRNA.
DR CCDS; CCDS26537.1; -. [Q8K1S4-1]
DR CCDS; CCDS79188.1; -. [Q8K1S4-2]
DR RefSeq; NP_001298057.1; NM_001311128.1. [Q8K1S4-2]
DR RefSeq; NP_694771.1; NM_153131.3. [Q8K1S4-1]
DR AlphaFoldDB; Q8K1S4; -.
DR SMR; Q8K1S4; -.
DR BioGRID; 223295; 4.
DR STRING; 10090.ENSMUSP00000026994; -.
DR GlyGen; Q8K1S4; 3 sites.
DR iPTMnet; Q8K1S4; -.
DR PhosphoSitePlus; Q8K1S4; -.
DR PaxDb; Q8K1S4; -.
DR PRIDE; Q8K1S4; -.
DR ProteomicsDB; 298200; -. [Q8K1S4-1]
DR ProteomicsDB; 298201; -. [Q8K1S4-2]
DR ProteomicsDB; 298202; -. [Q8K1S4-3]
DR Antibodypedia; 29143; 110 antibodies from 28 providers.
DR DNASU; 107448; -.
DR Ensembl; ENSMUST00000026994; ENSMUSP00000026994; ENSMUSG00000025876. [Q8K1S4-1]
DR Ensembl; ENSMUST00000109994; ENSMUSP00000105621; ENSMUSG00000025876. [Q8K1S4-2]
DR GeneID; 107448; -.
DR KEGG; mmu:107448; -.
DR UCSC; uc007qpp.1; mouse. [Q8K1S4-1]
DR UCSC; uc007qpq.1; mouse. [Q8K1S4-2]
DR CTD; 90249; -.
DR MGI; MGI:894682; Unc5a.
DR VEuPathDB; HostDB:ENSMUSG00000025876; -.
DR eggNOG; KOG1480; Eukaryota.
DR GeneTree; ENSGT00950000182815; -.
DR HOGENOM; CLU_014383_0_0_1; -.
DR InParanoid; Q8K1S4; -.
DR OMA; QKSACTT; -.
DR OrthoDB; 334938at2759; -.
DR PhylomeDB; Q8K1S4; -.
DR TreeFam; TF316767; -.
DR Reactome; R-MMU-373752; Netrin-1 signaling.
DR BioGRID-ORCS; 107448; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q8K1S4; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q8K1S4; protein.
DR Bgee; ENSMUSG00000025876; Expressed in dentate gyrus of hippocampal formation granule cell and 158 other tissues.
DR ExpressionAtlas; Q8K1S4; baseline and differential.
DR Genevisible; Q8K1S4; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0032589; C:neuron projection membrane; ISS:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005042; F:netrin receptor activity; ISO:MGI.
DR GO; GO:0033564; P:anterior/posterior axon guidance; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; ISO:MGI.
DR GO; GO:0038007; P:netrin-activated signaling pathway; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR CDD; cd08800; Death_UNC5A; 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; IPR042155; Death_UNC5A.
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; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR037936; UNC5.
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; 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; Cell projection;
KW Developmental protein; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..898
FT /note="Netrin receptor UNC5A"
FT /id="PRO_0000036069"
FT TOPO_DOM 26..361
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..898
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 44..141
FT /note="Ig-like"
FT DOMAIN 155..234
FT /note="Ig-like C2-type"
FT DOMAIN 242..296
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 298..350
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 497..640
FT /note="ZU5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 817..897
FT /note="Death"
FT REGION 661..679
FT /note="Interaction with DCC"
FT /evidence="ECO:0000250"
FT SITE 396..397
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250|UniProtKB:O08721"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 65..126
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 77..124
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 170..221
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 254..291
FT /evidence="ECO:0000250"
FT DISULFID 258..295
FT /evidence="ECO:0000250"
FT DISULFID 269..281
FT /evidence="ECO:0000250"
FT DISULFID 310..344
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 314..349
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 322..334
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT VAR_SEQ 1..790
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12693553"
FT /id="VSP_011696"
FT VAR_SEQ 241..296
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011697"
FT CONFLICT 217
FT /note="A -> P (in Ref. 3; AAH58084)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 898 AA; 98857 MW; 59F04BA2E196C1DB CRC64;
MAVRPGLWPA LLGIVLTAWL RGSGAQQSAT VANPVPGANP DLLPHFLVEP EDVYIVKNKP
VLLVCKAVPA TQIFFKCNGE WVRQVDHVIE RSTDGSSGLP TMEVRINVSR QQVEKVFGLE
EYWCQCVAWS SSGTTKSQKA YIRIAYLRKN FEQEPLAKEV SLEQGIVLPC RPPEGIPPAE
VEWLRNEDLV DPSLDPNVYI TREHSLVVRQ ARLADTANYT CVAKNIVARR RSASAAVIVY
VNGGWSTWTE WSVCSASCGR GWQKRSRSCT NPAPLNGGAF CEGQNVQKTA CATLCPVDGS
WSPWSKWSAC GLDCTHWRSR ECSDPAPRNG GEECRGADLD TRNCTSDLCL HTSSGPEDVA
LYIGLVAVAV CLILLLLVLV LIYCRKKEGL DSDVADSSIL TSGFQPVSIK PSKADNPHLL
TIQPDLSTTT TTYQGSLCPR QDGPSPKFQL SNGHLLSPLG SGRHTLHHSS PTSEAEDFVS
RLSTQNYFRS LPRGTSNMAY GTFNFLGGRL MIPNTGISLL IPPDAIPRGK IYEIYLTLHK
PEDVRLPLAG CQTLLSPIVS CGPPGVLLTR PVILAMDHCG EPSPDSWSLR LKKQSCEGSW
EDVLHLGEES PSHLYYCQLE AGACYVFTEQ LGRFALVGEA LSVAATKRLR LLLFAPVACT
SLEYNIRVYC LHDTHDALKE VVQLEKQLGG QLIQEPRVLH FKDSYHNLRL SIHDVPSSLW
KSKLLVSYQE IPFYHIWNGT QQYLHCTFTL ERVNASTSDL ACKVWVWQVE GDGQSFNINF
NITKDTRFAE MLALESEGGV PALVGPSAFK IPFLIRQKII TSLDPPCSRG ADWRTLAQKL
HLDSHLSFFA SKPSPTAMIL NLWEARHFPN GNLGQLAAAV AGLGQPDAGL FTVSEAEC
