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 13-JUL-2010, entry version 84. DE RecName: Full=Netrin receptor UNC5A; DE AltName: Full=Protein unc-5 homolog A; DE AltName: Full=Protein unc-5 homolog 1; DE Flags: Precursor; GN Name=Unc5a; Synonyms=Unc5h1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; 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 MEDLINE=97271897; 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 MEDLINE=99325507; 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 MEDLINE=21366013; 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. RX MEDLINE=21280795; 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, AND INTERACTION WITH MAGED1. RX MEDLINE=22615898; 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). CC -!- FUNCTION: Receptor for netrin required for axon guidance. Mediates CC axon repulsion of neuronal growth cones in the developing nervous CC system upon ligand binding. Axon repulsion in growth cones may be CC caused by its association with DCC that may trigger signaling for CC repulsion. It also acts as a dependence receptor required for CC apoptosis induction when not associated with netrin ligand. CC -!- SUBUNIT: Interacts with the cytoplasmic part of DCC. Interacts CC with MAGED1. Interacts with PRKCABP, possibly mediating some CC interaction with PKC. CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. Note=The interaction with PRKCABP regulates its surface CC expression and leads to its removal from surface of neurons and CC growth cones. 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 -!- DOMAIN: The ZU5 domain mediates the interaction with MAGED1, which CC participates in the induction of apoptosis. CC -!- PTM: Phosphorylated on cytoplasmic tyrosine residues (By CC similarity). Phosphorylated by PKC in vitro. 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. CC -!- SIMILARITY: Belongs to the unc-5 family. CC -!- SIMILARITY: Contains 1 death domain. CC -!- SIMILARITY: Contains 1 Ig-like (immunoglobulin-like) domain. CC -!- SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) CC domain. CC -!- SIMILARITY: Contains 2 TSP type-1 domains. CC -!- SIMILARITY: Contains 1 ZU5 domain. 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 IPI; IPI00195507; -. DR RefSeq; NP_071542.1; -. DR UniGene; Rn.44433; -. DR SMR; O08721; 242-349, 808-895. DR STRING; O08721; -. DR Ensembl; ENSRNOT00000034731; ENSRNOP00000032250; ENSRNOG00000025920; Rattus norvegicus. DR GeneID; 60629; -. DR KEGG; rno:60629; -. DR CTD; 60629; -. DR RGD; 621755; Unc5a. DR eggNOG; maNOG12483; -. DR HOVERGEN; HBG056483; -. DR InParanoid; O08721; -. DR NextBio; 612347; -. DR ArrayExpress; O08721; -. DR Genevestigator; O08721; -. DR GermOnline; ENSRNOG00000025920; Rattus norvegicus. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005042; F:netrin receptor activity; IDA:RGD. DR GO; GO:0005515; F:protein binding; IEA:InterPro. DR GO; GO:0006915; P:apoptosis; IEA:UniProtKB-KW. DR GO; GO:0007411; P:axon guidance; IDA:RGD. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR InterPro; IPR000488; Death. DR InterPro; IPR011029; DEATH-like. DR InterPro; IPR007110; Ig-like. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR000884; Thrombospondin_1_rpt. DR InterPro; IPR000906; ZU5. DR Gene3D; G3DSA:1.10.533.10; DEATH_like; 1. DR Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF07679; I-set; 1. DR Pfam; PF00090; TSP_1; 2. 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_like; 1. DR SUPFAM; SSF82895; TSP1; 2. DR PROSITE; PS50017; DEATH_DOMAIN; FALSE_NEG. 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; Developmental protein; Disulfide bond; KW Glycoprotein; Immunoglobulin domain; Membrane; Phosphoprotein; KW Receptor; Repeat; Signal; Transmembrane. FT SIGNAL 1 25 Potential. FT CHAIN 26 898 Netrin receptor UNC5A. FT /FTId=PRO_0000036070. FT TOPO_DOM 26 361 Extracellular (Potential). FT TRANSMEM 362 382 Helical; (Potential). FT TOPO_DOM 383 898 Cytoplasmic (Potential). FT DOMAIN 44 141 Ig-like. FT DOMAIN 155 238 Ig-like C2-type. FT DOMAIN 242 296 TSP type-1 1. FT DOMAIN 298 350 TSP type-1 2. FT DOMAIN 495 601 ZU5. FT DOMAIN 817 897 Death. FT REGION 661 679 Interaction with DCC (By similarity). FT SITE 396 397 Cleavage; by caspase-3 (By similarity). FT CARBOHYD 107 107 N-linked (GlcNAc...) (Potential). FT CARBOHYD 218 218 N-linked (GlcNAc...) (Potential). FT CARBOHYD 343 343 N-linked (GlcNAc...) (Potential). FT DISULFID 65 124 By similarity. FT DISULFID 170 221 By similarity. FT DISULFID 254 291 By similarity. FT DISULFID 258 295 By similarity. FT DISULFID 269 281 By similarity. FT MUTAGEN 896 898 Missing: Abolishes interaction with FT PRKCABP. 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 //