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Q9QYH7

- GHRL_RAT

UniProt

Q9QYH7 - GHRL_RAT

Protein

Appetite-regulating hormone

Gene

Ghrl

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    1. ghrelin receptor binding Source: RGD
    2. G-protein coupled receptor binding Source: UniProtKB
    3. growth hormone-releasing hormone activity Source: UniProtKB
    4. hormone activity Source: RGD
    5. protein tyrosine kinase activator activity Source: UniProtKB

    GO - Biological processi

    1. actin polymerization or depolymerization Source: UniProtKB
    2. activation of MAPK activity Source: UniProtKB
    3. adult feeding behavior Source: HGNC
    4. decidualization Source: UniProtKB
    5. dendrite development Source: Ensembl
    6. gastric acid secretion Source: UniProtKB
    7. G-protein coupled receptor signaling pathway Source: UniProtKB
    8. negative regulation of apoptotic process Source: UniProtKB
    9. negative regulation of circadian sleep/wake cycle, REM sleep Source: Ensembl
    10. negative regulation of endothelial cell proliferation Source: UniProtKB
    11. negative regulation of inflammatory response Source: UniProtKB
    12. negative regulation of insulin secretion Source: MGI
    13. negative regulation of interleukin-1 beta production Source: UniProtKB
    14. negative regulation of interleukin-6 biosynthetic process Source: UniProtKB
    15. negative regulation of locomotion Source: Ensembl
    16. negative regulation of tumor necrosis factor biosynthetic process Source: UniProtKB
    17. positive regulation of appetite Source: HGNC
    18. positive regulation of circadian sleep/wake cycle, non-REM sleep Source: Ensembl
    19. positive regulation of corticotropin secretion Source: Ensembl
    20. positive regulation of cortisol secretion Source: Ensembl
    21. positive regulation of cytosolic calcium ion concentration Source: UniProtKB
    22. positive regulation of growth hormone secretion Source: Ensembl
    23. positive regulation of insulin secretion Source: UniProtKB
    24. positive regulation of response to food Source: RGD
    25. positive regulation of synapse assembly Source: Ensembl
    26. regulation of cell proliferation Source: UniProtKB
    27. regulation of excitatory postsynaptic membrane potential Source: Ensembl
    28. regulation of response to food Source: RGD
    29. response to estrogen Source: UniProtKB
    30. response to hormone Source: UniProtKB

    Keywords - Molecular functioni

    Hormone

    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: Chromosome 4

    Organism-specific databases

    RGDi632283. Ghrl.

    Subcellular locationi

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. cytoplasm Source: Ensembl
    3. extracellular region Source: UniProtKB
    4. extracellular space Source: UniProtKB

    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

    GenevestigatoriQ9QYH7.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the motilin family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG45924.
    GeneTreeiENSGT00390000004064.
    HOGENOMiHOG000236303.
    HOVERGENiHBG018522.
    InParanoidiQ9QYH7.
    KOiK05254.
    OMAiSLGTICS.
    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. Align

    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

    MVSSATICSL LLLSMLWMDM AMAGSSFLSP EHQKAQQRKE SKKPPAKLQP    50
    RALEGWLHPE DRGQAEEAEE ELEIRFNAPF DVGIKLSGAQ YQQHGRALGK 100
    FLQDILWEEV KEAPANK 117
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB029433 mRNA. Translation: BAA89370.1 .
    AB035699 mRNA. Translation: BAB11956.1 .
    PIRi B59316.
    RefSeqi NP_067701.1. NM_021669.2. [Q9QYH7-1 ]
    UniGenei Rn.42103.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q9QYH7.

    Proteomic databases

    PaxDbi Q9QYH7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000014103 ; ENSRNOP00000014103 ; ENSRNOG00000010349 . [Q9QYH7-1 ]
    GeneIDi 59301.
    KEGGi rno:59301.
    UCSCi RGD:632283. rat. [Q9QYH7-1 ]

    Organism-specific databases

    CTDi 51738.
    RGDi 632283. Ghrl.

    Phylogenomic databases

    eggNOGi NOG45924.
    GeneTreei ENSGT00390000004064.
    HOGENOMi HOG000236303.
    HOVERGENi HBG018522.
    InParanoidi Q9QYH7.
    KOi K05254.
    OMAi SLGTICS.
    OrthoDBi EOG741Z4K.
    PhylomeDBi Q9QYH7.
    TreeFami TF336219.

    Miscellaneous databases

    NextBioi 611837.
    PROi Q9QYH7.

    Gene expression databases

    Genevestigatori Q9QYH7.

    Family and domain databases

    InterProi IPR006737. Motilin_assoc.
    IPR006738. Motilin_ghrelin.
    IPR005441. Preproghrelin.
    [Graphical view ]
    PANTHERi PTHR14122. PTHR14122. 1 hit.
    Pfami PF04643. Motilin_assoc. 1 hit.
    PF04644. Motilin_ghrelin. 1 hit.
    [Graphical view ]
    PRINTSi PR01624. GHRELIN.
    ProtoNeti Search...

    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: October 1, 2014
    This is version 108 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