1S3A
4695
17991
ENSG00000131495
ENSMUSG00000014294
O43678
Q9CQ75
NM_001185012NM_002488
NM_010885
NP_001171941NP_002479
NP_035015
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 is a protein that in humans is encoded by the NDUFA2 gene.[5][6] The NDUFA2 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[7] Mutations in the NDUFA2 gene are associated with Leigh's syndrome.[6]
The NDUFA2 gene is located on the long (q) arm of chromosome 5 at position 31.2 and it spans 2,422 base pairs.[6] The NDUFA2 gene produces an 11 kDa protein composed of 99 amino acids.[8][9] NDUFA2 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[7] NDUFA2 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH:ubiquinone oxidoreductase complex at the inner mitochondrial membrane.[6]
The human NDUFA2 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. NDUFA2 is an accessory subunit of Complex I that is believed not to be involved in catalysis but may be involved in regulating Complex I activity or its assembly via assistance in redox processes.[6][10] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[7]
Mutations in the NDUFA2 gene can result in Leigh's syndrome, a severe neurological disorder that typically arises in the first year of life.[6] One such mutation interferes with normal splicing patterns and results in exon 2 being skipped. This causes a reduction in Complex I activity and disturbs its assembly. The NDUFA2 mutation is also associated with the depolarization of the mitochondria.[11]
NDUFA2 has many protein interactions, including interactions with other members of the NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, other subunits of Complex I as well as with redox proteins. This may be due to its potential role in Complex I assembly and assistance in redox processes.[6]
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