ID   GRP_CANLF               Reviewed;         146 AA.
AC   P08989;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   25-MAY-2022, sequence version 2.
DT   03-AUG-2022, entry version 71.
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   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1] {ECO:0000312|Proteomes:UP000002254}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Boxer {ECO:0000312|Proteomes:UP000002254};
RX   PubMed=16341006; DOI=10.1038/nature04338;
RA   Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA   Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA   Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA   Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA   Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA   Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA   Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA   Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA   Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA   Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA   Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA   Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA   Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA   Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA   Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA   Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA   Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA   Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA   Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA   Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA   Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA   Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA   Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA   LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA   Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA   Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA   Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA   Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA   Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA   Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA   Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA   Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA   Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA   Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA   Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA   Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA   Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA   Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA   Zembek L., Zimmer A., Lander E.S.;
RT   "Genome sequence, comparative analysis and haplotype structure of the
RT   domestic dog.";
RL   Nature 438:803-819(2005).
RN   [2]
RP   PROTEIN SEQUENCE OF 24-50, AND AMIDATION AT MET-50.
RX   PubMed=6853532; DOI=10.1016/s0021-9258(20)81930-9;
RA   Reeve J.R. Jr., Walsh J.H., Chew P., Clark B., Hawke D., Shively J.E.;
RT   "Amino acid sequences of three bombesin-like peptides from canine intestine
RT   extracts.";
RL   J. Biol. Chem. 258:5582-5588(1983).
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   -!- 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   -!- SIMILARITY: Belongs to the bombesin/neuromedin-B/ranatensin family.
CC       {ECO:0000305}.
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DR   AlphaFoldDB; P08989; -.
DR   STRING; 9615.ENSCAFP00000000137; -.
DR   PaxDb; P08989; -.
DR   Ensembl; ENSCAFT00845000914; ENSCAFP00845000684; ENSCAFG00845000570.
DR   eggNOG; ENOG502S4DG; Eukaryota.
DR   GeneTree; ENSGT00940000154470; -.
DR   HOGENOM; CLU_144892_0_0_1; -.
DR   InParanoid; P08989; -.
DR   TreeFam; TF336391; -.
DR   Proteomes; UP000002254; Unplaced.
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: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; IEA:InterPro.
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   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; Direct protein sequencing; Mast cell degranulation;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000269|PubMed:6853532"
FT   PEPTIDE         24..50
FT                   /note="Gastrin-releasing peptide"
FT                   /evidence="ECO:0000269|PubMed:6853532"
FT                   /id="PRO_0000045913"
FT   PEPTIDE         41..50
FT                   /note="Neuromedin-C"
FT                   /evidence="ECO:0000269|PubMed:6853532"
FT                   /id="PRO_0000003033"
FT   PROPEP          54..146
FT                   /evidence="ECO:0000269|PubMed:6853532"
FT                   /id="PRO_0000455538"
FT   REGION          91..146
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        130..146
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         50
FT                   /note="Methionine amide"
FT                   /evidence="ECO:0000269|PubMed:6853532"
SQ   SEQUENCE   146 AA;  16131 MW;  4C3A6FB601B2A0E7 CRC64;
     MRGRELPLVL LALVLCQAPR GPAAPVPGGQ GTVLDKMYPR GNHWAVGHLM GKKSTRESPY
     VYEEGSLKQQ LQGYIRWEEA ARNLLSLMEA KGTRSHQTPQ REPLGIRQSA WDYQDDSNFK
     VIGPTREVGG LSASGSQPEG RNPPRN