prohormone convertase 2

プロホルモン転換酵素2

関

PC2、proprotein convertase 2

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/01 19:49:46」(JST)

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Proprotein convertase subtilisin/kexin type 2
Identifiers
Symbols	PCSK2; NEC 2; NEC-2; NEC2; PC2; SPC2
External IDs	OMIM: 162151 MGI: 97512 HomoloGene: 37640 ChEMBL: 2433 GeneCards: PCSK2 Gene
EC number	3.4.21.94
Gene Ontology Molecular function • serine-type endopeptidase activity • protein binding • protein complex binding Cellular component • extracellular space • membrane • transport vesicle • dendrite • secretory granule lumen • perikaryon Biological process • proteolysis • nervous system development • embryo development • protein autoprocessing • insulin processing • enkephalin processing • islet amyloid polypeptide processing • cellular protein metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5126	18549
Ensembl	ENSG00000125851	ENSMUSG00000027419
UniProt	P16519	P21661
RefSeq (mRNA)	NM_001201528	NM_008792
RefSeq (protein)	NP_001188457	NP_032818
Location (UCSC)	Chr 20: 17.21 – 17.47 Mb	Chr 2: 143.55 – 143.82 Mb
PubMed search	[1]	[2]

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 / EGO
Search PMC articles PubMed articles NCBI proteins

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.

In humans, proprotein convertase 2 is encoded by the PCSK2 gene. 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

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. 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. 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. PMC 2291188. PMID 7790360. 

External links

• Proprotein convertase 2 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 肥満の病因 pathogenesis of obesity
• 2. 心血管疾患の二次予防における脂質低下療法の強度 intensity of lipid lowering therapy in secondary prevention of cardiovascular disease
• 3. 薬剤の効きづらい高コレステロール血症の治療 treatment of drug resistant hypercholesterolemia
• 4. 補体経路 complement pathways
• 5. C3糸球体腎症：デンスデポジット病およびC3糸球体腎炎 c3 glomerulopathies dense deposit disease and c3 glomerulonephritis

English Journal

• Phenotype of entero-endocrine L cells becomes restricted during development.

• Grigoryan M, Kedees MH, Guz Y, Teitelman G.SourceDepartment of Cell Biology, SUNY-Downstate Medical Center, Brooklyn, New York.
• Developmental dynamics : an official publication of the American Association of Anatomists.Dev Dyn.2012 Dec;241(12):1986-92. doi: 10.1002/dvdy.23875. Epub 2012 Oct 29.
• Background: Glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are hormones secreted by L and K cells, respectively, and by LK cells. To characterize L and K cells during development, we examined ileum from embryonic (e)- 12 to e-17. Results: GLP-1 cells were first
• PMID 23027401

• The Neuroendocrine Protein 7B2 Is Intrinsically Disordered.

• Dasgupta I, Sanglas L, Enghild JJ, Lindberg I.SourceDepartment of Anatomy and Neurobiology, School of Medicine, University of Maryland-Baltimore , Baltimore, Maryland 21201, United States.
• Biochemistry.Biochemistry.2012 Sep 14. [Epub ahead of print]
• The small neuroendocrine protein 7B2 has been shown to be required for the productive maturation of proprotein convertase 2 (proPC2) to an active enzyme form; this action is accomplished via its ability to block aggregation of proPC2 into nonactivatable forms. Recent data show that 7B2 can also act
• PMID 22947085

Japanese Journal

• グレリンのプロセシングに関与する酵素とその性質 (内分泌) -- (基礎分野での進歩)

• 児島 将康
• Annual review, 糖尿病・代謝・内分泌 2011, 178-182, 2011
• NAID 40018711559

• 遺伝性肥満 プロホルモン変換酵素1(PC1)遺伝子異常症 (肥満症(第2版)--基礎・臨床研究の進歩) -- (肥満症の疫学・病態・診断学の進歩 症候性肥満--病因,病態,管理法)

• 新谷 光世
• 日本臨床 68(-) (972), 496-500, 2010-02
• NAID 40016964522

Related Links

• Prohormone Convertase 2 | definition of Prohormone ...

PCSK2 A gene on chromosome 20p11.2 that encodes a peptidase S8 family convertase located in secretory granules and involved in processing pairs of basic amino acid residues located on prohormones and other protein ...

• Prohormone Convertase 2 - Handbook of Biologically Active ...

Discovery and General Features Of PC2 Prohormone convertase 2 (PC2) was one of the earliest eukaryotic convertases to be discovered. Hutton and colleagues first showed the presence of two calcium-dependent enzymes in ...

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★リンクテーブル★

リンク元	「プロホルモン転換酵素2」「proprotein convertase 2」「PC2」
関連記事	「prohormone」「convertase」「prohormone convertase」

「プロホルモン転換酵素2」

　　[★]

英

prohormone convertase 2、PC2

関

プロタンパク質転換酵素2

「proprotein convertase 2」

　　[★]

プロタンパク質転換酵素2

関

prohormone convertase 2

「PC2」

　　[★]

• プロホルモン転換酵素2

関

prohormone convertase 2

「prohormone」

　　[★]

• プロホルモン、ホルモン前駆体

「convertase」

　　[★]

コンバターゼ、転換酵素

「prohormone convertase」

　　[★] プロホルモン変換酵素