proprotein convertase 2

プロタンパク質転換酵素2

関

prohormone convertase 2

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/25 16:50:48」(JST)

wiki en

[Wiki en表示]

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. LDLコレステロール代謝の遺伝性疾患 inherited disorders of ldl cholesterol metabolism
• 2. 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
• 3. 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
• 4. 病院における医療の近況 whats new in hospital medicine
• 5. 老年医学の新機能 whats new in geriatrics

English Journal

• [Differentiation of bone marrow mesenchymal stem cells into insulin producing cells induced by rat injured pancreatic tissue extract].

• Fei Y, Xie H, Wang Y, Qi H, Deng C, Ren L, Li F.
• Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery.Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi.2014 May;28(5):625-32.
• OBJECTIVE: To investigate the effects and mechanisms of differentiation of bone marrow mesenchymal stem cells (BMSCs) into insulin producing cells (IPCs) induced by injured pancreatic tissue extract of rat.METHODS: Eighty 6-week-old Sprague Dawley rats were selected. Forty rats underwent removal of
• PMID 25073286

• Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis.

• Jones HB1, Reens J, Brocklehurst SR, Betts CJ, Bickerton S, Bigley AL, Jenkins RP, Whalley NM, Morgan D, Smith DM.
• International journal of experimental pathology.Int J Exp Pathol.2014 Feb;95(1):29-48. doi: 10.1111/iep.12066.
• Antagonism of the effects of glucagon as an adjunct therapy with other glucose-lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is a
• PMID 24456331

• Modulation of circadian glucocorticoid oscillation via adrenal opioid-CXCR7 signaling alters emotional behavior.

• Ikeda Y1, Kumagai H, Skach A, Sato M, Yanagisawa M.
• Cell.Cell.2013 Dec 5;155(6):1323-36. doi: 10.1016/j.cell.2013.10.052.
• Circulating glucocorticoid levels oscillate with a robust circadian rhythm, yet the physiological relevance of this rhythmicity remains unclear. Here, we show that modulation of circadian glucocorticoid oscillation by enhancing its amplitude leads to anxiolytic-like behavior. We observed that mice w
• PMID 24315101

Japanese Journal

• Crucial role of the Rap G protein signal in Notch activation and leukemogenicity of T-cell acute lymphoblastic leukemia.

• Doi Keiko,Imai Takahiko,Kressler Christopher,Yagita Hideo,Agata Yasutoshi,Vooijs Marc,Hamazaki Yoko,Inoue Joe,Minato Nagahiro
• Scientific reports 5, 2015-01-23
• … Inhibition of the Rap1 prenylation with a geranylgeranyl transferase inhibitor abrogated its membrane-anchoring to Golgi-network and caused reduced proprotein convertase activity required for Adam10 maturation. …
• NAID 120005555511

• Report of the American College of Cardiology (ACC) Scientific Sessions 2015, San Diego

• Murohara Toyoaki
• Circulation Journal 79(6), 1193-1198, 2015
• The 64thAnnual Scientific Sessions and Exposition of the American College of Cardiology (ACC) were held at the San Diego Convention Center from March 14–16, 2015. The ACC Scientific Sessions are 1 of …
• NAID 130005073129

• Report of the American College of Cardiology (ACC) Scientific Sessions 2015, San Diego

• Murohara Toyoaki
• Circulation Journal advpub(0), 2015
• The 64thAnnual Scientific Sessions and Exposition of the American College of Cardiology (ACC) were held at the San Diego Convention Center from March 14–16, 2015. The ACC Scientific Sessions are 1 of …
• NAID 130005068483

Related Links

• Proprotein convertase - WIKI 2. Wikipedia Republished

Proprotein convertases are a family of proteins that activate other proteins. Many proteins are inactive when they are first synthesized, because they contain chains of amino acids that block their activity. Proprotein convertases ...

• Proprotein Convertase 2 - Handbook of Proteolytic Enzymes ...

The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contai ... Summary The third edition of the Handbook of Proteolytic ...

---

★リンクテーブル★

リンク元	「prohormone convertase 2」「プロタンパク質転換酵素2」
関連記事	「proprotein convertase」「convertase」

「prohormone convertase 2」

　　[★]

プロホルモン転換酵素2

関

PC2、proprotein convertase 2

「プロタンパク質転換酵素2」

　　[★]

英

proprotein convertase 2

関

プロホルモン転換酵素2

「proprotein convertase」

　　[★]

プロタンパク質転換酵素、前駆タンパク質転換酵素

「convertase」

　　[★]

コンバターゼ、転換酵素