Proprotein convertase 2: Difference between revisions
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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. Thus, 7B2 is both an activator and an inhibitor of PC2. | '''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. Thus, 7B2 is both an activator and an inhibitor of PC2. PC2 has been identified in a number of animals, including ''C. elegans''<ref>Gomez-Saladin, E., Wilson, DL., and Dickerson, IM. 1994. Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans. Cellualr and Molecular Neurobiology 14(1): 9-25</ref>. | ||
In humans, proprotein convertase 2 is encoded by the ''PCSK2'' [[gene]].<ref name="pmid1765368">{{cite journal |vauthors=Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, Chrétien M | title = 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) | journal = Genomics | volume = 11 | issue = 1 | pages = 103–7 |date=September 1991 | pmid = 1765368 | doi = 10.1016/0888-7543(91)90106-O | url = | issn = }}</ref> It is related to the bacterial enzyme subtilisin, and altogether there are 9 different subtilisin-like genes in mammals: [[furin]], [[PCSK6|PACE4]], [[PCSK4|PC4]], [[PCSK5|PC5/6]], [[PCSK7|PC7/8]], [[PCSK9]], and [[MBTPS1|SKI1/S1P]]. | In humans, proprotein convertase 2 is encoded by the ''PCSK2'' [[gene]].<ref name="pmid1765368">{{cite journal |vauthors=Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, Chrétien M | title = 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) | journal = Genomics | volume = 11 | issue = 1 | pages = 103–7 |date=September 1991 | pmid = 1765368 | doi = 10.1016/0888-7543(91)90106-O | url = | issn = }}</ref> It is related to the bacterial enzyme subtilisin, and altogether there are 9 different subtilisin-like genes in mammals: [[furin]], [[PCSK6|PACE4]], [[PCSK4|PC4]], [[PCSK5|PC5/6]], [[PCSK7|PC7/8]], [[PCSK9]], and [[MBTPS1|SKI1/S1P]]. | ||
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*{{cite journal |vauthors=Deloukas P, Matthews LH, Ashurst J, etal |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865–71 |year= 2001|pmid= 11780052 |doi= 10.1038/414865a }} | *{{cite journal |vauthors=Deloukas P, Matthews LH, Ashurst J, etal |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865–71 |year= 2001|pmid= 11780052 |doi= 10.1038/414865a }} | ||
*{{cite journal |vauthors=Mbikay M, Seidah NG, Chrétien M |title=Neuroendocrine secretory protein 7B2: structure, expression and functions. |journal=Biochem. J. |volume=357 |issue= Pt 2 |pages= 329–42 |year= 2001 |pmid= 11439082 |doi= 10.1042/0264-6021:3570329|pmc=1221959 }} | *{{cite journal |vauthors=Mbikay M, Seidah NG, Chrétien M |title=Neuroendocrine secretory protein 7B2: structure, expression and functions. |journal=Biochem. J. |volume=357 |issue= Pt 2 |pages= 329–42 |year= 2001 |pmid= 11439082 |doi= 10.1042/0264-6021:3570329|pmc=1221959 }} | ||
*{{cite journal |vauthors=Fuller JA, Brun-Zinkernagel AM, Clark AF, Wordinger RJ |title=Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head. |journal=Invest. Ophthalmol. Vis. Sci. |volume=50 |issue= 12 |pages= 5759–68 |year= 2009 |pmid= 19339735 |doi= 10.1167/iovs.08-2616 }} | *{{cite journal |vauthors=Fuller JA, Brun-Zinkernagel AM, Clark AF, Wordinger RJ |title=Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head. |journal=Invest. Ophthalmol. Vis. Sci. |volume=50 |issue= 12 |pages= 5759–68 |year= 2009 |pmid= 19339735 |doi= 10.1167/iovs.08-2616 |pmc=4155744 }} | ||
*{{cite journal |vauthors=Winsky-Sommerer R, Grouselle D, Rougeot C, etal |title=The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease. |journal=Neuroscience |volume=122 |issue= 2 |pages= 437–47 |year= 2003 |pmid= 14614908 |doi=10.1016/S0306-4522(03)00560-8 }} | *{{cite journal |vauthors=Winsky-Sommerer R, Grouselle D, Rougeot C, etal |title=The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease. |journal=Neuroscience |volume=122 |issue= 2 |pages= 437–47 |year= 2003 |pmid= 14614908 |doi=10.1016/S0306-4522(03)00560-8 }} | ||
*{{cite journal |vauthors=Wang J, Xu J, Finnerty J, etal |title=The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site. |journal=Diabetes |volume=50 |issue= 3 |pages= 534–9 |year= 2001 |pmid= 11246872 |doi=10.2337/diabetes.50.3.534 }} | *{{cite journal |vauthors=Wang J, Xu J, Finnerty J, etal |title=The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site. |journal=Diabetes |volume=50 |issue= 3 |pages= 534–9 |year= 2001 |pmid= 11246872 |doi=10.2337/diabetes.50.3.534 }} | ||
Revision as of 15:55, 26 September 2018
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| EC number | 3.4.21.94 | ||||||||
| CAS number | 130960-94-0 | ||||||||
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| MetaCyc | metabolic pathway | ||||||||
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| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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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. 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
- ↑ Gomez-Saladin, E., Wilson, DL., and Dickerson, IM. 1994. Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans. Cellualr and Molecular Neurobiology 14(1): 9-25
- ↑ Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, Chrétien M (September 1991). "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. doi:10.1016/0888-7543(91)90106-O. PMID 1765368.
Further reading
- Leak TS, Keene KL, Langefeld CD, et al. (2007). "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. doi:10.1016/j.ymgme.2007.05.014. PMC 2752824. PMID 17618154.
- Oguri M, Kato K, Yokoi K, et al. (2010). "Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals". Am. J. Hypertens. 23 (1): 70–7. doi:10.1038/ajh.2009.190. PMID 19851296.
- Zemunik T, Boban M, Lauc G, et al. (2009). "Genome-wide association study of biochemical traits in Korcula Island, Croatia". Croat. Med. J. 50 (1): 23–33. doi:10.3325/cmj.2009.50.23. PMC 2657564. PMID 19260141.
- Shen X, Li QL, Brent GA, Friedman TC (2005). "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. doi:10.1152/ajpendo.00144.2004. PMID 15585599.
- Rehfeld JF, Bundgaard JR, Hannibal J, et al. (2008). "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. doi:10.1210/en.2007-0278. PMC 2734493. PMID 18096669.
- Deloukas P, Matthews LH, Ashurst J, et al. (2001). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
- Mbikay M, Seidah NG, Chrétien M (2001). "Neuroendocrine secretory protein 7B2: structure, expression and functions". Biochem. J. 357 (Pt 2): 329–42. doi:10.1042/0264-6021:3570329. PMC 1221959. PMID 11439082.
- Fuller JA, Brun-Zinkernagel AM, Clark AF, Wordinger RJ (2009). "Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head". Invest. Ophthalmol. Vis. Sci. 50 (12): 5759–68. doi:10.1167/iovs.08-2616. PMC 4155744. PMID 19339735.
- Winsky-Sommerer R, Grouselle D, Rougeot C, et al. (2003). "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. doi:10.1016/S0306-4522(03)00560-8. PMID 14614908.
- Wang J, Xu J, Finnerty J, et al. (2001). "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. doi:10.2337/diabetes.50.3.534. PMID 11246872.
- Tzimas GN, Chevet E, Jenna S, et al. (2005). "Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases". BMC Cancer. 5: 149. doi:10.1186/1471-2407-5-149. PMC 1310616. PMID 16293189.
- Deftos LJ, Burton D, Hastings RH, et al. (2001). "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. doi:10.1385/ENDO:15:2:217. PMID 11720250.
- Ohagi S, Yoshida H, Nanjo K (1994). "[Analysis of the gene encoding human PC2, a prohormone processing enzyme]". Nippon Rinsho. 52 (10): 2544–9. PMID 7983775.
- Li QL, Jansen E, Brent GA, et al. (2000). "Interactions between the prohormone convertase 2 promoter and the thyroid hormone receptor". Endocrinology. 141 (9): 3256–66. doi:10.1210/en.141.9.3256. PMID 10965896.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Yoshida T, Kato K, Yokoi K, et al. (2009). "Association of gene polymorphisms with chronic kidney disease in Japanese individuals". Int. J. Mol. Med. 24 (4): 539–47. doi:10.3892/ijmm_00000263. PMID 19724895.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Bassi DE, Mahloogi H, Klein-Szanto AJ (2000). "The proprotein convertases furin and PACE4 play a significant role in tumor progression". Mol. Carcinog. 28 (2): 63–9. doi:10.1002/1098-2744(200006)28:2<63::AID-MC1>3.0.CO;2-C. PMID 10900462.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Takahashi T, Ida T, Sato T, et al. (2009). "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. doi:10.1093/jb/mvp112. PMID 19628676.
- Zhu X, Lindberg I (1995). "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. doi:10.1083/jcb.129.6.1641. PMC 2291188. PMID 7790360.
External links
- Proprotein+convertase+2 at the US National Library of Medicine Medical Subject Headings (MeSH)
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