Proprotein convertase 2: Difference between revisions

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'''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.
'''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. PC2 has been identified in a number of animals, including ''C. elegans''<ref>Gomez-Saladin, E., Wilson, DL., and Dickerson, IM. 1994. Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans. Cellualr and Molecular Neurobiology 14(1): 9-25</ref>.


In humans, proprotein convertase 2 is encoded by the ''PCSK2'' [[gene]].<ref name="pmid1765368">{{cite journal |vauthors=Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, Chrétien M | title = 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) | journal = Genomics | volume = 11 | issue = 1 | pages = 103–7 |date=September 1991 | pmid = 1765368 | doi = 10.1016/0888-7543(91)90106-O  | url =  | issn = }}</ref>  It is related to the bacterial enzyme subtilisin, and altogether there are 9 different subtilisin-like genes in mammals:  [[furin]], [[PCSK6|PACE4]], [[PCSK4|PC4]], [[PCSK5|PC5/6]], [[PCSK7|PC7/8]], [[PCSK9]], and [[MBTPS1|SKI1/S1P]].
In humans, proprotein convertase 2 is encoded by the ''PCSK2'' [[gene]].<ref name="pmid1765368">{{cite journal |vauthors=Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, Chrétien M | title = 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) | journal = Genomics | volume = 11 | issue = 1 | pages = 103–7 |date=September 1991 | pmid = 1765368 | doi = 10.1016/0888-7543(91)90106-O  | url =  | issn = }}</ref>  It is related to the bacterial enzyme subtilisin, and altogether there are 9 different subtilisin-like genes in mammals:  [[furin]], [[PCSK6|PACE4]], [[PCSK4|PC4]], [[PCSK5|PC5/6]], [[PCSK7|PC7/8]], [[PCSK9]], and [[MBTPS1|SKI1/S1P]].
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*{{cite journal  |vauthors=Deloukas P, Matthews LH, Ashurst J, etal |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865–71 |year=  2001|pmid= 11780052 |doi= 10.1038/414865a }}
*{{cite journal  |vauthors=Deloukas P, Matthews LH, Ashurst J, etal |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865–71 |year=  2001|pmid= 11780052 |doi= 10.1038/414865a }}
*{{cite journal  |vauthors=Mbikay M, Seidah NG, Chrétien M |title=Neuroendocrine secretory protein 7B2: structure, expression and functions. |journal=Biochem. J. |volume=357 |issue= Pt 2 |pages= 329–42 |year= 2001 |pmid= 11439082 |doi=  10.1042/0264-6021:3570329|pmc=1221959  }}
*{{cite journal  |vauthors=Mbikay M, Seidah NG, Chrétien M |title=Neuroendocrine secretory protein 7B2: structure, expression and functions. |journal=Biochem. J. |volume=357 |issue= Pt 2 |pages= 329–42 |year= 2001 |pmid= 11439082 |doi=  10.1042/0264-6021:3570329|pmc=1221959  }}
*{{cite journal  |vauthors=Fuller JA, Brun-Zinkernagel AM, Clark AF, Wordinger RJ |title=Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head. |journal=Invest. Ophthalmol. Vis. Sci. |volume=50 |issue= 12 |pages= 5759–68 |year= 2009 |pmid= 19339735 |doi= 10.1167/iovs.08-2616 }}
*{{cite journal  |vauthors=Fuller JA, Brun-Zinkernagel AM, Clark AF, Wordinger RJ |title=Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head. |journal=Invest. Ophthalmol. Vis. Sci. |volume=50 |issue= 12 |pages= 5759–68 |year= 2009 |pmid= 19339735 |doi= 10.1167/iovs.08-2616 |pmc=4155744 }}
*{{cite journal  |vauthors=Winsky-Sommerer R, Grouselle D, Rougeot C, etal |title=The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease. |journal=Neuroscience |volume=122 |issue= 2 |pages= 437–47 |year= 2003 |pmid= 14614908 |doi=10.1016/S0306-4522(03)00560-8  }}
*{{cite journal  |vauthors=Winsky-Sommerer R, Grouselle D, Rougeot C, etal |title=The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease. |journal=Neuroscience |volume=122 |issue= 2 |pages= 437–47 |year= 2003 |pmid= 14614908 |doi=10.1016/S0306-4522(03)00560-8  }}
*{{cite journal  |vauthors=Wang J, Xu J, Finnerty J, etal |title=The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site. |journal=Diabetes |volume=50 |issue= 3 |pages= 534–9 |year= 2001 |pmid= 11246872 |doi=10.2337/diabetes.50.3.534  }}
*{{cite journal  |vauthors=Wang J, Xu J, Finnerty J, etal |title=The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site. |journal=Diabetes |volume=50 |issue= 3 |pages= 534–9 |year= 2001 |pmid= 11246872 |doi=10.2337/diabetes.50.3.534  }}

Latest revision as of 07:11, 10 January 2019

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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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RefSeq (protein)

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proprotein convertase 2
Identifiers
EC number3.4.21.94
CAS number130960-94-0
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Gene OntologyAmiGO / QuickGO

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. PC2 has been identified in a number of animals, including C. elegans[1].

In humans, proprotein convertase 2 is encoded by the PCSK2 gene.[2] 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. Gomez-Saladin, E., Wilson, DL., and Dickerson, IM. 1994. Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans. Cellualr and Molecular Neurobiology 14(1): 9-25
  2. 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

External links