ID GHR_HUMAN Reviewed; 638 AA. AC P10912; Q9HCX2; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 245. DE RecName: Full=Growth hormone receptor; DE Short=GH receptor; DE AltName: Full=Somatotropin receptor; DE Contains: DE RecName: Full=Growth hormone-binding protein; DE Short=GH-binding protein; DE Short=GHBP; DE AltName: Full=Serum-binding protein; DE Flags: Precursor; GN Name=GHR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Liver; RX PubMed=2825030; DOI=10.1038/330537a0; RA Leung D.W., Spencer S.A., Cachianes G., Hammonds R.G., Collins C., RA Henzel W.J., Barnard R., Waters M.J., Wood W.I.; RT "Growth hormone receptor and serum binding protein: purification, cloning RT and expression."; RL Nature 330:537-543(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT LEU-544. RX PubMed=2813379; DOI=10.1073/pnas.86.20.8083; RA Godowski P.J., Leung D.W., Meacham L.R., Galgani J.P., Hellmiss R., RA Keret R., Rotwein P.S., Parks J.S., Laron Z., Wood W.I.; RT "Characterization of the human growth hormone receptor gene and RT demonstration of a partial gene deletion in two patients with Laron-type RT dwarfism."; RL Proc. Natl. Acad. Sci. U.S.A. 86:8083-8087(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RC TISSUE=Placenta; RX PubMed=1569971; DOI=10.1210/mend.6.2.1569971; RA Urbanek M., MacLeod J.N., Cooke N.E., Liebhaber S.A.; RT "Expression of a human growth hormone (hGH) receptor isoform is predicted RT by tissue-specific alternative splicing of exon 3 of the hGH receptor gene RT transcript."; RL Mol. Endocrinol. 6:279-287(1992). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Liver; RX PubMed=8855247; DOI=10.1073/pnas.93.20.10723; RA Dastot F., Sobrier M.-L., Duquesnoy P., Duriez B., Goossens M., Amselem S.; RT "Alternatively spliced forms in the cytoplasmic domain of the human growth RT hormone (GH) receptor regulate its ability to generate a soluble GH-binding RT protein."; RL Proc. Natl. Acad. Sci. U.S.A. 93:10723-10728(1996). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=9360546; DOI=10.1210/jcem.82.11.4358; RA Amit T., Bergman T., Dastot F., Youdim M.B.H., Amselem S., Hochberg Z.; RT "A membrane-fixed, truncated isoform of the human growth hormone RT receptor."; RL J. Clin. Endocrinol. Metab. 82:3813-3817(1997). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Liver; RX PubMed=9058373; DOI=10.1210/mend.11.3.9901; RA Ross R.J., Esposito N., Shen X.Y., Von Laue S., Chew S.L., Dobson P.R., RA Postel-Vinay M.-C., Finidori J.; RT "A short isoform of the human growth hormone receptor functions as a RT dominant negative inhibitor of the full-length receptor and generates large RT amounts of binding protein."; RL Mol. Endocrinol. 11:265-273(1997). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 263-336. RA Orlovsky I.V., Borovikova I.E., Rubtsov P.M.; RT "Comparing of nucleotide sequences of alternatively spliced region of RT mammalian growth hormone receptor genes."; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [8] RP CHARACTERIZATION (ISOFORM 4). RX PubMed=8360189; DOI=10.1016/s0021-9258(17)46730-5; RA Urbanek M., Russell J.E., Cooke N.E., Liebhaber S.A.; RT "Functional characterization of the alternatively spliced, placental human RT growth hormone receptor."; RL J. Biol. Chem. 268:19025-19032(1993). RN [9] RP MOLECULAR MECHANISM OF PRODUCTION (ISOFORM 4). RX PubMed=10764769; DOI=10.1074/jbc.m001615200; RA Pantel J., Machinis K., Sobrier M.-L., Duquesnoy P., Goossens M., RA Amselem S.; RT "Species-specific alternative splice mimicry at the growth hormone receptor RT locus revealed by the lineage of retroelements during primate evolution."; RL J. Biol. Chem. 275:18664-18669(2000). RN [10] RP DISULFIDE BONDS. RX PubMed=2406245; DOI=10.1016/s0021-9258(19)39741-8; RA Fuh G., Mulkerrin M.G., Bass S., McFarland N., Brochier M., Bourrel J.H., RA Light D.R., Wells J.A.; RT "The human growth hormone receptor. Secretion from Escherichia coli and RT disulfide bonding pattern of the extracellular binding domain."; RL J. Biol. Chem. 265:3111-3115(1990). RN [11] RP SITE CRITICAL TO PROTEOLYSIS, AND MUTAGENESIS OF GLU-260; GLU-261 AND RP ASP-262. RX PubMed=11785980; DOI=10.1006/bbrc.2001.6261; RA Conte F., Salles J.P., Raynal P., Fernandez L., Molinas C., Tauber M., RA Bieth E.; RT "Identification of a region critical for proteolysis of the human growth RT hormone receptor."; RL Biochem. Biophys. Res. Commun. 290:851-857(2002). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 19-254 IN COMPLEX WITH GROWTH RP HORMONE. RX PubMed=1549776; DOI=10.1126/science.1549776; RA de Vos A.M., Ultsch M., Kossiakoff A.A.; RT "Human growth hormone and extracellular domain of its receptor: crystal RT structure of the complex."; RL Science 255:306-312(1992). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 19-256 IN COMPLEX WITH GROWTH RP HORMONE. RX PubMed=8943276; DOI=10.1074/jbc.271.50.32197; RA Sundstroem M., Lundqvist T., Roedin J., Giebel L.B., Milligan D., RA Norstedt G.; RT "Crystal structure of an antagonist mutant of human growth hormone, G120R, RT in complex with its receptor at 2.9-A resolution."; RL J. Biol. Chem. 271:32197-32203(1996). RN [15] RP VARIANT LARS SER-114. RX PubMed=2779634; DOI=10.1056/nejm198910123211501; RA Amselem S., Duquesnoy P., Attree O., Novelli G., Bousnina S., RA Postel-Vinay M.-C., Goossens M.; RT "Laron dwarfism and mutations of the growth hormone-receptor gene."; RL N. Engl. J. Med. 321:989-995(1989). RN [16] RP VARIANT PHE-440. RX PubMed=8421103; DOI=10.1210/jcem.76.1.8421103; RA Kou K., Lajara R., Rotwein P.; RT "Amino acid substitutions in the intracellular part of the growth hormone RT receptor in a patient with the Laron syndrome."; RL J. Clin. Endocrinol. Metab. 76:54-59(1993). RN [17] RP VARIANTS LARS LYS-89; GLN-149; ASP-162; CYS-179 AND GLY-229. RX PubMed=8504296; DOI=10.1093/hmg/2.4.355; RA Amselem S., Duquesnoy P., Duriez B., Dastot F., Sobrier M.-L., Valleix S., RA Goossens M.; RT "Spectrum of growth hormone receptor mutations and associated haplotypes in RT Laron syndrome."; RL Hum. Mol. Genet. 2:355-359(1993). RN [18] RP CHARACTERIZATION OF VARIANT LARS SER-114. RX PubMed=8450064; DOI=10.1172/jci116304; RA Edery M., Rozakis-Adcock M., Goujon L., Finidori J., Levi-Meyrueis C., RA Paly J., Djiane J., Postel-Vinay M.-C., Kelly P.A.; RT "Lack of hormone binding in COS-7 cells expressing a mutated growth hormone RT receptor found in Laron dwarfism."; RL J. Clin. Invest. 91:838-844(1993). RN [19] RP VARIANT LARS HIS-170. RX PubMed=8137822; DOI=10.1002/j.1460-2075.1994.tb06392.x; RA Duquesnoy P., Sobrier M.-L., Duriez B., Dastot F., Buchanan C.R., RA Savage M.O., Preece M.A., Craescu C.T., Blouquit Y., Goossens M., RA Amselem S.; RT "A single amino acid substitution in the exoplasmic domain of the human RT growth hormone (GH) receptor confers familial GH resistance (Laron RT syndrome) with positive GH-binding activity by abolishing receptor RT homodimerization."; RL EMBO J. 13:1386-1395(1994). RN [20] RP VARIANTS GHIP LYS-62 AND CYS-179, AND VARIANTS HIS-229 AND ASP-242. RX PubMed=7565946; DOI=10.1056/nejm199510263331701; RA Goddard A.D., Covello R., Luoh S.-M., Clackson T., Attie K.M., RA Gesundheit N., Rundle A.C., Wells J.A., Carlsson L.M.S.; RT "Mutations of the growth hormone receptor in children with idiopathic short RT stature."; RL N. Engl. J. Med. 333:1093-1098(1995). RN [21] RP VARIANTS LARS SER-56; LEU-58 AND ARG-68. RX PubMed=9024232; DOI=10.1210/jcem.82.2.3725; RA Sobrier M.-L., Dastot F., Duquesnoy P., Kandemir N., Yordam N., RA Goossens M., Amselem S.; RT "Nine novel growth hormone receptor gene mutations in patients with Laron RT syndrome."; RL J. Clin. Endocrinol. Metab. 82:435-437(1997). RN [22] RP VARIANT LARS GLN-149, AND CHARACTERIZATION OF VARIANT LARS GLN-149. RX PubMed=9661642; DOI=10.1210/jcem.83.7.4954; RA Walker J.L., Crock P.A., Behncken S.N., Rowlinson S.W., Nicholson L.M., RA Boulton T.J.C., Waters M.J.; RT "A novel mutation affecting the interdomain link region of the growth RT hormone receptor in a Vietnamese girl, and response to long-term treatment RT with recombinant human insulin-like growth factor-I and luteinizing RT hormone-releasing hormone analogue."; RL J. Clin. Endocrinol. Metab. 83:2554-2561(1998). RN [23] RP VARIANT ILE-162. RX PubMed=9814495; DOI=10.1210/jcem.83.11.5238; RA Sanchez J.E., Perera E., Baumbach L., Cleveland W.W.; RT "Growth hormone receptor mutations in children with idiopathic short RT stature."; RL J. Clin. Endocrinol. Metab. 83:4079-4083(1998). RN [24] RP VARIANTS LARS HIS-170; THR-171; PRO-172 AND GLY-173, AND CHARACTERIZATION RP OF VARIANTS LARS THR-171; PRO-172 AND GLY-173. RX PubMed=9851797; DOI=10.1210/jcem.83.12.5357; RA Wojcik J., Berg M.A., Esposito N., Geffner M.E., Sakati N., Reiter E.O., RA Dower S., Francke U., Postel-Vinay M.-C., Finidori J.; RT "Four contiguous amino acid substitutions, identified in patients with RT Laron syndrome, differently affect the binding affinity and intracellular RT trafficking of the growth hormone receptor."; RL J. Clin. Endocrinol. Metab. 83:4481-4489(1998). RN [25] RP VARIANTS HIS-179; HIS-229; PHE-440; THR-495; LEU-544 AND THR-579. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [26] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [27] RP VARIANTS LARS CYS-226 AND ASN-262. RX PubMed=10870033; DOI=10.1530/eje.0.1430071; RA Enberg B., Luthman H., Segnestam K., Ritzen E.M., Sundstroem M., RA Norstedt G.; RT "Characterisation of novel missense mutations in the GH receptor gene RT causing severe growth retardation."; RL Eur. J. Endocrinol. 143:71-76(2000). RN [28] RP VARIANT LEU-544. RX PubMed=12910492; DOI=10.1002/ajmg.a.20172; RA Takada D., Ezura Y., Ono S., Iino Y., Katayama Y., Xin Y., Wu L.L., RA Larringa-Shum S., Stephenson S.H., Hunt S.C., Hopkins P.N., Emi M.; RT "Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol RT phenotype in familial hypercholesterolemia: intra-familial association RT study in an eight-generation hyperlipidemic kindred."; RL Am. J. Med. Genet. A 121:136-140(2003). RN [29] RP VARIANT LARS ILE-244. RX PubMed=14678285; DOI=10.1111/j.1365-2265.2004.01930.x; RA Jorge A.A.L., Souza S.C.A.L., Arnhold I.J.P., Mendonca B.B.; RT "The first homozygous mutation (S226I) in the highly-conserved WSXWS-like RT motif of the GH receptor causing Laron syndrome: suppression of GH RT secretion by GnRH analogue therapy not restored by dihydrotestosterone RT administration."; RL Clin. Endocrinol. (Oxf.) 60:36-40(2004). CC -!- FUNCTION: Receptor for pituitary gland growth hormone involved in CC regulating postnatal body growth. On ligand binding, couples to the CC JAK2/STAT5 pathway (By similarity). {ECO:0000250}. CC -!- FUNCTION: The soluble form (GHBP) acts as a reservoir of growth hormone CC in plasma and may be a modulator/inhibitor of GH signaling. CC -!- FUNCTION: Isoform 2 up-regulates the production of GHBP and acts as a CC negative inhibitor of GH signaling. CC -!- SUBUNIT: On growth hormone (GH) binding, forms homodimers and binds CC JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2 CC activation, binding to CIS and SOCS2 inhibits STAT5 activation. CC Interacts with ADAM17. {ECO:0000250}. CC -!- INTERACTION: CC P10912; Q16829: DUSP7; NbExp=2; IntAct=EBI-286316, EBI-1265847; CC P10912; P01241: GH1; NbExp=4; IntAct=EBI-286316, EBI-1026046; CC P10912; P10912: GHR; NbExp=4; IntAct=EBI-286316, EBI-286316; CC P10912; P16333: NCK1; NbExp=3; IntAct=EBI-286316, EBI-389883; CC P10912; P18031: PTPN1; NbExp=5; IntAct=EBI-286316, EBI-968788; CC P10912; P17706: PTPN2; NbExp=8; IntAct=EBI-286316, EBI-984930; CC P10912; P26045: PTPN3; NbExp=4; IntAct=EBI-286316, EBI-1047946; CC P10912; P43378: PTPN9; NbExp=2; IntAct=EBI-286316, EBI-742898; CC P10912; P23467: PTPRB; NbExp=3; IntAct=EBI-286316, EBI-1265766; CC P10912; Q9HD43: PTPRH; NbExp=4; IntAct=EBI-286316, EBI-1267176; CC P10912; Q12913: PTPRJ; NbExp=2; IntAct=EBI-286316, EBI-2264500; CC P10912; Q9JLI4: Ncoa6; Xeno; NbExp=2; IntAct=EBI-286316, EBI-286271; CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. Note=On growth hormone binding, GHR is ubiquitinated, CC internalized, down-regulated and transported into a degradative or non- CC degradative pathway. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I CC membrane protein. Note=Remains fixed to the cell membrane and is not CC internalized. CC -!- SUBCELLULAR LOCATION: [Growth hormone-binding protein]: Secreted. CC Note=Complexed to a substantial fraction of circulating GH. CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=GHRfl; CC IsoId=P10912-1; Sequence=Displayed; CC Name=2; Synonyms=GHRtr, GHR1-279; CC IsoId=P10912-2; Sequence=VSP_010227, VSP_010228; CC Name=3; Synonyms=GHR1-277; CC IsoId=P10912-3; Sequence=VSP_010229, VSP_010230; CC Name=4; Synonyms=GHRd3; CC IsoId=P10912-4; Sequence=VSP_010225, VSP_010226; CC -!- TISSUE SPECIFICITY: Expressed in various tissues with high expression CC in liver and skeletal muscle. Isoform 4 is predominantly expressed in CC kidney, bladder, adrenal gland and brain stem. Isoform 1 expression in CC placenta is predominant in chorion and decidua. Isoform 4 is highly CC expressed in placental villi. Isoform 2 is expressed in lung, stomach CC and muscle. Low levels in liver. CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein CC folding and thereby efficient intracellular transport and cell-surface CC receptor binding. CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or CC activation. CC -!- DOMAIN: The extracellular domain is the ligand-binding domain CC representing the growth hormone-binding protein (GHBP). CC -!- DOMAIN: The ubiquitination-dependent endocytosis motif (UbE) is CC required for recruitment of the ubiquitin conjugation system on to the CC receptor and for its internalization. CC -!- PTM: The soluble form (GHBP) is produced by phorbol ester-promoted CC proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE. CC Shedding is inhibited by growth hormone (GH) binding to the receptor CC probably due to a conformational change in GHR rendering the receptor CC inaccessible to ADAM17 (By similarity). {ECO:0000250}. CC -!- PTM: On GH binding, phosphorylated on tyrosine residues in the CC cytoplasmic domain by JAK2. {ECO:0000250}. CC -!- PTM: On ligand binding, ubiquitinated on lysine residues in the CC cytoplasmic domain. This ubiquitination is not sufficient for GHR CC internalization (By similarity). {ECO:0000250}. CC -!- POLYMORPHISM: Genetic variation in GHR may act as phenotype modifier in CC familial hypercholesterolemia [MIM:143890] patients carrying a mutation CC in the LDLR gene. CC -!- DISEASE: Laron syndrome (LARS) [MIM:262500]: A severe form of growth CC hormone insensitivity characterized by growth impairment, short CC stature, dysfunctional growth hormone receptor, and failure to generate CC insulin-like growth factor I in response to growth hormone. CC {ECO:0000269|PubMed:10870033, ECO:0000269|PubMed:14678285, CC ECO:0000269|PubMed:2779634, ECO:0000269|PubMed:8137822, CC ECO:0000269|PubMed:8450064, ECO:0000269|PubMed:8504296, CC ECO:0000269|PubMed:9024232, ECO:0000269|PubMed:9661642, CC ECO:0000269|PubMed:9851797}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Growth hormone insensitivity, partial (GHIP) [MIM:604271]: A CC disease characterized by partial resistance to growth hormone resulting CC in short stature. Short stature is defined by a standing height more CC than 2 standard deviations below the mean (or below the 2.5 percentile) CC for sex and chronological age, compared with a well-nourished, healthy, CC genetically relevant population. {ECO:0000269|PubMed:7565946}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 4]: Arises by species-specific retrovirus- CC mediated alternative splice mimicry. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1 CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X06562; CAA29808.1; -; mRNA. DR EMBL; M28466; AAA52555.1; -; Genomic_DNA. DR EMBL; M28458; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; M28459; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; M28460; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; M28461; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; M28462; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; M28463; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; M28464; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; M28465; AAA52555.1; JOINED; Genomic_DNA. DR EMBL; AJ278681; CAC06613.1; -; Genomic_DNA. DR CCDS; CCDS3940.1; -. [P10912-1] DR CCDS; CCDS56364.1; -. [P10912-4] DR PIR; A33991; A33991. DR RefSeq; NP_000154.1; NM_000163.4. [P10912-1] DR RefSeq; NP_001229328.1; NM_001242399.2. DR RefSeq; NP_001229329.1; NM_001242400.2. [P10912-1] DR RefSeq; NP_001229330.1; NM_001242401.3. [P10912-1] DR RefSeq; NP_001229331.1; NM_001242402.2. [P10912-1] DR RefSeq; NP_001229332.1; NM_001242403.2. [P10912-1] DR RefSeq; NP_001229333.1; NM_001242404.2. [P10912-1] DR RefSeq; NP_001229334.1; NM_001242405.2. [P10912-1] DR RefSeq; NP_001229335.1; NM_001242406.2. [P10912-1] DR RefSeq; NP_001229389.1; NM_001242460.1. [P10912-4] DR RefSeq; NP_001229391.1; NM_001242462.1. DR PDB; 1A22; X-ray; 2.60 A; B=19-256. DR PDB; 1AXI; X-ray; 2.10 A; B=19-254. DR PDB; 1HWG; X-ray; 2.50 A; B/C=19-255. DR PDB; 1HWH; X-ray; 2.90 A; B=19-255. DR PDB; 1KF9; X-ray; 2.60 A; B/C/E/F=19-256. DR PDB; 2AEW; X-ray; 2.70 A; A/B=47-251. DR PDB; 3HHR; X-ray; 2.80 A; B/C=50-254. DR PDB; 5OEK; NMR; -; A/B=254-294. DR PDB; 5OHD; NMR; -; A/B=254-294. DR PDBsum; 1A22; -. DR PDBsum; 1AXI; -. DR PDBsum; 1HWG; -. DR PDBsum; 1HWH; -. DR PDBsum; 1KF9; -. DR PDBsum; 2AEW; -. DR PDBsum; 3HHR; -. DR PDBsum; 5OEK; -. DR PDBsum; 5OHD; -. DR AlphaFoldDB; P10912; -. DR SMR; P10912; -. DR BioGRID; 108957; 44. DR DIP; DIP-630N; -. DR ELM; P10912; -. DR IntAct; P10912; 22. DR STRING; 9606.ENSP00000483403; -. DR ChEMBL; CHEMBL1976; -. DR DrugBank; DB16220; Lonapegsomatropin. DR DrugBank; DB00082; Pegvisomant. DR DrugBank; DB15093; Somapacitan. DR DrugBank; DB00052; Somatotropin. DR DrugBank; DB09098; Somatrem. DR DrugCentral; P10912; -. DR GuidetoPHARMACOLOGY; 1720; -. DR GlyCosmos; P10912; 6 sites, 1 glycan. DR GlyGen; P10912; 7 sites, 2 O-linked glycans (2 sites). DR iPTMnet; P10912; -. DR PhosphoSitePlus; P10912; -. DR BioMuta; GHR; -. DR DMDM; 121180; -. DR EPD; P10912; -. DR jPOST; P10912; -. DR MassIVE; P10912; -. DR PaxDb; 9606-ENSP00000483403; -. DR PeptideAtlas; P10912; -. DR ProteomicsDB; 52672; -. [P10912-1] DR ProteomicsDB; 52673; -. [P10912-2] DR ProteomicsDB; 52674; -. [P10912-3] DR ProteomicsDB; 52675; -. [P10912-4] DR Antibodypedia; 23220; 492 antibodies from 36 providers. DR DNASU; 2690; -. DR Ensembl; ENST00000230882.9; ENSP00000230882.4; ENSG00000112964.14. [P10912-1] DR Ensembl; ENST00000357703.6; ENSP00000350335.3; ENSG00000112964.14. [P10912-4] DR Ensembl; ENST00000537449.5; ENSP00000442206.2; ENSG00000112964.14. [P10912-1] DR Ensembl; ENST00000612382.4; ENSP00000478332.1; ENSG00000112964.14. [P10912-1] DR Ensembl; ENST00000612626.4; ENSP00000479846.1; ENSG00000112964.14. [P10912-1] DR Ensembl; ENST00000615111.4; ENSP00000478291.1; ENSG00000112964.14. [P10912-1] DR Ensembl; ENST00000618088.4; ENSP00000482373.1; ENSG00000112964.14. [P10912-1] DR GeneID; 2690; -. DR KEGG; hsa:2690; -. DR MANE-Select; ENST00000230882.9; ENSP00000230882.4; NM_000163.5; NP_000154.1. DR UCSC; uc003jmt.4; human. [P10912-1] DR AGR; HGNC:4263; -. DR CTD; 2690; -. DR DisGeNET; 2690; -. DR GeneCards; GHR; -. DR HGNC; HGNC:4263; GHR. DR HPA; ENSG00000112964; Tissue enhanced (adipose tissue, liver). DR MalaCards; GHR; -. DR MIM; 143890; phenotype. DR MIM; 262500; phenotype. DR MIM; 600946; gene. DR MIM; 604271; phenotype. DR neXtProt; NX_P10912; -. DR OpenTargets; ENSG00000112964; -. DR Orphanet; 633; Laron syndrome. DR Orphanet; 314802; Short stature due to partial GHR deficiency. DR PharmGKB; PA28674; -. DR VEuPathDB; HostDB:ENSG00000112964; -. DR eggNOG; KOG3555; Eukaryota. DR GeneTree; ENSGT00940000159987; -. DR HOGENOM; CLU_022322_0_0_1; -. DR InParanoid; P10912; -. DR OMA; YKPQLYN; -. DR OrthoDB; 5317462at2759; -. DR PhylomeDB; P10912; -. DR TreeFam; TF330851; -. DR PathwayCommons; P10912; -. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR SignaLink; P10912; -. DR SIGNOR; P10912; -. DR BioGRID-ORCS; 2690; 10 hits in 1159 CRISPR screens. DR ChiTaRS; GHR; human. DR EvolutionaryTrace; P10912; -. DR GeneWiki; Growth_hormone_receptor; -. DR GenomeRNAi; 2690; -. DR Pharos; P10912; Tclin. DR PRO; PR:P10912; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P10912; Protein. DR Bgee; ENSG00000112964; Expressed in skeletal muscle tissue of rectus abdominis and 167 other cell types or tissues. DR ExpressionAtlas; P10912; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0070195; C:growth hormone receptor complex; IDA:CAFA. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL. DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central. DR GO; GO:0019838; F:growth factor binding; IPI:BHF-UCL. DR GO; GO:0004903; F:growth hormone receptor activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008289; F:lipid binding; EXP:DisProt. DR GO; GO:0017046; F:peptide hormone binding; IPI:BHF-UCL. DR GO; GO:0070064; F:proline-rich region binding; ISS:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL. DR GO; GO:0019901; F:protein kinase binding; ISS:BHF-UCL. DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl. DR GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl. DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IEA:Ensembl. DR GO; GO:0032870; P:cellular response to hormone stimulus; IMP:BHF-UCL. DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0042445; P:hormone metabolic process; IMP:BHF-UCL. DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:BHF-UCL. DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IBA:GO_Central. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:BHF-UCL. DR GO; GO:0031623; P:receptor internalization; IDA:BHF-UCL. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISS:BHF-UCL. DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:BHF-UCL. DR GO; GO:0032107; P:regulation of response to nutrient levels; IEA:Ensembl. DR GO; GO:0046898; P:response to cycloheximide; IDA:BHF-UCL. DR GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL. DR GO; GO:0032094; P:response to food; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0009629; P:response to gravity; IEA:Ensembl. DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl. DR GO; GO:0019530; P:taurine metabolic process; ISS:BHF-UCL. DR CDD; cd00063; FN3; 1. DR DisProt; DP00033; -. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR025871; GHBP. DR InterPro; IPR015152; Growth/epo_recpt_lig-bind. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003528; Long_hematopoietin_rcpt_CS. DR PANTHER; PTHR23037; CYTOKINE RECEPTOR; 1. DR PANTHER; PTHR23037:SF41; CYTOKINE RECEPTOR-LIKE FACTOR 2-RELATED; 1. DR Pfam; PF09067; EpoR_lig-bind; 1. DR Pfam; PF00041; fn3; 1. DR Pfam; PF12772; GHBP; 1. DR SUPFAM; SSF49265; Fibronectin type III; 2. DR PROSITE; PS50853; FN3; 1. DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1. DR Genevisible; P10912; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; KW Direct protein sequencing; Disease variant; Disulfide bond; Dwarfism; KW Endocytosis; Glycoprotein; Membrane; Phosphoprotein; Receptor; KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..638 FT /note="Growth hormone receptor" FT /id="PRO_0000010957" FT CHAIN 19..256 FT /note="Growth hormone-binding protein" FT /evidence="ECO:0000250" FT /id="PRO_0000010958" FT TOPO_DOM 19..264 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 265..288 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 289..638 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 151..254 FT /note="Fibronectin type-III" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT REGION 260..262 FT /note="Required for ADAM17-mediated proteolysis" FT /evidence="ECO:0000250" FT REGION 353..391 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 240..244 FT /note="WSXWS motif" FT MOTIF 297..305 FT /note="Box 1 motif" FT MOTIF 340..349 FT /note="UbE motif" FT COMPBIAS 359..379 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 345 FT /note="Required for endocytosis and down-regulation" FT /evidence="ECO:0000250" FT MOD_RES 341 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT CARBOHYD 46 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 115 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 156 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 161 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 200 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 56..66 FT /evidence="ECO:0000269|PubMed:2406245" FT DISULFID 101..112 FT /evidence="ECO:0000269|PubMed:2406245" FT DISULFID 126..140 FT /evidence="ECO:0000269|PubMed:2406245" FT VAR_SEQ 24 FT /note="A -> D (in isoform 4)" FT /evidence="ECO:0000303|PubMed:1569971" FT /id="VSP_010225" FT VAR_SEQ 25..46 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:1569971" FT /id="VSP_010226" FT VAR_SEQ 292..297 FT /note="RIKMLI -> SSSSKD (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8855247, FT ECO:0000303|PubMed:9058373, ECO:0000303|PubMed:9360546" FT /id="VSP_010227" FT VAR_SEQ 292..294 FT /note="RIK -> KEN (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9058373" FT /id="VSP_010229" FT VAR_SEQ 295..638 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9058373" FT /id="VSP_010230" FT VAR_SEQ 298..638 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8855247, FT ECO:0000303|PubMed:9058373, ECO:0000303|PubMed:9360546" FT /id="VSP_010228" FT VARIANT 56 FT /note="C -> S (in LARS)" FT /evidence="ECO:0000269|PubMed:9024232" FT /id="VAR_018426" FT VARIANT 58 FT /note="S -> L (in LARS)" FT /evidence="ECO:0000269|PubMed:9024232" FT /id="VAR_018427" FT VARIANT 62 FT /note="E -> K (in GHIP; dbSNP:rs121909361)" FT /evidence="ECO:0000269|PubMed:7565946" FT /id="VAR_002708" FT VARIANT 68 FT /note="W -> R (in LARS)" FT /evidence="ECO:0000269|PubMed:9024232" FT /id="VAR_018428" FT VARIANT 89 FT /note="R -> K (in LARS)" FT /evidence="ECO:0000269|PubMed:8504296" FT /id="VAR_002709" FT VARIANT 114 FT /note="F -> S (in LARS; loss of ability to bind ligand; FT dbSNP:rs121909357)" FT /evidence="ECO:0000269|PubMed:2779634, FT ECO:0000269|PubMed:8450064" FT /id="VAR_002710" FT VARIANT 143 FT /note="V -> A (in LARS)" FT /id="VAR_002711" FT VARIANT 149 FT /note="P -> Q (in LARS; disrupts GH binding; FT dbSNP:rs121909365)" FT /evidence="ECO:0000269|PubMed:8504296, FT ECO:0000269|PubMed:9661642" FT /id="VAR_018429" FT VARIANT 162 FT /note="V -> D (in LARS)" FT /evidence="ECO:0000269|PubMed:8504296" FT /id="VAR_002712" FT VARIANT 162 FT /note="V -> F (in dbSNP:rs6413484)" FT /id="VAR_020002" FT VARIANT 162 FT /note="V -> I (found in a patient with idiopathic short FT stature; uncertain significance; dbSNP:rs6413484)" FT /evidence="ECO:0000269|PubMed:9814495" FT /id="VAR_018430" FT VARIANT 170 FT /note="D -> H (in LARS; abolishes receptor FT homodimerization; dbSNP:rs121909366)" FT /evidence="ECO:0000269|PubMed:8137822, FT ECO:0000269|PubMed:9851797" FT /id="VAR_002713" FT VARIANT 171 FT /note="I -> T (in LARS; almost completely abolishes FT GH-binding at cell surface: 53% binding to membrane FT fractions; dbSNP:rs121909367)" FT /evidence="ECO:0000269|PubMed:9851797" FT /id="VAR_018431" FT VARIANT 172 FT /note="Q -> P (in LARS; almost completely abolishes FT GH-binding at cell surface and in membrane fractions; FT dbSNP:rs121909368)" FT /evidence="ECO:0000269|PubMed:9851797" FT /id="VAR_018432" FT VARIANT 173 FT /note="V -> G (in LARS; almost completely abolishes FT GH-binding at cell surface: 26% binding to membrane FT fractions; dbSNP:rs121909369)" FT /evidence="ECO:0000269|PubMed:9851797" FT /id="VAR_018433" FT VARIANT 179 FT /note="R -> C (in LARS and GHIP; dbSNP:rs121909362)" FT /evidence="ECO:0000269|PubMed:7565946, FT ECO:0000269|PubMed:8504296" FT /id="VAR_002714" FT VARIANT 179 FT /note="R -> H (in dbSNP:rs6181)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_013937" FT VARIANT 226 FT /note="Y -> C (in LARS)" FT /evidence="ECO:0000269|PubMed:10870033" FT /id="VAR_018434" FT VARIANT 229 FT /note="R -> G (in LARS)" FT /evidence="ECO:0000269|PubMed:8504296" FT /id="VAR_002715" FT VARIANT 229 FT /note="R -> H (found in a patient with idiopathic short FT stature; uncertain significance; dbSNP:rs6177)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:7565946" FT /id="VAR_013938" FT VARIANT 242 FT /note="E -> D (found in a patient with idiopathic short FT stature; uncertain significance; dbSNP:rs45588036)" FT /evidence="ECO:0000269|PubMed:7565946" FT /id="VAR_002716" FT VARIANT 244 FT /note="S -> I (in LARS; dbSNP:rs1164396446)" FT /evidence="ECO:0000269|PubMed:14678285" FT /id="VAR_018435" FT VARIANT 262 FT /note="D -> N (in LARS)" FT /evidence="ECO:0000269|PubMed:10870033" FT /id="VAR_018436" FT VARIANT 440 FT /note="C -> F (in dbSNP:rs6182)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:8421103" FT /id="VAR_013939" FT VARIANT 465 FT /note="E -> K (in dbSNP:rs34283856)" FT /id="VAR_032704" FT VARIANT 495 FT /note="P -> T (in dbSNP:rs6183)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_013940" FT VARIANT 544 FT /note="I -> L (in dbSNP:rs6180)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:12910492, ECO:0000269|PubMed:2813379" FT /id="VAR_013941" FT VARIANT 579 FT /note="P -> T (in dbSNP:rs6184)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_013942" FT MUTAGEN 260 FT /note="E->A: No change in shedding activity: No change in FT hormone binding." FT /evidence="ECO:0000269|PubMed:11785980" FT MUTAGEN 261 FT /note="E->A: No change in shedding activity: No change in FT hormone binding." FT /evidence="ECO:0000269|PubMed:11785980" FT MUTAGEN 262 FT /note="D->A: No change in shedding activity: No change in FT hormone binding." FT /evidence="ECO:0000269|PubMed:11785980" FT STRAND 53..62 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 64..68 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 83..88 FT /evidence="ECO:0007829|PDB:1AXI" FT TURN 93..96 FT /evidence="ECO:0007829|PDB:1HWG" FT TURN 104..107 FT /evidence="ECO:0007829|PDB:3HHR" FT STRAND 111..114 FT /evidence="ECO:0007829|PDB:1AXI" FT HELIX 116..118 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 121..131 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 134..142 FT /evidence="ECO:0007829|PDB:1AXI" FT HELIX 143..146 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 153..159 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 167..176 FT /evidence="ECO:0007829|PDB:1AXI" FT TURN 183..186 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 190..198 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 210..221 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 226..234 FT /evidence="ECO:0007829|PDB:1AXI" FT STRAND 240..243 FT /evidence="ECO:0007829|PDB:2AEW" FT STRAND 247..249 FT /evidence="ECO:0007829|PDB:1AXI" FT HELIX 259..261 FT /evidence="ECO:0007829|PDB:5OHD" FT HELIX 266..292 FT /evidence="ECO:0007829|PDB:5OEK" SQ SEQUENCE 638 AA; 71500 MW; EAF77EADE4787822 CRC64; MDLWQLLLTL ALAGSSDAFS GSEATAAILS RAPWSLQSVN PGLKTNSSKE PKFTKCRSPE RETFSCHWTD EVHHGTKNLG PIQLFYTRRN TQEWTQEWKE CPDYVSAGEN SCYFNSSFTS IWIPYCIKLT SNGGTVDEKC FSVDEIVQPD PPIALNWTLL NVSLTGIHAD IQVRWEAPRN ADIQKGWMVL EYELQYKEVN ETKWKMMDPI LTTSVPVYSL KVDKEYEVRV RSKQRNSGNY GEFSEVLYVT LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QRIKMLILPP VPVPKIKGID PDLLKEGKLE EVNTILAIHD SYKPEFHSDD SWVEFIELDI DEPDEKTEES DTDRLLSSDH EKSHSNLGVK DGDSGRTSCC EPDILETDFN ANDIHEGTSE VAQPQRLKGE ADLLCLDQKN QNNSPYHDAC PATQQPSVIQ AEKNKPQPLP TEGAESTHQA AHIQLSNPSS LSNIDFYAQV SDITPAGSVV LSPGQKNKAG MSQCDMHPEM VSLCQENFLM DNAYFCEADA KKCIPVAPHI KVESHIQPSL NQEDIYITTE SLTTAAGRPG TGEHVPGSEM PVPDYTSIHI VQSPQGLILN ATALPLPDKE FLSSCGYVST DQLNKIMP //