Proprotein convertase 1

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.[5] PCSK1 and PCSK2 differentially cleave proopiomelanocortin and they act together to process proinsulin and proglucagon in pancreatic islets.[6]

PCSK1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPCSK1, BMIQ12, NEC1, PC1, PC3, SPC3, proprotein convertase subtilisin/kexin type 1, PC1/3, PCSK1 gene
External IDsOMIM: 162150; MGI: 97511; HomoloGene: 379; GeneCards: PCSK1; OMA:PCSK1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001177876
NM_000439
NM_001177875

NM_013628

RefSeq (protein)

NP_000430
NP_001171346

NP_038656

Location (UCSC)Chr 5: 96.39 – 96.43 MbChr 13: 75.24 – 75.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
proprotein convertase 1
Identifiers
EC no.3.4.21.93
CAS no.99676-46-7
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Function

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PC1/3 is an enzyme that performs the proteolytic cleavage of prohormones to their intermediate (or sometimes completely cleaved) forms.[6] 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.[citation needed]

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.

Proprotein convertase 1 converts prorenin into renin.[7]

Clinical significance

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Variants in the PCSK1 gene may be associated with obesity.[8]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000175426Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021587Ensembl, 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. ^ 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.
  6. ^ 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.
  7. ^ "EC 3.4.21.93". www.qmul.ac.uk.
  8. ^ 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.
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