Proproteinska konvertaza 2

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Proproteinska konvertaza, subtilisin/keksin tip 2
Identifikatori
SimboliPCSK2; NEC2; PC2; SPC2
Vanjski IDOMIM: 162151 MGI: 97512 HomoloGene: 37640 GeneCards: PCSK2 Gene
EC broj3.4.21.94
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
VrstaČovekMiš
Entrez512618549
EnsemblENSG00000125851ENSMUSG00000027419
UniProtP16519P21661
RefSeq (mRNA)NM_002594NM_008792
RefSeq (protein)NP_002585NP_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|

Spoljašnje veze

  • MeSH Proprotein+convertase+2
  • p
  • r
  • u
TemeTipovi
EC1 Oksidoreduktaze/spisak  • EC2 Transferaze/spisak  • EC3 Hidrolaze/spisak  • EC4 Lijaze/spisak  • EC5 Izomeraze/spisak  • EC6 Ligaze/spisak
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6