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P10912

- GHR_HUMAN

UniProt

P10912 - GHR_HUMAN

Protein

Growth hormone receptor

Gene

GHR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 177 (01 Oct 2014)
      Sequence version 1 (01 Jul 1989)
      Previous versions | rss
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    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. 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

    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. cartilage development involved in endochondral bone morphogenesis Source: Ensembl
    6. cellular response to hormone stimulus Source: BHF-UCL
    7. cellular response to insulin stimulus Source: Ensembl
    8. citrate metabolic process Source: BHF-UCL
    9. creatine metabolic process Source: BHF-UCL
    10. creatinine metabolic process Source: BHF-UCL
    11. endocytosis Source: UniProtKB-KW
    12. fatty acid metabolic process Source: BHF-UCL
    13. growth hormone receptor signaling pathway Source: BHF-UCL
    14. hormone-mediated signaling pathway Source: Ensembl
    15. insulin-like growth factor receptor signaling pathway Source: BHF-UCL
    16. isoleucine metabolic process Source: BHF-UCL
    17. JAK-STAT cascade Source: BHF-UCL
    18. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
    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

    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

    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

    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.9 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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. 1 Publication
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 – 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

    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

    ArrayExpressiP10912.
    BgeeiP10912.
    CleanExiHS_GHR.
    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 – 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP10912.

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei265 – 28824HelicalSequence AnalysisAdd
    BLAST

    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.
    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. 1 Publication
    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. 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:
    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...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108957. 32 interactions.
    DIPi DIP-630N.
    IntActi P10912. 23 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: October 1, 2014
    This is version 177 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