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    GHRL ghrelin and obestatin prepropeptide [ Homo sapiens (human) ]

    Gene ID: 51738, updated on 23-Apr-2017
    Official Symbol
    GHRLprovided by HGNC
    Official Full Name
    ghrelin and obestatin prepropeptideprovided by HGNC
    Primary source
    HGNC:HGNC:18129
    See related
    Ensembl:ENSG00000157017 MIM:605353; Vega:OTTHUMG00000155360
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MTLRP
    Summary
    This gene encodes the ghrelin-obestatin preproprotein that is cleaved to yield two peptides, ghrelin and obestatin. Ghrelin is a powerful appetite stimulant and plays an important role in energy homeostasis. Its secretion is initiated when the stomach is empty, whereupon it binds to the growth hormone secretagogue receptor in the hypothalamus which results in the secretion of growth hormone (somatotropin). Ghrelin is thought to regulate multiple activities, including hunger, reward perception via the mesolimbic pathway, gastric acid secretion, gastrointestinal motility, and pancreatic glucose-stimulated insulin secretion. It was initially proposed that obestatin plays an opposing role to ghrelin by promoting satiety and thus decreasing food intake, but this action is still debated. Recent reports suggest multiple metabolic roles for obestatin, including regulating adipocyte function and glucose metabolism. Alternative splicing results in multiple transcript variants. In addition, antisense transcripts for this gene have been identified and may potentially regulate ghrelin-obestatin preproprotein expression. [provided by RefSeq, Nov 2014]
    Orthologs
    Location:
    3p25.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 3 NC_000003.12 (10285750..10292947, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (10327434..10334631, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene TatD DNase domain containing 2 Neighboring gene long intergenic non-protein coding RNA 852 Neighboring gene ghrelin opposite strand/antisense RNA Neighboring gene SEC13 homolog, nuclear pore and COPII coat complex component Neighboring gene ATPase plasma membrane Ca2+ transporting 2 Neighboring gene microRNA 378b

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    • Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
      Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
    • Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
      Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
    • G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
      GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
    • GPCR ligand binding, organism-specific biosystem (from REACTOME)
      GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
    • Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
      Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • Peptide hormone metabolism, organism-specific biosystem (from REACTOME)
      Peptide hormone metabolism, organism-specific biosystemPeptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and...
    • Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
      Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystem (from REACTOME)
      Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystemGhrelin is a peptide hormone of 28 amino acid residues which is acylated at the serine-3 of the mature peptide. Ghrelin is synthesized in several tissues: X/A-like cells of the gastric mucosa (the ma...
    • cAMP signaling pathway, organism-specific biosystem (from KEGG)
      cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
    • cAMP signaling pathway, conserved biosystem (from KEGG)
      cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    G-protein coupled receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    ghrelin receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    ghrelin receptor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    growth hormone-releasing hormone activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    growth hormone-releasing hormone activity TAS
    Traceable Author Statement
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein tyrosine kinase activator activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    G-protein coupled receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    G-protein coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    actin polymerization or depolymerization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    activation of MAPK activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    adult feeding behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    cartilage development NAS
    Non-traceable Author Statement
    more info
    PubMed 
    cortisol secretion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    decidualization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    dendrite development IDA
    Inferred from Direct Assay
    more info
    PubMed 
    excitatory postsynaptic potential IEA
    Inferred from Electronic Annotation
    more info
     
    gastric acid secretion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    glucose metabolic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    growth hormone secretion TAS
    Traceable Author Statement
    more info
    PubMed 
    hormone-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of angiogenesis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of circadian sleep/wake cycle, REM sleep IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of endothelial cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of energy homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of inflammatory response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of interleukin-1 beta production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of interleukin-6 biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of locomotion IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of tumor necrosis factor biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of appetite ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of circadian sleep/wake cycle, non-REM sleep IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of corticotropin secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cortisol secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cytosolic calcium ion concentration ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of energy homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of growth hormone receptor signaling pathway IC
    Inferred by Curator
    more info
    PubMed 
    positive regulation of growth hormone secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of insulin secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of multicellular organism growth IC
    Inferred by Curator
    more info
    PubMed 
    positive regulation of protein tyrosine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of synapse assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of response to food IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    response to estrogen IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to hormone IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    axon IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
     
    extracellular region IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    postsynapse IEA
    Inferred from Electronic Annotation
    more info
     
    secretory granule lumen TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    appetite-regulating hormone
    Names
    In2c-preproghrelin
    ghrelin, growth hormone secretagogue receptor ligand
    ghrelin/obestatin preprohormone
    ghrelin/obestatin prepropeptide
    growth hormone-releasing peptide
    motilin-related peptide
    prepro-appetite regulatory hormone
    preproghrelin

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011560.1 RefSeqGene

      Range
      5001..12198
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001134941.2NP_001128413.1  appetite-regulating hormone isoform 2 preproprotein

      See identical proteins and their annotated locations for NP_001128413.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting isoform (2) contains the ligands ghrelin-27, which lacks a single amino acid compared to ghrelin-28 found in isoform 1, and obestatin. Variants 2 and 10 encode the same protein.
      Source sequence(s)
      BC025791, EF549561, EF549563, EU072084, EU072085
      Consensus CDS
      CCDS46750.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000287656.7, OTTHUMP00000207797, ENST00000287656.11, OTTHUMT00000339632
      Conserved Domains (2) summary
      pfam04643
      Location:56114
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2550
      Motilin_ghrelin; Motilin/ghrelin
    2. NM_001134944.1NP_001128416.1  appetite-regulating hormone isoform 3

      See identical proteins and their annotated locations for NP_001128416.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two alternate in-frame exons in the 5' coding region but maintains the reading frame, compared to variant 1. The resulting isoform (3) is shorter compared to isoform 1 and lacks the N-terminal region that encodes the signal peptide and ghrelin-28 ligand found in isoform 1.
      Source sequence(s)
      BC025791, EF549561, EF549574
      Consensus CDS
      CCDS46748.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000416768.2, OTTHUMP00000207793, ENST00000437422.6, OTTHUMT00000339628
      Conserved Domains (1) summary
      pfam04643
      Location:45103
      Motilin_assoc; Motilin/ghrelin-associated peptide
    3. NM_001134945.1NP_001128417.1  appetite-regulating hormone isoform 4

      See identical proteins and their annotated locations for NP_001128417.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks two alternate in-frame exons and uses an alternate in-frame splice site in the 5' coding region, but maintains the reading frame, compared to variant 1. The resulting isoform (4) is shorter compared to isoform 1 and lacks the N-terminal region that encodes the signal peptide and ghrelin-28 ligand found in isoform 1.
      Source sequence(s)
      BC025791, EF549561, EU072086
      Consensus CDS
      CCDS46749.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000388145.2, OTTHUMP00000207792, ENST00000449238.6, OTTHUMT00000339627
      Conserved Domains (1) summary
      pfam04643
      Location:44102
      Motilin_assoc; Motilin/ghrelin-associated peptide
    4. NM_001134946.1NP_001128418.1  appetite-regulating hormone isoform 5

      See identical proteins and their annotated locations for NP_001128418.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks three alternate in-frame exons in the 5' coding region but maintains the reading frame, compared to variant 1. The resulting isoform (5) is shorter compared to isoform 1 and lacks the N-terminal region that encodes the signal peptide and ghrelin-28 ligand found in isoform 1.
      Source sequence(s)
      BC025791, EF549561, EF549575
      Consensus CDS
      CCDS46747.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000403725.2, OTTHUMP00000226986, ENST00000439975.6, OTTHUMT00000379272
      Conserved Domains (1) summary
      pfam04643
      Location:2364
      Motilin_assoc; Motilin/ghrelin-associated peptide
    5. NM_001302821.1NP_001289750.1  appetite-regulating hormone isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_001289750.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 1. This isoform (8) contains the ligands ghrelin-28 and obestatin. Variants 1, 8, 9, 11 and 12 encode the same protein.
      Source sequence(s)
      AY359053, BC025791, EF549561, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    6. NM_001302822.1NP_001289751.1  appetite-regulating hormone isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_001289751.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) differs in the 5' UTR compared to variant 1. This isoform (9) contains the ligands ghrelin-28 and obestatin. Variants 1, 8, 9, 11 and 12 encode the same protein.
      Source sequence(s)
      AY359053, BC025791, EF549561, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000391406.1, OTTHUMP00000207798, ENST00000457360.5, OTTHUMT00000339633
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    7. NM_001302823.1NP_001289752.1  appetite-regulating hormone isoform 2 preproprotein

      See identical proteins and their annotated locations for NP_001289752.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) differs in the 5' UTR and uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting isoform (2) contains the ligands ghrelin-27, which lacks a single amino acid compared to ghrelin-28 found in isoform 1, and obestatin. Variants 2 and 10 encode the same protein.
      Source sequence(s)
      BC025791, EF549561, EU072084
      Consensus CDS
      CCDS46750.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000399922.1, OTTHUMP00000207795, ENST00000430179.5, OTTHUMT00000339630
      Conserved Domains (2) summary
      pfam04643
      Location:56114
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2550
      Motilin_ghrelin; Motilin/ghrelin
    8. NM_001302824.1NP_001289753.1  appetite-regulating hormone isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_001289753.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (11) differs in the 5' UTR compared to variant 1. This isoform (11) contains the ligands ghrelin-28 and obestatin. Variants 1, 8, 9, 11 and 12 encode the same protein.
      Source sequence(s)
      AY359053, BC025791, EF549561, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000414819.1, OTTHUMP00000207794, ENST00000429122.1, OTTHUMT00000339629
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    9. NM_001302825.1NP_001289754.1  appetite-regulating hormone isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_001289754.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (12) differs in the 5' UTR compared to variant 1. This isoform (12) contains the ligands ghrelin-28 and obestatin. Variants 1, 8, 9, 11 and 12 encode the same protein.
      Source sequence(s)
      AY359053, BC025791, EF549561
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    10. NM_016362.4NP_057446.1  appetite-regulating hormone isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_057446.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). This isoform (1) contains the ligands ghrelin-28 and obestatin. Variants 1, 8, 9, 11 and 12 encode the same protein.
      Source sequence(s)
      AY359053, BC025791, EF549561, EF549563, EU072083, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000335074.8, OTTHUMP00000207790, ENST00000335542.12, OTTHUMT00000339625
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin

    RNA

    1. NR_126505.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (13) lacks several alternate internal exons compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      BC025791, EF549557, EF549561
      Related
      ENST00000446937.2, OTTHUMT00000379273

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p7 Primary Assembly

      Range
      10285750..10292947 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017006613.1XP_016862102.1  appetite-regulating hormone isoform X2

      UniProtKB/Swiss-Prot
      Q9UBU3
      Conserved Domains (2) summary
      pfam04643
      Location:56114
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2550
      Motilin_ghrelin; Motilin/ghrelin
    2. XM_017006612.1XP_016862101.1  appetite-regulating hormone isoform X1

      UniProtKB/Swiss-Prot
      Q9UBU3
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin

    Alternate CHM1_1.1

    Genomic

    1. NC_018914.2 Alternate CHM1_1.1

      Range
      10277571..10284767 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Support Center