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proprotein convertase 1
proprotein convertase 1
Identifiers
EC no.	3.4.21.93
CAS no.	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 / QuickGO
PMC
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PMC	articles
PubMed	articles
NCBI	proteins

PCSK1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1KN6, 2KDT, 2KE3
Identifiers
Aliases	PCSK1, BMIQ12, NEC1, PC1, PC3, SPC3, proprotein convertase subtilisin/kexin type 1, PC1/3, PCSK1 gene
External IDs	OMIM: 162150; MGI: 97511; HomoloGene: 379; GeneCards: PCSK1; OMA:PCSK1 - orthologs
Gene location (Human)
Chr.	Chromosome 5 (human)
End	96,434,143 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	75,282,980 bp
RNA expression pattern
	Top expressed in
	beta cell; ; postcentral gyrus; ; superior frontal gyrus; ; orbitofrontal cortex; ; Brodmann area 23; ; Brodmann area 46; ; endothelial cell; ; Brodmann area 10; ; primary visual cortex; ; testicle;
	Top expressed in
	supraoptic nucleus; ; islet of Langerhans; ; pars distalis of adenohypophysis; ; lumbar spinal ganglion; ; dentate gyrus of hippocampal formation granule cell; ; paraventricular nucleus of hypothalamus; ; primary visual cortex; ; superior frontal gyrus; ; arcuate nucleus; ; central gray substance of midbrain;
	More reference expression data
	n/a
Gene ontology
Molecular function	peptidase activity; serine-type peptidase activity; endopeptidase activity; hydrolase activity; serine-type endopeptidase activity; identical protein binding;
Cellular component	secretory granule lumen; transport vesicle; cytoplasmic vesicle; extracellular space; membrane; neuron projection;
Biological process	peptide biosynthetic process; cell-cell signaling; peptide hormone processing; proteolysis; protein processing;
	Sources:Amigo / QuickGO
Orthologs
	5122
	18548
	ENSG00000175426
	ENSMUSG00000021587
	P29120
	P63239
	NM_001177876; NM_000439; NM_001177875
	NM_013628
	NP_000430; NP_001171346
	NP_038656
	Wikidata
View/Edit Human	View/Edit Mouse

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]

Function

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

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

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000175426 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021587 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ "EC 3.4.21.93". www.qmul.ac.uk.
^ 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 U.S. National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt: P63239 (Mouse Neuroendocrine convertase 1) at the PDBe-KB.