GHR_HUMAN » Growth hormone receptor

GHR_HUMAN » Growth hormone receptor
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
GHR_HUMAN » Growth hormone receptor » GH receptor; Somatotropin receptor;
Hydrophobic Thickness 38.8 ± 1.4 Å
Tilt Angle 1 ± 0°
ΔGtransfer -62.4 kcal/mol
ΔGfold -25.5 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 263-290 (260-293)
Pathways

Cytokine-cytokine receptor interaction (KEGG)

Immune System (Reactome)

Jak-STAT signaling pathway (KEGG)

Neuroactive ligand-receptor interaction (KEGG)

PI3K-Akt signaling pathway (KEGG)

Signal Transduction (Reactome)

PDB 2aew (47-251), 1kf9 (B/C/E/F=19-256), 1hwg (B/C=19-255), 3hhr (B/C=50-254), 1axi (B=19-254), 1hwh (B=19-255), 1a22 (B=19-256)
OPM none
Complexes none
Interactions

IGF1R, Complex: IGF1R:GHR:JAK2, PubMed

PRLR, Complex: GHR:PRLR, PubMed

PTN2, Complex: GHR:PTN2, PubMed

PTPRB, Complex: PTPRB:GHR, PubMed

PTPRC, Complex: GHR:PTPRC

PTPRH, Complex: GHR:PTPRH, PubMed

PTPRJ, Complex: GHR:PTPRJ

PTPRK, Complex: GHR:PTPRK

Domains

AA: 43-144, PDBID: 1A22, Subunit B, Seq Identity:100%, Erythropoietin receptor, ligand binding

AA: 159-244, PDBID: 1A22, Subunit B, Seq Identity:100%, Fibronectin type III domain

AA: 316-617, Growth hormone receptor binding

UniProt annotation for GHR_HUMAN » Growth hormone receptor
FUNCTION: Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity).

FUNCTION: The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.

FUNCTION: Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.

SUBUNIT: 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.

TISSUE SPECIFICITY: Expressed in various tissues with high expression in liver and skeletal muscle. Isoform 4 is predominantly expressed in kidney, bladder, adrenal gland and brain stem. Isoform 1 expression in placenta is predominant in chorion and decidua. Isoform 4 is highly expressed in placental villi. Isoform 2 is expressed in lung, stomach and muscle. Low levels in liver.

DOMAIN: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding.

DOMAIN: The box 1 motif is required for JAK interaction and/or activation.

DOMAIN: The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).

DOMAIN: The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.

DISEASE: Laron syndrome (LARS) OMIM: 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. disease is caused by mutations affecting the gene represented in this entry.

DISEASE: Growth hormone insensitivity, partial (GHIP) OMIM: A 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. caused by mutations affecting the gene represented in this entry.

UniProt features for GHR_HUMAN » Growth hormone receptor
SIGNAL 1 18 Potential.
CHAIN 19 638 Growth hormone receptor.
CHAIN 19 256 Growth hormone-binding protein (By similarity).
DOMAIN 149 251 Fibronectin type-III.
REGION 260 262 Required for ADAM17-mediated proteolysis (By similarity).
MOTIF 240 244 WSXWS motif.
MOTIF 297 305 Box 1 motif.
MOTIF 340 349 UbE motif.
SITE 345 345 Required for endocytosis and down- regulation (By similarity).
DISULFID 56 66
DISULFID 101 112
DISULFID 126 140
Amino Acid Sequence for GHR_HUMAN » Growth hormone receptor
MDLWQLLLTL ALAGSSDAFS GSEATAAILS RAPWSLQSVN PGLKTNSSKE PKFTKCRSPE RETFSCHWTD EVHHGTKNLG PIQLFYTRRN TQEWTQEWKE CPDYVSAGEN SCYFNSSFTS IWIPYCIKLT SNGGTVDEKC FSVDEIVQPD PPIALNWTLL NVSLTGIHAD IQVRWEAPRN ADIQKGWMVL EYELQYKEVN ETKWKMMDPI LTTSVPVYSL KVDKEYEVRV RSKQRNSGNY GEFSEVLYVT LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QRIKMLILPP VPVPKIKGID PDLLKEGKLE EVNTILAIHD SYKPEFHSDD SWVEFIELDI DEPDEKTEES DTDRLLSSDH EKSHSNLGVK DGDSGRTSCC EPDILETDFN ANDIHEGTSE VAQPQRLKGE ADLLCLDQKN QNNSPYHDAC PATQQPSVIQ AEKNKPQPLP TEGAESTHQA AHIQLSNPSS LSNIDFYAQV SDITPAGSVV LSPGQKNKAG MSQCDMHPEM VSLCQENFLM DNAYFCEADA KKCIPVAPHI KVESHIQPSL NQEDIYITTE SLTTAAGRPG TGEHVPGSEM PVPDYTSIHI VQSPQGLILN ATALPLPDKE FLSSCGYVST DQLNKIMP