NPBW2_HUMAN
ID NPBW2_HUMAN Reviewed; 333 AA.
AC P48146; Q6NWQ6; Q9H4K3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Neuropeptides B/W receptor type 2;
DE AltName: Full=G-protein coupled receptor 8;
GN Name=NPBWR2; Synonyms=GPR8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-206.
RX PubMed=7590751; DOI=10.1006/geno.1995.1109;
RA O'Dowd B.F., Scheideler M.A., Nguyen T., Cheng R., Rasmussen J.S.,
RA Marchese A., Zastawny R., Heng H.H.Q., Tsui L.-C., Shi X., Asa S., Puy L.,
RA George S.R.;
RT "The cloning and chromosomal mapping of two novel human opioid-
RT somatostatin-like receptor genes, GPR7 and GPR8, expressed in discrete
RT areas of the brain.";
RL Genomics 28:84-91(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY, AND INTERACTION WITH NEUROPEPTIDES B AND W.
RX PubMed=12401809; DOI=10.1074/jbc.m206396200;
RA Brezillon S., Lannoy V., Franssen J.-D., Le Poul E., Dupriez V.,
RA Lucchetti J., Detheux M., Parmentier M.;
RT "Identification of natural ligands for the orphan G protein-coupled
RT receptors GPR7 and GPR8.";
RL J. Biol. Chem. 278:776-783(2003).
RN [6]
RP INTERACTION WITH NEUROPEPTIDES B AND W.
RX PubMed=12719537; DOI=10.1073/pnas.0837789100;
RA Tanaka H., Yoshida T., Miyamoto N., Motoike T., Kurosu H., Shibata K.,
RA Yamanaka A., Williams S.C., Richardson J.A., Tsujino N., Garry M.G.,
RA Lerner M.R., King D.S., O'Dowd B.F., Sakurai T., Yanagisawa M.;
RT "Characterization of a family of endogenous neuropeptide ligands for the G
RT protein-coupled receptors GPR7 and GPR8.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6251-6256(2003).
RN [7]
RP VARIANT ARG-206.
RA Zeng J., Liu M., Grau O., Capron A., Bahr G.M.;
RT "Identification of a novel amino acid substitution (R206Q) in the second
RT extracellular loop of the opioid-somatostatin-like receptor gene GPR8.";
RL Hum. Mutat. 12:219-219(1998).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-92.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Interacts specifically with a number of opioid ligands.
CC Receptor for neuropeptides B and W, which may be involved in
CC neuroendocrine system regulation, food intake and the organization of
CC other signals.
CC -!- INTERACTION:
CC P48146; Q8N9W6: BOLL; NbExp=3; IntAct=EBI-10210114, EBI-998198;
CC P48146; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10210114, EBI-3867333;
CC P48146; Q5T749: KPRP; NbExp=3; IntAct=EBI-10210114, EBI-10981970;
CC P48146; Q15323: KRT31; NbExp=6; IntAct=EBI-10210114, EBI-948001;
CC P48146; O76011: KRT34; NbExp=3; IntAct=EBI-10210114, EBI-1047093;
CC P48146; Q6A162: KRT40; NbExp=3; IntAct=EBI-10210114, EBI-10171697;
CC P48146; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-10210114, EBI-11749135;
CC P48146; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-10210114, EBI-10172290;
CC P48146; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-10210114, EBI-10172052;
CC P48146; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-10210114, EBI-3958099;
CC P48146; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-10210114, EBI-11962084;
CC P48146; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10210114, EBI-945833;
CC P48146; Q9BSU1: PHAF1; NbExp=3; IntAct=EBI-10210114, EBI-946080;
CC P48146; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-10210114, EBI-302345;
CC P48146; P25788: PSMA3; NbExp=3; IntAct=EBI-10210114, EBI-348380;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Detected at high levels in caudate nucleus,
CC hippocampus and amygdala; at moderate levels in the adult brain,
CC thalamus, parietal cortex, pituitary gland, adrenal gland and lymph
CC nodes. {ECO:0000269|PubMed:12401809}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U22492; AAC50198.1; -; Genomic_DNA.
DR EMBL; AL121581; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75161.1; -; Genomic_DNA.
DR EMBL; BC067481; AAH67481.1; -; mRNA.
DR EMBL; BC067482; AAH67482.1; -; mRNA.
DR CCDS; CCDS13557.1; -.
DR PIR; I38974; I38974.
DR RefSeq; NP_005277.2; NM_005286.2.
DR AlphaFoldDB; P48146; -.
DR SMR; P48146; -.
DR BioGRID; 109093; 16.
DR IntAct; P48146; 15.
DR STRING; 9606.ENSP00000358783; -.
DR ChEMBL; CHEMBL4523864; -.
DR GuidetoPHARMACOLOGY; 304; -.
DR TCDB; 9.A.14.13.13; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P48146; 3 sites.
DR iPTMnet; P48146; -.
DR PhosphoSitePlus; P48146; -.
DR BioMuta; NPBWR2; -.
DR MassIVE; P48146; -.
DR PaxDb; P48146; -.
DR PeptideAtlas; P48146; -.
DR PRIDE; P48146; -.
DR Antibodypedia; 15539; 121 antibodies from 24 providers.
DR DNASU; 2832; -.
DR Ensembl; ENST00000369768.1; ENSP00000358783.1; ENSG00000125522.4.
DR Ensembl; ENST00000612646.2; ENSP00000484253.1; ENSG00000277339.2.
DR Ensembl; ENST00000684052.1; ENSP00000508236.1; ENSG00000125522.4.
DR GeneID; 2832; -.
DR KEGG; hsa:2832; -.
DR MANE-Select; ENST00000684052.1; ENSP00000508236.1; NM_005286.4; NP_005277.2.
DR UCSC; uc011abt.3; human.
DR CTD; 2832; -.
DR DisGeNET; 2832; -.
DR GeneCards; NPBWR2; -.
DR HGNC; HGNC:4530; NPBWR2.
DR HPA; ENSG00000125522; Not detected.
DR MIM; 600731; gene.
DR neXtProt; NX_P48146; -.
DR OpenTargets; ENSG00000125522; -.
DR PharmGKB; PA28923; -.
DR VEuPathDB; HostDB:ENSG00000125522; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000163127; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; P48146; -.
DR OMA; IISFCVW; -.
DR OrthoDB; 1011272at2759; -.
DR PhylomeDB; P48146; -.
DR TreeFam; TF315737; -.
DR PathwayCommons; P48146; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P48146; -.
DR BioGRID-ORCS; 2832; 12 hits in 1069 CRISPR screens.
DR GeneWiki; Neuropeptides_B/W_receptor_2; -.
DR GenomeRNAi; 2832; -.
DR Pharos; P48146; Tbio.
DR PRO; PR:P48146; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P48146; protein.
DR Bgee; ENSG00000125522; Expressed in primary visual cortex and 11 other tissues.
DR Genevisible; P48146; HS.
DR GO; GO:0016021; C:integral component of membrane; IC:HGNC-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004985; F:G protein-coupled opioid receptor activity; TAS:ProtInc.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR GO; GO:0008188; F:neuropeptide receptor activity; IEA:InterPro.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:HGNC-UCL.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR009150; Neuropept_B/W_rcpt.
DR InterPro; IPR027349; NPBW2.
DR PANTHER; PTHR24229:SF18; PTHR24229:SF18; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01855; NRPEPTIDEWR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..333
FT /note="Neuropeptides B/W receptor type 2"
FT /id="PRO_0000069522"
FT TOPO_DOM 1..45
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..69
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 70..80
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..105
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 106..120
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..140
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..185
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..211
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..233
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..257
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 258..282
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..292
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..307
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 308..333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 117..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 92
FT /note="G -> R (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs768724424)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035766"
FT VARIANT 206
FT /note="Q -> R (in dbSNP:rs4809401)"
FT /evidence="ECO:0000269|PubMed:7590751, ECO:0000269|Ref.7"
FT /id="VAR_003579"
FT CONFLICT 305
FT /note="S -> T (in Ref. 1; AAC50198)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 333 AA; 36861 MW; 8C416473FD80B0BA CRC64;
MQAAGHPEPL DSRGSFSLPT MGANVSQDNG TGHNATFSEP LPFLYVLLPA VYSGICAVGL
TGNTAVILVI LRAPKMKTVT NVFILNLAVA DGLFTLVLPV NIAEHLLQYW PFGELLCKLV
LAVDHYNIFS SIYFLAVMSV DRYLVVLATV RSRHMPWRTY RGAKVASLCV WLGVTVLVLP
FFSFAGVYSN ELQVPSCGLS FPWPEQVWFK ASRVYTLVLG FVLPVCTICV LYTDLLRRLR
AVRLRSGAKA LGKARRKVTV LVLVVLAVCL LCWTPFHLAS VVALTTDLPQ TPLVISMSYV
ITSLSYANSC LNPFLYAFLD DNFRKNFRSI LRC