GHRL_RAT
ID GHRL_RAT Reviewed; 117 AA.
AC Q9QYH7; Q9ET69;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Appetite-regulating hormone;
DE AltName: Full=Growth hormone secretagogue;
DE AltName: Full=Growth hormone-releasing peptide;
DE AltName: Full=Motilin-related peptide;
DE Contains:
DE RecName: Full=Ghrelin;
DE Contains:
DE RecName: Full=Obestatin-23;
DE Contains:
DE RecName: Full=Obestatin-13;
DE Flags: Precursor;
GN Name=Ghrl;
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] (ISOFORM 1), PROTEIN SEQUENCE OF 24-51, MASS
RP SPECTROMETRY, AND ACYLATION AT SER-26.
RC STRAIN=Sprague-Dawley; TISSUE=Stomach;
RX PubMed=10604470; DOI=10.1038/45230;
RA Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K.;
RT "Ghrelin is a growth-hormone-releasing acylated peptide from stomach.";
RL Nature 402:656-660(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 24-51,
RP MASS SPECTROMETRY, AND ACYLATION AT SER-26.
RC STRAIN=Sprague-Dawley; TISSUE=Stomach;
RX PubMed=10801861; DOI=10.1074/jbc.m002784200;
RA Hosoda H., Kojima M., Matsuo H., Kangawa K.;
RT "Purification and characterization of rat des-Gln14-ghrelin, a second
RT endogenous ligand for the growth hormone secretagogue receptor.";
RL J. Biol. Chem. 275:21995-22000(2000).
RN [3]
RP PROTEIN SEQUENCE OF 76-95, FUNCTION OF OBESTATIN, CHARACTERIZATION,
RP AMIDATION AT LEU-98, MASS SPECTROMETRY, AND INTERACTION WITH GPR39.
RX PubMed=16284174; DOI=10.1126/science.1117255;
RA Zhang J.V., Ren P.G., Avsian-Kretchmer O., Luo C.W., Rauch R., Klein C.,
RA Hsueh A.J.;
RT "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's
RT effects on food intake.";
RL Science 310:996-999(2005).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=11162448; DOI=10.1006/bbrc.2000.4039;
RA Hosoda H., Kojima M., Matsuo H., Kangawa K.;
RT "Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in
RT gastrointestinal tissue.";
RL Biochem. Biophys. Res. Commun. 279:909-913(2000).
RN [5]
RP STRUCTURE-ACTIVITY RELATIONSHIP.
RX PubMed=11549267; DOI=10.1006/bbrc.2001.5553;
RA Matsumoto M., Hosoda H., Kitajima Y., Morozumi N., Minamitake Y.,
RA Tanaka S., Matsuo H., Kojima M., Hayashi Y., Kangawa K.;
RT "Structure-activity relationship of ghrelin: pharmacological study of
RT ghrelin peptides.";
RL Biochem. Biophys. Res. Commun. 287:142-146(2001).
RN [6]
RP REVIEW.
RX PubMed=11306336; DOI=10.1016/s1043-2760(00)00362-3;
RA Kojima M., Hosoda H., Matsuo H., Kangawa K.;
RT "Ghrelin: discovery of the natural endogenous ligand for the growth hormone
RT secretagogue receptor.";
RL Trends Endocrinol. Metab. 12:118-122(2001).
RN [7]
RP FUNCTION OF OBESTATIN.
RX PubMed=17289961; DOI=10.1126/science.1135047;
RA Chartrel N., Alvear-Perez R., Leprince J., Iturrioz X.,
RA Reaux-Le Goazigo A., Audinot V., Chomarat P., Coge F., Nosjean O.,
RA Rodriguez M., Galizzi J.P., Boutin J.A., Vaudry H., Llorens-Cortes C.;
RT "Comment on 'Obestatin, a peptide encoded by the ghrelin gene, opposes
RT ghrelin's effects on food intake'.";
RL Science 315:766-766(2007).
CC -!- FUNCTION: [Ghrelin]: Ghrelin is the ligand for growth hormone
CC secretagogue receptor type 1 (GHSR). Induces the release of growth
CC hormone from the pituitary. Has an appetite-stimulating effect, induces
CC adiposity and stimulates gastric acid secretion. Involved in growth
CC regulation.
CC -!- FUNCTION: [Obestatin-23]: Obestatin may be the ligand for GPR39. May
CC have an appetite-reducing effect resulting in decreased food intake.
CC May reduce gastric emptying activity and jejunal motility.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Ghrelin;
CC IsoId=Q9QYH7-1; Sequence=Displayed;
CC Name=2; Synonyms=des-Gln14-ghrelin;
CC IsoId=Q9QYH7-2; Sequence=VSP_003248;
CC -!- TISSUE SPECIFICITY: Ghrelin is broadly expressed with higher expression
CC in the stomach. Very low levels are detected in the hypothalamus,
CC heart, lung, pancreas, intestine and adipose tissue. Obestatin is most
CC highly expressed in jejunum, and also found in duodenum, stomach,
CC pituitary, ileum, liver, hypothalamus and heart. Expressed in low
CC levels in pancreas, cerebellum, cerebrum, kidney, testis, ovary colon
CC and lung. {ECO:0000269|PubMed:11162448}.
CC -!- PTM: O-octanoylated by GOAT/MBOAT4 (By similarity). O-octanoylation is
CC essential for ghrelin activity. The replacement of Ser-26 by aromatic
CC tryptophan preserves ghrelin activity (PubMed:10604470,
CC PubMed:10801861). {ECO:0000250|UniProtKB:Q9EQX0,
CC ECO:0000269|PubMed:10604470, ECO:0000269|PubMed:10801861}.
CC -!- PTM: Amidation of Leu-98 is essential for obestatin activity.
CC {ECO:0000269|PubMed:16284174}.
CC -!- MASS SPECTROMETRY: [Isoform 1]: Mass=3314.9; Mass_error=0.7;
CC Method=Electrospray; Note=The measured range is 24-51.;
CC Evidence={ECO:0000269|PubMed:10604470};
CC -!- MASS SPECTROMETRY: [Isoform 2]: Mass=3187.1; Mass_error=0.6;
CC Method=Electrospray; Note=The measured range is 24-50.;
CC Evidence={ECO:0000269|PubMed:10801861};
CC -!- MASS SPECTROMETRY: [Obestatin-23]: Mass=2516.3; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:16284174};
CC -!- SIMILARITY: Belongs to the motilin family. {ECO:0000305}.
CC -!- CAUTION: PubMed:16284174 reports obestatin as ligand of GPR39. However,
CC PubMed:17289961 and others are unable to reproduce these results. It
CC also seems to be unclear whether obestatin has opposite effects on food
CC intake compared with ghrelin. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Gut feelings - Issue 66 of
CC January 2006;
CC URL="https://web.expasy.org/spotlight/back_issues/066";
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DR EMBL; AB029433; BAA89370.1; -; mRNA.
DR EMBL; AB035699; BAB11956.1; -; mRNA.
DR PIR; B59316; B59316.
DR RefSeq; NP_067701.1; NM_021669.2. [Q9QYH7-1]
DR AlphaFoldDB; Q9QYH7; -.
DR SMR; Q9QYH7; -.
DR IntAct; Q9QYH7; 2.
DR STRING; 10116.ENSRNOP00000014103; -.
DR iPTMnet; Q9QYH7; -.
DR PhosphoSitePlus; Q9QYH7; -.
DR PaxDb; Q9QYH7; -.
DR Ensembl; ENSRNOT00000014103; ENSRNOP00000014103; ENSRNOG00000010349. [Q9QYH7-1]
DR GeneID; 59301; -.
DR KEGG; rno:59301; -.
DR UCSC; RGD:632283; rat. [Q9QYH7-1]
DR CTD; 51738; -.
DR RGD; 632283; Ghrl.
DR eggNOG; ENOG502SFY3; Eukaryota.
DR GeneTree; ENSGT00390000004064; -.
DR HOGENOM; CLU_168380_0_0_1; -.
DR InParanoid; Q9QYH7; -.
DR OMA; QYQQYGR; -.
DR OrthoDB; 1600403at2759; -.
DR PhylomeDB; Q9QYH7; -.
DR TreeFam; TF336219; -.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR PRO; PR:Q9QYH7; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000010349; Expressed in stomach and 18 other tissues.
DR Genevisible; Q9QYH7; RN.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB.
DR GO; GO:0031768; F:ghrelin receptor binding; IMP:RGD.
DR GO; GO:0016608; F:growth hormone-releasing hormone activity; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IDA:RGD.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; ISS:UniProtKB.
DR GO; GO:0008154; P:actin polymerization or depolymerization; ISS:UniProtKB.
DR GO; GO:0008343; P:adult feeding behavior; ISS:HGNC-UCL.
DR GO; GO:0046697; P:decidualization; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; ISO:RGD.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0001696; P:gastric acid secretion; IDA:UniProtKB.
DR GO; GO:0035483; P:gastric emptying; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0042322; P:negative regulation of circadian sleep/wake cycle, REM sleep; ISO:RGD.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IDA:MGI.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IDA:RGD.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0040013; P:negative regulation of locomotion; ISO:RGD.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:RGD.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; IDA:RGD.
DR GO; GO:0032100; P:positive regulation of appetite; IMP:RGD.
DR GO; GO:1903012; P:positive regulation of bone development; IDA:RGD.
DR GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0051461; P:positive regulation of corticotropin secretion; ISO:RGD.
DR GO; GO:0051464; P:positive regulation of cortisol secretion; ISO:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR GO; GO:1904000; P:positive regulation of eating behavior; IDA:RGD.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IDA:RGD.
DR GO; GO:1904346; P:positive regulation of gastric mucosal blood circulation; IDA:RGD.
DR GO; GO:1904306; P:positive regulation of gastro-intestinal system smooth muscle contraction; IDA:RGD.
DR GO; GO:0045927; P:positive regulation of growth; IDA:RGD.
DR GO; GO:0060124; P:positive regulation of growth hormone secretion; IDA:CACAO.
DR GO; GO:0040010; P:positive regulation of growth rate; IDA:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IDA:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IDA:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0032097; P:positive regulation of response to food; IDA:RGD.
DR GO; GO:0120058; P:positive regulation of small intestinal transit; IDA:RGD.
DR GO; GO:1904349; P:positive regulation of small intestine smooth muscle contraction; IDA:RGD.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IDA:RGD.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IDA:RGD.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IDA:SynGO.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:1905333; P:regulation of gastric motility; IDA:RGD.
DR GO; GO:0099175; P:regulation of postsynapse organization; IDA:SynGO.
DR GO; GO:0032095; P:regulation of response to food; IDA:RGD.
DR GO; GO:0051969; P:regulation of transmission of nerve impulse; IDA:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; ISS:UniProtKB.
DR GO; GO:0009725; P:response to hormone; ISS:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0007416; P:synapse assembly; IEA:Ensembl.
DR InterPro; IPR006737; Motilin_assoc.
DR InterPro; IPR006738; Motilin_ghrelin.
DR InterPro; IPR005441; Preproghrelin.
DR PANTHER; PTHR14122; PTHR14122; 1.
DR Pfam; PF04643; Motilin_assoc; 1.
DR Pfam; PF04644; Motilin_ghrelin; 1.
DR PRINTS; PR01624; GHRELIN.
PE 1: Evidence at protein level;
KW Alternative splicing; Amidation; Direct protein sequencing; Hormone;
KW Lipoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:10604470,
FT ECO:0000269|PubMed:10801861"
FT PEPTIDE 24..51
FT /note="Ghrelin"
FT /id="PRO_0000019209"
FT PROPEP 52..75
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:16284174"
FT /id="PRO_0000019210"
FT PEPTIDE 76..98
FT /note="Obestatin-23"
FT /id="PRO_0000045146"
FT PEPTIDE 86..98
FT /note="Obestatin-13"
FT /evidence="ECO:0000305"
FT /id="PRO_0000045147"
FT PROPEP 99..117
FT /note="Removed in mature form"
FT /id="PRO_0000045148"
FT REGION 28..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..68
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 98
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:16284174"
FT LIPID 26
FT /note="O-decanoyl serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQX0"
FT LIPID 26
FT /note="O-hexanoyl serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9EQX0"
FT LIPID 26
FT /note="O-octanoyl serine; alternate"
FT /evidence="ECO:0000269|PubMed:10604470,
FT ECO:0000269|PubMed:10801861"
FT VAR_SEQ 37
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10801861"
FT /id="VSP_003248"
SQ SEQUENCE 117 AA; 13176 MW; 8857546FE51A7691 CRC64;
MVSSATICSL LLLSMLWMDM AMAGSSFLSP EHQKAQQRKE SKKPPAKLQP RALEGWLHPE
DRGQAEEAEE ELEIRFNAPF DVGIKLSGAQ YQQHGRALGK FLQDILWEEV KEAPANK
