Growth hormone receptor precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Growth hormone receptor
      Short name=GH receptor
Alternative name(s):
    Somatotropin receptor
Cleaved into the following chain:
    1- Recommended name:
            Growth hormone-binding protein
                Short name=GH-binding protein
                Short name=GHBP
        Alternative name(s):
            Serum-binding protein

Gene names

Name:

GHR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	638 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway By similarity. The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling. Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.
Subunit structure	On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain By similarity. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation By similarity. Interacts with ADAM17 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Note= On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway By similarity. Isoform 2: Cell membrane; Single-pass type I membrane protein. Note= Remains fixed to the cell membrane and is not internalized. Growth hormone-binding protein: Secreted.
Tissue specificity	Expressed in various tissues with high expression in liver and skeletal muscle. Isoform 4 is predominantly expressed in kidney, bladder, adrenal gland and brain stem. In the placenta, isoform 1 predominantly expressed in chorion and decidua, isoform 4 highly expressed in villi. Isoform 2 is expressed in lung, stomach and muscle. Low levels in liver.
Domain	The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation. The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP). The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.
Post-translational modification	The soluble form (GHBP) is produced by phorbol ester-promoted proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE. Shedding is inhibited by growth hormone (GH) binding to the receptor probably due to a conformational change in GHR rendering the receptor inaccessible to ADAM17 By similarity. On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2 By similarity. On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization By similarity.
Polymorphism	Genetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia [MIM:143890] patients carrying a mutation in the LDLR gene.
Involvement in disease	Defects in GHR are a cause of Laron dwarfism [MIM:262500]; also known as pituitary dwarfism II; Laron-type pituitary dwarfism I (LTD1) or Laron syndrome (LS). It is the most severe form of growth hormone insensitivity (GHI) characterized by growth impairment, dysmorphic facial features and truncal obesity. Levels of GHBP are low or undetectable in patients with Laron syndrome. Defects in GHR may be a cause of short stature [MIM:604271]. Short stature is defined by a subnormal rate of growth.
Sequence similarities	Belongs to the type I cytokine receptor family. Type 1 subfamily. Contains 1 fibronectin type-III domain.

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Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dwarfism
Domain	Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW growth Traceable author statement. Source: ProtInc skeletal system development Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	growth hormone receptor activity Traceable author statement. Source: ProtInc protein binding Ref.13 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRK	P46108	1	EBI-286316,EBI-886
DUSP7	Q16829	1	EBI-286316,EBI-1265847
GH1	P01241	2	EBI-286316,EBI-1026046
GRB2	P62993	1	EBI-286316,EBI-401755
NCK1	P16333	1	EBI-286316,EBI-389883
Ncoa6	Q9JLI4	1	EBI-286316,EBI-286271	From a different organism.
PIK3R1	P27986	1	EBI-286316,EBI-79464
PLCG1	P19174	1	EBI-286316,EBI-79387
PTPN1	P18031	2	EBI-286316,EBI-968788
PTPN2	P17706	2	EBI-286316,EBI-984930
PTPN3	P26045	2	EBI-286316,EBI-1047946
PTPN9	P43378	1	EBI-286316,EBI-742898
PTPRB	P23467	1	EBI-286316,EBI-1265766
PTPRH	Q9HD43	2	EBI-286316,EBI-1267176

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Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P10912-1) Also known as: GHRfl; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P10912-2) Also known as: GHRtr; GHR1-279; The sequence of this isoform differs from the canonical sequence as follows: 292-297: RIKMLI → SSSSKD 298-638: Missing.
Notes: Remains fixed to the cell membrane and is not internalized.

Isoform 3 (identifier: P10912-3) Also known as: GHR1-277; The sequence of this isoform differs from the canonical sequence as follows: 292-294: RIK → KEN 295-638: Missing.

Isoform 4 (identifier: P10912-4) Also known as: GHRd3; The sequence of this isoform differs from the canonical sequence as follows: 24-24: A → D 25-46: Missing.
Notes: Arises by species-specific retrovirus-mediated alternative splice mimicry.