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Reviewed, UniProtKB/Swiss-Prot P10912 (GHR_HUMAN)

Last modified June 16, 2009. Version 120. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Growth hormone receptor
      Short name=GH receptor
Alternative name(s):
    Somatotropin receptor
Cleaved into the following chain:
    1- Recommended name:
            Growth hormone-binding protein
                Short name=GH-binding protein
                Short name=GHBP
        Alternative name(s):
            Serum-binding protein
Gene names
Name: GHR
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length638 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway By similarity.

The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.

Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.

Subunit structure

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.

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.

Isoform 2: Cell membrane; Single-pass type I membrane protein. Note: Remains fixed to the cell membrane and is not internalized.

Growth hormone-binding protein: Secreted.

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. In the placenta, isoform 1 predominantly expressed in chorion and decidua, isoform 4 highly expressed in 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.

The box 1 motif is required for JAK interaction and/or activation.

The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).

The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.

Post-translational modification

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.

On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2 By similarity.

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.

Involvement in disease

Defects in GHR are a cause of Laron dwarfism [MIM:262500]; also known as pituitary dwarfism II; Laron-type pituitary dwarfism I (LTD1) or Laron syndrome (LS). It is the most severe form of growth hormone insensitivity (GHI) characterized by growth impairment, dysmorphic facial features and truncal obesity. Levels of GHBP are low or undetectable in patients with Laron syndrome.

Defects in GHR may be a cause of short stature [MIM:604271]. Short stature is defined by a subnormal rate of growth. Ref.19 Ref.22

Sequence similarities

Belongs to the type I cytokine receptor family. Type 1 subfamily.

Contains 1 fibronectin type-III domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Dwarfism
   DomainSignal
Transmembrane
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological process2-oxoglutarate metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

activation of JAK2 kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

activation of MAPK activity

Inferred from sequence or structural similarity. Source: UniProtKB

allantoin metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to hormone stimulus Ref.19

Inferred from mutant phenotype. Source: UniProtKB

citrate metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

creatine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

creatinine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

growth hormone receptor signaling pathway Ref.19

Inferred from mutant phenotype. Source: UniProtKB

insulin-like growth factor receptor signaling pathway Ref.19

Inferred from mutant phenotype. Source: UniProtKB

isoleucine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular organismal metabolic process Ref.18

Inferred from mutant phenotype. Source: UniProtKB

oxaloacetate metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of multicellular organism growth Ref.2

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat3 protein Ref.1

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat5 protein Ref.1

Inferred from sequence or structural similarity. Source: UniProtKB

succinate metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

taurine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

valine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular componentcell surface Ref.18

Inferred from direct assay. Source: UniProtKB

extracellular space Ref.1 Ref.18

Inferred from direct assay. Source: UniProtKB

growth hormone receptor complex Ref.18

Inferred from direct assay. Source: UniProtKB

integral to plasma membrane Ref.18

Inferred from direct assay. Source: UniProtKB

   Molecular functioncytokine receptor activity

Inferred from electronic annotation. Source: InterPro

peptide hormone binding Ref.1 Ref.12

Inferred from physical interaction. Source: UniProtKB

phosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

proline-rich region binding Ref.1

Inferred from sequence or structural similarity. Source: UniProtKB

protein homodimerization activity Ref.12 Ref.18

Inferred from direct assay. Source: UniProtKB

protein kinase binding

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin binding Ref.1

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P10912-1)

Also known as: GHRfl;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P10912-2)

Also known as: GHRtr; GHR1-279;

The sequence of this isoform differs from the canonical sequence as follows:
     292-297: RIKMLI → SSSSKD
     298-638: Missing.
Note: Remains fixed to the cell membrane and is not internalized.
Isoform 3 (identifier: P10912-3)

Also known as: GHR1-277;

The sequence of this isoform differs from the canonical sequence as follows:
     292-294: RIK → KEN
     295-638: Missing.
Isoform 4 (identifier: P10912-4)

Also known as: GHRd3;

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: A → D
     25-46: Missing.
Note: Arises by species-specific retrovirus-mediated alternative splice mimicry.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 638620Growth hormone receptor
PRO_0000010957
Chain19 – ?Growth hormone-binding proteinPRO_0000010958

Regions

Topological domain19 – 264246Extracellular Potential
Transmembrane265 – 28824 Potential
Topological domain289 – 638350Cytoplasmic Potential
Domain149 – 251103Fibronectin type-III
Region260 – 2623Required for ADAM17-mediated proteolysis By similarity
Motif240 – 2445WSXWS motif
Motif297 – 3059Box 1 motif
Motif340 – 34910UbE motif

Sites

Site3451Required for endocytosis and down-regulation By similarity

Amino acid modifications

Glycosylation461N-linked (GlcNAc...) Potential
Glycosylation1151N-linked (GlcNAc...) Potential
Glycosylation1561N-linked (GlcNAc...) Potential
Glycosylation1611N-linked (GlcNAc...) Potential
Glycosylation2001N-linked (GlcNAc...) Potential
Disulfide bond56 ↔ 66 Ref.10
Disulfide bond101 ↔ 112 Ref.10
Disulfide bond126 ↔ 140 Ref.10

Natural variations

Alternative sequence241A → D in isoform 4.
VSP_010225
Alternative sequence25 – 4622Missing in isoform 4.
VSP_010226
Alternative sequence292 – 2976RIKMLI → SSSSKD in isoform 2.
VSP_010227
Alternative sequence292 – 2943RIK → KEN in isoform 3.
VSP_010229
Alternative sequence295 – 638344Missing in isoform 3.
VSP_010230
Alternative sequence298 – 638341Missing in isoform 2.
VSP_010228
Natural variant561C → S in Laron dwarfism.
VAR_018426
Natural variant581S → L in Laron dwarfism.
VAR_018427
Natural variant621E → K in short stature; idiopathic autosomal. Ref.19
VAR_002708
Natural variant681W → R in Laron dwarfism.
VAR_018428
Natural variant891R → K in Laron dwarfism.
VAR_002709
Natural variant1141F → S in Laron dwarfism; loss of ability to bind ligand.
VAR_002710
Natural variant1431V → A in Laron dwarfism.
VAR_002711
Natural variant1491P → Q in Laron dwarfism; disrupts GH binding.
VAR_018429
Natural variant1621V → D in Laron dwarfism.
VAR_002712
Natural variant1621V → F: dbSNP rs6413484. Ref.22 Ref.16
VAR_020002
Natural variant1621V → I in short stature; idiopathic autosomal. Ref.22 Ref.16
VAR_018430
Natural variant1701D → H in Laron dwarfism; abolishes receptor homodimerization.
VAR_002713
Natural variant1711I → T in Laron dwarfism; almost completely abolishes GH-binding at cell surface: 53% binding to membrane fractions.
VAR_018431
Natural variant1721Q → P in Laron dwarfism; almost completely abolishes GH-binding at cell surface and in membrane fractions.
VAR_018432
Natural variant1731V → G in Laron dwarfism; almost completely abolishes GH-binding at cell surface: 26% binding to membrane fractions.
VAR_018433
Natural variant1791R → C in Laron dwarfism and short stature; idiopathic autosomal.
VAR_002714
Natural variant1791R → H: dbSNP rs6181. Ref.19 Ref.16 Ref.24
VAR_013937
Natural variant2261Y → C in Laron dwarfism.
VAR_018434
Natural variant2291R → G in Laron dwarfism.
VAR_002715
Natural variant2291R → H in short stature; idiopathic autosomal. dbSNP rs6177. Ref.19 Ref.16 Ref.24
VAR_013938
Natural variant2421E → D in short stature; idiopathic autosomal. Ref.19
VAR_002716
Natural variant2441S → I in Laron dwarfism.
VAR_018435
Natural variant2621D → N in Laron dwarfism.
VAR_018436
Natural variant4401C → F in Laron dwarfism. dbSNP rs6182.
VAR_013939
Natural variant4651E → K: dbSNP rs34283856.
VAR_032704
Natural variant4951P → T: dbSNP rs6183. Ref.24
VAR_013940
Natural variant5441I → L Polymorphism with a modifier effect on plasma HDL cholesterol levels in familial hypercholesterolemia patients. dbSNP rs6180. Ref.24 Ref.2 Ref.27
VAR_013941
Natural variant5791P → T: dbSNP rs6184. Ref.24
VAR_013942

Experimental info

Mutagenesis2601E → A: No change in shedding activity: No change in hormone binding. Ref.11
Mutagenesis2611E → A: No change in shedding activity: No change in hormone binding. Ref.11
Mutagenesis2621D → A: No change in shedding activity: No change in hormone binding. Ref.11

Secondary structure

.............................. 638
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (GHRfl) [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: EAF77EADE4787822

FASTA63871,500
        10         20         30         40         50         60 
MDLWQLLLTL ALAGSSDAFS GSEATAAILS RAPWSLQSVN PGLKTNSSKE PKFTKCRSPE 

        70         80         90        100        110        120 
RETFSCHWTD EVHHGTKNLG PIQLFYTRRN TQEWTQEWKE CPDYVSAGEN SCYFNSSFTS 

       130        140        150        160        170        180 
IWIPYCIKLT SNGGTVDEKC FSVDEIVQPD PPIALNWTLL NVSLTGIHAD IQVRWEAPRN 

       190        200        210        220        230        240 
ADIQKGWMVL EYELQYKEVN ETKWKMMDPI LTTSVPVYSL KVDKEYEVRV RSKQRNSGNY 

       250        260        270        280        290        300 
GEFSEVLYVT LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QRIKMLILPP 

       310        320        330        340        350        360 
VPVPKIKGID PDLLKEGKLE EVNTILAIHD SYKPEFHSDD SWVEFIELDI DEPDEKTEES 

       370        380        390        400        410        420 
DTDRLLSSDH EKSHSNLGVK DGDSGRTSCC EPDILETDFN ANDIHEGTSE VAQPQRLKGE 

       430        440        450        460        470        480 
ADLLCLDQKN QNNSPYHDAC PATQQPSVIQ AEKNKPQPLP TEGAESTHQA AHIQLSNPSS 

       490        500        510        520        530        540 
LSNIDFYAQV SDITPAGSVV LSPGQKNKAG MSQCDMHPEM VSLCQENFLM DNAYFCEADA 

       550        560        570        580        590        600 
KKCIPVAPHI KVESHIQPSL NQEDIYITTE SLTTAAGRPG TGEHVPGSEM PVPDYTSIHI 

       610        620        630 
VQSPQGLILN ATALPLPDKE FLSSCGYVST DQLNKIMP 

« Hide

Isoform 2 (GHRtr) (GHR1-279).

Checksum: F690295F6BB01AC8
Show »

FASTA29734,109
Isoform 3 (GHR1-277).

Checksum: 0E85069AC8F6FDBF
Show »

FASTA29433,889
Isoform 4 (GHRd3).

Checksum: 5F12CD731F49E1F1
Show »

FASTA61669,237

References

[1]"Growth hormone receptor and serum binding protein: purification, cloning and expression."
Leung D.W., Spencer S.A., Cachianes G., Hammonds R.G., Collins C., Henzel W.J., Barnard R., Waters M.J., Wood W.I.
Nature 330:537-543(1987) [PubMed: 2825030] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[2]"Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism."
Godowski P.J., Leung D.W., Meacham L.R., Galgani J.P., Hellmiss R., Keret R., Rotwein P.S., Parks J.S., Laron Z., Wood W.I.
Proc. Natl. Acad. Sci. U.S.A. 86:8083-8087(1989) [PubMed: 2813379] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT LEU-544.
[3]"Expression of a human growth hormone (hGH) receptor isoform is predicted by tissue-specific alternative splicing of exon 3 of the hGH receptor gene transcript."
Urbanek M., MacLeod J.N., Cooke N.E., Liebhaber S.A.
Mol. Endocrinol. 6:279-287(1992) [PubMed: 1569971] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
Tissue: Placenta.
[4]"Alternatively spliced forms in the cytoplasmic domain of the human growth hormone (GH) receptor regulate its ability to generate a soluble GH-binding protein."
Dastot F., Sobrier M.-L., Duquesnoy P., Duriez B., Goossens M., Amselem S.
Proc. Natl. Acad. Sci. U.S.A. 93:10723-10728(1996) [PubMed: 8855247] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Liver.
[5]"A membrane-fixed, truncated isoform of the human growth hormone receptor."
Amit T., Bergman T., Dastot F., Youdim M.B.H., Amselem S., Hochberg Z.
J. Clin. Endocrinol. Metab. 82:3813-3817(1997) [PubMed: 9360546] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[6]"A short isoform of the human growth hormone receptor functions as a dominant negative inhibitor of the full-length receptor and generates large amounts of binding protein."
Ross R.J., Esposito N., Shen X.Y., Von Laue S., Chew S.L., Dobson P.R., Postel-Vinay M.-C., Finidori J.
Mol. Endocrinol. 11:265-273(1997) [PubMed: 9058373] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Liver.
[7]"Comparing of nucleotide sequences of alternatively spliced region of mammalian growth hormone receptor genes."
Orlovsky I.V., Borovikova I.E., Rubtsov P.M.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 263-336.
[8]"Functional characterization of the alternatively spliced, placental human growth hormone receptor."
Urbanek M., Russell J.E., Cooke N.E., Liebhaber S.A.
J. Biol. Chem. 268:19025-19032(1993) [PubMed: 8360189] [Abstract]
Cited for: CHARACTERIZATION OF ISOFORM 4.
[9]"Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lineage of retroelements during primate evolution."
Pantel J., Machinis K., Sobrier M.-L., Duquesnoy P., Goossens M., Amselem S.
J. Biol. Chem. 275:18664-18669(2000) [PubMed: 10764769] [Abstract]
Cited for: MOLECULAR MECHANISM OF ISOFORM 4 PRODUCTION.
[10]"The human growth hormone receptor. Secretion from Escherichia coli and disulfide bonding pattern of the extracellular binding domain."
Fuh G., Mulkerrin M.G., Bass S., McFarland N., Brochier M., Bourrel J.H., Light D.R., Wells J.A.
J. Biol. Chem. 265:3111-3115(1990) [PubMed: 2406245] [Abstract]
Cited for: DISULFIDE BONDS.
[11]"Identification of a region critical for proteolysis of the human growth hormone receptor."
Conte F., Salles J.P., Raynal P., Fernandez L., Molinas C., Tauber M., Bieth E.
Biochem. Biophys. Res. Commun. 290:851-857(2002) [PubMed: 11785980] [Abstract]
Cited for: SITE CRITICAL TO PROTEOLYSIS, MUTAGENESIS OF GLU-260; GLU-261 AND ASP-262.
[12]"Human growth hormone and extracellular domain of its receptor: crystal structure of the complex."
de Vos A.M., Ultsch M., Kossiakoff A.A.
Science 255:306-312(1992) [PubMed: 1549776] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 19-254 IN COMPLEX WITH GROWTH HORMONE.
[13]"Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9-A resolution."
Sundstroem M., Lundqvist T., Roedin J., Giebel L.B., Milligan D., Norstedt G.
J. Biol. Chem. 271:32197-32203(1996) [PubMed: 8943276] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 19-256 IN COMPLEX WITH GROWTH HORMONE.
[14]"Laron dwarfism and mutations of the growth hormone-receptor gene."
Amselem S., Duquesnoy P., Attree O., Novelli G., Bousnina S., Postel-Vinay M.-C., Goossens M.
N. Engl. J. Med. 321:989-995(1989) [PubMed: 2779634] [Abstract]
Cited for: VARIANT LARON DWARFISM SER-114.
[15]"Amino acid substitutions in the intracellular part of the growth hormone receptor in a patient with the Laron syndrome."
Kou K., Lajara R., Rotwein P.
J. Clin. Endocrinol. Metab. 76:54-59(1993) [PubMed: 8421103] [Abstract]
Cited for: VARIANT LARON DWARFISM PHE-440.
[16]"Spectrum of growth hormone receptor mutations and associated haplotypes in Laron syndrome."
Amselem S., Duquesnoy P., Duriez B., Dastot F., Sobrier M.-L., Valleix S., Goossens M.
Hum. Mol. Genet. 2:355-359(1993) [PubMed: 8504296] [Abstract]
Cited for: VARIANTS LARON DWARFISM LYS-89; GLN-149; ASP-162; CYS-179 AND GLY-229.
[17]"Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism."
Edery M., Rozakis-Adcock M., Goujon L., Finidori J., Levi-Meyrueis C., Paly J., Djiane J., Postel-Vinay M.-C., Kelly P.A.
J. Clin. Invest. 91:838-844(1993) [PubMed: 8450064] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LARON DWARFISM SER-114.
[18]"A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization."
Duquesnoy P., Sobrier M.-L., Duriez B., Dastot F., Buchanan C.R., Savage M.O., Preece M.A., Craescu C.T., Blouquit Y., Goossens M., Amselem S.
EMBO J. 13:1386-1395(1994) [PubMed: 8137822] [Abstract]
Cited for: VARIANT LARON DWARFISM HIS-170.
[19]"Mutations of the growth hormone receptor in children with idiopathic short stature."
Goddard A.D., Covello R., Luoh S.-M., Clackson T., Attie K.M., Gesundheit N., Rundle A.C., Wells J.A., Carlsson L.M.S.
N. Engl. J. Med. 333:1093-1098(1995) [PubMed: 7565946] [Abstract]
Cited for: VARIANTS SHORT STATURE LYS-62; CYS-179; HIS-229 AND ASP-242.
[20]"Nine novel growth hormone receptor gene mutations in patients with Laron syndrome."
Sobrier M.-L., Dastot F., Duquesnoy P., Kandemir N., Yordam N., Goossens M., Amselem S.
J. Clin. Endocrinol. Metab. 82:435-437(1997) [PubMed: 9024232] [Abstract]
Cited for: VARIANTS LARON DWARFISM SER-56; LEU-58 AND ARG-68.
[21]"A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue."
Walker J.L., Crock P.A., Behncken S.N., Rowlinson S.W., Nicholson L.M., Boulton T.J.C., Waters M.J.
J. Clin. Endocrinol. Metab. 83:2554-2561(1998) [PubMed: 9661642] [Abstract]
Cited for: VARIANT LARON DWARFISM GLN-149, CHARACTERIZATION OF VARIANT LARON DWARFISM GLN-149.
[22]"Growth hormone receptor mutations in children with idiopathic short stature."
Sanchez J.E., Perera E., Baumbach L., Cleveland W.W.
J. Clin. Endocrinol. Metab. 83:4079-4083(1998) [PubMed: 9814495] [Abstract]
Cited for: VARIANT SHORT STATURE ILE-162.
[23]"Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor."
Wojcik J., Berg M.A., Esposito N., Geffner M.E., Sakati N., Reiter E.O., Dower S., Francke U., Postel-Vinay M.-C., Finidori J.
J. Clin. Endocrinol. Metab. 83:4481-4489(1998) [PubMed: 9851797] [Abstract]
Cited for: VARIANTS LARON DWARFISM HIS-170; THR-171; PRO-172 AND GLY-173, CHARACTERIZATION OF VARIANTS LARON DWARFISM THR-171; PRO-172 AND GLY-173.
[24]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract]
Cited for: VARIANTS HIS-179; HIS-229; PHE-440; THR-495; LEU-544 AND THR-579.
[25]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
[26]"Characterisation of novel missense mutations in the GH receptor gene causing severe growth retardation."
Enberg B., Luthman H., Segnestam K., Ritzen E.M., Sundstroem M., Norstedt G.
Eur. J. Endocrinol. 143:71-76(2000) [PubMed: 10870033] [Abstract]
Cited for: VARIANTS LARON DWARFISM CYS-226 AND ASN-262.
[27]"Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred."
Takada D., Ezura Y., Ono S., Iino Y., Katayama Y., Xin Y., Wu L.L., Larringa-Shum S., Stephenson S.H., Hunt S.C., Hopkins P.N., Emi M.
Am. J. Med. Genet. A 121:136-140(2003) [PubMed: 12910492] [Abstract]
Cited for: VARIANT LEU-544.
[28]"The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: suppression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration."
Jorge A.A.L., Souza S.C.A.L., Arnhold I.J.P., Mendonca B.B.
Clin. Endocrinol. (Oxf.) 60:36-40(2004) [PubMed: 14678285] [Abstract]
Cited for: VARIANT LARON DWARFISM ILE-244.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

X06562 mRNA. Translation: CAA29808.1.
M28466 expand/collapse EMBL AC list , M28458, M28459, M28460, M28461, M28462, M28463, M28464, M28465 Genomic DNA. Translation: AAA52555.1.
AJ278681 Genomic DNA. Translation: CAC06613.1.
IPIIPI00023599.
IPI00410327.
IPI00410328.
IPI00410329.
PIRA33991.
RefSeqNP_000154.1.
UniGeneHs.125180
Hs.684631

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1A22X-ray2.60B19-256[»]
1AXIX-ray2.10B19-254[»]
1HWGX-ray2.50B/C19-255[»]
1HWHX-ray2.90B19-255[»]
1KF9X-ray2.60B/C/E/F19-256[»]
2AEWX-ray2.70A/B47-251[»]
3HHRX-ray2.80B/C50-254[»]
DisProtDP00033.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:630N.
IntActP10912. 20 interactions.

PTM databases

PhosphoSiteP10912.

Proteomic databases

PRIDEP10912.

Genome annotation databases

EnsemblENSG00000112964. Homo sapiens. [Contig view]
GeneID2690.
KEGGhsa:2690.

Organism-specific databases

GeneCardsGC05P042459.
H-InvDBHIX0032116.
HGNCHGNC:4263. GHR.
MIM143890. phenotype.
262500. phenotype.
600946. gene.
604271. phenotype.
Orphanet631. Growth hormone deficiency, non acquired, isolated.
633. Short stature due to growth hormone resistance.
PharmGKBPA28674.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP10912.
HOVERGENP10912.
OMAP10912. TKCRSPE.

Gene expression databases

ArrayExpressP10912.
BgeeP10912.
CleanExHS_GHR.
GermOnlineENSG00000112964. Homo sapiens.

Family and domain databases

InterProIPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
Gene3DG3DSA:2.60.40.30. FN_III-like. 2 hits.
PfamPF00041. fn3. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 1 hit.
[Graphical view]
PROSITEPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00082. Pegvisomant.
DB00052. Somatropin recombinant.
NextBio10636.
PMAP-CutDBP10912.
SOURCESearch...

Entry information

Entry nameGHR_HUMAN
AccessionPrimary (citable) accession number: P10912
Secondary accession number(s): Q9HCX2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: June 16, 2009
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents