ABCC7 p.Lys946Arg
| ClinVar: |
c.2836A>T
,
p.Lys946*
?
, not provided
|
| Predicted by SNAP2: | A: D (53%), C: N (53%), D: D (75%), E: D (59%), F: D (66%), G: D (71%), H: N (57%), I: D (53%), L: D (59%), M: N (78%), N: D (59%), P: D (80%), Q: N (87%), R: N (87%), S: D (53%), T: N (53%), V: D (59%), W: D (80%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, L: D, M: D, N: N, P: D, Q: N, R: N, S: D, T: D, V: D, W: D, Y: D, |
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[hide] COMMD1-mediated ubiquitination regulates CFTR traf... PLoS One. 2011 Mar 31;6(3):e18334. Drevillon L, Tanguy G, Hinzpeter A, Arous N, de Becdelievre A, Aissat A, Tarze A, Goossens M, Fanen P
COMMD1-mediated ubiquitination regulates CFTR trafficking.
PLoS One. 2011 Mar 31;6(3):e18334., [PMID:21483833]
Abstract [show]
The CFTR (cystic fibrosis transmembrane conductance regulator) protein is a large polytopic protein whose biogenesis is inefficient. To better understand the regulation of CFTR processing and trafficking, we conducted a genetic screen that identified COMMD1 as a new CFTR partner. COMMD1 is a protein associated with multiple cellular pathways, including the regulation of hepatic copper excretion, sodium uptake through interaction with ENaC (epithelial sodium channel) and NF-kappaB signaling. In this study, we show that COMMD1 interacts with CFTR in cells expressing both proteins endogenously. This interaction promotes CFTR cell surface expression as assessed by biotinylation experiments in heterologously expressing cells through regulation of CFTR ubiquitination. In summary, our data demonstrate that CFTR is protected from ubiquitination by COMMD1, which sustains CFTR expression at the plasma membrane. Thus, increasing COMMD1 expression may provide an approach to simultaneously inhibit ENaC absorption and enhance CFTR trafficking, two major issues in cystic fibrosis.
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No. Sentence Comment
114 Three lysines were mutated to arginine in the ICL3 domain near Ser-945 (K946R and K951R) and Asp-979 (K978R).
X
ABCC7 p.Lys946Arg 21483833:114:72
status: NEW116 When COMMD1 was overexpressed, ubiquitination of K946R- and K951R-CFTR was increased (15263% and 126615%, respectively) whereas ubiquitination of wt-CFTR was decreased (70615%) (Figure 5A and 5B).
X
ABCC7 p.Lys946Arg 21483833:116:49
status: NEW119 However, ubiquitination of K946R-CFTR and K951R-CFTR was significantly increased compared to that of wt-CFTR (Figure 5B).
X
ABCC7 p.Lys946Arg 21483833:119:27
status: NEW172 (A) HeLa cells were transfected with CFTR constructs (wt, K946R, K951R or K978R-CFTR) and Myc-COMMD1 or empty vector as control (mock).
X
ABCC7 p.Lys946Arg 21483833:172:58
status: NEW180 (C) Representative gels for the same co-immunoprecipitation experiment between COMMD1 and wt, K946R, K951R or K978R-CFTR in heterologous system. HeLa cells were co-transfected with Myc-COMMD1 or empty vector (mock) and wt, K946R, K951R or K978R-CFTR.
X
ABCC7 p.Lys946Arg 21483833:180:94
status: NEWX
ABCC7 p.Lys946Arg 21483833:180:223
status: NEW185 COMMD1 overexpression clearly inhibited wt-CFTR ubiquitination, whereas it strongly induced ubiquitination of K946R- and K951R-CFTR.
X
ABCC7 p.Lys946Arg 21483833:185:110
status: NEW