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

Gene ID: 51738, updated on 10-Dec-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
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Genomic context

See GHRL in Genome Data Viewer
Location:
3p25.3
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (10285666..10292947, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (10278965..10286246, complement)
RS_2024_09 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 neuronal dense core vesicle lumen 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_2024_08

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)