Reviewed, UniProtKB/Swiss-Prot P10912 (GHR_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	638 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Endocytosis
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dwarfism
Domain	Signal Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	2-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 component	cell 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 function	cytokine 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRK	P46108	1	EBI-286316,EBI-886
DUSP7	Q16829	1	EBI-286316,EBI-1265847
GH1	P01241	2	EBI-286316,EBI-1026046
GRB2	P62993	1	EBI-286316,EBI-401755
NCK1	P16333	1	EBI-286316,EBI-389883
Ncoa6	Q9JLI4	1	EBI-286316,EBI-286271	From a different organism.
PIK3R1	P27986	1	EBI-286316,EBI-79464
PLCG1	P19174	1	EBI-286316,EBI-79387
PTPN1	P18031	2	EBI-286316,EBI-968788
PTPN12	Q05209	1	EBI-286316,EBI-2266035
PTPN2	P17706	2	EBI-286316,EBI-984930
PTPN22	Q9Y2R2	1	EBI-286316,EBI-1211241
PTPN3	P26045	2	EBI-286316,EBI-1047946
PTPN9	P43378	1	EBI-286316,EBI-742898
PTPRB	P23467	2	EBI-286316,EBI-1265766
PTPRC	P08575	1	EBI-286316,EBI-1341
PTPRH	Q9HD43	2	EBI-286316,EBI-1267176
PTPRJ	Q12913	1	EBI-286316,EBI-2264500
PTPRK	Q15262	1	EBI-286316,EBI-474052

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 638

620

Growth hormone receptor

PRO_0000010957

Chain

19 – ?

Growth hormone-binding protein

PRO_0000010958

Regions

Topological domain

19 – 264

246

Extracellular Potential

Transmembrane

265 – 288

24

Potential

Topological domain

289 – 638

350

Cytoplasmic Potential

Domain

149 – 251

103

Fibronectin type-III

Region

260 – 262

3

Required for ADAM17-mediated proteolysis By similarity

Motif

240 – 244

5

WSXWS motif

Motif

297 – 305

9

Box 1 motif

Motif

340 – 349

10

UbE motif

Sites

Site

345

1

Required for endocytosis and down-regulation By similarity

Amino acid modifications

Glycosylation

46

1

N-linked (GlcNAc...) Potential

Glycosylation

115

1

N-linked (GlcNAc...) Potential

Glycosylation

156

1

N-linked (GlcNAc...) Potential

Glycosylation

161

1

N-linked (GlcNAc...) Potential

Glycosylation

200

1

N-linked (GlcNAc...) Potential

Disulfide bond

56 ↔ 66

Ref.10

Disulfide bond

101 ↔ 112

Ref.10

Disulfide bond

126 ↔ 140

Ref.10

Natural variations

Alternative sequence

24

1

A → D in isoform 4.

VSP_010225

Alternative sequence

25 – 46

22

Missing in isoform 4.

VSP_010226

Alternative sequence

292 – 297

6

RIKMLI → SSSSKD in isoform 2.

VSP_010227

Alternative sequence

292 – 294

3

RIK → KEN in isoform 3.

VSP_010229

Alternative sequence

295 – 638

344

Missing in isoform 3.

VSP_010230

Alternative sequence

298 – 638

341

Missing in isoform 2.

VSP_010228

Natural variant

56

1

C → S in Laron dwarfism.

VAR_018426

Natural variant

58

1

S → L in Laron dwarfism.

VAR_018427

Natural variant

62

1

E → K in short stature; idiopathic autosomal. Ref.19

VAR_002708

Natural variant

68

1

W → R in Laron dwarfism.

VAR_018428

Natural variant

89

1

R → K in Laron dwarfism.

VAR_002709

Natural variant

114

1

F → S in Laron dwarfism; loss of ability to bind ligand.

VAR_002710

Natural variant

143

1

V → A in Laron dwarfism.

VAR_002711

Natural variant

149

1

P → Q in Laron dwarfism; disrupts GH binding.

VAR_018429

Natural variant

162

1

V → D in Laron dwarfism.

VAR_002712

Natural variant

162

1

V → F: dbSNP rs6413484. Ref.22 Ref.16

VAR_020002

Natural variant

162

1

V → I in short stature; idiopathic autosomal. Ref.22 Ref.16

VAR_018430

Natural variant

170

1

D → H in Laron dwarfism; abolishes receptor homodimerization.

VAR_002713

Natural variant

171

1

I → T in Laron dwarfism; almost completely abolishes GH-binding at cell surface: 53% binding to membrane fractions.

VAR_018431

Natural variant

172

1

Q → P in Laron dwarfism; almost completely abolishes GH-binding at cell surface and in membrane fractions.

VAR_018432

Natural variant

173

1

V → G in Laron dwarfism; almost completely abolishes GH-binding at cell surface: 26% binding to membrane fractions.

VAR_018433

Natural variant

179

1

R → C in Laron dwarfism and short stature; idiopathic autosomal.

VAR_002714

Natural variant

179

1

R → H: dbSNP rs6181. Ref.19 Ref.16 Ref.24

VAR_013937

Natural variant

226

1

Y → C in Laron dwarfism.

VAR_018434

Natural variant

229

1

R → G in Laron dwarfism.

VAR_002715

Natural variant

229

1

R → H in short stature; idiopathic autosomal. dbSNP rs6177. Ref.19 Ref.16 Ref.24

VAR_013938

Natural variant

242

1

E → D in short stature; idiopathic autosomal. Ref.19

VAR_002716

Natural variant

244

1

S → I in Laron dwarfism.

VAR_018435

Natural variant

262

1

D → N in Laron dwarfism.

VAR_018436

Natural variant

440

1

C → F in Laron dwarfism. dbSNP rs6182.

VAR_013939

Natural variant

465

1

E → K: dbSNP rs34283856.

VAR_032704

Natural variant

495

1

P → T: dbSNP rs6183. Ref.24

VAR_013940

Natural variant

544

1

I → 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 variant

579

1

P → T: dbSNP rs6184. Ref.24

VAR_013942

Experimental info

Mutagenesis

260

1

E → A: No change in shedding activity: No change in hormone binding. Ref.11

Mutagenesis

261

1

E → A: No change in shedding activity: No change in hormone binding. Ref.11

Mutagenesis

262

1

D → A: No change in shedding activity: No change in hormone binding. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

638

Helix Strand Turn

Details...

Beta strand

53 – 62

10

Beta strand

64 – 68

5

Beta strand

83 – 88

6

Beta strand

111 – 114

4

Helix

116 – 118

3

Beta strand

121 – 131

11

Beta strand

134 – 142

9

Helix

143 – 146

4

Beta strand

153 – 159

7

Beta strand

167 – 176

10

Turn

183 – 186

4

Beta strand

190 – 198

9

Beta strand

210 – 221

12

Beta strand

226 – 234

9

Beta strand

247 – 249

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (GHRfl) [UniParc]. Last modified July 1, 1989. Version 1. Checksum: EAF77EADE4787822	FASTA	638	71,500
	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
	Isoform 2 (GHRtr) (GHR1-279). Checksum: F690295F6BB01AC8	FASTA	297	34,109
	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 GEFSEVLYVT LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QSSSSKD
	Isoform 3 (GHR1-277). Checksum: 0E85069AC8F6FDBF	FASTA	294	33,889
	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 GEFSEVLYVT LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QKEN
	Isoform 4 (GHRd3). Checksum: 5F12CD731F49E1F1	FASTA	616	69,237
	10 20 30 40 50 60 MDLWQLLLTL ALAGSSDAFS GSEDSSKEPK FTKCRSPERE TFSCHWTDEV HHGTKNLGPI 70 80 90 100 110 120 QLFYTRRNTQ EWTQEWKECP DYVSAGENSC YFNSSFTSIW IPYCIKLTSN GGTVDEKCFS 130 140 150 160 170 180 VDEIVQPDPP IALNWTLLNV SLTGIHADIQ VRWEAPRNAD IQKGWMVLEY ELQYKEVNET 190 200 210 220 230 240 KWKMMDPILT TSVPVYSLKV DKEYEVRVRS KQRNSGNYGE FSEVLYVTLP QMSQFTCEED 250 260 270 280 290 300 FYFPWLLIII FGIFGLTVML FVFLFSKQQR IKMLILPPVP VPKIKGIDPD LLKEGKLEEV 310 320 330 340 350 360 NTILAIHDSY KPEFHSDDSW VEFIELDIDE PDEKTEESDT DRLLSSDHEK SHSNLGVKDG 370 380 390 400 410 420 DSGRTSCCEP DILETDFNAN DIHEGTSEVA QPQRLKGEAD LLCLDQKNQN NSPYHDACPA 430 440 450 460 470 480 TQQPSVIQAE KNKPQPLPTE GAESTHQAAH IQLSNPSSLS NIDFYAQVSD ITPAGSVVLS 490 500 510 520 530 540 PGQKNKAGMS QCDMHPEMVS LCQENFLMDN AYFCEADAKK CIPVAPHIKV ESHIQPSLNQ 550 560 570 580 590 600 EDIYITTESL TTAAGRPGTG EHVPGSEMPV PDYTSIHIVQ SPQGLILNAT ALPLPDKEFL 610 SSCGYVSTDQ LNKIMP

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

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

X06562 mRNA. Translation: CAA29808.1.
M28466 , M28458, M28459, M28460, M28461, M28462, M28463, M28464, M28465 Genomic DNA. Translation: AAA52555.1.
AJ278681 Genomic DNA. Translation: CAC06613.1.

IPI

IPI00023599.
IPI00410327.
IPI00410328.
IPI00410329.

PIR

A33991.

RefSeq

NP_000154.1.

UniGene

Hs.125180
Hs.684631

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A22	X-ray	2.60	B	19-256	[»]
1AXI	X-ray	2.10	B	19-254	[»]
1HWG	X-ray	2.50	B/C	19-255	[»]
1HWH	X-ray	2.90	B	19-255	[»]
1KF9	X-ray	2.60	B/C/E/F	19-256	[»]
2AEW	X-ray	2.70	A/B	47-251	[»]
3HHR	X-ray	2.80	B/C	50-254	[»]

DisProt

DP00033.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:630N.

IntAct

P10912. 20 interactions.

PTM databases

PhosphoSite

P10912.

Proteomic databases

PRIDE

P10912.

Genome annotation databases

Ensembl

ENSG00000112964. Homo sapiens. [Contig view]

GeneID

2690.

KEGG

hsa:2690.

Organism-specific databases

GeneCards

GC05P042459.

H-InvDB

HIX0032116.

HGNC

HGNC:4263. GHR.

MIM

143890. phenotype.
262500. phenotype.
600946. gene.
604271. phenotype.

Orphanet

631. Growth hormone deficiency, non acquired, isolated.
633. Short stature due to growth hormone resistance.

PharmGKB

PA28674.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P10912.

HOVERGEN

P10912.

OMA

P10912. TKCRSPE.

Gene expression databases

ArrayExpress

P10912.

Bgee

P10912.

CleanEx

HS_GHR.

GermOnline

ENSG00000112964. Homo sapiens.

Family and domain databases

InterPro

IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.30. FN_III-like. 2 hits.

Pfam

PF00041. fn3. 1 hit.
[Graphical view]

SMART

SM00060. FN3. 1 hit.
[Graphical view]

PROSITE

PS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00082. Pegvisomant.
DB00052. Somatropin recombinant.

NextBio

10636.

PMAP-CutDB

P10912.

SOURCE

Search...

Entry information

Entry name

GHR_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)