Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteins that fail to attain their correct three-dimensional structure are retained in the endoplasmic reticulum (ER) and eventually degraded within the cells. We investigated the degradation of mutant proteins, using naturally occurring protein C (PC) mutants (Arg178Gln and Cys331Arg) which lead to congenital deficiencies. Chinese hamster ovary (CHO) cells were transfected with normal or mutant expression vectors. The introduction of mutation at Asn329 of an unusual sequence Asn-X-Cys for N-linked glycosylation revealed that the mutation at Cys331, which may preclude a formation of disulfide bond with Cys345, resulted in no addition of N-linked oligosaccharides at Asn329. PC mutants with 4 glycosylation sites were gradually glycosylated in the ER, and the fourth glycosylation site is less accessible for glycosylation as reported for PC in plasma. The half lives of PC178 and PC331 mutants were about 5 and 4 h, respectively. PC mutants were degraded, but the degradation was inhibited by inhibitors for proteasome. Mannose trimming of N-linked oligosaccharides after glucose removal targeted PC mutants for degradation by proteasomes. And also the inhibition of glucose trimming immediately led to mannose trimming, resulting in the accelerated degradation of PC mutants. These degradations were inhibited by mannosidase I inhibitor, kifunensine. These results indicate that the initiation of mannose trimming by mannosidase I leads to the proteasomemediated degradation of glucose-trimmed or untrimmed PC mutants.
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PMID:Gradually glycosylated protein C mutants (Arg178Gln and Cys331Arg) are degraded by proteasome after mannose trimming. 1558 35

Oral Lichen Planus (OLP) is an oral inflammatory condition, mediated by host immune system reaction, presenting basal membrane damages with inflammatory lesions in the mouth and/or skin. In this study, the role of functional polymorphisms in the MBL2 gene, encoding for Mannose-Binding Protein C (MBP-C), a member of the innate immune response and an acute-phase protein able to activate the complement cascade, was investigated to assess a possible association with OLP susceptibility in Italian patients. Two variations at the promoter region (called H/L and X/Y) and three at the first exon (at codon 52, 54, and 57) of the MBL2 gene were analyzed in 69 OLP patients and 244 healthy controls from northeastern Italy. Considering the polymorphisms singularly, the MBL2 X allele and C/T genotype of the D allele (correlated with low MBP-C expression) were associated with susceptibility to develop OLP. Moreover, when taking into account MBL2 combined genotypes, more OLP patients were deficient MBP-C producers than not deficient, who were more represented among healthy controls. MBL2 combined genotypes, responsible for deficient MBP-C production, are associated with an increased risk of developing OLP.
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PMID:Mannose-Binding Lectin 2 (MBL2) combined genotypes deficiency is associated with susceptibility for Oral Lichen Planus. 3079 20