UNC5A_RAT
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 25-MAY-2022, entry version 147.
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}.
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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 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: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: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; 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 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
