GRP_MOUSE
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 03-AUG-2022, entry version 123.
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.ENSMUSP00000133437; -.
DR PhosphoSitePlus; Q8R1I2; -.
DR MaxQB; Q8R1I2; -.
DR PaxDb; Q8R1I2; -.
DR PRIDE; Q8R1I2; -.
DR ProteomicsDB; 271338; -.
DR Antibodypedia; 1534; 328 antibodies from 28 providers.
DR DNASU; 225642; -.
DR Ensembl; ENSMUST00000025395; ENSMUSP00000025395; ENSMUSG00000024517.
DR Ensembl; ENSMUST00000173985; ENSMUSP00000133437; ENSMUSG00000024517.
DR GeneID; 225642; -.
DR KEGG; mmu:225642; -.
DR UCSC; uc008ffk.2; mouse.
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; 1427338at2759; -.
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 72 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 104 other tissues.
DR Genevisible; Q8R1I2; MM.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; ISS:UniProtKB.
DR GO; GO:0005184; F:neuropeptide hormone activity; ISO:MGI.
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: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:0036343; P:psychomotor behavior; IMP:UniProtKB.
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 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 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
