Biology:Proprotein convertase 2
 Generic protein structure example |
| proprotein convertase 2 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 3.4.21.94 | ||||||||
| CAS number | 130960-94-0 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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Proprotein convertase 2 (PC2) also known as prohormone convertase 2 or neuroendocrine convertase 2 (NEC2) is a serine protease and proprotein convertase PC2, like proprotein convertase 1 (PC1), is an enzyme responsible for the first step in the maturation of many neuroendocrine peptides from their precursors, such as the conversion of proinsulin to insulin intermediates. To generate the bioactive form of insulin (and many other peptides), a second step involving the removal of C-terminal basic residues is required; this step is mediated by carboxypeptidases E and/or D. PC2 plays only a minor role in the first step of insulin biosynthesis, but a greater role in the first step of glucagon biosynthesis compared to PC1. PC2 binds to the neuroendocrine protein named 7B2, and if this protein is not present, proPC2 cannot become enzymatically active. 7B2 accomplishes this by preventing the aggregation of proPC2 to inactivatable forms. The C-terminal domain of 7B2 also inhibits PC2 activity until it is cleaved into smaller inactive forms that lack carboxy-terminal basic residues. Thus, 7B2 is both an activator and an inhibitor of PC2. PC2 has been identified in a number of animals, including C. elegans.[1]
In humans, proprotein convertase 2 is encoded by the PCSK2 gene.[2] It is related to the bacterial enzyme subtilisin, and altogether there are 9 different subtilisin-like genes in mammals: furin, PACE4, PC4, PC5/6, PC7/8, PCSK9, and SKI1/S1P.
References
- ↑ "Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans". Cellular and Molecular Neurobiology 14 (1): 9–25. 1994. doi:10.1007/bf02088586. PMID 7954663.
- ↑ "Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region)". Genomics 11 (1): 103–7. September 1991. doi:10.1016/0888-7543(91)90106-O. PMID 1765368.
Further reading
- "Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population.". Mol. Genet. Metab. 92 (1–2): 145–50. 2007. doi:10.1016/j.ymgme.2007.05.014. PMID 17618154.
- "Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals.". Am. J. Hypertens. 23 (1): 70–7. 2010. doi:10.1038/ajh.2009.190. PMID 19851296.
- "Genome-wide association study of biochemical traits in Korcula Island, Croatia.". Croat. Med. J. 50 (1): 23–33. 2009. doi:10.3325/cmj.2009.50.23. PMID 19260141.
- "Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter.". Am. J. Physiol. Endocrinol. Metab. 288 (1): E236–45. 2005. doi:10.1152/ajpendo.00144.2004. PMID 15585599.
- "The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6.". Endocrinology 149 (4): 1600–8. 2008. doi:10.1210/en.2007-0278. PMID 18096669.
- "The DNA sequence and comparative analysis of human chromosome 20.". Nature 414 (6866): 865–71. 2001. doi:10.1038/414865a. PMID 11780052. Bibcode: 2001Natur.414..865D.
- "Neuroendocrine secretory protein 7B2: structure, expression and functions.". Biochem. J. 357 (Pt 2): 329–42. 2001. doi:10.1042/0264-6021:3570329. PMID 11439082.
- "Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head.". Invest. Ophthalmol. Vis. Sci. 50 (12): 5759–68. 2009. doi:10.1167/iovs.08-2616. PMID 19339735.
- "The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease.". Neuroscience 122 (2): 437–47. 2003. doi:10.1016/S0306-4522(03)00560-8. PMID 14614908.
- "The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site.". Diabetes 50 (3): 534–9. 2001. doi:10.2337/diabetes.50.3.534. PMID 11246872.
- "Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases.". BMC Cancer 5: 149. 2005. doi:10.1186/1471-2407-5-149. PMID 16293189.
- "Comparative tissue distribution of the processing enzymes "prohormone thiol protease," and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocrine tissues.". Endocrine 15 (2): 217–24. 2001. doi:10.1385/ENDO:15:2:217. PMID 11720250.
- "[Analysis of the gene encoding human PC2, a prohormone processing enzyme]". Nippon Rinsho 52 (10): 2544–9. 1994. PMID 7983775.
- "Interactions between the prohormone convertase 2 promoter and the thyroid hormone receptor.". Endocrinology 141 (9): 3256–66. 2000. doi:10.1210/endo.141.9.7674. PMID 10965896.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Association of gene polymorphisms with chronic kidney disease in Japanese individuals.". Int. J. Mol. Med. 24 (4): 539–47. 2009. doi:10.3892/ijmm_00000263. PMID 19724895.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "The proprotein convertases furin and PACE4 play a significant role in tumor progression.". Mol. Carcinog. 28 (2): 63–9. 2000. doi:10.1002/1098-2744(200006)28:2<63::AID-MC1>3.0.CO;2-C. PMID 10900462.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Production of n-octanoyl-modified ghrelin in cultured cells requires prohormone processing protease and ghrelin O-acyltransferase, as well as n-octanoic acid.". J. Biochem. 146 (5): 675–82. 2009. doi:10.1093/jb/mvp112. PMID 19628676.
- "7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity.". J. Cell Biol. 129 (6): 1641–50. 1995. doi:10.1083/jcb.129.6.1641. PMID 7790360.
External links
- Proprotein+convertase+2 at the US National Library of Medicine Medical Subject Headings (MeSH)
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