RGD Reference Report - Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM. - Rat Genome Database

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Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM.

Authors: Ohagi, S  Sakaguchi, H  Sanke, T  Tatsuta, H  Hanabusa, T  Nanjo, K 
Citation: Ohagi S, etal., Diabetes. 1996 Jul;45(7):897-901.
RGD ID: 2308935
Pubmed: PMID:8666140   (View Abstract at PubMed)

Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3 (PC3). PC3 is a type I proinsulin-processing enzyme that initiates the sequential processing of proinsulin to insulin by cleaving the proinsulin molecule on the COOH-terminal side of the dibasic peptide, Arg31-Arg32, joining the B-chain and C-peptide. Thus, PC3 plays a key role in regulating insulin biosynthesis. Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing. NIDDM is associated with increased secretion of proinsulin and proinsulin-like molecules, suggesting that mutations in the PC3 gene may be involved in the development of this disorder. To examine this hypothesis, we have isolated and characterized the human PC3 gene and screened it for mutations in a group of Japanese subjects with NIDDM. The PC3 gene consists of 14 exons spanning more than 35 kb. The exon-intron organization of PC2 and PC3 genes are conserved, consistent with a common evolutionary origin for the prohormone convertase gene family. Single-strand conformational analysis and nucleotide sequencing of the entire coding region of the PC3 gene in 102 Japanese subjects with NIDDM revealed missense mutations in exons 2 (Arg/Gln53) and 14 (Gln/Glu638), neither of which was associated with NIDDM in this population. These data suggest that genetic variation in the PC3 gene is unlikely to be a major contributor to NIDDM susceptibility in Japanese.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus no_associationIAGP 2308935DNA:missense mutations:cds:p.R53Q and p.Q638E (human)RGD 
type 2 diabetes mellitus no_associationISOPCSK1 (Homo sapiens)2308935; 2308935DNA:missense mutations:cds:p.R53Q and p.Q638E (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pcsk1  (proprotein convertase subtilisin/kexin type 1)

Genes (Mus musculus)
Pcsk1  (proprotein convertase subtilisin/kexin type 1)

Genes (Homo sapiens)
PCSK1  (proprotein convertase subtilisin/kexin type 1)


Additional Information