A wide variety of biologically important polypeptides including hormones, enzymes, and receptors are initially synthesized
as large inactive precursors. To release the active component(s), these precursors must undergo limited proteolysis at pairs
of basic residues by specific convertases. There is, for example, a diarginyl-specific proalbumin convertase . Three mammalian convertases, PC1 (PCSK1), PC2 (PCSK2), and furin ,
belonging to the family of serine proteinases of the subtilisin family, are prohormone and proprotein convertases.
NCBI Summary:
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]
General function
Enzyme, Hydrolase, Peptidase/Protease
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Oogenesis, Oocyte maturation
Comment
Dai G, et al 1995 reported the characterization of multiple prohormone convertase PC1/3 transcripts in
porcine ovary.
Overlapping cDNAs encoding porcine prohormone convertase, PC1/3, have been isolated from a
pregnant sow ovary cDNA library using a mouse PC1/3 cDNA as a probe. Nucleotide sequence
analysis of these cDNAs predicts a PC1/3 precursor protein of 753 amino acid residues, which shares
an overall sequence homology of 96, 92, and 92% with the human, rat, and mouse counterparts,
respectively.
Gene whose expression is detected by cDNA array hybridization: transcription factors, cell signaling and extracellular communication. Also, relative transcript level reproducibly decreases during IVM Rozenn Dalbi?Tran and Pascal Mermilloda
Expression regulated by
Comment
Ovarian localization
Luteal cells, Large luteal cells
Comment
Renegar RH, et al 2000 reported the expression and localization of prohormone convertase 1/3 (SPC3)
in porcine ovary.
Tissue distribution and cellular localization of PC1/3 mRNA in porcine tissues
were examined by ribonuclease protection assay and in situ hybridization.
PC1/3 mRNA was detected mainly in the corpus luteum of pregnant sow and brain.
Within the ovary, PC1/3 and relaxin transcripts colocalized within large
luteal cells. Levels of PC1/3 transcripts in corpora lutea increased as
gestation advanced, parallel with an observed increase in relaxin transcripts.
Follicle stages
Corpus luteum
Comment
Phenotypes
Mutations
2 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: infertile - ovarian defect Comment: Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. O'Rahilly et al. (1995) reported a case of a third disorder. The patient, a 43-year-old woman, was referred for the evaluation
of symptoms suggestive of postprandial hypoglycemia. She had a history of severe childhood obesity, with weight of 36 kg at
the age of 3 years, for which she had been treated successfully with diet. Development of secondary sexual characteristics
was normal but she did not begin menstruating. Studies at the age of 21 detected no cause of her primary amenorrhea. At the
age of 30, ovulation was induced with gonadotropins.
Species: human
Mutation name: type: naturally occurring fertility: fertile Comment: Evaluation of PCSK9 levels and its genetic polymorphisms in women with polycystic ovary syndrome. Xavier LB et al. (2017) Dyslipidemia is one of the common metabolic disorders in Polycystic Ovary Syndrome (PCOS). Proprotein convertase subtilisin kexin type 9 (PCSK9) is a new component of lipid metabolism and correlated to the development of dyslipidemia and atherosclerosis. This protein acts by preventing the recycling of LDL receptors (LDL-r) back to the cell surface and thus generates higher levels of LDLc. The objective of this study was to evaluate the PCSK9 polymorphisms rs505151 (c.2009A>G), rs562556 (c.1420A>G) and rs11206510 (T>C) and plasma PCSK9 levels in PCOS. A group of women with PCOS (n=97), and a group of healthy women (control, n=99) were selected. Biochemical parameters were determined by using Vitros system and polymorphisms were assessed by TaqMan SNP Genotyping Assays. Plasma PCSK9 levels or PCSK9 polymorphisms were not associated with PCOS. The genotype rs11206510TT was associated with higher levels of PCSK9 in both groups. The population investigated (PCOS+control groups) with the rs505151AA genotype presented higher HDLc levels. The GG genotype regarding rs562556 polymorphism was associated with higher HDLc in PCOS group, while the AA genotype carriers had higher plasma testosterone levels when evaluated all women in a same group. The results were the same by comparing recessive and dominant model despite PCOS or both groups altogether. Our results suggest that PCSK9 is not altered specifically in PCOS, but it could be associated with in lipid and androgen metabolism in Brazilian women.//////////////////