GRP_RAT
ID GRP_RAT Reviewed; 147 AA.
AC P24393; G3V871;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 2.
DT 03-AUG-2022, entry version 119.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=2843761; DOI=10.1210/mend-2-6-556;
RA Lebacq-Verheyden A.-M., Krystal G., Sartor O., Way J., Battey J.F.;
RT "The rat prepro gastrin releasing peptide gene is transcribed from two
RT initiation sites in the brain.";
RL Mol. Endocrinol. 2:556-563(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|EMBL:EDM14697.1};
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=17208656; DOI=10.1016/j.brainresbull.2006.10.007;
RA Fekete E.M., Bagi E.E., Toth K., Lenard L.;
RT "Neuromedin C microinjected into the amygdala inhibits feeding.";
RL Brain Res. Bull. 71:386-392(2007).
RN [5]
RP 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 [6]
RP FUNCTION.
RX PubMed=33059246; DOI=10.1016/j.npep.2020.102080;
RA Yang J., Yang X., Xiao X., Ming D.;
RT "The effects of gastrin-releasing peptide on the voltage-gated channels in
RT rat hippocampal neurons.";
RL Neuropeptides 84:102080-102080(2020).
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 (PubMed:17208656). Inhibits voltage-gated
CC sodium channels but enhances voltage-gated potassium channels in
CC hippocampal neurons (PubMed:33059246). Induces sighing by acting
CC directly on the pre-Botzinger complex, a cluster of several thousand
CC neurons in the ventrolateral medulla responsible for inspiration during
CC respiratory activity (By similarity). {ECO:0000250|UniProtKB:P63153,
CC ECO:0000250|UniProtKB:Q8R1I2, ECO:0000269|PubMed:17208656,
CC ECO:0000269|PubMed:33059246}.
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P07492}.
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 -!- TISSUE SPECIFICITY: Expressed in several dozen cells in the dorsal
CC retrotrapezoid nucleus/parafacial respiratory group (at protein level).
CC {ECO:0000269|PubMed:26855425}.
CC -!- SIMILARITY: Belongs to the bombesin/neuromedin-B/ranatensin family.
CC {ECO:0000305}.
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DR EMBL; M31176; AAA41197.1; -; mRNA.
DR EMBL; AABR07032332; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473971; EDM14697.1; -; Genomic_DNA.
DR EMBL; CH473971; EDM14698.1; -; Genomic_DNA.
DR PIR; A40922; A40922.
DR RefSeq; NP_598254.2; NM_133570.5.
DR AlphaFoldDB; P24393; -.
DR STRING; 10116.ENSRNOP00000022845; -.
DR PhosphoSitePlus; P24393; -.
DR PaxDb; P24393; -.
DR Ensembl; ENSRNOT00000022845; ENSRNOP00000022845; ENSRNOG00000016999.
DR GeneID; 171101; -.
DR KEGG; rno:171101; -.
DR UCSC; RGD:621740; rat.
DR CTD; 2922; -.
DR RGD; 621740; Grp.
DR eggNOG; ENOG502S4DG; Eukaryota.
DR GeneTree; ENSGT00940000154470; -.
DR InParanoid; P24393; -.
DR OMA; KDMMDYL; -.
DR OrthoDB; 1427338at2759; -.
DR PhylomeDB; P24393; -.
DR TreeFam; TF336391; -.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR PRO; PR:P24393; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Proteomes; UP000234681; Chromosome 18.
DR Bgee; ENSRNOG00000016999; Expressed in stomach and 9 other tissues.
DR GO; GO:0005615; C:extracellular space; ISS: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; ISO:RGD.
DR GO; GO:0043303; P:mast cell degranulation; ISS:UniProtKB.
DR GO; GO:1903817; P:negative regulation of voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:1905151; P:negative regulation of voltage-gated sodium channel activity; IDA:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IMP:RGD.
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; ISO:RGD.
DR GO; GO:0043207; P:response to external biotic stimulus; ISO:RGD.
DR GO; GO:0035176; P:social behavior; ISO:RGD.
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_0000003039"
FT PEPTIDE 43..52
FT /note="Neuromedin-C"
FT /evidence="ECO:0000250|UniProtKB:Q863C3"
FT /id="PRO_0000003040"
FT PROPEP 56..147
FT /evidence="ECO:0000250|UniProtKB:P08989"
FT /id="PRO_0000003041"
FT REGION 95..123
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 95..96
FT /note="AG -> SR (in Ref. 1; AAA41197)"
SQ SEQUENCE 147 AA; 15702 MW; 54AF30AEF24E56B0 CRC64;
MRGSELSLLL LALVLCQAPR GPAAPVSTGA GGGTVLAKMY PRGSHWAVGH LMGKKSTDEL
PPLYAADRDG LKEQLRGYIR WEEAARNLLG LLEAAGNRSH QPPQDQPLGS LQPTWDPEDG
SYFSDAQNAK LVDSLLQVLK GKEGTAS
