Growth hormone-binding protein

[5] A precursor messenger RNA (mRNA) from the complete gene first is transcribed and then spliced to encode the full receptor protein.

Exons are peptide encoding regions of DNA genes that remain in the transcript after splicing and during the maturation of mRNA.

is postulated to play a significant role in the post-translational processing activity that sheds GHBP from GHR.

[18] When growth hormone is bound to two dimerized GH receptors, the shedding activity is inhibited.

[17][19] In humans, studies have shown that alternative splicing of the GHR gene can lead to increased rates of proteolysis.

[24] Growth hormone binds to GHBP and GHR via an interactive region of helices 1 and 4 of GH.

[4] Additionally, current literature provides evidence that the carrier-protein prolongs the half-life of growth hormone through its binding with the ligand.

[18][35] Studies have identified a GHBP isoform that exists due to gene polymorphism, or variable expression of the allele.

The presence or absence of exon 3 in humans is individual-specific, but one study suggests that gender may play a role in this variable splicing, as females were shown to express higher levels of deleted-exon 3 GHBP in their blood.

"Receptor Ectodomain Shedding" - Tumor-necrosis factor alpha converting enzyme (T.A.C.E.) proteolytically cleaves the extracellular domain off of (two) growth hormone receptor(s) to release the soluble carrier-protein growth hormone-binding protein. Adapted from Fisker. [ 7 ]
Two growth hormone-binding proteins (blue, pink) in a two-to-one ratio with growth hormone (green). Source: PDB 1HWG
Growth-hormone binding protein (blue) in a one-to-one ratio with modified growth hormone (green). Source: PDB 1HWH