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MGP001201

UniProt Annotations

Entry Information
Gene Namegrowth hormone receptor
Protein EntryGHR_HUMAN
UniProt IDP10912
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=GHRfl; IsoId=P10912-1; Sequence=Displayed; Name=2; Synonyms=GHRtr, GHR1-279; IsoId=P10912-2; Sequence=VSP_010227, VSP_010228; Name=3; Synonyms=GHR1-277; IsoId=P10912-3; Sequence=VSP_010229, VSP_010230; Name=4; Synonyms=GHRd3; IsoId=P10912-4; Sequence=VSP_010225, VSP_010226; Note=Arises by species-specific retrovirus-mediated alternative splice mimicry.;
DiseaseLaron syndrome (LARS) [MIM:262500]: A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone. {ECO:0000269|PubMed:10870033, ECO:0000269|PubMed:14678285, ECO:0000269|PubMed:2779634, ECO:0000269|PubMed:8137822, ECO:0000269|PubMed:8421103, ECO:0000269|PubMed:8504296, ECO:0000269|PubMed:9024232, ECO:0000269|PubMed:9661642, ECO:0000269|PubMed:9851797}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseShort stature, idiopathic, autosomal (ISSA) [MIM:604271]: A condition defined by a standing height more than 2 standard deviations below the mean (or below the 2.5 percentile) for sex and chronological age, compared with a well-nourished, genetically relevant population, in the absence of specific causative disorders. {ECO:0000269|PubMed:7565946}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe box 1 motif is required for JAK interaction and/or activation.
DomainThe extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).
DomainThe ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.
DomainThe WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding.
FunctionIsoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.
FunctionReceptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity). {ECO:0000250}.
FunctionThe soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.
InteractionQ16829:DUSP7; NbExp=2; IntAct=EBI-286316, EBI-1265847; P01241:GH1; NbExp=3; IntAct=EBI-286316, EBI-1026046; P16333:NCK1; NbExp=3; IntAct=EBI-286316, EBI-389883; Q9JLI4:Ncoa6 (xeno); NbExp=2; IntAct=EBI-286316, EBI-286271; P18031:PTPN1; NbExp=5; IntAct=EBI-286316, EBI-968788; P17706:PTPN2; NbExp=8; IntAct=EBI-286316, EBI-984930; P26045:PTPN3; NbExp=4; IntAct=EBI-286316, EBI-1047946; P43378:PTPN9; NbExp=2; IntAct=EBI-286316, EBI-742898; P23467:PTPRB; NbExp=3; IntAct=EBI-286316, EBI-1265766; Q9HD43:PTPRH; NbExp=4; IntAct=EBI-286316, EBI-1267176; Q12913:PTPRJ; NbExp=2; IntAct=EBI-286316, EBI-2264500;
PolymorphismGenetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia [MIM:143890] patients carrying a mutation in the LDLR gene.
PtmOn GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2. {ECO:0000250}.
PtmOn ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization (By similarity). {ECO:0000250}.
PtmThe soluble form (GHBP) is produced by phorbol ester-promoted proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE. Shedding is inhibited by growth hormone (GH) binding to the receptor probably due to a conformational change in GHR rendering the receptor inaccessible to ADAM17 (By similarity). {ECO:0000250}.
SimilarityBelongs to the type I cytokine receptor family. Type 1 subfamily. {ECO:0000305}.
SimilarityContains 1 fibronectin type-III domain. {ECO:0000255|PROSITE-ProRule:PRU00316}.
Subcellular LocationCell membrane; Single-pass type I membrane protein. Note=On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway. {ECO:0000250}.
Subcellular LocationGrowth hormone-binding protein: Secreted. Note=Complexed to a substantial fraction of circulating GH. {ECO:0000250}.
Subcellular LocationIsoform 2: Cell membrane; Single-pass type I membrane protein. Note=Remains fixed to the cell membrane and is not internalized.
SubunitOn growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation. Interacts with ADAM17. {ECO:0000250}.
Tissue SpecificityExpressed in various tissues with high expression in liver and skeletal muscle. Isoform 4 is predominantly expressed in kidney, bladder, adrenal gland and brain stem. Isoform 1 expression in placenta is predominant in chorion and decidua. Isoform 4 is highly expressed in placental villi. Isoform 2 is expressed in lung, stomach and muscle. Low levels in liver.
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