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Protein

Appetite-regulating hormone

Gene

Ghrl

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation.
Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility.

GO - Molecular functioni

  • ghrelin receptor binding Source: RGD
  • G-protein coupled receptor binding Source: UniProtKB
  • growth hormone-releasing hormone activity Source: UniProtKB
  • hormone activity Source: RGD
  • protein tyrosine kinase activator activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

ReactomeiREACT_276026. Synthesis, secretion, and deacylation of Ghrelin.
REACT_306851. Peptide ligand-binding receptors.
REACT_353304. G alpha (q) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Appetite-regulating hormone
Alternative name(s):
Growth hormone secretagogue
Growth hormone-releasing peptide
Motilin-related peptide
Cleaved into the following 3 chains:
Gene namesi
Name:Ghrl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi632283. Ghrl.

Subcellular locationi

GO - Cellular componenti

  • axon Source: UniProtKB
  • cytosol Source: GOC
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23232 PublicationsAdd
BLAST
Peptidei24 – 5128GhrelinPRO_0000019209Add
BLAST
Propeptidei52 – 7524Removed in mature form1 PublicationPRO_0000019210Add
BLAST
Peptidei76 – 9823Obestatin-23PRO_0000045146Add
BLAST
Peptidei86 – 9813Obestatin-13CuratedPRO_0000045147Add
BLAST
Propeptidei99 – 11719Removed in mature formPRO_0000045148Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi26 – 261O-octanoyl serine2 Publications
Modified residuei98 – 981Leucine amide1 Publication

Post-translational modificationi

O-octanoylation is essential for ghrelin activity. The replacement of Ser-26 by aromatic tryptophan preserves ghrelin activity (PubMed:10604470, PubMed:10801861).2 Publications
Amidation of Leu-98 is essential for obestatin activity.1 Publication

Keywords - PTMi

Amidation, Lipoprotein

Proteomic databases

PaxDbiQ9QYH7.

PTM databases

PhosphoSiteiQ9QYH7.

Expressioni

Tissue specificityi

Ghrelin is broadly expressed with higher expression in the stomach. Very low levels are detected in the hypothalamus, heart, lung, pancreas, intestine and adipose tissue. Obestatin is most highly expressed in jejunum, and also found in duodenum, stomach, pituitary, ileum, liver, hypothalamus and heart. Expressed in low levels in pancreas, cerebellum, cerebrum, kidney, testis, ovary colon and lung.1 Publication

Gene expression databases

GenevisibleiQ9QYH7. RN.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000014103.

Family & Domainsi

Sequence similaritiesi

Belongs to the motilin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG45924.
GeneTreeiENSGT00390000004064.
HOGENOMiHOG000236303.
HOVERGENiHBG018522.
InParanoidiQ9QYH7.
KOiK05254.
OMAiEIQFNAP.
OrthoDBiEOG741Z4K.
PhylomeDBiQ9QYH7.
TreeFamiTF336219.

Family and domain databases

InterProiIPR006737. Motilin_assoc.
IPR006738. Motilin_ghrelin.
IPR005441. Preproghrelin.
[Graphical view]
PANTHERiPTHR14122. PTHR14122. 1 hit.
PfamiPF04643. Motilin_assoc. 1 hit.
PF04644. Motilin_ghrelin. 1 hit.
[Graphical view]
PRINTSiPR01624. GHRELIN.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9QYH7-1) [UniParc]FASTAAdd to basket

Also known as: Ghrelin

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVSSATICSL LLLSMLWMDM AMAGSSFLSP EHQKAQQRKE SKKPPAKLQP
60 70 80 90 100
RALEGWLHPE DRGQAEEAEE ELEIRFNAPF DVGIKLSGAQ YQQHGRALGK
110
FLQDILWEEV KEAPANK
Length:117
Mass (Da):13,176
Last modified:May 1, 2000 - v1
Checksum:i8857546FE51A7691
GO
Isoform 2 (identifier: Q9QYH7-2) [UniParc]FASTAAdd to basket

Also known as: des-Gln14-ghrelin

The sequence of this isoform differs from the canonical sequence as follows:
     37-37: Missing.

Show »
Length:116
Mass (Da):13,048
Checksum:i88544ECA032C24F2
GO

Mass spectrometryi

Isoform 1 : Molecular mass is 3314.9±0.7 Da from positions 24 - 51. Determined by ESI. 1 Publication
Isoform 2 : Molecular mass is 3187.1±0.6 Da from positions 24 - 50. Determined by ESI. 1 Publication
Molecular mass is 2516.3 Da from positions 76 - 98. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei37 – 371Missing in isoform 2. 1 PublicationVSP_003248

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB029433 mRNA. Translation: BAA89370.1.
AB035699 mRNA. Translation: BAB11956.1.
PIRiB59316.
RefSeqiNP_067701.1. NM_021669.2. [Q9QYH7-1]
UniGeneiRn.42103.

Genome annotation databases

EnsembliENSRNOT00000014103; ENSRNOP00000014103; ENSRNOG00000010349. [Q9QYH7-1]
GeneIDi59301.
KEGGirno:59301.
UCSCiRGD:632283. rat. [Q9QYH7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Protein Spotlight

Gut feelings - Issue 66 of January 2006

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB029433 mRNA. Translation: BAA89370.1.
AB035699 mRNA. Translation: BAB11956.1.
PIRiB59316.
RefSeqiNP_067701.1. NM_021669.2. [Q9QYH7-1]
UniGeneiRn.42103.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000014103.

PTM databases

PhosphoSiteiQ9QYH7.

Proteomic databases

PaxDbiQ9QYH7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000014103; ENSRNOP00000014103; ENSRNOG00000010349. [Q9QYH7-1]
GeneIDi59301.
KEGGirno:59301.
UCSCiRGD:632283. rat. [Q9QYH7-1]

Organism-specific databases

CTDi51738.
RGDi632283. Ghrl.

Phylogenomic databases

eggNOGiNOG45924.
GeneTreeiENSGT00390000004064.
HOGENOMiHOG000236303.
HOVERGENiHBG018522.
InParanoidiQ9QYH7.
KOiK05254.
OMAiEIQFNAP.
OrthoDBiEOG741Z4K.
PhylomeDBiQ9QYH7.
TreeFamiTF336219.

Enzyme and pathway databases

ReactomeiREACT_276026. Synthesis, secretion, and deacylation of Ghrelin.
REACT_306851. Peptide ligand-binding receptors.
REACT_353304. G alpha (q) signalling events.

Miscellaneous databases

NextBioi611837.
PROiQ9QYH7.

Gene expression databases

GenevisibleiQ9QYH7. RN.

Family and domain databases

InterProiIPR006737. Motilin_assoc.
IPR006738. Motilin_ghrelin.
IPR005441. Preproghrelin.
[Graphical view]
PANTHERiPTHR14122. PTHR14122. 1 hit.
PfamiPF04643. Motilin_assoc. 1 hit.
PF04644. Motilin_ghrelin. 1 hit.
[Graphical view]
PRINTSiPR01624. GHRELIN.
ProtoNetiSearch...

Publicationsi

  1. "Ghrelin is a growth-hormone-releasing acylated peptide from stomach."
    Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K.
    Nature 402:656-660(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 24-51, MASS SPECTROMETRY, ACYLATION AT SER-26.
    Strain: Sprague-Dawley.
    Tissue: Stomach.
  2. "Purification and characterization of rat des-Gln14-ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor."
    Hosoda H., Kojima M., Matsuo H., Kangawa K.
    J. Biol. Chem. 275:21995-22000(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 24-51, MASS SPECTROMETRY, ACYLATION AT SER-26.
    Strain: Sprague-Dawley.
    Tissue: Stomach.
  3. "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake."
    Zhang J.V., Ren P.G., Avsian-Kretchmer O., Luo C.W., Rauch R., Klein C., Hsueh A.J.
    Science 310:996-999(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 76-95, FUNCTION OF OBESTATIN, CHARACTERIZATION, AMIDATION AT LEU-98, MASS SPECTROMETRY, INTERACTION WITH GPR39.
  4. "Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue."
    Hosoda H., Kojima M., Matsuo H., Kangawa K.
    Biochem. Biophys. Res. Commun. 279:909-913(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. Cited for: STRUCTURE-ACTIVITY RELATIONSHIP.
  6. "Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor."
    Kojima M., Hosoda H., Matsuo H., Kangawa K.
    Trends Endocrinol. Metab. 12:118-122(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  7. Cited for: FUNCTION OF OBESTATIN.

Entry informationi

Entry nameiGHRL_RAT
AccessioniPrimary (citable) accession number: Q9QYH7
Secondary accession number(s): Q9ET69
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2001
Last sequence update: May 1, 2000
Last modified: July 22, 2015
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

PubMed:16284174 reports obestatin as ligand of GPR39. However, PubMed:17289961 and others are unable to reproduce these results. It also seems to be unclear whether obestatin has opposite effects on food intake compared with ghrelin.Curated

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.