FASTKD2

FAST kinase domain-containing protein 2 (FASTKD2) is a is_associated_with::protein that in humans is encoded by the FASTKD2 is_associated_with::gene on chromosome 2. This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress. FASTKD2 has been implicated in mitochondrial encephalomyopathy and breast cancer.

Structure
FASTKD2 shares structural characteristics of the FASTKD family, including an amino terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP). The mitochondrial targeting domain directs FASTKD2 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.

Function
As a member of the FASTKD family, FASTKD2 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD2 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. Nonetheless, FASTKD2 has been observed to mediate apoptosis independent of import into the mitochondria, suggesting that it interacts with proteins on the outer mitochondrial membrane. This protein possibly contributes its proapoptotic function by activating proapoptotic factors or inhibit antiapoptotic factors. As a member of the FASTKD family, FASTKD2 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD2 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria.

Clinical significance
FASTKD2 has been linked to mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency (mitochondrial complex IV deficiency). Nonsense mutations in FASTKD2 produce a truncated protein that cuts off the RAP domain and part of the FAST domains, leading to dampened sensitivity to apoptotic stimuli. Moreover, breast cancer cells are protected against apoptosis by stimulating NRIF3/DD1 expression or DIF-1 knockdown, which thus suppresses the proapoptotic function of FASTKD2. Activating and enhancing expression of FASTKD2 may then prove effective in killing cancer cells.

Interactions
FASTKD2 has been shown to interact with FASTKD3. The FASTKD2 gene has been observed to bind the DIF-1 complex.