GRPR_HUMAN
ID GRPR_HUMAN Reviewed; 384 AA.
AC P30550; B2R910;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Gastrin-releasing peptide receptor;
DE Short=GRP-R;
DE AltName: Full=GRP-preferring bombesin receptor;
GN Name=GRPR;
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 [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Lung;
RX PubMed=1655761; DOI=10.1016/s0021-9258(18)55129-2;
RA Corjay M.H., Dobrzanski D.J., Way J.M., Viallet J., Shapira H., Worland P.,
RA Sausville E.A., Battey J.F.;
RT "Two distinct bombesin receptor subtypes are expressed and functional in
RT human lung carcinoma cells.";
RL J. Biol. Chem. 266:18771-18779(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=11245983; DOI=10.1016/s0378-1119(00)00596-5;
RA Xiao D., Wang J., Hampton L.L., Weber H.C.;
RT "The human gastrin-releasing peptide receptor gene structure, its tissue
RT expression and promoter.";
RL Gene 264:95-103(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=34610277; DOI=10.1016/j.cell.2021.09.013;
RA Melzer S., Newmark E.R., Mizuno G.O., Hyun M., Philson A.C., Quiroli E.,
RA Righetti B., Gregory M.R., Huang K.W., Levasseur J., Tian L.,
RA Sabatini B.L.;
RT "Bombesin-like peptide recruits disinhibitory cortical circuits and
RT enhances fear memories.";
RL Cell 184:5622-5634(2021).
CC -!- FUNCTION: Receptor for gastrin-releasing peptide (GRP)
CC (PubMed:1655761). Signals via association with G proteins that activate
CC a phosphatidylinositol-calcium second messenger system, resulting in
CC Akt phosphorylation. Contributes to the regulation of food intake.
CC Contributes to the perception of prurient stimuli and transmission of
CC itch signals in the spinal cord that promote scratching behavior, but
CC does not play a role in the perception of pain. Contributes primarily
CC to nonhistaminergic itch sensation. In one study, shown to act in the
CC amygdala as part of an inhibitory network which inhibits memory
CC specifically related to learned fear (By similarity). In another study,
CC shown to contribute to disinhibition of glutamatergic cells in the
CC auditory cortex via signaling on vasoactive intestinal peptide-
CC expressing cells which leads to enhanced auditory fear memories (By
CC similarity). Contributes to the induction of sighing through signaling
CC in the pre-Botzinger complex, a cluster of several thousand neurons in
CC the ventrolateral medulla responsible for inspiration during
CC respiratory activity (By similarity). {ECO:0000250|UniProtKB:P21729,
CC ECO:0000269|PubMed:1655761}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1655761};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in pancreas (PubMed:11245983).
CC Also expressed in stomach, adrenal cortex and brain (PubMed:11245983).
CC In brain, expressed in cells throughout the cortex (PubMed:34610277).
CC {ECO:0000269|PubMed:11245983, ECO:0000269|PubMed:34610277}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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; M73481; AAA88050.1; -; mRNA.
DR EMBL; AF293323; AAL96377.1; -; Genomic_DNA.
DR EMBL; AF293321; AAL96377.1; JOINED; Genomic_DNA.
DR EMBL; AF293322; AAL96377.1; JOINED; Genomic_DNA.
DR EMBL; AK313588; BAG36357.1; -; mRNA.
DR EMBL; CH471074; EAW98909.1; -; Genomic_DNA.
DR EMBL; BC074733; AAH74733.1; -; mRNA.
DR CCDS; CCDS14174.1; -.
DR PIR; A41007; A41007.
DR RefSeq; NP_005305.1; NM_005314.2.
DR AlphaFoldDB; P30550; -.
DR SMR; P30550; -.
DR BioGRID; 109181; 81.
DR IntAct; P30550; 51.
DR STRING; 9606.ENSP00000369643; -.
DR BindingDB; P30550; -.
DR ChEMBL; CHEMBL4959; -.
DR GuidetoPHARMACOLOGY; 39; -.
DR GlyGen; P30550; 1 site.
DR iPTMnet; P30550; -.
DR PhosphoSitePlus; P30550; -.
DR BioMuta; GRPR; -.
DR DMDM; 232185; -.
DR EPD; P30550; -.
DR MassIVE; P30550; -.
DR PaxDb; P30550; -.
DR PeptideAtlas; P30550; -.
DR PRIDE; P30550; -.
DR ProteomicsDB; 54720; -.
DR Antibodypedia; 23994; 283 antibodies from 29 providers.
DR DNASU; 2925; -.
DR Ensembl; ENST00000380289.3; ENSP00000369643.2; ENSG00000126010.6.
DR GeneID; 2925; -.
DR KEGG; hsa:2925; -.
DR MANE-Select; ENST00000380289.3; ENSP00000369643.2; NM_005314.3; NP_005305.1.
DR CTD; 2925; -.
DR DisGeNET; 2925; -.
DR GeneCards; GRPR; -.
DR HGNC; HGNC:4609; GRPR.
DR HPA; ENSG00000126010; Tissue enriched (pancreas).
DR MIM; 305670; gene.
DR neXtProt; NX_P30550; -.
DR OpenTargets; ENSG00000126010; -.
DR PharmGKB; PA29002; -.
DR VEuPathDB; HostDB:ENSG00000126010; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244862; -.
DR HOGENOM; CLU_009579_6_2_1; -.
DR InParanoid; P30550; -.
DR OMA; TMINGRQ; -.
DR OrthoDB; 1153238at2759; -.
DR PhylomeDB; P30550; -.
DR TreeFam; TF331292; -.
DR PathwayCommons; P30550; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P30550; -.
DR SIGNOR; P30550; -.
DR BioGRID-ORCS; 2925; 9 hits in 695 CRISPR screens.
DR GeneWiki; Gastrin-releasing_peptide_receptor; -.
DR GenomeRNAi; 2925; -.
DR Pharos; P30550; Tchem.
DR PRO; PR:P30550; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P30550; protein.
DR Bgee; ENSG00000126010; Expressed in buccal mucosa cell and 67 other tissues.
DR ExpressionAtlas; P30550; baseline and differential.
DR Genevisible; P30550; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042923; F:neuropeptide binding; IEA:Ensembl.
DR GO; GO:0008188; F:neuropeptide receptor activity; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0061744; P:motor behavior; ISS:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:2000987; P:positive regulation of behavioral fear response; ISS:UniProtKB.
DR GO; GO:1903942; P:positive regulation of respiratory gaseous exchange; ISS:UniProtKB.
DR GO; GO:0036343; P:psychomotor behavior; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043207; P:response to external biotic stimulus; IEA:Ensembl.
DR GO; GO:0035176; P:social behavior; ISS:UniProtKB.
DR InterPro; IPR001556; Bombsn_rcpt-like.
DR InterPro; IPR001966; Gastrin_pep_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00358; BOMBESINR.
DR PRINTS; PR00640; GASTRINRELPR.
DR PRINTS; PR00237; GPCRRHODOPSN.
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 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..384
FT /note="Gastrin-releasing peptide receptor"
FT /id="PRO_0000069662"
FT TOPO_DOM 1..38
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..62
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..96
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..136
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..152
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..174
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..208
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..234
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 235..264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..298
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..325
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54799"
FT LIPID 339
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 113..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 384 AA; 43199 MW; 70A75F11D9C82F19 CRC64;
MALNDCFLLN LEVDHFMHCN ISSHSADLPV NDDWSHPGIL YVIPAVYGVI ILIGLIGNIT
LIKIFCTVKS MRNVPNLFIS SLALGDLLLL ITCAPVDASR YLADRWLFGR IGCKLIPFIQ
LTSVGVSVFT LTALSADRYK AIVRPMDIQA SHALMKICLK AAFIWIISML LAIPEAVFSD
LHPFHEESTN QTFISCAPYP HSNELHPKIH SMASFLVFYV IPLSIISVYY YFIAKNLIQS
AYNLPVEGNI HVKKQIESRK RLAKTVLVFV GLFAFCWLPN HVIYLYRSYH YSEVDTSMLH
FVTSICARLL AFTNSCVNPF ALYLLSKSFR KQFNTQLLCC QPGLIIRSHS TGRSTTCMTS
LKSTNPSVAT FSLINGNICH ERYV
