GHRL (ghrelin/obestatin prepropeptide)

2001-03-01   Catherine Tomasetto 

I.G.B.M.C., BP 163, 1 rue Laurent Fries, 67404 Illkirch, France

Identity

HGNC
LOCATION
3p25.3
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
MTLRP

DNA/RNA

Transcription

600 bp, two mRNAs are encoded by the same genes, they are identical except for the lack of one codon (CAG) located at an exon intron boundary.

Proteins

Description

  • two precursor s of 117 and 116 amino acids encoding preproGhrelin/MTLRP and prepro-des-Gln14-Ghrelin/ delta Gln14 MTLRP, respectively. The 28 amino-acids Ghrelin/MTLRP and the 27 amino-acids des-Gln14-Ghrelin/delta Gln14 MTLRP are modified post-translationally by the addition of a n-octanoic acid on Serine 3.
  • The 28 amino acids Ghrelin/MTLRP is produced from a protein precursor of 117 residues that contains a signal peptide from residues 1to 23, the ghrelin/MTLRP moity from residues 24 to 51, the MTLRP-associated peptide moity from residues 52 to 117.
  • The 27 amino acids des-Gln14-Ghrelin/delta Gln 14 MTLRP is produced from a protein precursor of 116 residues identical to the 117 aa precursor excep that the des-Gln14-Ghrelin/delta Gln14 MTLRP moity corresponds to residues 24 to 50 and accordingly the MTLRP-associated peptide moity from resisues 51 to 116.
  • Expression

    Ghrelin/MTLRP is mainly expressed by the enteroendocrine cells of the stomach; its expression decreased gradually along the gastro-intestinal tract and a faint expression was also detected in testis. By Immnunochemistry Ghrelin-immuno reactive neurons were found in the hypothalamic arcuate nucleus.

    Localisation

    As a peptide hormone Ghrelin/MTLRP is secreted in the blood.

    Function

    As the endogenous ligand of the growth hormone secretagogues (GHS) receptor, Ghrelin/MTLRP is involved in the pulsatile secretion of Growth hormone. In addition to this role Ghrelin/MTLRP is in the regulation of feeding. In rodent In contrast to leptin, Ghrelin/MTLRP promotes food intake and obesity. In addition Ghrelin/MTLRP stimulates motricity of the gastrointestinal tract and acid secretion.

    Homology

    ppGhrelin/MTLRP share 47% of similarity with the precursor of Motilin. In addition Ghrelin receptor (GHS-R) and Motilin receptor (GPR38) share 52% identity.

    Implicated in

    Bibliography

    Pubmed IDLast YearTitleAuthors
    108018612000Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor.Hosoda H et al
    106044701999Ghrelin is a growth-hormone-releasing acylated peptide from stomach.Kojima M et al
    110275672000Ghrelin stimulates gastric acid secretion and motility in rats.Masuda Y et al
    111966432001A role for ghrelin in the central regulation of feeding.Nakazato M et al
    109303752000Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide.Tomasetto C et al
    110576702000Ghrelin induces adiposity in rodents.Tschöp M et al
    110895702000The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion.Wren AM et al

    Other Information

    Locus ID:

    NCBI: 51738
    MIM: 605353
    HGNC: 18129
    Ensembl: ENSG00000157017

    Variants:

    dbSNP: 51738
    ClinVar: 51738
    TCGA: ENSG00000157017
    COSMIC: GHRL

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000157017ENST00000287656Q9UBU3
    ENSG00000157017ENST00000335542Q9UBU3
    ENSG00000157017ENST00000422159Q9UBU3
    ENSG00000157017ENST00000425479E7ESW0
    ENSG00000157017ENST00000429122Q9UBU3
    ENSG00000157017ENST00000430179Q9UBU3
    ENSG00000157017ENST00000437422Q9UBU3
    ENSG00000157017ENST00000439975Q9UBU3
    ENSG00000157017ENST00000446937A8DN24
    ENSG00000157017ENST00000449238Q9UBU3
    ENSG00000157017ENST00000457360Q9UBU3

    Expression (GTEx)

    0
    50
    100
    150

    Pathways

    PathwaySourceExternal ID
    cAMP signaling pathwayKEGGhsa04024
    cAMP signaling pathwayKEGGko04024
    Metabolism of proteinsREACTOMER-HSA-392499
    Peptide hormone metabolismREACTOMER-HSA-2980736
    Synthesis, secretion, and deacylation of GhrelinREACTOMER-HSA-422085
    Signal TransductionREACTOMER-HSA-162582
    Signaling by GPCRREACTOMER-HSA-372790
    GPCR ligand bindingREACTOMER-HSA-500792
    Class A/1 (Rhodopsin-like receptors)REACTOMER-HSA-373076
    Peptide ligand-binding receptorsREACTOMER-HSA-375276
    GPCR downstream signalingREACTOMER-HSA-388396
    G alpha (q) signalling eventsREACTOMER-HSA-416476
    Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    PharmGKB

    Entity IDNameTypeEvidenceAssociationPKPDPMIDs
    PA128406954Weight gainDiseaseMultilinkAnnotationassociated24279860

    References

    Pubmed IDYearTitleCitations
    162841742005Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake.178
    149629952004Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein.156
    129077572003High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist.115
    120918832002Elevated plasma ghrelin levels in Prader Willi syndrome.107
    151178402004Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells.106
    238676192013A link between FTO, ghrelin, and impaired brain food-cue responsivity.102
    199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
    145146392003Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes.81
    166010732006Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers.76
    169598332007GPR39 signaling is stimulated by zinc ions but not by obestatin.76

    Citation

    Catherine Tomasetto

    GHRL (ghrelin/obestatin prepropeptide)

    Atlas Genet Cytogenet Oncol Haematol. 2001-03-01

    Online version: http://atlasgeneticsoncology.org/gene/327/ghrl