Q9QYH7 (GHRL_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	117 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. 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 component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Hormone
PTM	Amidation Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-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 elevation of cytosolic calcium ion concentration Inferred from direct assay PubMed 11756331. Source: UniProtKB 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: Compara 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: Compara 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: Compara positive regulation of corticotropin secretion Inferred from electronic annotation. Source: Compara positive regulation of cortisol secretion Inferred from electronic annotation. Source: Compara positive regulation of growth hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from direct assay PubMed 11756331. Source: UniProtKB regulation of excitatory postsynaptic membrane potential Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	axon Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ghrelin receptor binding Inferred from mutant phenotype PubMed 17109695. Source: RGD growth hormone-releasing hormone activity Inferred from direct assay Ref.1. Source: UniProtKB 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Ref.1 Ref.2
	Peptide	24 – 51	28	Ghrelin Ref.1 Ref.2		PRO_0000019209
	Propeptide	52 – 75	24	Removed in mature form		PRO_0000019210
	Peptide	76 – 98	23	Obestatin-23		PRO_0000045146
	Peptide	86 – 98	13	Obestatin-13 Probable		PRO_0000045147
	Propeptide	99 – 117	19	Removed in mature form		PRO_0000045148
Amino acid modifications
	Modified residue	98	1	Leucine amide
	Lipidation	26	1	O-octanoyl serine
Natural variations
	Alternative sequence	37	1	Missing in isoform 2.		VSP_003248

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Ghrelin) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 8857546FE51A7691	FASTA	117	13,176
	10 20 30 40 50 60 MVSSATICSL LLLSMLWMDM AMAGSSFLSP EHQKAQQRKE SKKPPAKLQP RALEGWLHPE 70 80 90 100 110 DRGQAEEAEE ELEIRFNAPF DVGIKLSGAQ YQQHGRALGK FLQDILWEEV KEAPANK
	Isoform 2 (des-Gln14-ghrelin) [UniParc]. Checksum: 88544ECA032C24F2	FASTA	116	13,048
	10 20 30 40 50 60 MVSSATICSL LLLSMLWMDM AMAGSSFLSP EHQKAQRKES KKPPAKLQPR ALEGWLHPED 70 80 90 100 110 RGQAEEAEEE LEIRFNAPFD VGIKLSGAQY QQHGRALGKF LQDILWEEVK EAPANK

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, 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, 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.
IPI	IPI00214108. IPI00231242.
PIR	B59316.
RefSeq	NP_067701.1. NM_021669.2.
UniGene	Rn.42103.
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q9QYH7.
Proteomic databases
PaxDb	Q9QYH7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000014103; ENSRNOP00000014103; ENSRNOG00000010349.
GeneID	59301.
KEGG	rno:59301.
UCSC	RGD:632283. rat.
Organism-specific databases
CTD	51738.
RGD	632283. Ghrl.
Phylogenomic databases
eggNOG	NOG45924.
GeneTree	ENSGT00390000004064.
HOGENOM	HOG000236303.
HOVERGEN	HBG018522.
InParanoid	Q9QYH7.
KO	K05254.
OMA	AQYQQHG.
OrthoDB	EOG4CRM1Q.
Enzyme and pathway databases
Reactome	REACT_111984. Signal Transduction.
Gene expression databases
ArrayExpress	Q9QYH7.
Genevestigator	Q9QYH7.
GermOnline	ENSRNOG00000010349. Rattus norvegicus.
Family and domain databases
InterPro	IPR006737. Motilin_assoc. IPR006738. Motilin_ghrelin. IPR005441. Preproghrelin. [Graphical view]
PANTHER	PTHR14122. PTHR14122. 1 hit.
Pfam	PF04643. Motilin_assoc. 1 hit. PF04644. Motilin_ghrelin. 1 hit. [Graphical view]
PRINTS	PR01624. GHRELIN.
ProtoNet	Search...
Other
NextBio	611837.

Entry information

Entry name

GHRL_RAT

Accession

Primary (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 3, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program