Proprotein convertase 2

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]

PCSK2
Identifiers
AliasesPCSK2, NEC 2, NEC-2, NEC2, PC2, SPC2, proprotein convertase subtilisin/kexin type 2
External IDsOMIM: 162151 MGI: 97512 HomoloGene: 37640 GeneCards: PCSK2
Orthologs
SpeciesHumanMouse
Entrez

5126

18549

Ensembl

ENSG00000125851

ENSMUSG00000027419

UniProt

P16519

P21661

RefSeq (mRNA)

NM_002594
NM_001201528
NM_001201529

NM_008792

RefSeq (protein)

NP_001188457
NP_001188458
NP_002585

NP_032818

Location (UCSC)Chr 20: 17.23 – 17.48 MbChr 2: 143.39 – 143.66 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
proprotein convertase 2
Identifiers
EC no.3.4.21.94
CAS no.130960-94-0
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

In 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

  1. GRCh38: Ensembl release 89: ENSG00000125851 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000027419 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. 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 reading


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