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

Gene ID: 51738, updated on 7-Dec-2014
Official Symbol
GHRLprovided by HGNC
Official Full Name
ghrelin/obestatin prepropeptideprovided by HGNC
Primary source
HGNC:HGNC:18129
Locus tag
UNQ524/PRO1066
See related
Ensembl:ENSG00000157017; HPRD:05638; 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]
See GHRL in Epigenomics, MapViewer
Location:
3p26-p25
Exon count:
6
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 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 (S. cerevisiae) Neighboring gene ATPase, Ca++ transporting, plasma membrane 2 Neighboring gene microRNA 378b

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  • 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 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 
cellular protein metabolic process TAS
Traceable Author Statement
more info
 
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 
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 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 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 IMP
Inferred from Mutant Phenotype
more info
PubMed 
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 excitatory postsynaptic membrane potential IEA
Inferred from Electronic Annotation
more info
 
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 
secretory granule lumen TAS
Traceable Author Statement
more info
 
Preferred Names
appetite-regulating hormone
Names
appetite-regulating hormone
motilin-related peptide
ghrelin/obestatin preprohormone
growth hormone-releasing peptide
prepro-appetite regulatory hormone
ghrelin, growth hormone secretagogue receptor ligand

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 

    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 proteins identical to 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
    Conserved Domains (2) summary
    pfam04643
    Location:55116
    Motilin_assoc; Motilin/ghrelin-associated peptide
    pfam04644
    Location:2450
    Motilin_ghrelin; Motilin/ghrelin
  2. NM_001134944.1NP_001128416.1  appetite-regulating hormone isoform 3

    See proteins identical to 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 contains ghrelin, but does contain obestatin.
    Source sequence(s)
    BC025791, EF549561, EF549574
    Consensus CDS
    CCDS46748.1
    UniProtKB/Swiss-Prot
    Q9UBU3
    Related
    ENSP00000416768, OTTHUMP00000207793, ENST00000437422, OTTHUMT00000339628
    Conserved Domains (1) summary
    pfam04643
    Location:44105
    Motilin_assoc; Motilin/ghrelin-associated peptide
  3. NM_001134945.1NP_001128417.1  appetite-regulating hormone isoform 4

    See proteins identical to 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 contains ghrelin, but does contain obestatin.
    Source sequence(s)
    BC025791, EF549561, EU072086
    Consensus CDS
    CCDS46749.1
    UniProtKB/Swiss-Prot
    Q9UBU3
    Related
    ENSP00000388145, OTTHUMP00000207792, ENST00000449238, OTTHUMT00000339627
    Conserved Domains (1) summary
    pfam04643
    Location:43104
    Motilin_assoc; Motilin/ghrelin-associated peptide
  4. NM_001134946.1NP_001128418.1  appetite-regulating hormone isoform 5

    See proteins identical to 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 contains ghrelin, but does contain obestatin.
    Source sequence(s)
    BC025791, EF549561, EF549575
    Consensus CDS
    CCDS46747.1
    UniProtKB/Swiss-Prot
    Q9UBU3
    Related
    ENSP00000403725, OTTHUMP00000226986, ENST00000439975, OTTHUMT00000379272
    Conserved Domains (1) summary
    pfam04643
    Location:2266
    Motilin_assoc; Motilin/ghrelin-associated peptide
  5. NM_001302821.1NP_001289750.1  appetite-regulating hormone isoform 1 preproprotein

    See proteins identical to NP_001289750.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 1. Variants 1, 8, 9, 11 and 12 encode the same protein.
    Source sequence(s)
    AY359053, BC025791, EF549561, EU072084
  6. NM_001302822.1NP_001289751.1  appetite-regulating hormone isoform 1 preproprotein

    See proteins identical to NP_001289751.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9) differs in the 5' UTR compared to variant 1. Variants 1, 8, 9, 11 and 12 encode the same protein.
    Source sequence(s)
    AY359053, BC025791, EF549561, EU072084
  7. NM_001302823.1NP_001289752.1  appetite-regulating hormone isoform 2 preproprotein

    See proteins identical to 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
  8. NM_001302824.1NP_001289753.1  appetite-regulating hormone isoform 1 preproprotein

    See proteins identical to NP_001289753.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (11) differs in the 5' UTR compared to variant 1. Variants 1, 8, 9, 11 and 12 encode the same protein.
    Source sequence(s)
    AY359053, BC025791, EF549561, EU072084
  9. NM_001302825.1NP_001289754.1  appetite-regulating hormone isoform 1 preproprotein

    See proteins identical to NP_001289754.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (12) differs in the 5' UTR compared to variant 1. Variants 1, 8, 9, 11 and 12 encode the same protein.
    Source sequence(s)
    AY359053, BC025791, EF549561
  10. NM_016362.4NP_057446.1  appetite-regulating hormone isoform 1 preproprotein

    See proteins identical to 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
    Conserved Domains (2) summary
    pfam04643
    Location:56117
    Motilin_assoc; Motilin/ghrelin-associated peptide
    pfam04644
    Location:2451
    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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000003.12 

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

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 

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

Alternate HuRef

Genomic

  1. AC_000135.1 

    Range
    10262844..10269999
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)