ID UNC5A_RAT Reviewed; 898 AA. AC O08721; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1997, sequence version 1. DT 14-DEC-2022, entry version 148. 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; GN Synonyms=Unc5h1 {ECO:0000303|PubMed:12598531, ECO:0000303|PubMed:14672991, GN ECO:0000303|PubMed:9126742}; 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; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Ventral spinal cord; RX PubMed=9126742; DOI=10.1038/386833a0; RA Leonardo E.D., Hinck L., Masu M., Keino-Masu K., Ackerman S.L., RA Tessier-Lavigne M.; RT "Vertebrate homologues of C. elegans UNC-5 are candidate netrin RT receptors."; RL Nature 386:833-838(1997). RN [2] RP FUNCTION, AND INTERACTION WITH DCC. RX PubMed=10399920; DOI=10.1016/s0092-8674(00)80804-1; RA Hong K., Hinck L., Nishiyama M., Poo M.-M., Tessier-Lavigne M., Stein E.; RT "A ligand-gated association between cytoplasmic domains of UNC5 and DCC RT family receptors converts netrin-induced growth cone attraction to RT repulsion."; RL Cell 97:927-941(1999). RN [3] RP TISSUE SPECIFICITY. RX PubMed=11472849; DOI=10.1016/s0925-4773(01)00415-4; RA Barrett C., Guthrie S.; RT "Expression patterns of the netrin receptor UNC5H1 among developing motor RT neurons in the embryonic rat hindbrain."; RL Mech. Dev. 106:163-166(2001). RN [4] RP FUNCTION, AND PROTEOLYTIC CLEAVAGE. RX PubMed=11387206; DOI=10.1093/emboj/20.11.2715; RA Llambi F., Causeret F., Bloch-Gallego E., Mehlen P.; RT "Netrin-1 acts as a survival factor via its receptors UNC5H and DCC."; RL EMBO J. 20:2715-2722(2001). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAGED1, AND DOMAIN. RX PubMed=12598531; DOI=10.1074/jbc.m300415200; RA Williams M.E., Strickland P., Watanabe K., Hinck L.; RT "UNC5H1 induces apoptosis via its juxtamembrane region through an RT interaction with NRAGE."; RL J. Biol. Chem. 278:17483-17490(2003). RN [6] RP INTERACTION WITH PRKCABP, PHOSPHORYLATION, AND MUTAGENESIS OF RP 896-ALA--CYS-898. RX PubMed=14672991; DOI=10.1523/jneurosci.23-36-11279.2003; RA Williams M.E., Wu S.C.-Y., McKenna W.L., Hinck L.; RT "Surface expression of the netrin receptor UNC5H1 is regulated through a RT protein kinase C-interacting protein/protein kinase-dependent mechanism."; RL J. Neurosci. 23:11279-11288(2003). RN [7] RP SUBCELLULAR LOCATION. RX PubMed=18582460; DOI=10.1016/j.yexcr.2008.06.001; RA Maisse C., Rossin A., Cahuzac N., Paradisi A., Klein C., Haillot M.L., RA Herincs Z., Mehlen P., Hueber A.O.; RT "Lipid raft localization and palmitoylation: identification of two RT requirements for cell death induction by the tumor suppressors UNC5H."; RL Exp. Cell Res. 314:2544-2552(2008). RN [8] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=19755150; DOI=10.1016/j.cellsig.2009.09.004; RA Picard M., Petrie R.J., Antoine-Bertrand J., Saint-Cyr-Proulx E., RA Villemure J.F., Lamarche-Vane N.; RT "Spatial and temporal activation of the small GTPases RhoA and Rac1 by the RT netrin-1 receptor UNC5a during neurite outgrowth."; RL Cell. Signal. 21:1961-1973(2009). CC -!- FUNCTION: Receptor for netrin required for axon guidance CC (PubMed:9126742, PubMed:10399920). Functions in the netrin signaling CC pathway and promotes neurite outgrowth in response to NTN1 CC (PubMed:19755150). Mediates axon repulsion of neuronal growth cones in CC the developing nervous system in response to netrin (PubMed:10399920). CC Axon repulsion in growth cones may be mediated by its association with CC DCC that may trigger signaling for repulsion (PubMed:10399920). It also CC acts as a dependence receptor required for apoptosis induction when not CC associated with netrin ligand (PubMed:11387206, PubMed:12598531). CC {ECO:0000269|PubMed:10399920, ECO:0000269|PubMed:11387206, CC ECO:0000269|PubMed:12598531, ECO:0000269|PubMed:9126742, CC ECO:0000305|PubMed:9126742}. CC -!- SUBUNIT: Homodimer and homooligomer (PubMed:19755150). Interacts with CC the cytoplasmic part of DCC (PubMed:10399920). Interacts with MAGED1 CC (PubMed:12598531). Interacts with PRKCABP, possibly mediating some CC interaction with PKC (PubMed:14672991). Interacts (via extracellular CC domain) with FLRT2 (via extracellular domain) (By similarity). CC Interacts (via extracellular domain) with FLRT3 (via extracellular CC domain) (By similarity). {ECO:0000250|UniProtKB:Q6ZN44, CC ECO:0000250|UniProtKB:Q8K1S4, ECO:0000269|PubMed:10399920, CC ECO:0000269|PubMed:12598531, ECO:0000269|PubMed:14672991}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12598531, CC ECO:0000269|PubMed:19755150, ECO:0000269|PubMed:9126742}; Single-pass CC type I membrane protein {ECO:0000269|PubMed:12598531, CC ECO:0000269|PubMed:9126742, ECO:0000305}. Membrane raft CC {ECO:0000269|PubMed:18582460}. Cell projection, neuron projection CC {ECO:0000269|PubMed:19755150}. Note=The interaction with PRKCABP CC regulates its surface expression and leads to its removal from the CC surface of neurons and growth cones (PubMed:14672991). CC {ECO:0000269|PubMed:14672991}. CC -!- TISSUE SPECIFICITY: Mainly expressed in regions of differentiating CC neurons. Expressed at early stages of neural tube development in the CC ventral spinal cord. In developing hindbrain, it colocalizes with a CC number of cranial motor neuron subpopulations from embryonic E11 to CC E14, while DCC is expressed by motor neurons at E12. Also expressed in CC non-neural structures, such as the basal plane of the hindbrain and CC midbrain, in the developing hypothalamus, thalamus and in the pallidum. CC {ECO:0000269|PubMed:11472849, ECO:0000269|PubMed:9126742}. CC -!- DOMAIN: The ZU5 domain mediates the interaction with MAGED1, which CC participates in the induction of apoptosis. CC {ECO:0000269|PubMed:12598531}. CC -!- PTM: Phosphorylated on cytoplasmic tyrosine residues (By similarity). CC Phosphorylated by PKC in vitro. {ECO:0000250, CC ECO:0000269|PubMed:14672991}. 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:11387206}. CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U87305; AAB57678.1; -; mRNA. DR RefSeq; NP_071542.1; NM_022206.1. DR AlphaFoldDB; O08721; -. DR SMR; O08721; -. DR BioGRID; 248879; 1. DR DIP; DIP-60742N; -. DR IntAct; O08721; 1. DR STRING; 10116.ENSRNOP00000032250; -. DR GlyGen; O08721; 3 sites. DR iPTMnet; O08721; -. DR PhosphoSitePlus; O08721; -. DR PaxDb; O08721; -. DR GeneID; 60629; -. DR KEGG; rno:60629; -. DR UCSC; RGD:621755; rat. DR AGR; RGD:621755; -. DR CTD; 90249; -. DR RGD; 621755; Unc5a. DR eggNOG; KOG1480; Eukaryota. DR InParanoid; O08721; -. DR OrthoDB; 334938at2759; -. DR PhylomeDB; O08721; -. DR Reactome; R-RNO-373752; Netrin-1 signaling. DR PRO; PR:O08721; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell. DR GO; GO:0032589; C:neuron projection membrane; IMP:UniProtKB. DR GO; GO:0032809; C:neuronal cell body membrane; IMP:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005042; F:netrin receptor activity; IDA:RGD. DR GO; GO:0033564; P:anterior/posterior axon guidance; ISO:RGD. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0007411; P:axon guidance; IDA:RGD. DR GO; GO:0038007; P:netrin-activated signaling pathway; IMP:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IMP: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; NETRIN RECEPTOR UNC5; 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; 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. PE 1: Evidence at protein level; KW Apoptosis; Cell membrane; Cell projection; Developmental protein; KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; KW 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_0000036070" 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..238 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:0000305|PubMed:11387206" 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 MUTAGEN 896..898 FT /note="Missing: Abolishes interaction with PRKCABP." FT /evidence="ECO:0000269|PubMed:14672991" SQ SEQUENCE 898 AA; 98841 MW; 7A3CBCB9E7ACA135 CRC64; MAVRPGLWPV LLGIVLAAWL RGSGAQQSAT VANPVPGANP DLLPHFLVEP EDVYIVKNKP VLLVCKAVPA TQIFFKCNGE WVRQVDHVIE RSTDSSSGLP TMEVRINVSR QQVEKVFGLE EYWCQCVAWS SSGTTKSQKA YIRIAYLRKN FEQEPLAKEV SLEQGIVLPC RPPEGIPPAE VEWLRNEDLV DPSLDPNVYI TREHSLVVRQ ARLADTANYT CVAKNIVARR RSTSAAVIVY VNGGWSTWTE WSVCSASCGR GWQKRSRSCT NPAPLNGGAF CEGQNVQKTA CATLCPVDGS WSSWSKWSAC GLDCTHWRSR ECSDPAPRNG GEECRGADLD TRNCTSDLCL HTASCPEDVA LYIGLVAVAV CLFLLLLALG LIYCRKKEGL DSDVADSSIL TSGFQPVSIK PSKADNPHLL TIQPDLSTTT TTYQGSLCSR QDGPSPKFQL SNGHLLSPLG SGRHTLHHSS PTSEAEDFVS RLSTQNYFRS LPRGTSNMAY GTFNFLGGRL MIPNTGISLL IPPDAIPRGK IYEIYLTLHK PEDVRLPLAG CQTLLSPVVS CGPPGVLLTR PVILAMDHCG EPSPDSWSLR LKKQSCEGSW EDVLHLGEES PSHLYYCQLE AGACYVFTEQ LGRFALVGEA LSVAATKRLR LLLFAPVACT SLEYNIRVYC LHDTHDALKE VVQLEKQLGG QLIQEPRVLH FKDSYHNLRL SIHDVPSSLW KSKLLVSYQE IPFYHIWNGT QQYLHCTFTL ERINASTSDL ACKVWVWQVE GDGQSFNINF NITKDTRFAE LLALESEGGV PALVGPSAFK IPFLIRQKII ASLDPPCSRG ADWRTLAQKL HLDSHLSFFA SKPSPTAMIL NLWEARHFPN GNLGQLAAAV AGLGQPDAGL FTVSEAEC //