InterPro domain: IPR003399

This domain is found in all 24 mce genes associated with the four mammalian cell entry (mce) operons of Mycobacterium tuberculosis and MlaD proteins from other Actinomycetales [ 1 , 2 ]. The archetype (mce1A, Rv0169), was isolated as being necessary for colonisation of, and survival within, the macrophage [ 3 ]. The domain is also found in:

• Chloroplast Ycf22 and related cyanobacterial homologues, the majority of which have an N-terminal transmembrane domain and are putative ABC transporters.
• Proteobacterial homologues, which include MlaD, PqiB, YrbD, YebT, VpsC and Ttg2C. MlaD is part of the ABC transporter complex MlaFEDB that actively prevents phospholipid accumulation at the cell surface [ 4 ]. MlaFEDB complex is composed of two ATP-binding proteins (MlaF), two transmembrane proteins (MlaE), two cytoplasmic solute-binding proteins (MlaB) and a probable periplamic solute-binding protein (MlaD). Through the Mla pathway, Gram-negative bacteria maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane [ 5 ].

1. Mycobacterium tuberculosis mammalian cell entry operon (mce) homologs in Mycobacterium other than tuberculosis (MOTT). FEMS Immunol. Med. Microbiol. 33, 125-32
2. Analysis of expression profile of mammalian cell entry (mce) operons of Mycobacterium tuberculosis. Infect. Immun. 71, 6083-7
3. Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells. Science 261, 1454-7
4. An ABC transport system that maintains lipid asymmetry in the gram-negative outer membrane. Proc. Natl. Acad. Sci. U.S.A. 106, 8009-14