関: prohormone convertase 1

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/14 20:56:52」(JST)

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Proprotein convertase 1, also known as prohormone convertase, prohormone convertase 3, or neuroendocrine convertase 1 and often abbreviated as PC1/3 is an enzyme that in humans is encoded by the PCSK1 gene.^[1] PCSK1 and PCSK2 differentially cleave proopiomelanocortin and they act together to process proinsulin and proglucagon in pancreatic islets.^[2]

Function

PC1/3 is an enzyme that performs the proteolytic cleavage of prohormones to their intermediate (or sometimes completely cleaved) forms.^[2] It is present only in neuroendocrine cells such as brain, pituitary and adrenal, and most often cleaves after a pair of basic residues within prohormones but can occasionally cleave after a single arginine. It binds to a protein known as proSAAS, which also represents its endogenous inhibitor. PC1 is synthesized as a 99 kDa proform quickly converted to an 87 kDa major active form, which itself is nearly completely cleaved to a 66 kDa active form within neuroendocrine cells.

Proprotein convertase 1 is the enzyme largely responsible for the first step in the biosynthesis of insulin. Following the action of proprotein convertase 1, a carboxypeptidase is required to remove the basic residues from the processing intermediate and generate the bioactive form of insulin. Another prohormone convertase, proprotein convertase 2 plays a more minor role in the first step of insulin biosynthesis, but a greater role in the first step of glucagon biosynthesis. The knockout of proprotein convertase 1 is not lethal in mice or humans, most likely due to the presence of the second convertase, although mice lacking proprotein convertase 1 activity show a number of defects including slow growth.

Proprotein convertase 1 is a calcium (Ca²⁺) activated serine endoprotease (meaning that a serine residue is part of the active site that hydrolyzes the peptide bond within the substrate). It is related to the bacterial enzyme known as subtilisin. There are nine subtilisin homologs in mammals; in addition to proprotein convertase 1 and 2, other members of this enzyme family include furin, PACE4, PC4, PC5/6, PC7/8, PCSK9, and SKI1/S1P.

Clinical significance

Variants in the PCSK1 gene may be associated with obesity.^[3]

References

^ 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.
^ ^a ^b Jansen E, Ayoubi TA, Meulemans SM, Van de Ven WJ (June 1995). "Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct cAMP response elements". J. Biol. Chem. 270 (25): 15391–7. doi:10.1074/jbc.270.25.15391. PMID 7797529.
^ Renström F, Payne F, Nordström A et al. (April 2009). "Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden". Hum. Mol. Genet. 18 (8): 1489–96. doi:10.1093/hmg/ddp041. PMC 2664142. PMID 19164386.

External links

Proprotein Convertase 1 at the US National Library of Medicine Medical Subject Headings (MeSH)

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Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs.

Fontanesi L, Bertolini F, Scotti E, Trevisi P, Buttazzoni L, Dall'olio S, Davoli R, Bosi P, Russo V.SourceDepartment of Agro-Food Science and Technology, Sezione di Allevamenti Zootecnici, Faculty of Agriculture, University of Bologna, Viale Fanin 48, 40127 Bologna, Italy. luca.fontanesi@unibo.it
Animal : an international journal of animal bioscience.Animal.2012 Dec;6(12):1913-24. doi: 10.1017/S1751731112001280. Epub 2012 Jul 20.
The proprotein convertase subtilisin/kexin type 1 (PCSK1) gene encodes the prohormone convertase 1/3 enzyme that processes prohormones into functional hormones that, in turn, regulate central and peripheral energy metabolism. Mutations in the human PCSK1 gene cause severe monogenic obesity or confer
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Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3.

Dillon SL, Williamson DM, Elferich J, Radler D, Joshi R, Thomas G, Shinde U.SourceDepartment of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97229, USA.
Journal of molecular biology.J Mol Biol.2012 Oct 12;423(1):47-62. doi: 10.1016/j.jmb.2012.06.023. Epub 2012 Jun 25.
The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that fu
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TIS21/BTG2/PC3 enhances downregulation of c-Myc during differentiation of HL-60 cells by activating Erk1/2 and inhibiting Akt in response to all-trans-retinoic acid.

Imran M, Park TJ, Lim IK.SourceDepartment of Biochemistry and Molecular Biology, BK21 Cell Transformation and Restoration, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
European journal of cancer (Oxford, England : 1990).Eur J Cancer.2012 Oct;48(15):2474-85. doi: 10.1016/j.ejca.2012.01.028. Epub 2012 Feb 14.
Mouse 12-O-tetradecanoyl phorbol-13-acetate inducible sequence 21 (TIS21), an orthologue of human B-cell translocation gene 2 (BTG2) and rat PC3, is a tumour suppressor that belongs to the antiproliferative gene family, and is implicated in a variety of biological processes. c-Myc is a transcription
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Japanese Journal

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Lipoprotein(a) in Familial Hypercholesterolemia With Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Gain-of-Function Mutations

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Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer

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NAID 130005104098

「プロタンパク質転換酵素1」

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proprotein convertase 1
Identifiers
EC number	3.4.21.93
CAS number	99676-46-7
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 subtilisin/kexin type 1
	PDB rendering based on 1kn6, the NMR structure of the pro-domain.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1kn6
Identifiers
Symbols	PCSK1 ; BMIQ12; NEC1; PC1; PC3; SPC3
External IDs	OMIM: 162150 MGI: 97511 HomoloGene: 379 IUPHAR: 2382 ChEMBL: 3182 GeneCards: PCSK1 Gene
EC number	3.4.21.93
Gene ontology
Molecular function	• serine-type endopeptidase activity;
Cellular component	• extracellular space; • transport vesicle; • secretory granule lumen;
Biological process	• proteolysis; • cell-cell signaling; • metabolic process; • protein processing; • peptide hormone processing; • peptide biosynthetic process; • cellular protein metabolic process; • regulation of insulin secretion;
	Sources: Amigo / QuickGO
Orthologs
	v; t; e;