ABCMdb

PMID: 11001817

Chen JM, Scotet V, Ferec C
Definition of a "functional R domain" of the cystic fibrosis transmembrane conductance regulator.
Mol Genet Metab. 2000 Sep-Oct;71(1-2):245-9., [PubMed]

Sentences

No. Mutations Sentence Comment

30 ABCC7 p.Ala613Thr ABCC7 p.Asp648Val ABCC7 p.Asp614Gly ABCC7 p.Gly628Arg ABCC7 p.Thr665Ser ABCC7 p.Leu619Ser ABCC7 p.Ile618Thr ABCC7 p.His620Pro ABCC7 p.Leu610Ser ABCC7 p.Ile601Phe ABCC7 p.Leu633Pro Second, while I601F, L610S, A613T, D614G, I618T, L619S, H620P, G628R, and L633P resulted in aberrant processing, neither D648V or T665S caused an arrest in protein maturation (8). Login to comment 31 ABCC7 p.Asp648Val Additionally, D648V did not significantly affect chloride transport ability compared with wild-type CFTR channels (8). Login to comment 32 ABCC7 p.Asp651Asn Another missense mutation D651N that changes a conserved, negatively charged residue was reported to be a neutral polymorphism (11). Login to comment 45 ABCC7 p.Val754Met ABCC7 p.Ala800Gly ABCC7 p.Phe693Leu ABCC7 p.Thr760Met For example, F693L, V754M, T760M, and A800G may be assigned as neutral polymorphisms. Login to comment 46 ABCC7 p.Phe693Leu Indeed, F693L was considered to be a neutral polymorphism due to its presence in healthy subjects (unpublished data) and this was confirmed by functional analysis (8). Login to comment 47 ABCC7 p.Glu826Lys ABCC7 p.Glu822Lys Conversely, E822K and E826K both change a stringently or well-conserved, negatively charged residue to a positively charged one and therefore would be speculated to produce some functional consequences. Login to comment 49 ABCC7 p.Asp836Tyr ABCC7 p.Glu725Lys Similarly, E725K and D836Y both occur in well-conserved, FIG. 1. Login to comment 60 ABCC7 p.Lys698Arg For example, while the K698R substitution affects a strictly conserved residue, it retains the consensus phosphorylation sequence (R-R/K-X-S). Login to comment 61 ABCC7 p.Lys698Arg Thus, K698R appears to be a neutral polymorphism. Login to comment 62 ABCC7 p.Arg766Met ABCC7 p.Arg766Met ABCC7 p.Arg766Met The fact that R766M changes a most favorable phosphorylation sequence (R-R/K-X-S) to a less favorable one (R-X-X-S) suggests that even if R766M produces any effect, its effect must be minor and, in this regard, R766M did not show significant functional difference compared with wild-type CFTR (8). Login to comment 63 ABCC7 p.Arg792Gly In contrast, R792G, which disrupts a consensus recognition site for PKA, gave rise to chloride channels with significantly lower Po than the wild-type channel (8). Login to comment