Reviewed, UniProtKB/Swiss-Prot Q9UBU3 (GHRL_HUMAN)

Names and origin

Protein names

Recommended name:
    Appetite-regulating hormone
Alternative name(s):
    Growth hormone secretagogue
    Growth hormone-releasing peptide
    Motilin-related peptide
    M46 protein
Cleaved into 3 chains:
  Recommended name:
      Ghrelin-27
  Recommended name:
      Ghrelin-28
        Short name(s)=Ghrelin
  Recommended name:
      Obestatin

Gene names

Name:	GHRL
Synonyms:	MTLRP
ORF Names:	UNQ524/PRO1066

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. 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 By similarity.
Subcellular location	Secreted.
Tissue specificity	Highest level in stomach. All forms are found in serum as well. Other tissues compensate for the loss of ghrelin synthesis in the stomach following gastrectomy.
Post-translational modification	O-octanoylation or O-decanoylation is essential for ghrelin activity. The O-decanoylated forms Ghrelin-27-C10 and Ghrelin-28-C10 differ in the length of the carbon backbone of the carboxylic acid bound to Ser-26. A small fraction of ghrelin, ghrelin-28-C10:1, may be modified with a singly unsaturated carboxylic acid. Amidation of Leu-98 is essential for obestatin activity By similarity.
Sequence similarities	Belongs to the motilin family.
Mass spectrometry	Molecular weight is 3398.9±0.3 Da from positions 24 - 51. Determined by ESI. Ghrelin-28-C10, O-decanoylated form Molecular weight is 3397.2±0.5 Da from positions 24 - 51. Determined by ESI. Ghrelin-28-C10:1, O-decenoylated form Molecular weight is 3371.3±0.1 Da from positions 24 - 51. Determined by ESI. Ghrelin-28-C8, O-octanoylated form Molecular weight is 3243.6±0.4 Da from positions 24 - 50. Determined by ESI. Ghrelin-27-C10, O-decanoylated form Molecular weight is 3214.6±0.6 Da from positions 24 - 50. Determined by ESI. Ghrelin-27-C8, O-octanoylated form

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Amidation Lipoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB actin polymerization and/or depolymerization Inferred from direct assay. Source: UniProtKB activation of MAPK activity Inferred from mutant phenotype. Source: UniProtKB adult feeding behavior Inferred from sequence or structural similarity. Source: HGNC cartilage development Non-traceable author statement. Source: UniProtKB cortisol secretion Non-traceable author statement. Source: UniProtKB decidualization Inferred from direct assay. Source: UniProtKB dendrite development Inferred from direct assay. Source: MGI elevation of cytosolic calcium ion concentration Inferred from sequence or structural similarity. Source: UniProtKB glucose metabolic process Non-traceable author statement. Source: UniProtKB growth hormone secretion Traceable author statement. Source: HGNC hormone-mediated signaling Traceable author statement. Source: HGNC negative regulation of angiogenesis Non-traceable author statement. Source: UniProtKB negative regulation of apoptosis Inferred from direct assay. Source: UniProtKB negative regulation of endothelial cell proliferation Inferred from direct assay. Source: UniProtKB negative regulation of inflammatory response Inferred from direct assay. Source: UniProtKB negative regulation of interleukin-1 beta production Inferred from direct assay. Source: UniProtKB negative regulation of interleukin-6 biosynthetic process Inferred from direct assay. Source: UniProtKB negative regulation of tumor necrosis factor biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of appetite Inferred from sequence or structural similarity. Source: HGNC positive regulation of insulin secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of multicellular organism growth Inferred by curator. Source: HGNC positive regulation of synaptogenesis Inferred from direct assay. Source: MGI response to estrogen stimulus Inferred from direct assay. Source: UniProtKB
Cellular component	axon Inferred from direct assay. Source: UniProtKB extracellular space Inferred from direct assay. Source: UniProtKB
Molecular function	ghrelin receptor binding Inferred from sequence or structural similarity. Source: UniProtKB growth hormone-releasing hormone activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB protein tyrosine kinase activator activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBU3-1)

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: Q9UBU3-2)

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

Molecule processing

Signal peptide

1 – 23

23

Peptide

24 – 51

28

Ghrelin-28

Peptide

24 – 50

27

Ghrelin-27

Propeptide

52 – 75

24

Removed in mature form

Peptide

76 – 98

23

Obestatin By similarity

Propeptide

99 – 117

19

Removed in mature form By similarity

Amino acid modifications

Modified residue

98

1

Leucine amide By similarity

Lipidation

26

1

O-decanoyl serine; alternate

Lipidation

26

1

O-octanoyl serine; alternate

Natural variations

Alternative sequence

37

1

Missing in isoform 2.

Natural variant

90

1

Q → L: dbSNP rs4684677.

Experimental info

Sequence conflict

72

1

L → M in AAH25791. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

117

Helix Strand Turn

Details...

Beta strand

8 – 14

7

Beta strand

17 – 24

8

Beta strand

27 – 29

3

Helix

30 – 35

6

Beta strand

57 – 60

4

Beta strand

63 – 70

8

Beta strand

73 – 77

5

Helix

90 – 93

4

Helix

95 – 104

10

Helix

107 – 115

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Ghrelin) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 39C0572EBECA2755	FASTA	117	12,911
	10 20 30 40 50 60 MPSPGTVCSL LLLGMLWLDL AMAGSSFLSP EHQRVQQRKE SKKPPAKLQP RALAGWLRPE 70 80 90 100 110 DGGQAEGAED ELEVRFNAPF DVGIKLSGVQ YQQHSQALGK FLQDILWEEA KEAPADK
	Isoform 2 (des-Gln14-ghrelin) [UniParc]. Checksum: F0DEBEEE880DC951		116	12,783
	10 20 30 40 50 60 MPSPGTVCSL LLLGMLWLDL AMAGSSFLSP EHQRVQRKES KKPPAKLQPR ALAGWLRPED 70 80 90 100 110 GGQAEGAEDE LEVRFNAPFD VGIKLSGVQY QQHSQALGKF LQDILWEEAK EAPADK

References

	« Hide 'large scale' referencesShow 'large scale' 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: 10604470] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ACYLATION AT SER-26. Tissue: Stomach.
[2]	"Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide." Tomasetto C., Karam S.M., Ribieras S., Masson R., Lefebvre O., Staub A., Alexander G., Chenard M.-P., Rio M.-C. Gastroenterology 119:395-405(2000) [PubMed: 10930375] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 24-33. Tissue: Stomach.
[3]	"Genomic organization of the human Ghrelin gene." Wajnrajch M.P., Ten I.S., Gertner J.M., Leibel R.L. J. Endocr. Genet. 1:231-233(2000) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing." Hosoda H., Kojima M., Mizushima T., Shimizu S., Kangawa K. J. Biol. Chem. 278:64-70(2003) [PubMed: 12414809] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, ACYLATION AT SER-26, MASS SPECTROMETRY. Tissue: Stomach.
[5]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Blood.
[7]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-38.
[8]	"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: 11306336] [Abstract] Cited for: REVIEW.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Protein Spotlight

Gut feelings - Issue 66 of January 2006

Wikipedia

Ghrelin entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB029434 mRNA. Translation: BAA89371.1.
AJ252278 mRNA. Translation: CAB65733.1.
AF296558 Genomic DNA. Translation: AAG10300.1.
AB035700 mRNA. Translation: BAB19045.1.
AY359053 mRNA. Translation: AAQ89412.1.
BC025791 mRNA. Translation: AAH25791.1.

PIR

A59316.

RefSeq

NP_057446.1.

UniGene

Hs.590080

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P7X	model	-	A	1-117	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q9UBU3.

Genome annotation databases

Ensembl

ENSG00000157017. Homo sapiens. [Contig view]

GeneID

51738.

KEGG

hsa:51738.

NMPDR

fig|9606.3.peg.22121.

Organism-specific databases

H-InvDB

HIX0003050.

HGNC

HGNC:18129. GHRL.

HPA

HPA014246.

MIM

605353. gene.

PharmGKB

PA142671740.

GenAtlas

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GeneCards

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GeneLynx

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Phylogenomic databases

HOGENOM

Q9UBU3.

HOVERGEN

Q9UBU3.

Gene expression databases

ArrayExpress

Q9UBU3.

CleanEx

HS_GHRL.

GermOnline

ENSG00000157017. Homo sapiens.

Family and domain databases

InterPro

IPR006737. Motilin_assoc.
IPR006738. Motilin_ghrelin.
IPR005441. Preproghrelin.
[Graphical view]

PANTHER

PTHR14122. Preproghrelin. 1 hit.

Pfam

PF04643. Motilin_assoc. 1 hit.
PF04644. Motilin_ghrelin. 1 hit.
[Graphical view]

PRINTS

PR01624. GHRELIN.

ProDom

PD332162. Preproghrelin. 2 hits.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

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Other Resources

SOURCE

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ProtoNet

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Entry information

Entry name

GHRL_HUMAN

Accession

Primary (citable) accession number: Q9UBU3
Secondary accession number(s): Q8TAT9, Q9H3R3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2001
Last sequence update:	May 1, 2000
Last modified:	July 22, 2008
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)