Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0013421 (
dystonia
)
8,418
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Defects in mitochondrial cytochrome
c
oxidase or respiratory chain complex IV (CIV) assembly are a frequent cause of human mitochondrial disorders. Specifically, mutations in four conserved assembly factors impinging the biogenesis of the mitochondrion-encoded catalytic core subunit 2 (
COX2
) result in myopathies. These factors afford stability of newly synthesized
COX2
(the
dystonia
-ataxia syndrome protein COX20), a protein with two transmembrane domains, and maturation of its copper center, Cu
A
(cardiomyopathy proteins SCO1, SCO2, and COA6). COX18 is an additional
COX2
assembly factor that belongs to the Oxa1 family of membrane protein insertases. Here, we used a gene-editing approach to generate a human
COX18
knock-out HEK293T cell line that displays isolated complete CIV deficiency. We demonstrate that COX20 stabilizes
COX2
during insertion of its N-proximal transmembrane domain, and subsequently, COX18 transiently interacts with
COX2
to promote translocation across the inner membrane of the
COX2
C-tail that contains the apo-Cu
A
site. The release of COX18 from this complex coincides with the binding of the SCO1-SCO2-COA6 copper metallation module to
COX2
-COX20 to finalize
COX2
biogenesis. Therefore, COX18 is a new candidate when screening for mitochondrial disorders associated with isolated CIV deficiency.
...
PMID:Human mitochondrial cytochrome
c
oxidase assembly factor COX18 acts transiently as a membrane insertase within the subunit 2 maturation module. 2833 Aug 71
COX20/FAM36A
encodes a mitochondrial complex IV assembly factor important for
COX2
activation. Only one homozygous
COX20
missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria,
dystonia
, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel
COX20
variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.
...
PMID:Novel pathogenic
COX20
variants causing dysarthria, ataxia, and sensory neuropathy. 3065 93
