Sequence information
Variant position: 432 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 606 The length of the canonical sequence.
Location on the sequence:
SEGQSLLITGNTGTGKTSLL
R VLGGLWTSTRGSVQMLTDFG
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human SEGQSLLITGNTGTGKTSLLR VLGGLWTSTRGSVQMLTDFG
Mouse CEGQSLLITGNTGTGKTSLLR VLGGLWEGMKGSVQMLADFG
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:Type: the type of sequence feature. Positions: endpoints of the sequence feature. Description: contains additional information about the feature.
Type Positions Description
Chain
1 – 606
Lysosomal cobalamin transporter ABCD4
Domain
389 – 603
ABC transporter
Mutagenesis
426 – 426
G -> A. Decreases interaction with LMBD1. Decreases colocalization with LMBD1. Decreases cobalamin transport activity.
Mutagenesis
427 – 427
K -> A. Loss of ATPase activity. Loss of cobalamin transport activity.
Mutagenesis
427 – 427
K -> L. Decreases interaction with LMBD1. Decreases colocalization with LMBD1. Decreases cobalamin transport activity. Reduces synthesis of adenosylcobalamin and methylcobalamin.
Literature citations
Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B12-trafficking proteins ABCD4 and LMBD1.
Fettelschoss V.; Burda P.; Sagne C.; Coelho D.; De Laet C.; Lutz S.; Suormala T.; Fowler B.; Pietrancosta N.; Gasnier B.; Bornhauser B.; Froese D.S.; Baumgartner M.R.;
J. Biol. Chem. 292:11980-11991(2017)
Cited for: INVOLVEMENT IN MAHCJ; VARIANT MAHCJ GLN-432; CHARACTERIZATION OF VARIANTS MAHCJ LYS-141 AND GLN-432; SUBCELLULAR LOCATION; INTERACTION WITH LMBRD1; MUTAGENESIS OF GLY-426; LYS-427 AND ASP-548; FUNCTION; CATALYTIC ACTIVITY;
Cryo-EM structure of human lysosomal cobalamin exporter ABCD4.
Xu D.; Feng Z.; Hou W.T.; Jiang Y.L.; Wang L.; Sun L.; Zhou C.Z.; Chen Y.;
Cell Res. 29:1039-1041(2019)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 2-606; CHARACTERIZATION OF VARIANTS MAHCJ CYS-319 AND GLN-432; MUTAGENESIS OF GLU-549; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;
Disclaimer:
Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.