SLC25A13
Domain
The EF-hand 2 domain within the regulatory N-terminal domain binds one calcium in the mitochondrial intermembrane space. Calcium triggers the binding of the regulatory N-terminal domain to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain (PubMed:25410934). In the absence of calcium, the linker loop domain may close the vestibule and prevent substrates from entering the carrier domain (By similarity).
Function
Mitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle (PubMed:11566871). Also mediates the uptake of L-cysteinesulfinate by mitochondria in exchange of L-glutamate and proton. Can also exchange L-cysteinesulfinate with aspartate in their anionic form without any proton translocation (PubMed:11566871).
Involvement in disease
Citrullinemia 2
CTLN2
A form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. Citrullinemia type 2 is characterized by neuropsychiatric symptoms including abnormal behaviors, loss of memory, seizures and coma. Death can result from brain edema. Onset is sudden and usually between the ages of 20 and 50 years.
None
The disease is caused by variants affecting the gene represented in this entry.
Cholestasis, neonatal intrahepatic, caused by citrin deficiency
NICCD
A form of citrullinemia type 2 with neonatal onset, characterized by suppression of the bile flow, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, variable liver dysfunction. Neonatal intrahepatic cholestasis due to citrin deficiency is generally not severe and symptoms disappear by one year of age with an appropriate diet. Years or even decades later, however, some individuals develop the characteristic features of citrullinemia type 2 with neuropsychiatric symptoms.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Tissue Specificity
High levels in liver and low levels in kidney, pancreas, placenta, heart and brain.
Cellular localization
- Mitochondrion inner membrane
- Multi-pass membrane protein
Alternative names
Calcium-binding mitochondrial carrier protein Aralar2, Citrin, Mitochondrial aspartate glutamate carrier 2, Solute carrier family 25 member 13, ARALAR-related gene 2, ARALAR2, SLC25A13