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.[5]
In humans, proprotein convertase 2 is encoded by the PCSK2gene.[6] 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.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000125851 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000027419 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Gomez-Saladin E, Wilson DL, Dickerson IM (1994). "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. doi:10.1007/bf02088586. PMID 7954663. S2CID 43015859.
^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 readingedit
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. PMC2752824. 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. PMC2657564. 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. PMC2734493. 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. Bibcode:2001Natur.414..865D. 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. PMC1221959. 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. PMC4155744. 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. CiteSeerX10.1.1.621.1259. doi:10.1016/S0306-4522(03)00560-8. PMID 14614908. S2CID 16055552.
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. PMC1310616. 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. S2CID 21101668.
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/endo.141.9.7674. 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. PMC528928. 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. S2CID 22849623.
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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. 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. PMC2291188. PMID 7790360.
External linksedit
Proprotein+convertase+2 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
proprotein, convertase, also, known, prohormone, convertase, neuroendocrine, convertase, nec2, serine, protease, proprotein, convertase, like, proprotein, convertase, enzyme, responsible, first, step, maturation, many, neuroendocrine, peptides, from, their, pr. 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 5 PCSK2IdentifiersAliasesPCSK2 NEC 2 NEC 2 NEC2 PC2 SPC2 proprotein convertase subtilisin kexin type 2External IDsOMIM 162151 MGI 97512 HomoloGene 37640 GeneCards PCSK2Gene location Human Chr Chromosome 20 human 1 Band20p12 1Start17 226 107 bp 1 End17 484 578 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 G1 2 70 89 cMStart143 388 076 bp 2 End143 658 205 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inislet of LangerhansBrodmann area 23right lobe of thyroid glandRegion I of hippocampus properendothelial cellmiddle temporal gyrussuperior frontal gyrusBrodmann area 46orbitofrontal cortexentorhinal cortexTop expressed inislet of Langerhansmedial dorsal nucleushabenulaprimary motor cortexmammillary bodyolfactory tuberclelateral geniculate nucleusprefrontal cortexmedial geniculate nucleusventromedial nucleusMore reference expression dataBioGPSn aGene ontologyMolecular functionendopeptidase activity peptidase activity protein binding serine type peptidase activity hydrolase activity serine type endopeptidase activity protein containing complex bindingCellular componentperikaryon membrane transport vesicle secretory granule neuronal cell body dendrite secretory granule lumen cytoplasmic vesicle extracellular space nucleus intracellular membrane bounded organelle extracellular region neuron projectionBiological processprotein processing insulin processing protein autoprocessing nervous system development proteolysis enkephalin processing islet amyloid polypeptide processing peptide hormone processingSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez512618549EnsemblENSG00000125851ENSMUSG00000027419UniProtP16519P21661RefSeq mRNA NM 002594NM 001201528NM 001201529NM 008792RefSeq protein NP 001188457NP 001188458NP 002585NP 032818Location UCSC Chr 20 17 23 17 48 MbChr 2 143 39 143 66 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouseproprotein convertase 2IdentifiersEC no 3 4 21 94CAS no 130960 94 0DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteinsIn humans proprotein convertase 2 is encoded by the PCSK2 gene 6 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 edit a b c GRCh38 Ensembl release 89 ENSG00000125851 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000027419 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Gomez Saladin E Wilson DL Dickerson IM 1994 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 doi 10 1007 bf02088586 PMID 7954663 S2CID 43015859 Seidah NG Mattei MG Gaspar L Benjannet S Mbikay M Chretien 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 editLeak 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 Bibcode 2001Natur 414 865D doi 10 1038 414865a PMID 11780052 Mbikay M Seidah NG Chretien 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 CiteSeerX 10 1 1 621 1259 doi 10 1016 S0306 4522 03 00560 8 PMID 14614908 S2CID 16055552 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 S2CID 21101668 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 endo 141 9 7674 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 lt 63 AID MC1 gt 3 0 CO 2 C PMID 10900462 S2CID 22849623 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 Bibcode 2002PNAS 9916899M 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 editProprotein convertase 2 at the U S National Library of Medicine Medical Subject Headings MeSH Portal nbsp Biology nbsp This hydrolase article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Proprotein convertase 2 amp oldid 1188064919, wikipedia, wiki, book, books, library,
