ABCB2 p.Cys12Ser
| Predicted by SNAP2: | A: D (75%), D: D (91%), E: D (91%), F: D (91%), G: D (91%), H: D (85%), I: D (85%), K: D (85%), L: D (91%), M: D (85%), N: D (85%), P: D (91%), Q: D (85%), R: D (71%), S: D (85%), T: D (85%), V: D (85%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Formation of two intramolecular disulfide bonds is... J Biol Chem. 2009 Apr 24;284(17):11293-300. Epub 2009 Mar 3. Hozoji M, Kimura Y, Kioka N, Ueda K
Formation of two intramolecular disulfide bonds is necessary for ApoA-I-dependent cholesterol efflux mediated by ABCA1.
J Biol Chem. 2009 Apr 24;284(17):11293-300. Epub 2009 Mar 3., [PMID:19258317]
Abstract [show]
ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism. ABCA1 contains disulfide bond(s) between its N- and C-terminal halves, but it remains unclear whether disulfide bond formation is important for the functions of ABCA1 and which cysteines are involved in disulfide bond formation. To answer these questions, we constructed >30 ABCA1 mutants in which 16 extracellular domain (ECD) cysteines were replaced with serines and examined disulfide bond formation, apoA-I binding, and HDL formation in these mutants. From the single cysteine replacements, two cysteines (Cys(75) and Cys(309)) in ECD1 were found to be essential for apoA-I binding. In contrast, in ECD2, only Cys(1477) was found to be essential for HDL formation, and no single cysteine replacement impaired apoA-I binding. The concurrent replacement of two cysteines, Cys(1463) and Cys(1465), impaired apoA-I binding and HDL formation, suggesting that four of five extracellular cysteines (Cys(75), Cys(309), Cys(1463), Cys(1465), and Cys(1477)) are involved in these functions of ABCA1. Trypsin digestion experiments suggested that one disulfide bond is not sufficient and that two intramolecular disulfide bonds (between Cys(75) and Cys(309) in ECD1 and either Cys(1463) or Cys(1465) and Cys(1477) in ECD2) are required for ABCA1 to be fully functional.
Comments [show]
None has been submitted yet.
No. Sentence Comment
124 TABLE 1 Cysteine mutants of ABCA1 Protein ApoA-I binding Cholesterol efflux Mutations Wild type ϩ ϩ None C1S ϩ ϩ C54S C2S - - C75S C3S ϩ ϩ C81S C4S ϩ ϩ C195S C5S ϩ ϩ C215S C6S - - C309S C7S ϩ ϩ C355S C8S ϩ ϩ C504S C9S ϩ ϩ C626S C10S ϩ ϩ C791S C11S ϩ ϩ C1418S C12S ϩ ϩ C1429S C13S ϩ ϩ C1463S C14S ϩ ϩ C1465S C15S ϩ - C1477S C16S ϩ ϩ C1814S C2/6S - - C75S/C309S C11/12S ϩ ϩ C1418S/C1429S C13/14S - - C1463S/C1465S C13/14/15S - - C1463S/C1465S/C1477S C11/12/13/14S - - C1418S/C1429S/C1463S/C1465S C11/12/13/15S - - C1418S/C1429S/C1463S/C1477S C11/12/14/15S - - C1418S/C1429S/C1465S/C1477S C11/13/14/15S - - C1418S/C1463S/C1465S/C1477S C12/13/14/15S - - C1429S/C1463S/C1465S/C1477S C11/12/13/14/15S - - C1418S/C1429S/C1463S/C1465S/C1477S C2/6/13/14/15S - - C75S/C309S/C1463S/C1465S/C1477S Cys4#1 ϩ ϩ C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1465S/1814S Cys4#2 ϩ ϩ C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1463S/1814S Cys5 ϩ ϩ C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1814S irreversibly abolished apoA-I binding to cells expressing ABCA1(Cys5)-GFP (supplemental Fig. 4).
X
ABCB2 p.Cys12Ser 19258317:124:379
status: NEW[hide] Functional cysteine-less subunits of the transport... FEBS Lett. 2003 Jan 2;533(1-3):42-6. Heintke S, Chen M, Ritz U, Lankat-Buttgereit B, Koch J, Abele R, Seliger B, Tampe R
Functional cysteine-less subunits of the transporter associated with antigen processing (TAP1 and TAP2) by de novo gene assembly.
FEBS Lett. 2003 Jan 2;533(1-3):42-6., [PMID:12505156]
Abstract [show]
Within the adaptive immune system the transporter associated with antigen processing (TAP) plays a pivotal role in loading of peptides onto major histocompatibility (MHC) class I molecules. As a central tool to investigate the structure and function of the TAP complex, we created cysteine-less human TAP subunits by de novo gene synthesis, replacing all 19 cysteines in TAP1 and TAP2. After expression in TAP-deficient human fibroblasts, cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport and inhibition by ICP47 from herpes simplex virus. Cysteine-less TAP1 and TAP2 restore maturation and intracellular trafficking of MHC class I molecules to the cell surface.
Comments [show]
None has been submitted yet.
No. Sentence Comment
84 FEBS 26839 19-12-02 S. Heintke et al./FEBS Letters 533 (2003) 42^46 43 by serines (C6S, C12S, C14S, C73S, C179S, C488S, C662S, C735S of TAP1; C70S, C213S, C353S, C363S, C571S, C641S of TAP2); however, cysteines located within predicted transmembrane helices were exchanged to alanines (C315A of TAP1; C197A, C209A of TAP2).
X
ABCB2 p.Cys12Ser 12505156:84:89
status: NEW82 by serines (C6S, C12S, C14S, C73S, C179S, C488S, C662S, C735S of TAP1; C70S, C213S, C353S, C363S, C571S, C641S of TAP2); however, cysteines located within predicted transmembrane helices were exchanged to alanines (C315A of TAP1; C197A, C209A of TAP2).
X
ABCB2 p.Cys12Ser 12505156:82:17
status: NEW