ID:GHR_HUMAN DESCRIPTION: RecName: Full=Growth hormone receptor; Short=GH receptor; AltName: Full=Somatotropin receptor; Contains: RecName: Full=Growth hormone-binding protein; Short=GH-binding protein; Short=GHBP; AltName: Full=Serum-binding protein; Flags: Precursor; FUNCTION: Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity). FUNCTION: The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling. FUNCTION: Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling. SUBUNIT: On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain (By similarity). Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation (By similarity). Interacts with ADAM17 (By similarity). INTERACTION: Q16829:DUSP7; NbExp=2; IntAct=EBI-286316, EBI-1265847; P01241:GH1; NbExp=3; IntAct=EBI-286316, EBI-1026046; P16333:NCK1; NbExp=2; 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; SUBCELLULAR LOCATION: Cell 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 (By similarity). SUBCELLULAR LOCATION: Isoform 2: Cell membrane; Single-pass type I membrane protein. Note=Remains fixed to the cell membrane and is not internalized. SUBCELLULAR LOCATION: Growth hormone-binding protein: Secreted. Note=Complexed to a substantial fraction of circulating GH (By similarity). TISSUE SPECIFICITY: Expressed 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. DOMAIN: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding. DOMAIN: The box 1 motif is required for JAK interaction and/or activation. DOMAIN: The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP). DOMAIN: The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization. PTM: The 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). PTM: On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2 (By similarity). PTM: On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization (By similarity). POLYMORPHISM: Genetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia [MIM:143890] patients carrying a mutation in the LDLR gene. DISEASE: Defects in GHR are a cause of Laron 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. DISEASE: Defects in GHR may be a cause of idiopathic short stature autosomal (ISSA) [MIM:604271]. Short stature is defined by a subnormal rate of growth. SIMILARITY: Belongs to the type I cytokine receptor family. Type 1 subfamily. SIMILARITY: Contains 1 fibronectin type-III domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GHR";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P10912
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
