GHRL_MOUSE
ID GHRL_MOUSE Reviewed; 117 AA.
AC Q9EQX0; Q9WUZ1;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
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 AltName: Full=Protein M46;
DE Contains:
DE RecName: Full=Ghrelin;
DE Contains:
DE RecName: Full=Obestatin;
DE Flags: Precursor;
GN Name=Ghrl; Synonyms=Mtlrp;
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 [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 24-30,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Stomach;
RX PubMed=10930375; DOI=10.1053/gast.2000.9371;
RA Tomasetto C., Karam S.M., Ribieras S., Masson R., Lefebvre O., Staub A.,
RA Alexander G., Chenard M.-P., Rio M.-C.;
RT "Identification and characterization of a novel gastric peptide hormone:
RT the motilin-related peptide.";
RL Gastroenterology 119:395-405(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kojima M.;
RT "Mouse mRNA for preproghrelin.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RA Tanaka M., Hayashida Y., Iguchi T., Nakao N., Nakai N., Nakashima K.;
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Stomach;
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 [5]
RP DEVELOPMENTAL STAGE, AND ACYLATION AT SER-26.
RX PubMed=15746259; DOI=10.1210/en.2004-0645;
RA Nishi Y., Hiejima H., Mifune H., Sato T., Kangawa K., Kojima M.;
RT "Developmental changes in the pattern of ghrelin's acyl modification and
RT the levels of acyl-modified ghrelins in murine stomach.";
RL Endocrinology 146:2709-2715(2005).
RN [6]
RP ACYLATION AT SER-26.
RX PubMed=15677766; DOI=10.1210/en.2004-0695;
RA Nishi Y., Hiejima H., Hosoda H., Kaiya H., Mori K., Fukue Y., Yanase T.,
RA Nawata H., Kangawa K., Kojima M.;
RT "Ingested medium-chain fatty acids are directly utilized for the acyl
RT modification of ghrelin.";
RL Endocrinology 146:2255-2264(2005).
RN [7]
RP MASS SPECTROMETRY, AND ACYLATION AT SER-26.
RC STRAIN=BALB/cJ;
RX PubMed=18443287; DOI=10.1073/pnas.0800708105;
RA Gutierrez J.A., Solenberg P.J., Perkins D.R., Willency J.A., Knierman M.D.,
RA Jin Z., Witcher D.R., Luo S., Onyia J.E., Hale J.E.;
RT "Ghrelin octanoylation mediated by an orphan lipid transferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6320-6325(2008).
RN [8]
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 [9]
RP STRUCTURE BY NMR OF 76-98, AND AMIDATION AT LEU-98.
RX PubMed=17904104; DOI=10.1016/j.bbrc.2007.08.200;
RA Scrima M., Campiglia P., Esposito C., Gomez-Monterrey I., Novellino E.,
RA D'Ursi A.M.;
RT "Obestatin conformational features: a strategy to unveil obestatin's
RT biological role ?";
RL Biochem. Biophys. Res. Commun. 363:500-505(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]: Obestatin may be the ligand for GPR39. May have
CC an appetite-reducing effect resulting in decreased food intake. May
CC reduce gastric emptying activity and jejunal motility (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10930375}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Ghrelin;
CC IsoId=Q9EQX0-1; Sequence=Displayed;
CC Name=2; Synonyms=des-Gln14-ghrelin;
CC IsoId=Q9EQX0-2; Sequence=VSP_003246;
CC -!- TISSUE SPECIFICITY: Mainly expressed in the gastrointestinal tract with
CC higher levels in the stomach, medium levels in the duodenum, jejunum,
CC ileum and colon. Low expression in the testis and brain. Not detected
CC in the salivary gland, pancreas, liver and lung.
CC {ECO:0000269|PubMed:10930375}.
CC -!- DEVELOPMENTAL STAGE: Levels of n-octanoylated and n-decanoylated
CC ghrelin drop by one third and 3-fold, respectively, between postnatal
CC weeks 3 and 4 due to change of diet during weaning.
CC {ECO:0000269|PubMed:15746259}.
CC -!- PTM: O-octanoylated by GOAT/MBOAT4 (PubMed:18443287). O-octanoylation
CC or O-decanoylation is essential for ghrelin activity (By similarity).
CC The O-decanoylated form ghrelin-C10 differs in the length of the carbon
CC backbone of the carboxylic acid bound to Ser-26 (PubMed:15746259).
CC {ECO:0000250, ECO:0000269|PubMed:15746259,
CC ECO:0000269|PubMed:18443287}.
CC -!- PTM: Amidation of Leu-98 is essential for obestatin activity.
CC {ECO:0000250}.
CC -!- MASS SPECTROMETRY: [Ghrelin]: Mass=3314; Method=MALDI; Note=Ghrelin, O-
CC octanoylated form.; Evidence={ECO:0000269|PubMed:18443287};
CC -!- SIMILARITY: Belongs to the motilin family. {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; AJ243503; CAB46500.1; -; mRNA.
DR EMBL; AB035701; BAB19046.1; -; mRNA.
DR EMBL; AB060078; BAB69857.1; -; Genomic_DNA.
DR EMBL; AK008658; BAB25814.1; -; mRNA.
DR EMBL; AK008860; BAB25934.1; -; mRNA.
DR CCDS; CCDS20432.1; -. [Q9EQX0-1]
DR CCDS; CCDS85127.1; -. [Q9EQX0-2]
DR RefSeq; NP_001273333.1; NM_001286404.1. [Q9EQX0-2]
DR RefSeq; NP_001273334.1; NM_001286405.1.
DR RefSeq; NP_001273335.1; NM_001286406.1.
DR RefSeq; NP_067463.2; NM_021488.5. [Q9EQX0-1]
DR RefSeq; XP_006506509.1; XM_006506446.3.
DR PDB; 2JSH; NMR; -; A=76-98.
DR PDB; 2JSI; NMR; -; A=86-98.
DR PDB; 2JSJ; NMR; -; A=76-98.
DR PDBsum; 2JSH; -.
DR PDBsum; 2JSI; -.
DR PDBsum; 2JSJ; -.
DR AlphaFoldDB; Q9EQX0; -.
DR SMR; Q9EQX0; -.
DR STRING; 10090.ENSMUSP00000069567; -.
DR PhosphoSitePlus; Q9EQX0; -.
DR MaxQB; Q9EQX0; -.
DR PaxDb; Q9EQX0; -.
DR PeptideAtlas; Q9EQX0; -.
DR PRIDE; Q9EQX0; -.
DR ProteomicsDB; 267445; -. [Q9EQX0-1]
DR ProteomicsDB; 267446; -. [Q9EQX0-2]
DR Antibodypedia; 2526; 890 antibodies from 41 providers.
DR DNASU; 58991; -.
DR Ensembl; ENSMUST00000064993; ENSMUSP00000069567; ENSMUSG00000064177. [Q9EQX0-1]
DR Ensembl; ENSMUST00000203770; ENSMUSP00000145281; ENSMUSG00000064177. [Q9EQX0-1]
DR Ensembl; ENSMUST00000204163; ENSMUSP00000145096; ENSMUSG00000064177. [Q9EQX0-2]
DR GeneID; 58991; -.
DR KEGG; mmu:58991; -.
DR UCSC; uc009dhj.1; mouse. [Q9EQX0-2]
DR UCSC; uc009dhl.2; mouse. [Q9EQX0-1]
DR CTD; 51738; -.
DR MGI; MGI:1930008; Ghrl.
DR VEuPathDB; HostDB:ENSMUSG00000064177; -.
DR eggNOG; ENOG502SFY3; Eukaryota.
DR GeneTree; ENSGT00390000004064; -.
DR HOGENOM; CLU_168380_0_0_1; -.
DR InParanoid; Q9EQX0; -.
DR OMA; QYQQYGR; -.
DR PhylomeDB; Q9EQX0; -.
DR TreeFam; TF336219; -.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR Reactome; R-MMU-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR BioGRID-ORCS; 58991; 6 hits in 71 CRISPR screens.
DR ChiTaRS; Ghrl; mouse.
DR EvolutionaryTrace; Q9EQX0; -.
DR PRO; PR:Q9EQX0; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9EQX0; protein.
DR Bgee; ENSMUSG00000064177; Expressed in epithelium of stomach and 90 other tissues.
DR ExpressionAtlas; Q9EQX0; baseline and differential.
DR Genevisible; Q9EQX0; MM.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
DR GO; GO:0031768; F:ghrelin receptor binding; ISS:UniProtKB.
DR GO; GO:0016608; F:growth hormone-releasing hormone activity; ISS:UniProtKB.
DR GO; GO:0005179; F:hormone activity; ISS:UniProtKB.
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; IDA:HGNC-UCL.
DR GO; GO:0046697; P:decidualization; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; IMP:MGI.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0001696; P:gastric acid secretion; ISO:MGI.
DR GO; GO:0035483; P:gastric emptying; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0042322; P:negative regulation of circadian sleep/wake cycle, REM sleep; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0040013; P:negative regulation of locomotion; IMP:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; ISO:MGI.
DR GO; GO:0032100; P:positive regulation of appetite; IDA:HGNC-UCL.
DR GO; GO:1903012; P:positive regulation of bone development; ISO:MGI.
DR GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0051461; P:positive regulation of corticotropin secretion; ISO:MGI.
DR GO; GO:0051464; P:positive regulation of cortisol secretion; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:1904000; P:positive regulation of eating behavior; ISO:MGI.
DR GO; GO:2000253; P:positive regulation of feeding behavior; ISO:MGI.
DR GO; GO:1904346; P:positive regulation of gastric mucosal blood circulation; ISO:MGI.
DR GO; GO:1904306; P:positive regulation of gastro-intestinal system smooth muscle contraction; ISO:MGI.
DR GO; GO:0045927; P:positive regulation of growth; ISO:MGI.
DR GO; GO:0060124; P:positive regulation of growth hormone secretion; ISO:MGI.
DR GO; GO:0040010; P:positive regulation of growth rate; ISO:MGI.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0032097; P:positive regulation of response to food; ISS:UniProtKB.
DR GO; GO:0120058; P:positive regulation of small intestinal transit; ISO:MGI.
DR GO; GO:1904349; P:positive regulation of small intestine smooth muscle contraction; ISO:MGI.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:MGI.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:MGI.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:1905333; P:regulation of gastric motility; ISO:MGI.
DR GO; GO:0099175; P:regulation of postsynapse organization; ISO:MGI.
DR GO; GO:0032095; P:regulation of response to food; ISS:UniProtKB.
DR GO; GO:0051969; P:regulation of transmission of nerve impulse; ISO:MGI.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; ISS:UniProtKB.
DR GO; GO:0009725; P:response to hormone; ISS:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; IMP:MGI.
DR GO; GO:0008542; P:visual learning; ISO:MGI.
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 3D-structure; Alternative splicing; Amidation; Direct protein sequencing;
KW Hormone; Lipoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:10930375"
FT PEPTIDE 24..51
FT /note="Ghrelin"
FT /id="PRO_0000019205"
FT PROPEP 52..75
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000019206"
FT PEPTIDE 76..98
FT /note="Obestatin"
FT /id="PRO_0000045142"
FT PROPEP 99..117
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000045143"
FT REGION 28..69
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..69
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:17904104"
FT LIPID 26
FT /note="O-decanoyl serine; alternate"
FT /evidence="ECO:0000269|PubMed:15677766,
FT ECO:0000269|PubMed:15746259"
FT LIPID 26
FT /note="O-hexanoyl serine; alternate"
FT /evidence="ECO:0000269|PubMed:15677766"
FT LIPID 26
FT /note="O-octanoyl serine; alternate"
FT /evidence="ECO:0000269|PubMed:15677766,
FT ECO:0000269|PubMed:15746259, ECO:0000269|PubMed:18443287"
FT VAR_SEQ 37
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10930375"
FT /id="VSP_003246"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:2JSH"
FT HELIX 87..90
FT /evidence="ECO:0007829|PDB:2JSH"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:2JSH"
SQ SEQUENCE 117 AA; 13207 MW; EACB49D2E3CA7203 CRC64;
MLSSGTICSL LLLSMLWMDM AMAGSSFLSP EHQKAQQRKE SKKPPAKLQP RALEGWLHPE
DRGQAEETEE ELEIRFNAPF DVGIKLSGAQ YQQHGRALGK FLQDILWEEV KEAPADK
