Characterization of HACD1 K64Q mutant found in arrhythmogenic right ventricular dysplasia patients.
Arrhythmogenic right ventricular dysplasia (ARVD) is an autosomal dominant heart disease. A K64Q mutation was found in ARVD-affected individuals in the HACD1 gene, which encodes an enzyme involved in very long-chain fatty acid (VLCFA) elongation, although any relationship between mutation and pathology remained unclear. Here, we demonstrate that HACD1 (K64Q) exhibits normal enzyme activity, intracellular localization and interaction with other VLCFA enzymes, with no dominant negative effect on VLCFA elongation. Thus, it appears unlikely that this mutation is ARVD-causative. Moreover, through these analyses we found that HACD1 interacts with KAR and TER, the reductase enzymes involved in the second and fourth VLCFA elongation cycle, respectively. This finding indicates that the enzymes responsible for the VLCFA elongation cycle form an elongase complex.
Konishi
Hiroyuki
H
Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan.
Okuda
Ayaka
A
Ohno
Yusuke
Y
Kihara
Akio
A
D019943:Amino Acid Substitution; D000818:Animals; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism
C404489:HACD1 protein, human; D017027:Protein Tyrosine Phosphatases