NDUFA13

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 is an is_associated_with::enzyme that in humans is encoded by the NDUFA13 is_associated_with::gene. The NDUFA13 protein is a subunit of is_associated_with::NADH dehydrogenase (ubiquinone), which is located in the is_associated_with::mitochondrial inner membrane and is the largest of the five complexes of the is_associated_with::electron transport chain.

Structure
The NDUFA13 gene is located on the p arm of is_associated_with::chromosome 19 in position 13.2 and spans 11,995 base pairs. The gene produces a 17 kDa protein composed of 144 is_associated_with::amino acids. NDUFA13 is a subunit of the enzyme is_associated_with::NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, is_associated_with::hydrophobic is_associated_with::transmembrane domain and a is_associated_with::hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an is_associated_with::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 is_associated_with::NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA13 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis. The predicted is_associated_with::secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.

Function
The human NDUFA13 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to is_associated_with::ubiquinone. is_associated_with::NADH binds to Complex I and transfers two electrons to the is_associated_with::isoalloxazine ring of the is_associated_with::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 is_associated_with::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.

NDUFA13 has a homologous protein known as GRIM-19, a cell-death regulatory protein. It is involved in is_associated_with::interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This form of apoptotic activity is inhibited by interaction with viral is_associated_with::IRF1. GRIM-19 prevents the is_associated_with::transactivation of signal-transducer and activator of transcription 3 (STAT3) target genes.

Clinical significance
The homologous protein to NDUFA13, GRIM-19, may play a role in is_associated_with::Chron's disease (CD), an is_associated_with::inflammatory bowel disease (IBD) characterized by chronic inflammation of the intestinal epithelium. Its expression is decreased in the inflamed mucosa of patients with these diseases. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), functions as a mammalian cytosolic pathogen recognition molecule and plays an anti-bacterial role by limiting survival of intracellular invasive bacteria. GRIM-19 acts as a downstream anti-bacterial effector in CARD15-mediated innate mucosal responses by regulating intestinal epithelial cell responses to microbes. Following NOD2-mediated recognition of bacterial muramyl dipeptide, GRIM-19 is required for is_associated_with::NF-κB activation, a key component in regulating the immune response to infection.

Interactions
NDUFA13 has been shown to interact with is_associated_with::STAT3.