Summary for peptidase S08.072: PCSK1 peptidase

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS NamePCSK1 peptidase
Other namesneuroendocrine convertase 1 (NEC1), PC1, PC1/3, prohormone convertase 3 [obs.], PC3 [obs.], PCSK1 g.p. (Homo sapiens), proprotein convertase 1, proprotein convertase subtilisin/kexin type 1
Domain architecture
MEROPS Classification
Classification Clan SB >> Subclan (none) >> Family S8 >> Subfamily B >> S08.072
HolotypePCSK1 peptidase (Homo sapiens), Uniprot accession P29120 (peptidase unit: 143-441), MERNUM MER0000376
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeSerine
PeplistIncluded in the Peplist with identifier PL00359
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase 3.4.21.93
EnzymologyBRENDA database
Proteolytic eventsCutDB database (54 cleavages)
Activity statushuman: active (Seidah & Chretien, 2004)
mouse: active (Jean et al., 1993)
PhysiologyProcesses various preproteins by cleavage at paired basic amino acids.
KnockoutWork with a mouse knock-out led to the conclusion that proprotein convertase 1 plays a major role in processing proinsulin, but that its coordinated action with PC2 is necessary for the most efficient and complete processing of this prohormone (Zhu et al., 2002). Impaired intestinal proglucagon processing was detected in mice lacking prohormone convertase 1 (Ugleholdt et al., 2003). Jackson et al. (2003) have described two human cases of deficiency, both presenting obesity, hypoadrenalism and reactive hypoglycemia.
Other databases TREEFAMhttp://www.treefam.org/family/TF314277
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/Kr/RScissile bond-/-/ep/- (based on 92 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 2 17 0 0 4 10 11 18
Pro 9 2 3 0 1 3 16 3
Ala 1 6 2 0 10 18 1 2
Val 6 3 1 0 0 7 5 0
Leu 9 7 2 0 1 8 4 1
Ile 8 1 0 0 1 5 1 1
Met 3 2 0 0 0 0 1 3
Phe 8 6 0 0 3 7 0 10
Tyr 5 1 0 0 8 2 2 3
Trp 1 0 0 0 0 0 1 2
Ser 0 11 1 0 15 5 2 2
Thr 0 7 3 0 0 1 0 1
Cys 0 0 0 0 0 1 1 0
Asn 4 0 0 0 4 1 4 5
Gln 4 9 0 0 12 3 5 2
Asp 0 1 1 0 8 3 5 11
Glu 6 8 3 0 7 1 25 11
Lys 6 1 48 6 3 1 0 4
Arg 16 1 25 86 1 3 1 4
His 2 5 1 0 9 8 1 2
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
PCSK1 5q15-q21 ENSG00000175426 5122 PCSK1 162150
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Pcsk1 13:C2 ENSMUSG00000021587 18548 MGI:97511