Ghr
Developmental stage
During gestation, both hepatic and serum expression begins at day 9 (PubMed:12379490). Levels increased 8-fold in liver and 30-fold in serum by late gestation (PubMed:12379490). Levels of isoform 1 and isoform 2 similarly begin at day 9 with isoform 1 expression reaching maximum levels by day 13, isoform 2 levels continue to increase until the end of pregnancy (PubMed:12379490).
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.
Function
Receptor for pituitary gland growth hormone (GH1) involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway.
Growth hormone-binding protein
The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.
Post-translational modifications
The soluble form (GHBP) is produced by phorbol ester-promoted proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE (By similarity). 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.
Ubiquitinated by the ECS(SOCS2) complex following ligand-binding and phosphorylation by JAK2, leading to its degradation by the proteasome (PubMed:21980433). Regulation by the ECS(SOCS2) complex acts as a negative feedback loop of growth hormone receptor signaling (PubMed:21980433). Ubiquitination is not sufficient for GHR internalization (By similarity).
Sequence Similarities
Belongs to the type I cytokine receptor family. Type 1 subfamily.
Tissue Specificity
Expressed in all tissues tested including, liver, heart, adipose tissue, mammary gland, testes, ovary, brain, kidney and muscle. Highest levels in liver.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway.
- Growth hormone-binding protein
- Secreted
- Complexed to a substantial fraction of circulating GH.
Alternative names
Growth hormone receptor, GH receptor, Somatotropin receptor, Ghr