PCSK6
Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
Proprotein convertase subtilisin/kexin type 6 is an protease that in humans is encoded by the PCSK6 gene which is located in chromosome 15.[5][6] Pcsk6 is a calcium-dependent serine endoprotease that catalyzes the post-translational modification of precursor proteins from its ‘latent’ form to the cleaved ‘active’ form.[5] Active Pcsk6 has been reported to process substrates such as transforming growth factor β,[7] pro-albumin,[8] von Willebrand factor,[9] and corin.[10] Clinically, Pcsk6 is suggested to play a role in left/right asymmetry,[11] structural asymmetry of the brain,[12] handedness,[13][14][15] tumor progression,[16] hemostasis,[9][8][7] and cardiovascular diseases.[10][17]
Function
The protein encoded by this gene belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein is a calcium-dependent serine endoprotease that can cleave precursor protein at their paired basic amino acid processing sites. Some of its substrates are - transforming growth factor beta related proteins,[7] pro-albumin,[8] von Willebrand factor,[9] and corin.[10] Alternatively spliced transcript variants encoding different isoforms have been identified.[6]
Clinical significance
Summarize
Perspective
During development: Throughout development, the spatial and temporal expression of pcsk6 regulates embryogenesis by activating TGFβ related differentiation factors, which include BMP and Nodal.[7][18] Elevated levels of Pcsk6 was detected in maternal decidual cells of the implantation site and the extraembryonic ectoderm.[19] The regulation of proper gradient of Nodal and BMPs is crucial for gastrulation,[20] proximal-distal axis,[21] and establishment of left-right axis patterning.[22]
Developmental Pcsk6 knockout studies found that mice embryos that lack Pcsk6 develop heterotaxia, left pulmonary isomerism, and/or craniofacial malformations due to disruption in specification of anterior-posterior and left-right axis that resulted from the dysregulation of Nodal and BMP signaling.[11]
In humans, Pcsk6 VNTR polymorphism is associated with the structural asymmetry of the frontal and temporal lobe,[12] and degree of handedness.[13][14]
Cardiovascular disease: Pcsk6 is increasing interest as indicator and factor of cardiovascular disease. Pcsk6 KO mice was shown to develop salt-sensitive hypertension due to failure of pro-corin activation crucial to atrial natriuretic peptide regulation of blood pressure.[10] A hypertensive patient was found to have a G/A mutation on the PCSK6 gene that resulted in an Asp282Asn (D282N) substitution at the Pcsk6 catalytic domain, which in turn, hinders corin processing.[10] In vascular remodeling, Pcsk6 was found to induce smooth muscle cell migration in response to PDGFB by activating MMP14.[17] When Pcsk6 was knocked out, the intimal hyperplasia response to in vivo carotid ligation was lowered.[17]
Other: This gene is thought to play a role in tumor progression.[6][16]
References
Further reading
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