Proproteinska konvertaza 2

edit

Proproteinska konvertaza, subtilisin/keksin tip 2
Identifikatori
Simboli	PCSK2; NEC2; PC2; SPC2
Vanjski ID	OMIM: 162151 MGI: 97512 HomoloGene: 37640 GeneCards: PCSK2 Gene
EC broj	3.4.21.94
Ontologija gena Molekularna funkcija • aktivnost endopeptidaze serinskog tipa • aktivnost peptidaze • proteinsko vezivanje • aktivnost proproteinske konvertaze 2 • vezivanje proteinskog kompleksa • aktivnost subtilaze Celularna komponenta • membrana • sekretorne granule • ekstracelularni prostor • citoplasmične vezikule • rastvorna frakcija Biološki proces • razvoj nervnog sistema • transformacija ostrvaca amiloidnog polipeptida • transformacija peptidnog hormona • proteinska auto transformacija • proteoliza • enkefalinska transformacija • insulinska transformacija
Ortolozi
Vrsta	Čovek	Miš
Entrez	5126	18549
Ensembl	ENSG00000125851	ENSMUSG00000027419
UniProt	P16519	P21661
RefSeq (mRNA)	NM_002594	NM_008792
RefSeq (protein)	NP_002585	NP_032818
Lokacija (UCSC)	Chr 20: 17.15 - 17.41 Mb	Chr 2: 143.37 - 143.64 Mb
PubMed pretraga	[1]	[2]

Proproteinska konvertaza 2
Identifikatori
EC broj	3.4.21.94
CAS broj	130960-94-0
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB	RCSB PDB PDBe PDBj PDBsum
Ontologija gena	AmiGO / EGO
Pretraga PMC articles PubMed articles NCBI Protein search

Proproteinska konvertaza 2 (PC2), (prohormonska konvertaza 2, neuroendokrinska konvertaza 2 (NEC2)) je serinska proteaza i proproteinska konvertaza PC2. Poput proproteinske konvertaze 1 (PC1), to je enzim odgovoran za prvi korak u maturaciji mnogih neuroendokrinih peptida iz njihovih prekursora, kao što je konverzija proinsulina u insulinske međuprodukte. Da bi se generisala bioaktivna forma insulina (i mnogih drugih peptida), sekundarni korak koji se sastoji od uklanjanja C-terminalnih baznih ostataka je neophodan. Taj korak je posredovan karboksipeptidazama E i/ili D. PC2 ima samo manju ulogu u prvom koraku biosinteze insulina, dok je njegova uloga značajnija u prvom stepenu biosinteze glukagona u poređenju sa PC1. PC2 se vezuje za neuroendokrini protein 7B2, i ako taj protein nije prisutan, proPC2 ne može da postane enzimatski aktivan. 7B2 takođe inhibira PC2 dejstvo dok se 7B2 ne ispreseca u manje neaktivne forme. Stoga je 7B2 aktivator i inhibitor PC2 enzima.

Kod čoveka, proproteinska konvertaza 2 je kodirana PCSK2 genom.^[1] On je srodan sa bakterijskim enzimom subtilisinom. Sve zajedno postoji devet različitih subtilisinu-sličnih gena kod sisara: furin, PACE4, PC4, PC5/6, PC7/8, PCSK9 i SKI1/S1P.

Literatura

1. 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. 

Dodatna literatura

• 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. 
• {{cite journal |author=Zhu X, Lindberg I |title=7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity. |journal=J Cell Biol. |volume=129 |issue= 6 |pages= 1641–50 |year= 1995 |pmid= 7790360| pmc=2291188|

Vanjske veze

• MeSH Proprotein+convertase+2