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UniProtKB/Swiss-Prot entry Q9UBU3


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name GHRL_HUMAN
Primary accession number Q9UBU3
Secondary accession numbers Q8TAT9 Q9H3R3
Integrated into Swiss-Prot on December 13, 2001
Sequence was last modified on May 1, 2000 (Sequence version 1)
Annotations were last modified on    April 29, 2008 (Entry version 82)
Name and origin of the protein
Protein name Appetite-regulating hormone [Precursor]
Synonyms Growth hormone secretagogue
Growth hormone-releasing peptide
Motilin-related peptide
M46 protein
Contains Ghrelin-27
Ghrelin-28
     (Ghrelin)
Obestatin
Gene name
Name: GHRL
Synonyms: MTLRP
ORFNames: UNQ524/PRO1066
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ACYLATION AT SER-26.
TISSUE=Stomach;
DOI=10.1038/45230; PubMed=10604470 [NCBI, ExPASy, EBI, Israel, Japan]
Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K.;
"Ghrelin is a growth-hormone-releasing acylated peptide from stomach.";
Nature 402:656-660(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 24-33.
TISSUE=Stomach;
PubMed=10930375 [NCBI, ExPASy, EBI, Israel, Japan]
Tomasetto C., Karam S.M., Ribieras S., Masson R., Lefebvre O., Staub A., Alexander G., Chenard M.-P., Rio M.-C.;
"Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide.";
Gastroenterology 119:395-405(2000).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Wajnrajch M.P., Ten I.S., Gertner J.M., Leibel R.L.;
"Genomic organization of the human Ghrelin gene.";
J. Endocr. Genet. 1:231-233(2000).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, ACYLATION AT SER-26, AND MASS SPECTROMETRY.
TISSUE=Stomach;
DOI=10.1074/jbc.M205366200; PubMed=12414809 [NCBI, ExPASy, EBI, Israel, Japan]
Hosoda H., Kojima M., Mizushima T., Shimizu S., Kangawa K.;
"Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing.";
J. Biol. Chem. 278:64-70(2003).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
DOI=10.1101/gr.1293003; PubMed=12975309 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Blood;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
PROTEIN SEQUENCE OF 24-38.
DOI=10.1110/ps.04682504; PubMed=15340161 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang Z., Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
[8]
REVIEW.
DOI=10.1016/S1043-2760(00)00362-3; PubMed=11306336 [NCBI, ExPASy, EBI, Israel, Japan]
Kojima M., Hosoda H., Matsuo H., Kangawa K.;
"Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor.";
Trends Endocrinol. Metab. 12:118-122(2001).
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.
  • FUNCTION: 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.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    SynonymsGhrelin
    Isoform IDQ9UBU3-1
    This is the isoform sequence displayed in this entry.
    Name2
    Synonymsdes-Gln14-ghrelin
    Isoform IDQ9UBU3-2
    Features which should be applied to build the isoform sequence: VSP_003245.
  • 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.
  • PTM: 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.
  • PTM: Amidation of Leu-98 is essential for obestatin activity (By similarity).
  • MASS SPECTROMETRY: Mass=3398.9; Mass_error=0.3; Method=Electrospray; Range=24-51; Note=Ghrelin-28-C10, O-decanoylated form; Source=PubMed:12414809;.
  • MASS SPECTROMETRY: Mass=3397.2; Mass_error=0.5; Method=Electrospray; Range=24-51; Note=Ghrelin-28-C10:1, O-decenoylated form; Source=PubMed:12414809;.
  • MASS SPECTROMETRY: Mass=3371.3; Mass_error=0.1; Method=Electrospray; Range=24-51; Note=Ghrelin-28-C8, O-octanoylated form; Source=PubMed:12414809;.
  • MASS SPECTROMETRY: Mass=3243.6; Mass_error=0.4; Method=Electrospray; Range=24-50; Note=Ghrelin-27-C10, O-decanoylated form; Source=PubMed:12414809;.
  • MASS SPECTROMETRY: Mass=3214.6; Mass_error=0.6; Method=Electrospray; Range=24-50; Note=Ghrelin-27-C8, O-octanoylated form; Source=PubMed:12414809;.
  • SIMILARITY: Belongs to the motilin family.
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GhrelinID327.html";.
  • WEB RESOURCE: Name=Protein Spotlight; Note=Gut feelings - Issue 66 of January 2006; URL="http://www.expasy.org/spotlight/back_issues/sptlt066.shtml";.
  • WEB RESOURCE: Name=Wikipedia; Note=Ghrelin entry; URL="http://en.wikipedia.org/wiki/Ghrelin";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AB029434; BAA89371.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ252278; CAB65733.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF296558; AAG10300.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB035700; BAB19045.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY359053; AAQ89412.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC025791; AAH25791.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A59316; A59316.
RefSeq NP_057446.1; -.
UniGene Hs.590080
3D structure databases
PDB
1P7X; Model; -; A=1-117.[ExPASy / RCSB / EBI]
PDBsum 1P7X; -.
ModBase Q9UBU3.
Organism-specific databases
H-InvDB HIX0003050; -.
HGNC HGNC:18129; GHRL.
GeneLynx GHRL; Homo sapiens.
GenAtlas GHRL.
MIM 605353; gene. [NCBI / EBI]
PharmGKB PA142671740; -.
GeneCards Q9UBU3.
Gene expression databases
ArrayExpress Q9UBU3; -.
CleanEx HS_GHRL; -.
GermOnline ENSG00000157017; Homo sapiens.
Ontologies
GO
GO:0030424; Cellular component: axon (inferred from direct assay from UniProtKB).
GO:0005615; Cellular component: extracellular space (inferred from direct assay from UniProtKB).
GO:0031768; Molecular function: ghrelin receptor binding (inferred from sequence or structural similarity from UniProtKB).
GO:0016608; Molecular function: growth hormone-releasing hormone activity (inferred from sequence or structural similarity from UniProtKB).
GO:0030296; Molecular function: protein tyrosine kinase activator activity (inferred from mutant phenotype from UniProtKB).
GO:0008154; Biological process: actin polymerization and/or depolymerization (inferred from direct assay from UniProtKB).
GO:0000187; Biological process: activation of MAPK activity (inferred from mutant phenotype from UniProtKB).
GO:0008343; Biological process: adult feeding behavior (inferred from sequence or structural similarity from HGNC).
GO:0051216; Biological process: cartilage development (non-traceable author statement from UniProtKB).
GO:0043400; Biological process: cortisol secretion (non-traceable author statement from UniProtKB).
GO:0046697; Biological process: decidualization (inferred from direct assay from UniProtKB).
GO:0016358; Biological process: dendrite development (inferred from direct assay from MGI).
GO:0007204; Biological process: elevation of cytosolic calcium ion concentration (inferred from sequence or structural similarity from UniProtKB).
GO:0007186; Biological process: G-protein coupled receptor protein signaling pathway (inferred from sequence or structural similarity from UniProtKB).
GO:0006006; Biological process: glucose metabolic process (non-traceable author statement from UniProtKB).
GO:0030252; Biological process: growth hormone secretion (traceable author statement from HGNC).
GO:0009755; Biological process: hormone-mediated signaling (traceable author statement from HGNC).
GO:0016525; Biological process: negative regulation of angiogenesis (non-traceable author statement from UniProtKB).
GO:0043066; Biological process: negative regulation of apoptosis (inferred from direct assay from UniProtKB).
GO:0001937; Biological process: negative regulation of endothelial cell proliferation (inferred from direct assay from UniProtKB).
GO:0050728; Biological process: negative regulation of inflammatory response (inferred from direct assay from UniProtKB).
GO:0032691; Biological process: negative regulation of interleukin-1 beta production (inferred from direct assay from UniProtKB).
GO:0045409; Biological process: negative regulation of interleukin-6 biosynthetic process (inferred from direct assay from UniProtKB).
GO:0042536; Biological process: negative regulation of tumor necrosis factor biosynthetic process (inferred from direct assay from UniProtKB).
GO:0032100; Biological process: positive regulation of appetite (inferred from sequence or structural similarity from HGNC).
GO:0032024; Biological process: positive regulation of insulin secretion (inferred from sequence or structural similarity from UniProtKB).
GO:0040018; Biological process: positive regulation of multicellular organism growth (inferred by curator from HGNC).
GO:0051965; Biological process: positive regulation of synaptogenesis (inferred from direct assay from MGI).
GO:0043627; Biological process: response to estrogen stimulus (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR006737; Motilin_assoc.
IPR006738; Motilin_ghrelin.
IPR005441; Preproghrelin.
Graphical view of domain structure.
PANTHER PTHR14122; Preproghrelin; 1.
Pfam PF04643; Motilin_assoc; 1.
PF04644; Motilin_ghrelin; 1.
Pfam graphical view of domain structure.
PRINTS PR01624; GHRELIN.
ProDom PD332162; Preproghrelin; 2.
[Domain structure / List of seq. sharing at least 1 domain]
BLOCKS Q9UBU3.
Genome annotation databases
Ensembl ENSG00000157017; Homo sapiens. [Contig view]
GeneID 51738; -.
KEGG hsa:51738; -.
NMPDR fig|9606.3.peg.22121; -.
Other
SOURCE GHRL; Homo sapiens.
ProtoNet Q9UBU3.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Amidation; Direct protein sequencing; Hormone; Lipoprotein; Polymorphism; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    23  23      
PEPTIDE   24    51  28     Ghrelin-28. PRO_0000019202
PEPTIDE   24    50  27     Ghrelin-27. PRO_0000019203
PROPEP   52    75  24     Removed in mature form. PRO_0000019204
PEPTIDE   76    98  23     Obestatin (By similarity). PRO_0000045140
PROPEP   99   117  19     Removed in mature form (By similarity). PRO_0000045141
MOD_RES   98    98        Leucine amide (By similarity). 
LIPID   26    26        O-decanoyl serine; alternate. 
LIPID   26    26        O-octanoyl serine; alternate. 
VAR_SEQ   37    37        Missing (in isoform 2). VSP_003245
VARIANT   90    90  1     Q -> L (in dbSNP:rs4684677 [NCBI]). VAR_029135 
CONFLICT   72    72        L -> M (in Ref. 6; AAH25791). 
STRAND   8    14  7      
STRAND   17    24  8      
STRAND   27    29  3      
HELIX   30    35  6      
STRAND   57    60  4      
STRAND   63    70  8      
STRAND   73    77  5      
HELIX   90    93  4      
HELIX   95   104  10      
HELIX   107   115  9      
Sequence information
Length: 117 AA [This is the length of the unprocessed precursor] Molecular weight: 12911 Da [This is the MW of the unprocessed precursor] CRC64: 39C0572EBECA2755 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MPSPGTVCSL LLLGMLWLDL AMAGSSFLSP EHQRVQQRKE SKKPPAKLQP RALAGWLRPE 

        70         80         90        100        110 
DGGQAEGAED ELEVRFNAPF DVGIKLSGVQ YQQHSQALGK FLQDILWEEA KEAPADK 

Q9UBU3 in FASTA format

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