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P10912

- GHR_HUMAN

UniProt

P10912 - GHR_HUMAN

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Protein
Growth hormone receptor
Gene
GHR
Organism
Homo sapiens (Human)
Status
Reviewed - 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.
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-regulation By similarity

GO - Molecular functioni

  1. growth factor binding Source: BHF-UCL
  2. growth hormone receptor activity Source: Ensembl
  3. peptide hormone binding Source: BHF-UCL
  4. proline-rich region binding Source: BHF-UCL
  5. protein binding Source: IntAct
  6. protein homodimerization activity Source: BHF-UCL
  7. protein kinase binding Source: BHF-UCL
Complete GO annotation...

GO - Biological processi

  1. 2-oxoglutarate metabolic process Source: BHF-UCL
  2. JAK-STAT cascade Source: BHF-UCL
  3. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  4. activation of JAK2 kinase activity Source: BHF-UCL
  5. activation of MAPK activity Source: BHF-UCL
  6. allantoin metabolic process Source: BHF-UCL
  7. cartilage development involved in endochondral bone morphogenesis Source: Ensembl
  8. cellular response to hormone stimulus Source: BHF-UCL
  9. cellular response to insulin stimulus Source: Ensembl
  10. citrate metabolic process Source: BHF-UCL
  11. creatine metabolic process Source: BHF-UCL
  12. creatinine metabolic process Source: BHF-UCL
  13. endocytosis Source: UniProtKB-KW
  14. fatty acid metabolic process Source: BHF-UCL
  15. growth hormone receptor signaling pathway Source: BHF-UCL
  16. hormone-mediated signaling pathway Source: Ensembl
  17. insulin-like growth factor receptor signaling pathway Source: BHF-UCL
  18. isoleucine metabolic process Source: BHF-UCL
  19. multicellular organismal metabolic process Source: BHF-UCL
  20. negative regulation of neuron death Source: Ensembl
  21. oxaloacetate metabolic process Source: BHF-UCL
  22. positive regulation of cell differentiation Source: Ensembl
  23. positive regulation of multicellular organism growth Source: BHF-UCL
  24. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  25. positive regulation of tyrosine phosphorylation of Stat3 protein Source: BHF-UCL
  26. positive regulation of tyrosine phosphorylation of Stat5 protein Source: BHF-UCL
  27. receptor internalization Source: BHF-UCL
  28. regulation of multicellular organism growth Source: BHF-UCL
  29. response to cycloheximide Source: BHF-UCL
  30. response to estradiol Source: BHF-UCL
  31. response to food Source: Ensembl
  32. response to glucocorticoid Source: Ensembl
  33. response to interleukin-1 Source: Ensembl
  34. response to morphine Source: Ensembl
  35. succinate metabolic process Source: BHF-UCL
  36. taurine metabolic process Source: BHF-UCL
  37. 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: Chromosome 5

Organism-specific databases

HGNCiHGNC:4263. GHR.

Subcellular locationi

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.
Chain Growth hormone-binding protein : Secreted
Note: Complexed to a substantial fraction of circulating GH By similarity.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 264246Extracellular Reviewed prediction
Add
BLAST
Transmembranei265 – 28824Helical; Reviewed prediction
Add
BLAST
Topological domaini289 – 638350Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. extracellular region Source: Reactome
  3. extracellular space Source: BHF-UCL
  4. extrinsic component of membrane Source: Ensembl
  5. growth hormone receptor complex Source: BHF-UCL
  6. integral component of membrane Source: BHF-UCL
  7. integral component of plasma membrane Source: BHF-UCL
  8. mitochondrion Source: Ensembl
  9. neuronal cell body Source: Ensembl
  10. nucleus Source: Ensembl
  11. plasma membrane Source: Reactome
  12. receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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.10 Publications
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 ISSA. 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
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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti62 – 621E → K in ISSA. 1 Publication
VAR_002708
Natural varianti179 – 1791R → C in LARS and ISSA. 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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818 Reviewed prediction
Add
BLAST
Chaini19 – 638620Growth hormone receptor
PRO_0000010957Add
BLAST
Chaini19 – 256238Growth hormone-binding protein By similarity
PRO_0000010958Add
BLAST

Amino acid modifications

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

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.
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.

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

ArrayExpressiP10912.
BgeeiP10912.
CleanExiHS_GHR.
GenevestigatoriP10912.

Interactioni

Subunit structurei

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.

Binary interactionsi

WithEntry#Exp.IntActNotes
DUSP7Q168292EBI-286316,EBI-1265847
GH1P012413EBI-286316,EBI-1026046
NCK1P163332EBI-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. 21 interactions.
MINTiMINT-1528703.
STRINGi9606.ENSP00000230882.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Miscellaneous databases

EvolutionaryTraceiP10912.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini151 – 254104Fibronectin type-III
Add
BLAST

Region

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR003961. Fibronectin_type3.
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. Align

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

MDLWQLLLTL ALAGSSDAFS GSEATAAILS RAPWSLQSVN PGLKTNSSKE    50
PKFTKCRSPE RETFSCHWTD EVHHGTKNLG PIQLFYTRRN TQEWTQEWKE 100
CPDYVSAGEN SCYFNSSFTS IWIPYCIKLT SNGGTVDEKC FSVDEIVQPD 150
PPIALNWTLL NVSLTGIHAD IQVRWEAPRN ADIQKGWMVL EYELQYKEVN 200
ETKWKMMDPI LTTSVPVYSL KVDKEYEVRV RSKQRNSGNY GEFSEVLYVT 250
LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QRIKMLILPP 300
VPVPKIKGID PDLLKEGKLE EVNTILAIHD SYKPEFHSDD SWVEFIELDI 350
DEPDEKTEES DTDRLLSSDH EKSHSNLGVK DGDSGRTSCC EPDILETDFN 400
ANDIHEGTSE VAQPQRLKGE ADLLCLDQKN QNNSPYHDAC PATQQPSVIQ 450
AEKNKPQPLP TEGAESTHQA AHIQLSNPSS LSNIDFYAQV SDITPAGSVV 500
LSPGQKNKAG MSQCDMHPEM VSLCQENFLM DNAYFCEADA KKCIPVAPHI 550
KVESHIQPSL NQEDIYITTE SLTTAAGRPG TGEHVPGSEM PVPDYTSIHI 600
VQSPQGLILN ATALPLPDKE FLSSCGYVST DQLNKIMP 638
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 ISSA. 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 ISSA. 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.
VSP_010225
Alternative sequencei25 – 4622Missing in isoform 4.
VSP_010226Add
BLAST
Alternative sequencei292 – 2976RIKMLI → SSSSKD in isoform 2.
VSP_010227
Alternative sequencei292 – 2943RIK → KEN in isoform 3.
VSP_010229
Alternative sequencei295 – 638344Missing in isoform 3.
VSP_010230Add
BLAST
Alternative sequencei298 – 638341Missing in isoform 2.
VSP_010228Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
XP_005248345.1. XM_005248288.1. [P10912-4]
UniGeneiHs.125180.
Hs.684632.
Hs.688223.

Genome annotation databases

EnsembliENST00000230882; ENSP00000230882; ENSG00000112964. [P10912-1]
ENST00000357703; ENSP00000350335; ENSG00000112964. [P10912-4]
GeneIDi2690.
KEGGihsa:2690.
UCSCiuc003jmt.3. human. [P10912-1]
uc021xyb.1. human. [P10912-2]
uc021xyc.1. human. [P10912-3]
uc021xyd.1. human. [P10912-4]

Polymorphism databases

DMDMi121180.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS3940.1. [P10912-1 ]
CCDS56364.1. [P10912-4 ]
PIRi A33991.
RefSeqi NP_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.
XP_005248345.1. XM_005248288.1. [P10912-4 ]
UniGenei Hs.125180.
Hs.684632.
Hs.688223.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
DisProti DP00033.
ProteinModelPortali P10912.
SMRi P10912. Positions 50-252.
ModBasei Search...

Protein-protein interaction databases

BioGridi 108957. 32 interactions.
DIPi DIP-630N.
IntActi P10912. 21 interactions.
MINTi MINT-1528703.
STRINGi 9606.ENSP00000230882.

Chemistry

ChEMBLi CHEMBL1976.
DrugBanki DB00082. Pegvisomant.
DB00052. Somatropin recombinant.
GuidetoPHARMACOLOGYi 1720.

PTM databases

PhosphoSitei P10912.

Polymorphism databases

DMDMi 121180.

Proteomic databases

PaxDbi P10912.
PRIDEi P10912.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000230882 ; ENSP00000230882 ; ENSG00000112964 . [P10912-1 ]
ENST00000357703 ; ENSP00000350335 ; ENSG00000112964 . [P10912-4 ]
GeneIDi 2690.
KEGGi hsa:2690.
UCSCi uc003jmt.3. human. [P10912-1 ]
uc021xyb.1. human. [P10912-2 ]
uc021xyc.1. human. [P10912-3 ]
uc021xyd.1. human. [P10912-4 ]

Organism-specific databases

CTDi 2690.
GeneCardsi GC05P042429.
HGNCi HGNC:4263. GHR.
MIMi 143890. phenotype.
262500. phenotype.
600946. gene.
604271. phenotype.
neXtProti NX_P10912.
Orphaneti 633. Laron syndrome.
314802. Short stature due to partial GHR deficiency.
PharmGKBi PA28674.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG45313.
HOGENOMi HOG000015773.
HOVERGENi HBG005836.
InParanoidi P10912.
KOi K05080.
OMAi IDFYAQV.
OrthoDBi EOG79W94T.
PhylomeDBi P10912.
TreeFami TF330851.

Enzyme and pathway databases

Reactomei REACT_111133. Growth hormone receptor signaling.
REACT_115697. Prolactin receptor signaling.
SignaLinki P10912.

Miscellaneous databases

EvolutionaryTracei P10912.
GeneWikii Growth_hormone_receptor.
GenomeRNAii 2690.
NextBioi 10636.
PMAP-CutDB P10912.
PROi P10912.
SOURCEi Search...

Gene expression databases

ArrayExpressi P10912.
Bgeei P10912.
CleanExi HS_GHR.
Genevestigatori P10912.

Family and domain databases

Gene3Di 2.60.40.10. 2 hits.
InterProi IPR003961. Fibronectin_type3.
IPR025871. GHBP.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view ]
Pfami PF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view ]
SMARTi SM00060. FN3. 1 hit.
[Graphical view ]
SUPFAMi SSF49265. SSF49265. 2 hits.
PROSITEi PS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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. Cited for: VARIANTS HIS-179; HIS-229; PHE-440; THR-495; LEU-544 AND THR-579.
  25. "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.
  26. "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.
  27. "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: September 3, 2014
This is version 176 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

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