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P10912 (GHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 172. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth hormone receptor

Short name=GH receptor
Alternative name(s):
Somatotropin receptor

Cleaved into the following chain:

  1. 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) [Reference proteome]
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. 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.

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

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.23 Ref.26 Ref.28

Short 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

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
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_process2-oxoglutarate metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

JAK-STAT cascade

Inferred from sequence or structural similarity. Source: BHF-UCL

JAK-STAT cascade involved in growth hormone signaling pathway

Traceable author statement. Source: Reactome

activation of JAK2 kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

activation of MAPK activity

Inferred from sequence or structural similarity. Source: BHF-UCL

allantoin metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

cartilage development involved in endochondral bone morphogenesis

Inferred from electronic annotation. Source: Ensembl

cellular response to hormone stimulus

Inferred from mutant phenotype Ref.19. Source: BHF-UCL

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

citrate metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

creatine metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

creatinine metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

growth hormone receptor signaling pathway

Inferred from mutant phenotype Ref.19. Source: BHF-UCL

hormone-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

insulin-like growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.19. Source: BHF-UCL

isoleucine metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

multicellular organismal metabolic process

Inferred from mutant phenotype Ref.18. Source: BHF-UCL

negative regulation of neuron death

Inferred from electronic annotation. Source: Ensembl

oxaloacetate metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of multicellular organism growth

Inferred from mutant phenotype Ref.2. Source: BHF-UCL

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

receptor internalization

Inferred from direct assay Ref.5. Source: BHF-UCL

regulation of multicellular organism growth

Inferred from sequence or structural similarity. Source: BHF-UCL

response to cycloheximide

Inferred from direct assay Ref.5. Source: BHF-UCL

response to estradiol

Inferred from direct assay PubMed 12552091. Source: BHF-UCL

response to food

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

response to morphine

Inferred from electronic annotation. Source: Ensembl

succinate metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

taurine metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

valine metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcell surface

Inferred from direct assay Ref.18. Source: BHF-UCL

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay Ref.18Ref.5. Source: BHF-UCL

extrinsic component of membrane

Inferred from electronic annotation. Source: Ensembl

growth hormone receptor complex

Inferred from direct assay Ref.18. Source: BHF-UCL

integral component of membrane

Inferred from direct assay Ref.12. Source: BHF-UCL

integral component of plasma membrane

Inferred from direct assay Ref.18. Source: BHF-UCL

mitochondrion

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

receptor complex

Inferred from direct assay Ref.18. Source: BHF-UCL

   Molecular_functiongrowth factor binding

Inferred from physical interaction Ref.5. Source: BHF-UCL

growth hormone receptor activity

Inferred from electronic annotation. Source: Ensembl

peptide hormone binding

Inferred from physical interaction Ref.12Ref.1. Source: BHF-UCL

proline-rich region binding

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

protein homodimerization activity

Inferred from direct assay Ref.12Ref.18. Source: BHF-UCL

protein kinase binding

Inferred from sequence or structural similarity. Source: BHF-UCL

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.
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 – 256238Growth hormone-binding protein By similarity
PRO_0000010958

Regions

Topological domain19 – 264246Extracellular Potential
Transmembrane265 – 28824Helical; Potential
Topological domain289 – 638350Cytoplasmic Potential
Domain151 – 254104Fibronectin 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 LARS. Ref.20
VAR_018426
Natural variant581S → L in LARS. Ref.20
VAR_018427
Natural variant621E → K in ISSA. Ref.19
VAR_002708
Natural variant681W → R in LARS. Ref.20
VAR_018428
Natural variant891R → K in LARS. Ref.16
VAR_002709
Natural variant1141F → S in LARS; loss of ability to bind ligand. Ref.14 Ref.17
VAR_002710
Natural variant1431V → A in LARS.
VAR_002711
Natural variant1491P → Q in LARS; disrupts GH binding. Ref.16 Ref.21
VAR_018429
Natural variant1621V → D in LARS. Ref.16
VAR_002712
Natural variant1621V → F.
Corresponds to variant rs6413484 [ dbSNP | Ensembl ].
VAR_020002
Natural variant1621V → I Found in a patient with idiopathic short stature; unknown pathological significance. Ref.22
Corresponds to variant rs6413484 [ dbSNP | Ensembl ].
VAR_018430
Natural variant1701D → H in LARS; abolishes receptor homodimerization. Ref.18 Ref.23
VAR_002713
Natural variant1711I → T in LARS; almost completely abolishes GH-binding at cell surface: 53% binding to membrane fractions. Ref.23
VAR_018431
Natural variant1721Q → P in LARS; almost completely abolishes GH-binding at cell surface and in membrane fractions. Ref.23
VAR_018432
Natural variant1731V → G in LARS; almost completely abolishes GH-binding at cell surface: 26% binding to membrane fractions. Ref.23
VAR_018433
Natural variant1791R → C in LARS and ISSA. Ref.16 Ref.19
Corresponds to variant rs121909362 [ dbSNP | Ensembl ].
VAR_002714
Natural variant1791R → H. Ref.24
Corresponds to variant rs6181 [ dbSNP | Ensembl ].
VAR_013937
Natural variant2261Y → C in LARS. Ref.26
VAR_018434
Natural variant2291R → G in LARS. Ref.16
VAR_002715
Natural variant2291R → H Found in a patient with idiopathic short stature; unknown pathological significance. Ref.19 Ref.24
Corresponds to variant rs6177 [ dbSNP | Ensembl ].
VAR_013938
Natural variant2421E → D Found in a patient with idiopathic short stature; unknown pathological significance. Ref.19
Corresponds to variant rs45588036 [ dbSNP | Ensembl ].
VAR_002716
Natural variant2441S → I in LARS. Ref.28
VAR_018435
Natural variant2621D → N in LARS. Ref.26
VAR_018436
Natural variant4401C → F in LARS. Ref.15 Ref.24
Corresponds to variant rs6182 [ dbSNP | Ensembl ].
VAR_013939
Natural variant4651E → K.
Corresponds to variant rs34283856 [ dbSNP | Ensembl ].
VAR_032704
Natural variant4951P → T. Ref.24
Corresponds to variant rs6183 [ dbSNP | Ensembl ].
VAR_013940
Natural variant5441I → L Polymorphism with a modifier effect on plasma HDL cholesterol levels in familial hypercholesterolemia patients. Ref.2 Ref.24 Ref.27
Corresponds to variant rs6180 [ dbSNP | Ensembl ].
VAR_013941
Natural variant5791P → T. Ref.24
Corresponds to variant rs6184 [ dbSNP | Ensembl ].
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) [UniParc].

Checksum: F690295F6BB01AC8
Show »

FASTA29734,109
Isoform 3 (GHR1-277) [UniParc].

Checksum: 0E85069AC8F6FDBF
Show »

FASTA29433,889
Isoform 4 (GHRd3) [UniParc].

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION (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] [Europe PMC] [Abstract]
Cited for: MOLECULAR MECHANISM OF PRODUCTION (ISOFORM 4).
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT LARS 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] [Europe PMC] [Abstract]
Cited for: VARIANT LARS 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] [Europe PMC] [Abstract]
Cited for: VARIANTS LARS 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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LARS 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] [Europe PMC] [Abstract]
Cited for: VARIANT LARS 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] [Europe PMC] [Abstract]
Cited for: VARIANTS ISSA LYS-62 AND CYS-179, VARIANTS 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] [Europe PMC] [Abstract]
Cited for: VARIANTS LARS 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] [Europe PMC] [Abstract]
Cited for: VARIANT LARS GLN-149, CHARACTERIZATION OF VARIANT LARS 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] [Europe PMC] [Abstract]
Cited for: VARIANT 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] [Europe PMC] [Abstract]
Cited for: VARIANTS LARS HIS-170; THR-171; PRO-172 AND GLY-173, CHARACTERIZATION OF VARIANTS LARS 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANTS LARS 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT LARS ILE-244.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA33991.
RefSeqNP_000154.1. NM_000163.4.
NP_001229328.1. NM_001242399.2.
NP_001229329.1. NM_001242400.2.
NP_001229330.1. NM_001242401.3.
NP_001229331.1. NM_001242402.2.
NP_001229332.1. NM_001242403.2.
NP_001229333.1. NM_001242404.2.
NP_001229334.1. NM_001242405.2.
NP_001229335.1. NM_001242406.2.
NP_001229389.1. NM_001242460.1.
NP_001229391.1. NM_001242462.1.
XP_005248345.1. XM_005248288.1.
UniGeneHs.125180.
Hs.684632.
Hs.688223.

3D structure databases

PDBe
RCSB PDB
PDBj
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.
ProteinModelPortalP10912.
SMRP10912. Positions 50-252.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108957. 30 interactions.
DIPDIP-630N.
IntActP10912. 21 interactions.
MINTMINT-1528703.
STRING9606.ENSP00000230882.

Chemistry

ChEMBLCHEMBL1976.
DrugBankDB00082. Pegvisomant.
DB00052. Somatropin recombinant.
GuidetoPHARMACOLOGY1720.

PTM databases

PhosphoSiteP10912.

Polymorphism databases

DMDM121180.

Proteomic databases

PaxDbP10912.
PRIDEP10912.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000230882; ENSP00000230882; ENSG00000112964. [P10912-1]
ENST00000357703; ENSP00000350335; ENSG00000112964. [P10912-4]
GeneID2690.
KEGGhsa:2690.
UCSCuc003jmt.3. human. [P10912-1]
uc021xyb.1. human. [P10912-2]
uc021xyc.1. human. [P10912-3]
uc021xyd.1. human. [P10912-4]

Organism-specific databases

CTD2690.
GeneCardsGC05P042429.
HGNCHGNC:4263. GHR.
MIM143890. phenotype.
262500. phenotype.
600946. gene.
604271. phenotype.
neXtProtNX_P10912.
Orphanet633. Laron syndrome.
314802. Short stature due to partial GHR deficiency.
PharmGKBPA28674.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45313.
HOGENOMHOG000015773.
HOVERGENHBG005836.
InParanoidP10912.
KOK05080.
OMAIDFYAQV.
OrthoDBEOG79W94T.
PhylomeDBP10912.
TreeFamTF330851.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6900. Immune System.
SignaLinkP10912.

Gene expression databases

ArrayExpressP10912.
BgeeP10912.
CleanExHS_GHR.
GenevestigatorP10912.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR003961. Fibronectin_type3.
IPR025871. GHBP.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10912.
GeneWikiGrowth_hormone_receptor.
GenomeRNAi2690.
NextBio10636.
PMAP-CutDBP10912.
PROP10912.
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: April 16, 2014
This is version 172 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

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