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Q9QYH7 (GHRL_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Appetite-regulating hormone
Alternative name(s):
Growth hormone secretagogue
Growth hormone-releasing peptide
Motilin-related peptide

Cleaved into the following 3 chains:

  1. Ghrelin
  2. Obestatin-23
  3. Obestatin-13
Gene names
Name:Ghrl
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length117 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.7

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. Ref.3 Ref.7

Subcellular location

Secreted.

Tissue specificity

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. Ref.4

Post-translational modification

O-octanoylation is essential for ghrelin activity. The replacement of Ser-26 by aromatic tryptophan preserves ghrelin activity (Ref.1, Ref.2).

Amidation of Leu-98 is essential for obestatin activity.

Sequence similarities

Belongs to the motilin family.

Caution

Ref.3 reports obestatin as ligand of GPR39. However, Ref.7 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.

Mass spectrometry

Isoform 1: Molecular mass is 3314.9±0.7 Da from positions 24 - 51. Determined by ESI. Ref.1

Isoform 2: Molecular mass is 3187.1±0.6 Da from positions 24 - 50. Determined by ESI. Ref.2

Molecular mass is 2516.3 Da from positions 76 - 98. Ref.3

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DomainSignal
   Molecular functionHormone
   PTMAmidation
Lipoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from direct assay Ref.1. Source: UniProtKB

actin polymerization or depolymerization

Inferred from sequence or structural similarity. Source: UniProtKB

activation of MAPK activity

Inferred from sequence or structural similarity. Source: UniProtKB

adult feeding behavior

Inferred from sequence or structural similarity. Source: HGNC

decidualization

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite development

Inferred from electronic annotation. Source: Ensembl

gastric acid secretion

Inferred from direct assay PubMed 17705669. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay PubMed 17543279. Source: UniProtKB

negative regulation of circadian sleep/wake cycle, REM sleep

Inferred from electronic annotation. Source: Ensembl

negative regulation of endothelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of insulin secretion

Inferred from direct assay PubMed 17130496. Source: MGI

negative regulation of interleukin-1 beta production

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-6 biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of locomotion

Inferred from electronic annotation. Source: Ensembl

negative regulation of tumor necrosis factor biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of appetite

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of circadian sleep/wake cycle, non-REM sleep

Inferred from electronic annotation. Source: Ensembl

positive regulation of corticotropin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of cortisol secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay PubMed 11756331. Source: UniProtKB

positive regulation of growth hormone secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from direct assay PubMed 11756331. Source: UniProtKB

positive regulation of response to food

Inferred from direct assay PubMed 17065340. Source: RGD

positive regulation of synapse assembly

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of excitatory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of response to food

Inferred from direct assay PubMed 17065340. Source: RGD

response to estrogen

Inferred from sequence or structural similarity. Source: UniProtKB

response to hormone

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentaxon

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular region

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular space

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionG-protein coupled receptor binding

Inferred from physical interaction Ref.1. Source: UniProtKB

ghrelin receptor binding

Inferred from mutant phenotype PubMed 17109695. Source: RGD

growth hormone-releasing hormone activity

Inferred from direct assay Ref.1. Source: UniProtKB

hormone activity

Inferred from direct assay PubMed 17109695. Source: RGD

protein tyrosine kinase activator activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9QYH7-1)

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.
Isoform 2 (identifier: Q9QYH7-2)

Also known as: des-Gln14-ghrelin;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.1 Ref.2
Peptide24 – 5128Ghrelin Ref.1 Ref.2
PRO_0000019209
Propeptide52 – 7524Removed in mature form
PRO_0000019210
Peptide76 – 9823Obestatin-23
PRO_0000045146
Peptide86 – 9813Obestatin-13 Probable
PRO_0000045147
Propeptide99 – 11719Removed in mature form
PRO_0000045148

Amino acid modifications

Modified residue981Leucine amide
Lipidation261O-octanoyl serine

Natural variations

Alternative sequence371Missing in isoform 2.
VSP_003248

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Ghrelin) [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 8857546FE51A7691

FASTA11713,176
        10         20         30         40         50         60 
MVSSATICSL LLLSMLWMDM AMAGSSFLSP EHQKAQQRKE SKKPPAKLQP RALEGWLHPE 

        70         80         90        100        110 
DRGQAEEAEE ELEIRFNAPF DVGIKLSGAQ YQQHGRALGK FLQDILWEEV KEAPANK 

« Hide

Isoform 2 (des-Gln14-ghrelin) [UniParc].

Checksum: 88544ECA032C24F2
Show »

FASTA11613,048

References

[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, LIPIDATION 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, LIPIDATION 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, 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]"Structure-activity relationship of ghrelin: pharmacological study of ghrelin peptides."
Matsumoto M., Hosoda H., Kitajima Y., Morozumi N., Minamitake Y., Tanaka S., Matsuo H., Kojima M., Hayashi Y., Kangawa K.
Biochem. Biophys. Res. Commun. 287:142-146(2001) [PubMed] [Europe PMC] [Abstract]
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]"Comment on 'Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake'."
Chartrel N., Alvear-Perez R., Leprince J., Iturrioz X., Reaux-Le Goazigo A., Audinot V., Chomarat P., Coge F., Nosjean O., Rodriguez M., Galizzi J.P., Boutin J.A., Vaudry H., Llorens-Cortes C.
Science 315:766-766(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF OBESTATIN.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Gut feelings - Issue 66 of January 2006

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB029433 mRNA. Translation: BAA89370.1.
AB035699 mRNA. Translation: BAB11956.1.
PIRB59316.
RefSeqNP_067701.1. NM_021669.2.
UniGeneRn.42103.

3D structure databases

ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ9QYH7.

Proteomic databases

PaxDbQ9QYH7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000014103; ENSRNOP00000014103; ENSRNOG00000010349. [Q9QYH7-1]
GeneID59301.
KEGGrno:59301.
UCSCRGD:632283. rat. [Q9QYH7-1]

Organism-specific databases

CTD51738.
RGD632283. Ghrl.

Phylogenomic databases

eggNOGNOG45924.
GeneTreeENSGT00390000004064.
HOGENOMHOG000236303.
HOVERGENHBG018522.
InParanoidQ9QYH7.
KOK05254.
OMAEIQFNAP.
OrthoDBEOG741Z4K.
PhylomeDBQ9QYH7.
TreeFamTF336219.

Gene expression databases

GenevestigatorQ9QYH7.

Family and domain databases

InterProIPR006737. Motilin_assoc.
IPR006738. Motilin_ghrelin.
IPR005441. Preproghrelin.
[Graphical view]
PANTHERPTHR14122. PTHR14122. 1 hit.
PfamPF04643. Motilin_assoc. 1 hit.
PF04644. Motilin_ghrelin. 1 hit.
[Graphical view]
PRINTSPR01624. GHRELIN.
ProtoNetSearch...

Other

NextBio611837.
PROQ9QYH7.

Entry information

Entry nameGHRL_RAT
AccessionPrimary (citable) accession number: Q9QYH7
Secondary accession number(s): Q9ET69
Entry history
Integrated into UniProtKB/Swiss-Prot: December 13, 2001
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries