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

    Gene ID: 51738, updated on 5-Mar-2024

    Summary

    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; AllianceGenome:HGNC:18129
    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]
    Expression
    Biased expression in stomach (RPKM 63.9) and duodenum (RPKM 5.6) See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See GHRL in Genome Data Viewer
    Location:
    3p25.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (10285666..10292947, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (10278965..10286246, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (10327350..10334631, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene U6 spliceosomal RNA Neighboring gene interleukin 1 receptor associated kinase 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:10266988-10267770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19421 Neighboring gene Sharpr-MPRA regulatory region 8698 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:10275792-10276394 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14057 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14058 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:10290711-10291579 Neighboring gene 3p25 TatD DNase domain containing 2 Alu-mediated recombination region Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14059 Neighboring gene Sharpr-MPRA regulatory region 7129 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:10329829-10330444 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:10332275-10332877 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19422 Neighboring gene TatD DNase domain containing 2 Neighboring gene Sharpr-MPRA regulatory region 4342 Neighboring gene long intergenic non-protein coding RNA 852 Neighboring gene microRNA 12127 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:10362509-10363104 Neighboring gene ghrelin opposite strand/antisense RNA Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:10369968-10370516 Neighboring gene SEC13 homolog, nuclear pore and COPII coat complex component Neighboring gene microRNA 378b Neighboring gene ATPase plasma membrane Ca2+ transporting 2

    Genomic regions, transcripts, and products

    Expression

    • 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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G protein-coupled receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    enables ghrelin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables ghrelin receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables ghrelin receptor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables growth hormone-releasing hormone activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables growth hormone-releasing hormone activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    enables growth hormone-releasing hormone activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein tyrosine kinase activator activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in actin polymerization or depolymerization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in adult feeding behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cartilage development NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in cortisol secretion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in decidualization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within dendrite development IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in excitatory postsynaptic potential IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in gastric acid secretion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in glucose metabolic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in growth hormone secretion TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in hormone-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of angiogenesis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of circadian sleep/wake cycle, REM sleep IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of endothelial cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in negative regulation of inflammatory response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of interleukin-1 beta production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of interleukin-6 production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of locomotion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of tumor necrosis factor production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of MAPK cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of adipose tissue development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of appetite ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of bone development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of circadian sleep/wake cycle, non-REM sleep IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cold-induced thermogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of corticotropin secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cortisol secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cytosolic calcium ion concentration ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of eating behavior IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of gastric mucosal blood circulation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of growth hormone receptor signaling pathway IC
    Inferred by Curator
    more info
    PubMed 
    involved_in positive regulation of growth hormone secretion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of growth hormone secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of growth rate IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of insulin secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of multicellular organism growth IC
    Inferred by Curator
    more info
    PubMed 
    involved_in positive regulation of small intestinal transit IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of small intestine smooth muscle contraction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of sprouting angiogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within positive regulation of synapse assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of vascular endothelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in postsynaptic modulation of chemical synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of cell population proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of gastric motility IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of postsynapse organization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of response to food IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of transmission of nerve impulse IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to electrical stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to estrogen IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to hormone IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in synapse assembly IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in Schaffer collateral - CA1 synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in axon IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
     
    located_in extracellular region IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in postsynapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in secretory granule lumen TAS
    Traceable Author Statement
    more info
     

    General protein information

    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

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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..12282
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001134941.3NP_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)
      AC022384, BC025791, EF549561, EF549563, EU072084, EU072085
      Consensus CDS
      CCDS46750.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000287656.7, ENST00000287656.11
      Conserved Domains (2) summary
      pfam04643
      Location:56114
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2550
      Motilin_ghrelin; Motilin/ghrelin
    2. NM_001134944.2NP_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)
      AC022384, BC025791, EF549561, EF549574
      Consensus CDS
      CCDS46748.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000416768.2, ENST00000437422.6
      Conserved Domains (1) summary
      pfam04643
      Location:45103
      Motilin_assoc; Motilin/ghrelin-associated peptide
    3. NM_001134945.2NP_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)
      AC022384, BC025791, EF549561, EU072086
      Consensus CDS
      CCDS46749.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000388145.2, ENST00000449238.6
      Conserved Domains (1) summary
      pfam04643
      Location:44102
      Motilin_assoc; Motilin/ghrelin-associated peptide
    4. NM_001134946.2NP_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)
      AC022384, BC025791, EF549561, EF549575
      Consensus CDS
      CCDS46747.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000403725.2, ENST00000439975.6
      Conserved Domains (1) summary
      pfam04643
      Location:2364
      Motilin_assoc; Motilin/ghrelin-associated peptide
    5. NM_001302821.2NP_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)
      AC022384, AY359053, BC025791, EF549561, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      A8CF34, A8CF38, A8CF42, A8DN29, A8DN30, Q86YP8, Q8TAT9, Q9H3R3, Q9UBU3
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    6. NM_001302822.2NP_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)
      AC022384, AY359053, BC025791, EF549561, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      A8CF34, A8CF38, A8CF42, A8DN29, A8DN30, Q86YP8, Q8TAT9, Q9H3R3, Q9UBU3
      Related
      ENSP00000391406.1, ENST00000457360.5
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    7. NM_001302823.2NP_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)
      AC022384, BC025791, EF549561, EU072084
      Consensus CDS
      CCDS46750.1
      UniProtKB/Swiss-Prot
      Q9UBU3
      Related
      ENSP00000399922.1, ENST00000430179.5
      Conserved Domains (2) summary
      pfam04643
      Location:56114
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2550
      Motilin_ghrelin; Motilin/ghrelin
    8. NM_001302824.2NP_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)
      AC022384, AY359053, BC025791, EF549561, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      A8CF34, A8CF38, A8CF42, A8DN29, A8DN30, Q86YP8, Q8TAT9, Q9H3R3, Q9UBU3
      Related
      ENSP00000414819.1, ENST00000429122.1
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    9. NM_001302825.2NP_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)
      AC022384, AY359053, BC025791, EF549561
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      A8CF34, A8CF38, A8CF42, A8DN29, A8DN30, Q86YP8, Q8TAT9, Q9H3R3, Q9UBU3
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin
    10. NM_016362.5NP_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)
      AC022384, AY359053, BC025791, EF549561, EF549563, EU072083, EU072084
      Consensus CDS
      CCDS33700.1
      UniProtKB/Swiss-Prot
      A8CF34, A8CF38, A8CF42, A8DN29, A8DN30, Q86YP8, Q8TAT9, Q9H3R3, Q9UBU3
      Related
      ENSP00000335074.8, ENST00000335542.13
      Conserved Domains (2) summary
      pfam04643
      Location:57115
      Motilin_assoc; Motilin/ghrelin-associated peptide
      pfam04644
      Location:2551
      Motilin_ghrelin; Motilin/ghrelin

    RNA

    1. NR_126505.2 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)
      AC022384, BC025791, EF549557, EF549561

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      10285666..10292947 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      10278965..10286246 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)