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 10-MAY-2017, entry version 129. 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, GN ECO:0000303|PubMed:14672991, ECO:0000303|PubMed:9126742}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; 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., RA Stein E.; RT "A ligand-gated association between cytoplasmic domains of UNC5 and RT DCC 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 RT motor 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; RA Williams M.E., Wu S.C.-Y., McKenna W.L., Hinck L.; RT "Surface expression of the netrin receptor UNC5H1 is regulated through RT a protein kinase C-interacting protein/protein kinase-dependent RT 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 RT 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 RT the 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 CC signaling pathway and promotes neurite outgrowth in response to CC NTN1 (PubMed:19755150). Mediates axon repulsion of neuronal growth CC cones in the developing nervous system in response to netrin CC (PubMed:10399920). Axon repulsion in growth cones may be mediated CC by its association with DCC that may trigger signaling for CC repulsion (PubMed:10399920). It also acts as a dependence receptor CC required for apoptosis induction when not associated with netrin CC 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 CC with the cytoplasmic part of DCC (PubMed:10399920). Interacts with CC MAGED1 (PubMed:12598531). Interacts with PRKCABP, possibly CC mediating some interaction with PKC (PubMed:14672991). Interacts CC (via extracellular domain) with FLRT2 (via extracellular domain) CC (By similarity). Interacts (via extracellular domain) with FLRT3 CC (via extracellular domain) (By similarity). CC {ECO:0000250|UniProtKB:Q6ZN44, ECO:0000250|UniProtKB:Q8K1S4, CC ECO:0000269|PubMed:10399920, ECO:0000269|PubMed:12598531, CC ECO:0000269|PubMed:14672991}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12598531, CC ECO:0000269|PubMed:19755150, ECO:0000269|PubMed:9126742}; Single- CC pass type I membrane protein {ECO:0000269|PubMed:12598531, CC ECO:0000269|PubMed:9126742, ECO:0000305}. Membrane raft CC {ECO:0000269|PubMed:18582460}. Cell 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). Detected in CC neurites (PubMed:19755150). {ECO:0000269|PubMed:14672991}. CC -!- TISSUE SPECIFICITY: Mainly expressed in regions of differentiating CC neurons. Expressed at early stages of neural tube development in CC the ventral spinal cord. In developing hindbrain, it colocalizes CC with a number of cranial motor neuron subpopulations from CC embryonic E11 to E14, while DCC is expressed by motor neurons at CC E12. Also expressed in non-neural structures, such as the basal CC plane of the hindbrain and midbrain, in the developing CC 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 CC similarity). Phosphorylated by PKC in vitro. {ECO:0000250, CC ECO:0000269|PubMed:14672991}. CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The CC cleavage does not take place when the receptor is associated with CC netrin ligand. Its cleavage by caspases is required to induce CC apoptosis. {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 UniGene; Rn.44433; -. DR ProteinModelPortal; O08721; -. DR SMR; O08721; -. DR DIP; DIP-60742N; -. DR STRING; 10116.ENSRNOP00000032250; -. DR iPTMnet; O08721; -. DR PhosphoSitePlus; O08721; -. DR PaxDb; O08721; -. DR GeneID; 60629; -. DR KEGG; rno:60629; -. DR UCSC; RGD:621755; rat. DR CTD; 90249; -. DR RGD; 621755; Unc5a. DR eggNOG; KOG1480; Eukaryota. DR eggNOG; ENOG410XRS6; LUCA. DR HOGENOM; HOG000060306; -. DR HOVERGEN; HBG056483; -. DR InParanoid; O08721; -. DR KO; K07521; -. DR PhylomeDB; O08721; -. DR PRO; PR:O08721; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB. 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; TAS:Reactome. DR GO; GO:0005042; F:netrin receptor activity; IDA: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 Gene3D; 2.20.100.10; -; 2. DR Gene3D; 2.60.40.10; -; 2. DR InterPro; IPR011029; DEATH-like_dom. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR000884; TSP1_rpt. DR InterPro; IPR033772; UPA. DR InterPro; IPR000906; ZU5_dom. 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 Apoptosis; Cell membrane; Cell projection; Complete proteome; KW Developmental protein; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Membrane; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 25 {ECO:0000255}. FT CHAIN 26 898 Netrin receptor UNC5A. FT /FTId=PRO_0000036070. FT TOPO_DOM 26 361 Extracellular. {ECO:0000255}. FT TRANSMEM 362 382 Helical. {ECO:0000255}. FT TOPO_DOM 383 898 Cytoplasmic. {ECO:0000255}. FT DOMAIN 44 141 Ig-like. FT DOMAIN 155 238 Ig-like C2-type. FT DOMAIN 242 296 TSP type-1 1. {ECO:0000255|PROSITE- FT ProRule:PRU00210}. FT DOMAIN 298 350 TSP type-1 2. {ECO:0000255|PROSITE- FT ProRule:PRU00210}. FT DOMAIN 497 640 ZU5. {ECO:0000255|PROSITE- FT ProRule:PRU00485}. FT DOMAIN 817 897 Death. FT REGION 661 679 Interaction with DCC. {ECO:0000250}. FT SITE 396 397 Cleavage; by caspase-3. FT {ECO:0000305|PubMed:11387206}. FT CARBOHYD 107 107 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 218 218 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 343 343 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 65 126 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 77 124 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 170 221 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 254 291 {ECO:0000250}. FT DISULFID 258 295 {ECO:0000250}. FT DISULFID 269 281 {ECO:0000250}. FT DISULFID 310 344 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 314 349 {ECO:0000250|UniProtKB:Q6ZN44}. FT DISULFID 322 334 {ECO:0000250|UniProtKB:Q6ZN44}. FT MUTAGEN 896 898 Missing: Abolishes interaction with FT PRKCABP. {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 //