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| Proprotein convertase subtilisin/kexin type 1 |
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PDB rendering based on 1kn6, the NMR structure of the pro-domain.
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| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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1kn6
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| 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
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| Cellular component |
• extracellular space
• transport vesicle
• secretory granule lumen
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| Biological process |
• proteolysis
• cell-cell signaling
• metabolic process
• protein processing
• peptide hormone processing
• peptide biosynthetic process
• cellular protein metabolic process
• regulation of insulin secretion
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| Sources: Amigo / QuickGO |
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| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
5122 |
18548 |
| Ensembl |
ENSG00000175426 |
ENSMUSG00000021587 |
| UniProt |
P29120 |
P63239 |
| RefSeq (mRNA) |
NM_000439 |
NM_013628 |
| RefSeq (protein) |
NP_000430 |
NP_038656 |
| Location (UCSC) |
Chr 5:
96.39 – 96.43 Mb |
Chr 13:
75.09 – 75.13 Mb |
| PubMed search |
[1] |
[2] |
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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 |
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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]
Contents
- 1 Function
- 2 Clinical significance
- 3 References
- 4 External links
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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Endopeptidases: serine proteases/serine endopeptidases (EC 3.4.21)
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| Digestive enzymes |
- Enteropeptidase
- Trypsin
- Chymotrypsin
- Elastase
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| Coagulation |
- factors: Thrombin
- Factor VIIa
- Factor IXa
- Factor Xa
- Factor XIa
- Factor XIIa
- Kallikrein
- PSA
- KLK1
- KLK2
- KLK3
- KLK4
- KLK5
- KLK6
- KLK7
- KLK8
- KLK9
- KLK10
- KLK11
- KLK12
- KLK13
- KLK14
- KLK15
- fibrinolysis: Plasmin
- Plasminogen activator
- Tissue plasminogen activator
- Urinary plasminogen activator
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| Complement system |
- Factor B
- Factor D
- Factor I
- MASP
- C3-convertase
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| Other immune system |
- Chymase
- Granzyme
- Tryptase
- Proteinase 3/Myeloblastin
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| Venombin |
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| Other |
- Acrosin
- Prolyl endopeptidase
- Pronase
- Proprotein convertases
- Prostasin
- Reelin
- Subtilisin/Furin
- Streptokinase
- S1P
- Cathepsin
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- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15-99
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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UpToDate Contents
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English Journal
- The Association of Common Variants in PCSK1 With Obesity: A HuGE Review and Meta-Analysis.
- Stijnen P, Tuand K, Varga TV, Franks PW, Aertgeerts B, Creemers JW.
- American journal of epidemiology.Am J Epidemiol.2014 Dec 1;180(11):1051-65. doi: 10.1093/aje/kwu237. Epub 2014 Oct 29.
- Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated w
- PMID 25355447
- Obesity Associated with Type 2 Diabetes Mellitus Is Linked to Decreased PC1/3 mRNA Expression in the Jejunum.
- Rohden F1, Costa CS, Hammes TO, Margis R, Padoin AV, Mottin CC, Guaragna RM.
- Obesity surgery.Obes Surg.2014 Dec;24(12):2075-81. doi: 10.1007/s11695-014-1279-x.
- BACKGROUND: Bariatric surgery is the most effective therapeutic option for obesity and its complications, especially in type 2 diabetes. The aim of this study was to investigate the messenger RNA (mRNA) gene expression of proglucagon, glucose-dependent insulinotropic peptide (GIP), prohormone conver
- PMID 24831459
Japanese Journal
- グレリンのプロセシングに関与する酵素とその性質 (内分泌) -- (基礎分野での進歩)
Related Links
- 600955 - PROPROTEIN CONVERTASE 1/3 DEFICIENCY - OBESITY AND ENDOCRINOPATHY DUE TO IMPAIRED PROCESSING OF PROHORMONES ... Farooqi, I. S., Volders, K., Stanhope, R., Heuschkel, R ...
- Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene Robert S. Jackson 1, *, John W.M. Creemers 2, *, Shinya Ohagi 3, Marie-Laure Raffin-Sanson 4 5, Carl T 5 6 7 ...
Related Pictures
★リンクテーブル★
[★]
- 英
- prohormone convertase 1、PC1
- 関
- プロタンパク質転換酵素1
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プロタンパク質転換酵素1
- 関
- prohormone convertase 1
[★]
- 関
- prohormone convertase 1
[★]
[★]
コンバターゼ、転換酵素
[★]
プロホルモン変換酵素