ID   GRP_MOUSE               Reviewed;         146 AA.
AC   Q8R1I2; Q3UTL2;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   27-MAR-2024, entry version 131.
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:0000303|PubMed:21933692};
DE   Flags: Precursor;
GN   Name=Grp;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain cortex;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon;
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   [3]
RP   TISSUE SPECIFICITY, AND FUNCTION IN CONTROL OF FEAR.
RX   PubMed=12526815; DOI=10.1016/s0092-8674(02)01116-9;
RA   Shumyatsky G.P., Tsvetkov E., Malleret G., Vronskaya S., Hatton M.,
RA   Hampton L., Battey J.F., Dulac C., Kandel E.R., Bolshakov V.Y.;
RT   "Identification of a signaling network in lateral nucleus of amygdala
RT   important for inhibiting memory specifically related to learned fear.";
RL   Cell 111:905-918(2002).
RN   [4]
RP   FUNCTION.
RX   PubMed=12176666; DOI=10.1677/joe.0.1740273;
RA   Ladenheim E.E., Hampton L.L., Whitney A.C., White W.O., Battey J.F.,
RA   Moran T.H.;
RT   "Disruptions in feeding and body weight control in gastrin-releasing
RT   peptide receptor deficient mice.";
RL   J. Endocrinol. 174:273-281(2002).
RN   [5]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=17653196; DOI=10.1038/nature06029;
RA   Sun Y.G., Chen Z.F.;
RT   "A gastrin-releasing peptide receptor mediates the itch sensation in the
RT   spinal cord.";
RL   Nature 448:700-703(2007).
RN   [6]
RP   FUNCTION.
RX   PubMed=21933692; DOI=10.1016/j.peptides.2011.09.003;
RA   Andoh T., Kuwazono T., Lee J.B., Kuraishi Y.;
RT   "Gastrin-releasing peptide induces itch-related responses through mast cell
RT   degranulation in mice.";
RL   Peptides 32:2098-2103(2011).
RN   [7]
RP   FUNCTION.
RX   PubMed=26658875; DOI=10.1523/jneurosci.2310-15.2015;
RA   Pereira P.J., Machado G.D., Danesi G.M., Canevese F.F., Reddy V.B.,
RA   Pereira T.C., Bogo M.R., Cheng Y.C., Laedermann C., Talbot S., Lerner E.A.,
RA   Campos M.M.;
RT   "GRPR/PI3Kgamma: partners in central transmission of itch.";
RL   J. Neurosci. 35:16272-16281(2015).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=26855425; DOI=10.1038/nature16964;
RA   Li P., Janczewski W.A., Yackle K., Kam K., Pagliardini S., Krasnow M.A.,
RA   Feldman J.L.;
RT   "The peptidergic control circuit for sighing.";
RL   Nature 530:293-297(2016).
RN   [9]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX   PubMed=28280205; DOI=10.1126/science.aak9748;
RA   Yu Y.Q., Barry D.M., Hao Y., Liu X.T., Chen Z.F.;
RT   "Molecular and neural basis of contagious itch behavior in mice.";
RL   Science 355:1072-1076(2017).
RN   [10]
RP   FUNCTION, AND 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: 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 (PubMed:28280205, PubMed:17653196,
CC       PubMed:26658875). Contributes primarily to nonhistaminergic itch
CC       sensation (PubMed:28280205). In one study, shown to act in the amygdala
CC       as part of an inhibitory network which inhibits memory specifically
CC       related to learned fear (PubMed:12526815). In another study, shown to
CC       act on vasoactive intestinal peptide (VIP)-expressing cells in the
CC       auditory cortex, most likely via extrasynaptic diffusion from local and
CC       long-range sources, to mediate disinhibition of glutamatergic cells via
CC       VIP cell-specific GRPR signaling which leads to enhanced auditory fear
CC       memories (PubMed:34610277). Contributes to the regulation of food
CC       intake (PubMed:12176666). Inhibits voltage-gated sodium channels but
CC       enhances voltage-gated potassium channels in hippocampal neurons (By
CC       similarity). Contributes to the induction of 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 (PubMed:26855425). {ECO:0000250|UniProtKB:P24393,
CC       ECO:0000250|UniProtKB:P63153, ECO:0000269|PubMed:12176666,
CC       ECO:0000269|PubMed:12526815, ECO:0000269|PubMed:17653196,
CC       ECO:0000269|PubMed:26658875, ECO:0000269|PubMed:26855425,
CC       ECO:0000269|PubMed:28280205, ECO:0000269|PubMed:34610277}.
CC   -!- FUNCTION: [Neuromedin-C]: Induces an itch response through activation
CC       of receptors present on mast cells, triggering mast cell degranulation.
CC       {ECO:0000269|PubMed:21933692}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P07492}.
CC       Cytoplasmic vesicle, secretory vesicle lumen
CC       {ECO:0000250|UniProtKB:Q863C3}. Cell projection, neuron projection
CC       {ECO:0000269|PubMed:26855425}. 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:0000269|PubMed:26855425}.
CC   -!- TISSUE SPECIFICITY: Detected in peptidergic dorsal root ganglion
CC       neurons (at protein level) (PubMed:17653196). Expressed in several
CC       dozen neurons throughout the dorsal retrotrapezoid nucleus/parafacial
CC       respiratory group (RTN/pFRG) as well as in scattered cells in the
CC       nucleus tractus solitarius and parabrachial nucleus (at protein level)
CC       (PubMed:26855425). Within the RTN/pFRG, expressed in neuronal
CC       subpopulations distinct from those expressing Nmb (at protein level)
CC       (PubMed:26855425). Expressed in L6 corticothalamic neurons (at protein
CC       level) (PubMed:34610277). Strongly expressed in several input areas of
CC       the auditory cortex including the lateral amygdala, contralateral
CC       auditory cortex, temporal association area, perirhinal cortex and
CC       auditory thalamic nuclei (at protein level) (PubMed:34610277). Detected
CC       in the suprachiasmatic nucleus in the hypothalamus (PubMed:28280205).
CC       Detected in a subset of glutamatergic cells in the cortex
CC       (PubMed:34610277). Highly expressed both in the lateral nucleus of the
CC       amygdala, and in regions sending synaptic projections to the lateral
CC       nucleus (PubMed:12526815). {ECO:0000269|PubMed:12526815,
CC       ECO:0000269|PubMed:17653196, ECO:0000269|PubMed:26855425,
CC       ECO:0000269|PubMed:28280205, ECO:0000269|PubMed:34610277}.
CC   -!- DISRUPTION PHENOTYPE: Contrary to wild-type, mutant mice do not display
CC       imitative scratching after observing spontaneous scratching behavior in
CC       another mouse (PubMed:28280205). {ECO:0000269|PubMed:28280205}.
CC   -!- SIMILARITY: Belongs to the bombesin/neuromedin-B/ranatensin family.
CC       {ECO:0000305}.
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DR   EMBL; AK133508; BAE21694.1; -; mRNA.
DR   EMBL; AK139345; BAE23968.1; -; mRNA.
DR   EMBL; BC024515; AAH24515.1; -; mRNA.
DR   CCDS; CCDS29310.1; -.
DR   RefSeq; NP_778177.1; NM_175012.4.
DR   RefSeq; XP_006525949.1; XM_006525886.3.
DR   AlphaFoldDB; Q8R1I2; -.
DR   SMR; Q8R1I2; -.
DR   STRING; 10090.ENSMUSP00000025395; -.
DR   PhosphoSitePlus; Q8R1I2; -.
DR   MaxQB; Q8R1I2; -.
DR   PaxDb; 10090-ENSMUSP00000133437; -.
DR   ProteomicsDB; 271338; -.
DR   Antibodypedia; 1534; 371 antibodies from 28 providers.
DR   DNASU; 225642; -.
DR   Ensembl; ENSMUST00000025395.10; ENSMUSP00000025395.9; ENSMUSG00000024517.18.
DR   Ensembl; ENSMUST00000173985.10; ENSMUSP00000133437.2; ENSMUSG00000024517.18.
DR   GeneID; 225642; -.
DR   KEGG; mmu:225642; -.
DR   UCSC; uc008ffk.2; mouse.
DR   AGR; MGI:95833; -.
DR   CTD; 2922; -.
DR   MGI; MGI:95833; Grp.
DR   VEuPathDB; HostDB:ENSMUSG00000024517; -.
DR   eggNOG; ENOG502S4DG; Eukaryota.
DR   GeneTree; ENSGT00940000154470; -.
DR   InParanoid; Q8R1I2; -.
DR   OMA; KDMMDYL; -.
DR   OrthoDB; 4332967at2759; -.
DR   PhylomeDB; Q8R1I2; -.
DR   TreeFam; TF336391; -.
DR   Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR   Reactome; R-MMU-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR   Reactome; R-MMU-416476; G alpha (q) signalling events.
DR   BioGRID-ORCS; 225642; 1 hit in 77 CRISPR screens.
DR   ChiTaRS; Grp; mouse.
DR   PRO; PR:Q8R1I2; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; Q8R1I2; Protein.
DR   Bgee; ENSMUSG00000024517; Expressed in subiculum and 106 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR   GO; GO:0098992; C:neuronal dense core vesicle; ISO:MGI.
DR   GO; GO:0034774; C:secretory granule lumen; ISS:UniProtKB.
DR   GO; GO:0005184; F:neuropeptide hormone activity; ISO:MGI.
DR   GO; GO:1904384; P:cellular response to sodium phosphate; IEA:Ensembl.
DR   GO; GO:0043303; P:mast cell degranulation; IDA: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; ISO:MGI.
DR   GO; GO:0001503; P:ossification; ISO:MGI.
DR   GO; GO:2000987; P:positive regulation of behavioral fear response; IMP: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; IMP:UniProtKB.
DR   GO; GO:1903942; P:positive regulation of respiratory gaseous exchange; IDA:UniProtKB.
DR   GO; GO:1905461; P:positive regulation of vascular associated smooth muscle cell apoptotic process; ISO:MGI.
DR   GO; GO:0036343; P:psychomotor behavior; IMP:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR   GO; GO:0043207; P:response to external biotic stimulus; IMP:UniProtKB.
DR   GO; GO:0035176; P:social behavior; IMP:UniProtKB.
DR   InterPro; IPR000874; Bombesin.
DR   PANTHER; PTHR16866; GASTRIN-RELEASING PEPTIDE; 1.
DR   PANTHER; PTHR16866:SF2; GASTRIN-RELEASING PEPTIDE; 1.
DR   Pfam; PF02044; Bombesin; 1.
DR   PROSITE; PS00257; BOMBESIN; 1.
DR   Genevisible; Q8R1I2; MM.
PE   1: Evidence at protein level;
KW   Amidation; Cell projection; Cleavage on pair of basic residues;
KW   Cytoplasmic vesicle; Mast cell degranulation; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000250|UniProtKB:P08989"
FT   PEPTIDE         24..52
FT                   /note="Gastrin-releasing peptide"
FT                   /evidence="ECO:0000250|UniProtKB:P08989"
FT                   /id="PRO_0000262472"
FT   PEPTIDE         43..52
FT                   /note="Neuromedin-C"
FT                   /evidence="ECO:0000250|UniProtKB:Q863C3"
FT                   /id="PRO_0000262473"
FT   PROPEP          56..146
FT                   /evidence="ECO:0000250|UniProtKB:P08989"
FT                   /id="PRO_0000262474"
FT   REGION          94..121
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         52
FT                   /note="Methionine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P63153"
FT   CONFLICT        134
FT                   /note="L -> Q (in Ref. 1; BAE23968)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   146 AA;  15659 MW;  83FD03C40E670CA5 CRC64;
     MRGSELSLLL LALVLCQAPR GPAAPVSTGA GGGTVLAKMY PRGSHWAVGH LMGKKSTDES
     PSLYAADRDG LKEQLRGYVR WEEAARDLLD LLEAAGNQSH QPPQHPPLSL QPTWDPEDGS
     YFNDVQTAKL VDSLLQVLKE KGGTAS
//