ABCB6 p.Lys629Met
| Predicted by SNAP2: | A: D (91%), C: D (91%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), L: D (95%), M: D (95%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (95%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Shifting the paradigm: the putative mitochondrial ... PLoS One. 2012;7(5):e37378. Epub 2012 May 24. Kiss K, Brozik A, Kucsma N, Toth A, Gera M, Berry L, Vallentin A, Vial H, Vidal M, Szakacs G
Shifting the paradigm: the putative mitochondrial protein ABCB6 resides in the lysosomes of cells and in the plasma membrane of erythrocytes.
PLoS One. 2012;7(5):e37378. Epub 2012 May 24., [PMID:22655043]
Abstract [show]
ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria.
Comments [show]
None has been submitted yet.
No. Sentence Comment
213 DNA Constructs cDNA encoding wild-type human ABCB6 (NM_005689) bearing an HA-tag at its C-terminus [17] was mutated by mutagenic PCR to generate a variant harboring mutation of a universally conserved lysine residue in the Walker A sequence (K629M).
X
ABCB6 p.Lys629Met 22655043:213:242
status: NEW215 An untagged form of both the wild-type and the non-functional mutant variant of ABCB6 (K629M, ABCB6-KM) were cloned into pSEW lentiviral vectors.
X
ABCB6 p.Lys629Met 22655043:215:87
status: NEW[hide] Role of the N-terminal transmembrane domain in the... Biochem J. 2015 Apr 1;467(1):127-39. doi: 10.1042/BJ20141085. Kiss K, Kucsma N, Brozik A, Tusnady GE, Bergam P, van Niel G, Szakacs G
Role of the N-terminal transmembrane domain in the endo-lysosomal targeting and function of the human ABCB6 protein.
Biochem J. 2015 Apr 1;467(1):127-39. doi: 10.1042/BJ20141085., [PMID:25627919]
Abstract [show]
ATP-binding cassette, subfamily B (ABCB) 6 is a homodimeric ATP-binding cassette (ABC) transporter present in the plasma membrane and in the intracellular organelles. The intracellular localization of ABCB6 has been a matter of debate, as it has been suggested to reside in the mitochondria and the endo-lysosomal system. Using a variety of imaging modalities, including confocal microscopy and EM, we confirm the endo-lysosomal localization of ABCB6 and show that the protein is internalized from the plasma membrane through endocytosis, to be distributed to multivesicular bodies and lysosomes. In addition to the canonical nucleotide-binding domain (NBD) and transmembrane domain (TMD), ABCB6 contains a unique N-terminal TMD (TMD0), which does not show sequence homology to known proteins. We investigated the functional role of these domains through the molecular dissection of ABCB6. We find that the folding, dimerization, membrane insertion and ATP binding/hydrolysis of the core-ABCB6 complex devoid of TMD0 are preserved. However, in contrast with the full-length transporter, the core-ABCB6 construct is retained at the plasma membrane and does not appear in Rab5-positive endosomes. TMD0 is directly targeted to the lysosomes, without passage to the plasma membrane. Collectively, our results reveal that TMD0 represents an independently folding unit, which is dispensable for catalysis, but has a crucial role in the lysosomal targeting of ABCB6.
Comments [show]
None has been submitted yet.
No. Sentence Comment
41 Site-directed mutagenesis was performed to replace the conserved Walker A lysine at position 629 to methionine (K629 M), as described previously [15].
X
ABCB6 p.Lys629Met 25627919:41:74
status: NEW