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   27-MAR-2024, entry version 199.
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   GlyCosmos; P48146; 3 sites, No reported glycans.
DR   GlyGen; P48146; 3 sites.
DR   iPTMnet; P48146; -.
DR   PhosphoSitePlus; P48146; -.
DR   BioMuta; NPBWR2; -.
DR   MassIVE; P48146; -.
DR   PaxDb; 9606-ENSP00000358783; -.
DR   Antibodypedia; 15539; 139 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   AGR; HGNC:4530; -.
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; VPMCTLC; -.
DR   OrthoDB; 5393360at2759; -.
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 1147 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 cell types or tissues.
DR   GO; GO:0016020; C:membrane; IC:HGNC-UCL.
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:0007186; P:G protein-coupled receptor signaling pathway; IDA:HGNC-UCL.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   CDD; cd15087; 7tmA_NPBWR; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR009150; Neuropept_B/W_rcpt.
DR   PANTHER; PTHR24229:SF18; NEUROPEPTIDES B_W RECEPTOR TYPE 2; 1.
DR   PANTHER; PTHR24229; NEUROPEPTIDES RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01855; NRPEPTIDEWR.
DR   SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; P48146; HS.
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
//