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Protein

Growth hormone receptor

Gene

GHR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei345 – 3451Required for endocytosis and down-regulationBy similarity

GO - Molecular functioni

  1. cytokine receptor activity Source: InterPro
  2. growth factor binding Source: BHF-UCL
  3. peptide hormone binding Source: BHF-UCL
  4. proline-rich region binding Source: BHF-UCL
  5. protein homodimerization activity Source: BHF-UCL
  6. protein kinase binding Source: BHF-UCL

GO - Biological processi

  1. 2-oxoglutarate metabolic process Source: BHF-UCL
  2. activation of JAK2 kinase activity Source: BHF-UCL
  3. activation of MAPK activity Source: BHF-UCL
  4. allantoin metabolic process Source: BHF-UCL
  5. cellular response to hormone stimulus Source: BHF-UCL
  6. citrate metabolic process Source: BHF-UCL
  7. creatine metabolic process Source: BHF-UCL
  8. creatinine metabolic process Source: BHF-UCL
  9. endocytosis Source: UniProtKB-KW
  10. fatty acid metabolic process Source: BHF-UCL
  11. growth hormone receptor signaling pathway Source: BHF-UCL
  12. insulin-like growth factor receptor signaling pathway Source: BHF-UCL
  13. isoleucine metabolic process Source: BHF-UCL
  14. JAK-STAT cascade Source: BHF-UCL
  15. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  16. multicellular organismal metabolic process Source: BHF-UCL
  17. oxaloacetate metabolic process Source: BHF-UCL
  18. positive regulation of multicellular organism growth Source: BHF-UCL
  19. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  20. positive regulation of tyrosine phosphorylation of Stat3 protein Source: BHF-UCL
  21. positive regulation of tyrosine phosphorylation of Stat5 protein Source: BHF-UCL
  22. receptor internalization Source: BHF-UCL
  23. regulation of multicellular organism growth Source: BHF-UCL
  24. response to cycloheximide Source: BHF-UCL
  25. response to estradiol Source: BHF-UCL
  26. succinate metabolic process Source: BHF-UCL
  27. taurine metabolic process Source: BHF-UCL
  28. valine metabolic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Endocytosis

Enzyme and pathway databases

ReactomeiREACT_111133. Growth hormone receptor signaling.
REACT_115697. Prolactin receptor signaling.
SignaLinkiP10912.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth hormone receptor
Short name:
GH receptor
Alternative name(s):
Somatotropin receptor
Cleaved into the following chain:
Growth hormone-binding protein
Short name:
GH-binding protein
Short name:
GHBP
Alternative name(s):
Serum-binding protein
Gene namesi
Name:GHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:4263. GHR.

Subcellular locationi

  1. Cell membrane; Single-pass type I membrane protein

  2. Note: On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway.By similarity
Isoform 2 :
  1. Cell membrane; Single-pass type I membrane protein

  2. Note: Remains fixed to the cell membrane and is not internalized.
Chain Growth hormone-binding protein :
  1. Secreted

  2. Note: Complexed to a substantial fraction of circulating GH.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 264246ExtracellularSequence AnalysisAdd
BLAST
Transmembranei265 – 28824HelicalSequence AnalysisAdd
BLAST
Topological domaini289 – 638350CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. extracellular region Source: Reactome
  3. extracellular space Source: BHF-UCL
  4. growth hormone receptor complex Source: BHF-UCL
  5. integral component of membrane Source: BHF-UCL
  6. integral component of plasma membrane Source: BHF-UCL
  7. plasma membrane Source: Reactome
  8. receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Laron syndrome (LARS)9 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:262500
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti56 – 561C → S in LARS. 1 Publication
VAR_018426
Natural varianti58 – 581S → L in LARS. 1 Publication
VAR_018427
Natural varianti68 – 681W → R in LARS. 1 Publication
VAR_018428
Natural varianti89 – 891R → K in LARS. 1 Publication
VAR_002709
Natural varianti114 – 1141F → S in LARS; loss of ability to bind ligand. 2 Publications
VAR_002710
Natural varianti143 – 1431V → A in LARS.
VAR_002711
Natural varianti149 – 1491P → Q in LARS; disrupts GH binding. 2 Publications
VAR_018429
Natural varianti162 – 1621V → D in LARS. 1 Publication
VAR_002712
Natural varianti170 – 1701D → H in LARS; abolishes receptor homodimerization. 2 Publications
VAR_002713
Natural varianti171 – 1711I → T in LARS; almost completely abolishes GH-binding at cell surface: 53% binding to membrane fractions. 1 Publication
VAR_018431
Natural varianti172 – 1721Q → P in LARS; almost completely abolishes GH-binding at cell surface and in membrane fractions. 1 Publication
VAR_018432
Natural varianti173 – 1731V → G in LARS; almost completely abolishes GH-binding at cell surface: 26% binding to membrane fractions. 1 Publication
VAR_018433
Natural varianti179 – 1791R → C in LARS and GHIP. 2 Publications
Corresponds to variant rs121909362 [ dbSNP | Ensembl ].
VAR_002714
Natural varianti226 – 2261Y → C in LARS. 1 Publication
VAR_018434
Natural varianti229 – 2291R → G in LARS. 1 Publication
VAR_002715
Natural varianti244 – 2441S → I in LARS. 1 Publication
VAR_018435
Natural varianti262 – 2621D → N in LARS. 1 Publication
VAR_018436
Natural varianti440 – 4401C → F in LARS. 2 Publications
Corresponds to variant rs6182 [ dbSNP | Ensembl ].
VAR_013939
Growth hormone insensitivity, partial (GHIP)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disease characterized by partial resistance to growth hormone resulting in short stature. Short stature is 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, healthy, genetically relevant population.

See also OMIM:604271
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti62 – 621E → K in GHIP. 1 Publication
VAR_002708
Natural varianti179 – 1791R → C in LARS and GHIP. 2 Publications
Corresponds to variant rs121909362 [ dbSNP | Ensembl ].
VAR_002714

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi260 – 2601E → A: No change in shedding activity: No change in hormone binding. 1 Publication
Mutagenesisi261 – 2611E → A: No change in shedding activity: No change in hormone binding. 1 Publication
Mutagenesisi262 – 2621D → A: No change in shedding activity: No change in hormone binding. 1 Publication

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

MIMi143890. phenotype.
262500. phenotype.
604271. phenotype.
Orphaneti633. Laron syndrome.
314802. Short stature due to partial GHR deficiency.
PharmGKBiPA28674.

Chemistry

DrugBankiDB00082. Pegvisomant.
DB00052. Somatropin recombinant.

Polymorphism and mutation databases

BioMutaiGHR.
DMDMi121180.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 638620Growth hormone receptorPRO_0000010957Add
BLAST
Chaini19 – 256238Growth hormone-binding proteinBy similarityPRO_0000010958Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi46 – 461N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi56 ↔ 661 Publication
Disulfide bondi101 ↔ 1121 Publication
Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi126 ↔ 1401 Publication
Glycosylationi156 – 1561N-linked (GlcNAc...)Sequence Analysis
Glycosylationi161 – 1611N-linked (GlcNAc...)Sequence Analysis
Glycosylationi200 – 2001N-linked (GlcNAc...)Sequence Analysis
Modified residuei341 – 3411Phosphoserine1 Publication

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP10912.
PRIDEiP10912.

PTM databases

PhosphoSiteiP10912.

Miscellaneous databases

PMAP-CutDBP10912.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiP10912.
CleanExiHS_GHR.
ExpressionAtlasiP10912. baseline and differential.
GenevestigatoriP10912.

Interactioni

Subunit structurei

On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation. Interacts with ADAM17.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
DUSP7Q168292EBI-286316,EBI-1265847
GH1P012413EBI-286316,EBI-1026046
NCK1P163333EBI-286316,EBI-389883
Ncoa6Q9JLI42EBI-286316,EBI-286271From a different organism.
PTPN1P180315EBI-286316,EBI-968788
PTPN2P177068EBI-286316,EBI-984930
PTPN3P260454EBI-286316,EBI-1047946
PTPN9P433782EBI-286316,EBI-742898
PTPRBP234673EBI-286316,EBI-1265766
PTPRHQ9HD434EBI-286316,EBI-1267176
PTPRJQ129132EBI-286316,EBI-2264500

Protein-protein interaction databases

BioGridi108957. 32 interactions.
DIPiDIP-630N.
IntActiP10912. 23 interactions.
MINTiMINT-1528703.
STRINGi9606.ENSP00000230882.

Structurei

Secondary structure

1
638
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi53 – 6210Combined sources
Beta strandi64 – 685Combined sources
Beta strandi83 – 886Combined sources
Turni93 – 964Combined sources
Turni104 – 1074Combined sources
Beta strandi111 – 1144Combined sources
Helixi116 – 1183Combined sources
Beta strandi121 – 13111Combined sources
Beta strandi134 – 1429Combined sources
Helixi143 – 1464Combined sources
Beta strandi153 – 1597Combined sources
Beta strandi167 – 17610Combined sources
Turni183 – 1864Combined sources
Beta strandi190 – 1989Combined sources
Beta strandi210 – 22112Combined sources
Beta strandi226 – 2349Combined sources
Beta strandi240 – 2434Combined sources
Beta strandi247 – 2493Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
DisProtiDP00033.
ProteinModelPortaliP10912.
SMRiP10912. Positions 50-252.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10912.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini151 – 254104Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni260 – 2623Required for ADAM17-mediated proteolysisBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi240 – 2445WSXWS motif
Motifi297 – 3059Box 1 motif
Motifi340 – 34910UbE motif

Domaini

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.

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG45313.
GeneTreeiENSGT00530000063112.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiP10912.
KOiK05080.
OMAiIDFYAQV.
OrthoDBiEOG79W94T.
PhylomeDBiP10912.
TreeFamiTF330851.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR003961. FN3_dom.
IPR025871. GHBP.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamiPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P10912-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDLWQLLLTL ALAGSSDAFS GSEATAAILS RAPWSLQSVN PGLKTNSSKE
60 70 80 90 100
PKFTKCRSPE RETFSCHWTD EVHHGTKNLG PIQLFYTRRN TQEWTQEWKE
110 120 130 140 150
CPDYVSAGEN SCYFNSSFTS IWIPYCIKLT SNGGTVDEKC FSVDEIVQPD
160 170 180 190 200
PPIALNWTLL NVSLTGIHAD IQVRWEAPRN ADIQKGWMVL EYELQYKEVN
210 220 230 240 250
ETKWKMMDPI LTTSVPVYSL KVDKEYEVRV RSKQRNSGNY GEFSEVLYVT
260 270 280 290 300
LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QRIKMLILPP
310 320 330 340 350
VPVPKIKGID PDLLKEGKLE EVNTILAIHD SYKPEFHSDD SWVEFIELDI
360 370 380 390 400
DEPDEKTEES DTDRLLSSDH EKSHSNLGVK DGDSGRTSCC EPDILETDFN
410 420 430 440 450
ANDIHEGTSE VAQPQRLKGE ADLLCLDQKN QNNSPYHDAC PATQQPSVIQ
460 470 480 490 500
AEKNKPQPLP TEGAESTHQA AHIQLSNPSS LSNIDFYAQV SDITPAGSVV
510 520 530 540 550
LSPGQKNKAG MSQCDMHPEM VSLCQENFLM DNAYFCEADA KKCIPVAPHI
560 570 580 590 600
KVESHIQPSL NQEDIYITTE SLTTAAGRPG TGEHVPGSEM PVPDYTSIHI
610 620 630
VQSPQGLILN ATALPLPDKE FLSSCGYVST DQLNKIMP
Length:638
Mass (Da):71,500
Last modified:July 1, 1989 - v1
Checksum:iEAF77EADE4787822
GO
Isoform 2 (identifier: P10912-2) [UniParc]FASTAAdd to basket

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.

Show »
Length:297
Mass (Da):34,109
Checksum:iF690295F6BB01AC8
GO
Isoform 3 (identifier: P10912-3) [UniParc]FASTAAdd to basket

Also known as: GHR1-277

The sequence of this isoform differs from the canonical sequence as follows:
     292-294: RIK → KEN
     295-638: Missing.

Show »
Length:294
Mass (Da):33,889
Checksum:i0E85069AC8F6FDBF
GO
Isoform 4 (identifier: P10912-4) [UniParc]FASTAAdd to basket

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.

Show »
Length:616
Mass (Da):69,237
Checksum:i5F12CD731F49E1F1
GO

Polymorphismi

Genetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia [MIMi:143890] patients carrying a mutation in the LDLR gene.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti56 – 561C → S in LARS. 1 Publication
VAR_018426
Natural varianti58 – 581S → L in LARS. 1 Publication
VAR_018427
Natural varianti62 – 621E → K in GHIP. 1 Publication
VAR_002708
Natural varianti68 – 681W → R in LARS. 1 Publication
VAR_018428
Natural varianti89 – 891R → K in LARS. 1 Publication
VAR_002709
Natural varianti114 – 1141F → S in LARS; loss of ability to bind ligand. 2 Publications
VAR_002710
Natural varianti143 – 1431V → A in LARS.
VAR_002711
Natural varianti149 – 1491P → Q in LARS; disrupts GH binding. 2 Publications
VAR_018429
Natural varianti162 – 1621V → D in LARS. 1 Publication
VAR_002712
Natural varianti162 – 1621V → F.
Corresponds to variant rs6413484 [ dbSNP | Ensembl ].
VAR_020002
Natural varianti162 – 1621V → I Found in a patient with idiopathic short stature; unknown pathological significance. 1 Publication
Corresponds to variant rs6413484 [ dbSNP | Ensembl ].
VAR_018430
Natural varianti170 – 1701D → H in LARS; abolishes receptor homodimerization. 2 Publications
VAR_002713
Natural varianti171 – 1711I → T in LARS; almost completely abolishes GH-binding at cell surface: 53% binding to membrane fractions. 1 Publication
VAR_018431
Natural varianti172 – 1721Q → P in LARS; almost completely abolishes GH-binding at cell surface and in membrane fractions. 1 Publication
VAR_018432
Natural varianti173 – 1731V → G in LARS; almost completely abolishes GH-binding at cell surface: 26% binding to membrane fractions. 1 Publication
VAR_018433
Natural varianti179 – 1791R → C in LARS and GHIP. 2 Publications
Corresponds to variant rs121909362 [ dbSNP | Ensembl ].
VAR_002714
Natural varianti179 – 1791R → H.1 Publication
Corresponds to variant rs6181 [ dbSNP | Ensembl ].
VAR_013937
Natural varianti226 – 2261Y → C in LARS. 1 Publication
VAR_018434
Natural varianti229 – 2291R → G in LARS. 1 Publication
VAR_002715
Natural varianti229 – 2291R → H Found in a patient with idiopathic short stature; unknown pathological significance. 2 Publications
Corresponds to variant rs6177 [ dbSNP | Ensembl ].
VAR_013938
Natural varianti242 – 2421E → D Found in a patient with idiopathic short stature; unknown pathological significance. 1 Publication
Corresponds to variant rs45588036 [ dbSNP | Ensembl ].
VAR_002716
Natural varianti244 – 2441S → I in LARS. 1 Publication
VAR_018435
Natural varianti262 – 2621D → N in LARS. 1 Publication
VAR_018436
Natural varianti440 – 4401C → F in LARS. 2 Publications
Corresponds to variant rs6182 [ dbSNP | Ensembl ].
VAR_013939
Natural varianti465 – 4651E → K.
Corresponds to variant rs34283856 [ dbSNP | Ensembl ].
VAR_032704
Natural varianti495 – 4951P → T.1 Publication
Corresponds to variant rs6183 [ dbSNP | Ensembl ].
VAR_013940
Natural varianti544 – 5441I → L Polymorphism with a modifier effect on plasma HDL cholesterol levels in familial hypercholesterolemia patients. 3 Publications
Corresponds to variant rs6180 [ dbSNP | Ensembl ].
VAR_013941
Natural varianti579 – 5791P → T.1 Publication
Corresponds to variant rs6184 [ dbSNP | Ensembl ].
VAR_013942

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei24 – 241A → D in isoform 4. 1 PublicationVSP_010225
Alternative sequencei25 – 4622Missing in isoform 4. 1 PublicationVSP_010226Add
BLAST
Alternative sequencei292 – 2976RIKMLI → SSSSKD in isoform 2. 3 PublicationsVSP_010227
Alternative sequencei292 – 2943RIK → KEN in isoform 3. 1 PublicationVSP_010229
Alternative sequencei295 – 638344Missing in isoform 3. 1 PublicationVSP_010230Add
BLAST
Alternative sequencei298 – 638341Missing in isoform 2. 3 PublicationsVSP_010228Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3940.1. [P10912-1]
CCDS56364.1. [P10912-4]
PIRiA33991.
RefSeqiNP_000154.1. NM_000163.4. [P10912-1]
NP_001229328.1. NM_001242399.2.
NP_001229329.1. NM_001242400.2. [P10912-1]
NP_001229330.1. NM_001242401.3. [P10912-1]
NP_001229331.1. NM_001242402.2. [P10912-1]
NP_001229332.1. NM_001242403.2. [P10912-1]
NP_001229333.1. NM_001242404.2. [P10912-1]
NP_001229334.1. NM_001242405.2. [P10912-1]
NP_001229335.1. NM_001242406.2. [P10912-1]
NP_001229389.1. NM_001242460.1. [P10912-4]
NP_001229391.1. NM_001242462.1.
UniGeneiHs.125180.
Hs.684632.
Hs.688223.

Genome annotation databases

EnsembliENST00000230882; ENSP00000230882; ENSG00000112964. [P10912-1]
ENST00000357703; ENSP00000350335; ENSG00000112964. [P10912-4]
ENST00000537449; ENSP00000442206; ENSG00000112964. [P10912-1]
ENST00000612382; ENSP00000478332; ENSG00000112964. [P10912-1]
ENST00000612626; ENSP00000479846; ENSG00000112964. [P10912-1]
ENST00000615111; ENSP00000478291; ENSG00000112964. [P10912-1]
ENST00000618088; ENSP00000482373; ENSG00000112964. [P10912-1]
GeneIDi2690.
KEGGihsa:2690.
UCSCiuc003jmt.3. human. [P10912-1]
uc021xyb.1. human. [P10912-2]
uc021xyc.1. human. [P10912-3]
uc021xyd.1. human. [P10912-4]

Polymorphism and mutation databases

BioMutaiGHR.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3940.1. [P10912-1]
CCDS56364.1. [P10912-4]
PIRiA33991.
RefSeqiNP_000154.1. NM_000163.4. [P10912-1]
NP_001229328.1. NM_001242399.2.
NP_001229329.1. NM_001242400.2. [P10912-1]
NP_001229330.1. NM_001242401.3. [P10912-1]
NP_001229331.1. NM_001242402.2. [P10912-1]
NP_001229332.1. NM_001242403.2. [P10912-1]
NP_001229333.1. NM_001242404.2. [P10912-1]
NP_001229334.1. NM_001242405.2. [P10912-1]
NP_001229335.1. NM_001242406.2. [P10912-1]
NP_001229389.1. NM_001242460.1. [P10912-4]
NP_001229391.1. NM_001242462.1.
UniGeneiHs.125180.
Hs.684632.
Hs.688223.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
DisProtiDP00033.
ProteinModelPortaliP10912.
SMRiP10912. Positions 50-252.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108957. 32 interactions.
DIPiDIP-630N.
IntActiP10912. 23 interactions.
MINTiMINT-1528703.
STRINGi9606.ENSP00000230882.

Chemistry

ChEMBLiCHEMBL1976.
DrugBankiDB00082. Pegvisomant.
DB00052. Somatropin recombinant.
GuidetoPHARMACOLOGYi1720.

PTM databases

PhosphoSiteiP10912.

Polymorphism and mutation databases

BioMutaiGHR.
DMDMi121180.

Proteomic databases

PaxDbiP10912.
PRIDEiP10912.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230882; ENSP00000230882; ENSG00000112964. [P10912-1]
ENST00000357703; ENSP00000350335; ENSG00000112964. [P10912-4]
ENST00000537449; ENSP00000442206; ENSG00000112964. [P10912-1]
ENST00000612382; ENSP00000478332; ENSG00000112964. [P10912-1]
ENST00000612626; ENSP00000479846; ENSG00000112964. [P10912-1]
ENST00000615111; ENSP00000478291; ENSG00000112964. [P10912-1]
ENST00000618088; ENSP00000482373; ENSG00000112964. [P10912-1]
GeneIDi2690.
KEGGihsa:2690.
UCSCiuc003jmt.3. human. [P10912-1]
uc021xyb.1. human. [P10912-2]
uc021xyc.1. human. [P10912-3]
uc021xyd.1. human. [P10912-4]

Organism-specific databases

CTDi2690.
GeneCardsiGC05P042429.
HGNCiHGNC:4263. GHR.
MIMi143890. phenotype.
262500. phenotype.
600946. gene.
604271. phenotype.
neXtProtiNX_P10912.
Orphaneti633. Laron syndrome.
314802. Short stature due to partial GHR deficiency.
PharmGKBiPA28674.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG45313.
GeneTreeiENSGT00530000063112.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiP10912.
KOiK05080.
OMAiIDFYAQV.
OrthoDBiEOG79W94T.
PhylomeDBiP10912.
TreeFamiTF330851.

Enzyme and pathway databases

ReactomeiREACT_111133. Growth hormone receptor signaling.
REACT_115697. Prolactin receptor signaling.
SignaLinkiP10912.

Miscellaneous databases

ChiTaRSiGHR. human.
EvolutionaryTraceiP10912.
GeneWikiiGrowth_hormone_receptor.
GenomeRNAii2690.
NextBioi10636.
PMAP-CutDBP10912.
PROiP10912.
SOURCEiSearch...

Gene expression databases

BgeeiP10912.
CleanExiHS_GHR.
ExpressionAtlasiP10912. baseline and differential.
GenevestigatoriP10912.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR003961. FN3_dom.
IPR025871. GHBP.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamiPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  13. "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.
  14. "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.
  15. Cited for: VARIANT LARS SER-114.
  16. "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.
  17. "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.
  18. "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.
  19. "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.
  20. "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 GHIP LYS-62 AND CYS-179, VARIANTS HIS-229 AND ASP-242.
  21. "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.
  22. "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.
  23. "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.
  24. "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.
  25. Cited for: VARIANTS HIS-179; HIS-229; PHE-440; THR-495; LEU-544 AND THR-579.
  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.

Entry informationi

Entry nameiGHR_HUMAN
AccessioniPrimary (citable) accession number: P10912
Secondary accession number(s): Q9HCX2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 29, 2015
This is version 183 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.