GRP_HUMAN
ID GRP_HUMAN Reviewed; 148 AA.
AC P07492; P07491; P81553; Q14454; Q53YA0; Q9BSY7;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Gastrin-releasing peptide;
DE Short=GRP;
DE Contains:
DE RecName: Full=Neuromedin-C;
DE AltName: Full=GRP-10;
DE AltName: Full=GRP18-27 {ECO:0000250|UniProtKB:Q8R1I2};
DE Flags: Precursor;
GN Name=GRP;
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] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 70-148 (ISOFORM 2), AND VARIANT SER-4.
RX PubMed=3001723; DOI=10.1073/pnas.83.1.19;
RA Spindel E.R., Zilberberg M.D., Habener J.F., Chin W.W.;
RT "Two prohormones for gastrin-releasing peptide are encoded by two mRNAs
RT differing by 19 nucleotides.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:19-23(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AMIDATION AT MET-50, AND SUBCELLULAR LOCATION.
RX PubMed=3211139; DOI=10.1128/mcb.8.8.3129-3135.1988;
RA Lebacq-Verheyden A.-M., Kasprzyk P.G., Raum M.G., van Wyke Coelingh K.,
RA Lebacq J.A., Battey J.F.;
RT "Posttranslational processing of endogenous and of baculovirus-expressed
RT human gastrin-releasing peptide precursor.";
RL Mol. Cell. Biol. 8:3129-3135(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=3003116; DOI=10.1016/s0021-9258(17)35956-2;
RA Sausville E.A., Lebacq-Verheyden A.-M., Spindel E.R., Cuttitta F.,
RA Gazdar A.F., Battey J.F.;
RT "Expression of the gastrin-releasing peptide gene in human small cell lung
RT cancer. Evidence for alternative processing resulting in three distinct
RT mRNAs.";
RL J. Biol. Chem. 261:2451-2457(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [8]
RP STRUCTURE BY NMR OF 41-50.
RX DOI=10.1039/C5RA12753J;
RA Adrover M., Sanchis P., Vilanova B., Pauwels K., Martorell G., Perez J.J.;
RT "Conformational ensembles of neuromedin C reveal a progressive coil-helix
RT transition within a binding-induced folding mechanism.";
RL RSC Adv. 5:83074-83088(2015).
CC -!- FUNCTION: Stimulates the release of gastrin and other gastrointestinal
CC hormones (By similarity). Contributes to the perception of prurient
CC stimuli and to the transmission of itch signals in the spinal cord that
CC promote scratching behavior (By similarity). Contributes primarily to
CC nonhistaminergic itch sensation (By similarity). In one study, shown to
CC act in the amygdala as part of an inhibitory network which inhibits
CC memory specifically related to learned fear (By similarity). In another
CC study, shown to act on vasoactive intestinal peptide (VIP)-expressing
CC cells in the auditory cortex, most likely via extrasynaptic diffusion
CC from local and long-range sources, to mediate disinhibition of
CC glutamatergic cells via VIP cell-specific GRPR signaling which leads to
CC enhanced auditory fear memories (By similarity). Contributes to the
CC regulation of food intake (By similarity). Inhibits voltage-gated
CC sodium channels but enhances voltage-gated potassium channels in
CC hippocampal neurons (By similarity). Induces sighing by acting directly
CC on 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:P24393,
CC ECO:0000250|UniProtKB:P63153, ECO:0000250|UniProtKB:Q8R1I2}.
CC -!- FUNCTION: [Neuromedin-C]: Induces an itch response through activation
CC of receptors present on mast cells, triggering mast cell degranulation.
CC {ECO:0000250|UniProtKB:Q8R1I2}.
CC -!- INTERACTION:
CC P07492; Q15699: ALX1; NbExp=3; IntAct=EBI-12821367, EBI-750671;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3211139}.
CC Cytoplasmic vesicle, secretory vesicle lumen
CC {ECO:0000250|UniProtKB:Q863C3}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q8R1I2}. Note=In neurons of the retrotrapezoid
CC nucleus/parafacial respiratory group, expressed on neuron projections
CC which project into the pre-Botzinger complex.
CC {ECO:0000250|UniProtKB:Q8R1I2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P07492-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P07492-2; Sequence=VSP_000549;
CC Name=3;
CC IsoId=P07492-3; Sequence=VSP_000550;
CC -!- SIMILARITY: Belongs to the bombesin/neuromedin-B/ranatensin family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA52612.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Gastrin-releasing peptide entry;
CC URL="https://en.wikipedia.org/wiki/Gastrin_releasing_peptide";
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DR EMBL; K02054; AAA52613.1; -; mRNA.
DR EMBL; M12550; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M12512; AAA52612.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M12511; AAA52612.1; JOINED; Genomic_DNA.
DR EMBL; M12512; AAA52611.1; -; Genomic_DNA.
DR EMBL; M12511; AAA52611.1; JOINED; Genomic_DNA.
DR EMBL; BT006803; AAP35449.1; -; mRNA.
DR EMBL; AC067859; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471096; EAW63091.1; -; Genomic_DNA.
DR EMBL; BC004488; AAH04488.1; -; mRNA.
DR CCDS; CCDS11971.1; -. [P07492-1]
DR CCDS; CCDS45877.1; -. [P07492-3]
DR CCDS; CCDS45878.1; -. [P07492-2]
DR PIR; A26182; A26182.
DR PIR; B26182; B26182.
DR RefSeq; NP_001012530.1; NM_001012512.2. [P07492-3]
DR RefSeq; NP_001012531.1; NM_001012513.2. [P07492-2]
DR RefSeq; NP_002082.2; NM_002091.4. [P07492-1]
DR PDB; 2N0B; NMR; -; A=41-50.
DR PDB; 2N0C; NMR; -; A=41-50.
DR PDB; 2N0D; NMR; -; A=41-50.
DR PDB; 2N0E; NMR; -; A=41-50.
DR PDB; 2N0F; NMR; -; A=41-50.
DR PDB; 2N0G; NMR; -; A=41-50.
DR PDB; 2N0H; NMR; -; A=41-50.
DR PDBsum; 2N0B; -.
DR PDBsum; 2N0C; -.
DR PDBsum; 2N0D; -.
DR PDBsum; 2N0E; -.
DR PDBsum; 2N0F; -.
DR PDBsum; 2N0G; -.
DR PDBsum; 2N0H; -.
DR AlphaFoldDB; P07492; -.
DR SMR; P07492; -.
DR BioGRID; 109179; 4.
DR IntAct; P07492; 1.
DR STRING; 9606.ENSP00000256857; -.
DR BindingDB; P07492; -.
DR GlyGen; P07492; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P07492; -.
DR PhosphoSitePlus; P07492; -.
DR BioMuta; GRP; -.
DR DMDM; 308153451; -.
DR MassIVE; P07492; -.
DR PaxDb; P07492; -.
DR PeptideAtlas; P07492; -.
DR PRIDE; P07492; -.
DR ProteomicsDB; 52008; -. [P07492-1]
DR ProteomicsDB; 52009; -. [P07492-2]
DR ProteomicsDB; 52010; -. [P07492-3]
DR Antibodypedia; 1534; 328 antibodies from 28 providers.
DR DNASU; 2922; -.
DR Ensembl; ENST00000256857.7; ENSP00000256857.2; ENSG00000134443.10. [P07492-1]
DR Ensembl; ENST00000420468.6; ENSP00000389696.2; ENSG00000134443.10. [P07492-3]
DR Ensembl; ENST00000529320.2; ENSP00000434101.1; ENSG00000134443.10. [P07492-2]
DR GeneID; 2922; -.
DR KEGG; hsa:2922; -.
DR MANE-Select; ENST00000256857.7; ENSP00000256857.2; NM_002091.5; NP_002082.2.
DR UCSC; uc002lhu.4; human. [P07492-1]
DR CTD; 2922; -.
DR DisGeNET; 2922; -.
DR GeneCards; GRP; -.
DR HGNC; HGNC:4605; GRP.
DR HPA; ENSG00000134443; Tissue enhanced (brain, lung, stomach).
DR MIM; 137260; gene.
DR neXtProt; NX_P07492; -.
DR OpenTargets; ENSG00000134443; -.
DR PharmGKB; PA28999; -.
DR VEuPathDB; HostDB:ENSG00000134443; -.
DR eggNOG; ENOG502S4DG; Eukaryota.
DR GeneTree; ENSGT00940000154470; -.
DR HOGENOM; CLU_144892_0_0_1; -.
DR InParanoid; P07492; -.
DR OMA; KDMMDYL; -.
DR OrthoDB; 1427338at2759; -.
DR PhylomeDB; P07492; -.
DR TreeFam; TF336391; -.
DR PathwayCommons; P07492; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P07492; -.
DR SIGNOR; P07492; -.
DR BioGRID-ORCS; 2922; 11 hits in 1075 CRISPR screens.
DR GeneWiki; Gastrin-releasing_peptide; -.
DR GenomeRNAi; 2922; -.
DR Pharos; P07492; Tbio.
DR PRO; PR:P07492; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P07492; protein.
DR Bgee; ENSG00000134443; Expressed in hair follicle and 121 other tissues.
DR ExpressionAtlas; P07492; baseline and differential.
DR Genevisible; P07492; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; ISS:UniProtKB.
DR GO; GO:0005184; F:neuropeptide hormone activity; IDA:MGI.
DR GO; GO:0005102; F:signaling receptor binding; NAS:ProtInc.
DR GO; GO:0043303; P:mast cell degranulation; ISS:UniProtKB.
DR GO; GO:1903817; P:negative regulation of voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:1905151; P:negative regulation of voltage-gated sodium channel activity; ISS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:MGI.
DR GO; GO:2000987; P:positive regulation of behavioral fear response; ISS:UniProtKB.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; ISS:UniProtKB.
DR GO; GO:1900738; P:positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway; 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:0043207; P:response to external biotic stimulus; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR InterPro; IPR000874; Bombesin.
DR InterPro; IPR015674; Gastrin-RP.
DR PANTHER; PTHR16866; PTHR16866; 1.
DR PANTHER; PTHR16866:SF2; PTHR16866:SF2; 1.
DR Pfam; PF02044; Bombesin; 1.
DR PROSITE; PS00257; BOMBESIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amidation; Cell projection;
KW Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Mast cell degranulation; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000250|UniProtKB:P08989"
FT PEPTIDE 24..50
FT /note="Gastrin-releasing peptide"
FT /evidence="ECO:0000250|UniProtKB:P08989"
FT /id="PRO_0000003035"
FT PEPTIDE 41..50
FT /note="Neuromedin-C"
FT /evidence="ECO:0000250|UniProtKB:Q863C3"
FT /id="PRO_0000003036"
FT PROPEP 54..148
FT /evidence="ECO:0000250|UniProtKB:P08989"
FT /id="PRO_0000003037"
FT REGION 89..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..117
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Methionine amide"
FT /evidence="ECO:0000269|PubMed:3211139"
FT VAR_SEQ 122..148
FT /note="VGSKGKVGRLSAPGSQREGRNPQLNQQ -> LVDSLLQVLNVKEGTPS (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:3001723"
FT /id="VSP_000549"
FT VAR_SEQ 128..134
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_000550"
FT VARIANT 4
FT /note="R -> S (in dbSNP:rs1062557)"
FT /evidence="ECO:0000269|PubMed:3001723"
FT /id="VAR_027834"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:2N0E"
SQ SEQUENCE 148 AA; 16213 MW; 6A9ED9E2748255BD CRC64;
MRGRELPLVL LALVLCLAPR GRAVPLPAGG GTVLTKMYPR GNHWAVGHLM GKKSTGESSS
VSERGSLKQQ LREYIRWEEA ARNLLGLIEA KENRNHQPPQ PKALGNQQPS WDSEDSSNFK
DVGSKGKVGR LSAPGSQREG RNPQLNQQ
