UNC5B_RAT
ID UNC5B_RAT Reviewed; 945 AA.
AC O08722;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 25-MAY-2022, entry version 145.
DE RecName: Full=Netrin receptor UNC5B;
DE AltName: Full=Protein unc-5 homolog 2;
DE AltName: Full=Protein unc-5 homolog B;
DE Flags: Precursor;
GN Name=Unc5b; Synonyms=Unc5h2;
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.
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 FUNCTION, MUTAGENESIS OF ASP-412, 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 [4]
RP FUNCTION, AND INTERACTION WITH DAPK1.
RX PubMed=15729359; DOI=10.1038/sj.emboj.7600584;
RA Llambi F., Lourenco F.C., Gozuacik D., Guix C., Pays L., Del Rio G.,
RA Kimchi A., Mehlen P.;
RT "The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase.";
RL EMBO J. 24:1192-1201(2005).
RN [5]
RP FUNCTION, PALMITOYLATION AT CYS-403, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH DAPK1.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 543-945, DOMAIN ZU5, AND DOMAIN
RP UPA.
RX PubMed=19328064; DOI=10.1016/j.molcel.2009.02.016;
RA Wang R., Wei Z., Jin H., Wu H., Yu C., Wen W., Chan L.N., Wen Z., Zhang M.;
RT "Autoinhibition of UNC5b revealed by the cytoplasmic domain structure of
RT the receptor.";
RL Mol. Cell 33:692-703(2009).
CC -!- FUNCTION: Receptor for netrin required for axon guidance. Mediates axon
CC repulsion of neuronal growth cones in the developing nervous system
CC upon ligand binding. Axon repulsion in growth cones may be caused by
CC its association with DCC that may trigger signaling for repulsion
CC (PubMed:10399920, PubMed:9126742). Functions as netrin receptor that
CC negatively regulates vascular branching during angiogenesis. Mediates
CC retraction of tip cell filopodia on endothelial growth cones in
CC response to netrin (By similarity). It also acts as a dependence
CC receptor required for apoptosis induction when not associated with
CC netrin ligand (PubMed:11387206). Mediates apoptosis by activating DAPK1
CC (PubMed:18582460). In the absence of NTN1, activates DAPK1 by reducing
CC its autoinhibitory phosphorylation at Ser-308 thereby increasing its
CC catalytic activity (PubMed:15729359). {ECO:0000250|UniProtKB:Q8K1S3,
CC ECO:0000269|PubMed:10399920, ECO:0000269|PubMed:11387206,
CC ECO:0000269|PubMed:15729359, ECO:0000269|PubMed:18582460,
CC ECO:0000305|PubMed:9126742}.
CC -!- SUBUNIT: Interacts with the cytoplasmic part of DCC (PubMed:10399920).
CC Interacts with GNAI2 via its cytoplasmic part (By similarity).
CC Interacts (via death domain) with DAPK1 (via death domain)
CC (PubMed:15729359, PubMed:18582460). Interacts (via extracellular
CC domain) with FLRT3 (via extracellular domain); the interaction is
CC direct. Interacts (via extracellular domain) with FLRT2 and FLRT3 (via
CC extracellular domain), but has higher affinity for FLRT3. Identified in
CC a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by
CC itself (By similarity). {ECO:0000250|UniProtKB:Q8IZJ1,
CC ECO:0000269|PubMed:10399920, ECO:0000269|PubMed:15729359,
CC ECO:0000269|PubMed:18582460}.
CC -!- INTERACTION:
CC O08722; Q8CGU4: Agap2; NbExp=6; IntAct=EBI-4404185, EBI-4409108;
CC O08722; P30154: PPP2R1B; Xeno; NbExp=4; IntAct=EBI-4404185, EBI-357094;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9126742};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:9126742}.
CC Membrane raft {ECO:0000269|PubMed:18582460}. Note=Associated with lipid
CC rafts (PubMed:18582460). {ECO:0000269|PubMed:18582460}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in regions of differentiating
CC neurons. Expressed in the developing sensory ganglia that flank the
CC spinal cord from E12, peaking at E14. Expressed in the roof plate
CC region of the spinal cord from E14. {ECO:0000269|PubMed:9126742}.
CC -!- PTM: Phosphorylated on cytoplasmic tyrosine residues. {ECO:0000250}.
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 -!- PTM: Palmitoylation is required for pro-apoptotic activity, but not for
CC location at lipid rafts. {ECO:0000269|PubMed:18582460}.
CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
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DR EMBL; U87306; AAB57679.1; -; mRNA.
DR RefSeq; NP_071543.1; NM_022207.1.
DR PDB; 3G5B; X-ray; 2.00 A; A=541-945.
DR PDBsum; 3G5B; -.
DR AlphaFoldDB; O08722; -.
DR SMR; O08722; -.
DR DIP; DIP-60743N; -.
DR IntAct; O08722; 5.
DR STRING; 10116.ENSRNOP00000034951; -.
DR GlyGen; O08722; 2 sites.
DR iPTMnet; O08722; -.
DR PhosphoSitePlus; O08722; -.
DR jPOST; O08722; -.
DR PaxDb; O08722; -.
DR PRIDE; O08722; -.
DR GeneID; 60630; -.
DR KEGG; rno:60630; -.
DR UCSC; RGD:621756; rat.
DR CTD; 219699; -.
DR RGD; 621756; Unc5b.
DR eggNOG; KOG1480; Eukaryota.
DR InParanoid; O08722; -.
DR OrthoDB; 334938at2759; -.
DR PhylomeDB; O08722; -.
DR EvolutionaryTrace; O08722; -.
DR PRO; PR:O08722; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IDA: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:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR CDD; cd08802; Death_UNC5B; 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; IPR042156; Death_UNC5B.
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; IPR003598; Ig_sub2.
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; 2.
DR SMART; SM00408; IGc2; 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; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS50092; TSP1; 2.
DR PROSITE; PS51145; ZU5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cell membrane; Developmental protein;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..945
FT /note="Netrin receptor UNC5B"
FT /id="PRO_0000036073"
FT TOPO_DOM 27..377
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..945
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 48..145
FT /note="Ig-like"
FT DOMAIN 153..242
FT /note="Ig-like C2-type"
FT DOMAIN 246..300
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 302..354
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 543..686
FT /note="ZU5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 865..943
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 689..838
FT /note="UPA domain"
FT REGION 707..725
FT /note="Interaction with DCC"
FT /evidence="ECO:0000269|PubMed:10399920"
FT SITE 412..413
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000305|PubMed:11387206"
FT MOD_RES 581
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O08747"
FT LIPID 403
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:18582460"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 69..130
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 81..128
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 174..225
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 258..295
FT /evidence="ECO:0000250"
FT DISULFID 262..299
FT /evidence="ECO:0000250"
FT DISULFID 273..285
FT /evidence="ECO:0000250"
FT DISULFID 314..348
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 318..353
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT DISULFID 326..338
FT /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT MUTAGEN 403
FT /note="C->V: Abolishes palmitoylation. Impairs interaction
FT with DAPK1. No effect on location on lipid rafts."
FT /evidence="ECO:0000269|PubMed:18582460"
FT MUTAGEN 412
FT /note="D->N: Abolishes cleavage by caspase-3 and subsequent
FT induction of apoptosis."
FT /evidence="ECO:0000269|PubMed:11387206"
FT STRAND 544..549
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 554..558
FT /evidence="ECO:0007829|PDB:3G5B"
FT TURN 559..562
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 563..567
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 578..584
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 587..593
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 598..600
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 605..608
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 618..623
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 629..631
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 634..642
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 646..651
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 660..665
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 667..676
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 678..685
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 692..703
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 707..720
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 721..734
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 736..738
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 743..751
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 754..759
FT /evidence="ECO:0007829|PDB:3G5B"
FT TURN 763..765
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 766..768
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 771..773
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 775..777
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 779..783
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 791..800
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 805..814
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 819..827
FT /evidence="ECO:0007829|PDB:3G5B"
FT STRAND 849..851
FT /evidence="ECO:0007829|PDB:3G5B"
FT TURN 852..855
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 860..870
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 880..886
FT /evidence="ECO:0007829|PDB:3G5B"
FT TURN 891..893
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 894..897
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 902..914
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 920..929
FT /evidence="ECO:0007829|PDB:3G5B"
FT HELIX 934..940
FT /evidence="ECO:0007829|PDB:3G5B"
SQ SEQUENCE 945 AA; 103521 MW; 6E9C2A262E560B9B CRC64;
MRARSGARGA LLLALLLCWD PTPSLAGIDS GGQALPDSFP SAPAEQLPHF LLEPEDAYIV
KNKPVELHCR AFPATQIYFK CNGEWVSQKG HVTQESLDEA TGLRIREVQI EVSRQQVEEL
FGLEDYWCQC VAWSSSGTTK SRRAYIRIAY LRKNFDQEPL AKEVPLDHEV LLQCRPPEGV
PVAEVEWLKN EDVIDPAQDT NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT
VIVYVNGGWS SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAC QKTACTTVCP
VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD GLCVLNQRTL
NDPKSRPLEP SGDVALYAGL VVAVFVVLAV LMAVGVIVYR RNCRDFDTDI TDSSAALTGG
FHPVNFKTAR PSNPQLLHPS APPDLTASAG IYRGPVYALQ DSADKIPMTN SPLLDPLPSL
KIKVYDSSTI GSGAGLADGA DLLGVLPPGT YPGDFSRDTH FLHLRSASLG SQHLLGLPRD
PSSSVSGTFG CLGGRLTIPG TGVSLLVPNG AIPQGKFYDL YLRINKTEST LPLSEGSQTV
LSPSVTCGPT GLLLCRPVVL TVPHCAEVIA GDWIFQLKTQ AHQGHWEEVV TLDEETLNTP
CYCQLEAKSC HILLDQLGTY VFTGESYSRS AVKRLQLAIF APALCTSLEY SLRVYCLEDT
PAALKEVLEL ERTLGGYLVE EPKTLLFKDS YHNLRLSLHD IPHAHWRSKL LAKYQEIPFY
HVWNGSQKAL HCTFTLERHS LASTEFTCKV CVRQVEGEGQ IFQLHTTLAE TPAGSLDALC
SAPGNAATTQ LGPYAFKIPL SIRQKICNSL DAPNSRGNDW RLLAQKLSMD RYLNYFATKA
SPTGVILDLW EARQQDDGDL NSLASALEEM GKSEMLVAMT TDGDC
