Characterization of a second member of the subfamily of calcium-binding mitochondrial carriers expressed in human non-excitable tissues.
We have recently identified a subfamily of mitochondrial carriers that bind calcium, and cloned ARALAR1, a member of this subfamily expressed in human muscle and brain. We have now cloned a second human ARALAR gene (ARALAR2) coding for a protein 78.3% identical to Aralar1, but expressed in liver and non-excitable tissues. Aralar2 is identical to citrin, the product of the gene mutated in type-II citrullinaemia [Kobayashi, Sinasac, Iijima, Boright, Begum, Lee, Yasuda, Ikeda, Hirano, Terazono et al. (1999) Nat. Genet. 22, 159-163]. A related protein, DmAralar, 69% identical to Aralar1, was found in Drosophila melanogaster, the DMARALAR locus lying on the right arm of the third chromosome, band 99F. The N-terminal half of Aralar2/citrin is able to bind calcium and this requires the presence of the two most distal EF-hands. The localization of Aralar2/citrin expressed in human cell lines is mitochondrial, the C-terminal half containing sufficient information for import and assembly into mitochondria. The C-terminal half of Aralar proteins is related to the yeast YPR020c gene, with a very high sequence conservation (54.3% identity), suggesting that these proteins play an important role. Thus Aralar proteins are probably expressed in all tissues in an isoform-specific fashion, where they function as calcium-regulated metabolite (possibly anionic) carriers.
Del Arco
A
A
Departamento de Biología Molecular, Centro de Biología Molecular 'Severo Ochoa', Campus de Cantoblanco, 28049-Madrid, Spain.
Agudo
M
M
Satrústegui
J
J
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D002675:Child, Preschool; D003001:Cloning, Molecular; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D006801:Humans; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters; D017386:Sequence Homology, Amino Acid
C405492:Aralar protein, Drosophila; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; C114606:SLC25A12 protein, human; C008822:citrin