9.B.325. The Putative ABC4 (ABC4) Family
The members of this family exhibit a variety of topologies and sizes. They are annotated as ABC-4 proteins, suggesting that they function together with an ATPase of the ABC type. However almost all of the membrane proteins of this family are encoded within gene clusters that do not include an ABC-type ATPase, leading to doubt about this suggestion.
The members of this family include (1) proteins of about 230 aas and 5 TMSs, (2) larger proteins of about 450 aas with 9 TMSs in a 4 + 5 TMS arrangement, where the 4 TMS domain does not appear to be similar to the 5 TMS domain, (3) 10 TMS proteins where the two halves, each with 5 TMSs, appear to be similar in sequence, each comprising a repeat unit, and (4) variations on these topologies. It is the 5 TMS unit that is common to members of this family. Although the family is annotated as the ABC-4 family in NCBI and Pfam, there seems to be little evidence that these proteins function as ATP-driven transporters. The one publication suggesting a role as an ABC-type system is described in the next paragraph.
A transporter gene from Clostridium hathewayi of the 'ABC4 family' was cloned (Rafii and Park 2008). It had duplicated ATPase domains in addition to a transmembrane protein. Its deduced amino acid sequence has conserved functional domains with ATPase components of the multidrug efflux pump genes of several bacteria. Cloning this gene into C. perfringens and E. coli resulted in decreased sensitivities of these bacteria to fluoroquinolones. It also decreased the accumulation and increased the efflux of ethidium bromide from cells containing the cloned gene. Carbonyl cyanide-m-chlorophenylhydrazone (CCCP) inhibited both accumulation and efflux of ethidium bromide from these cells. The ATPase mRNA was overexpressed in the fluoroquinolone-resistant strain when exposed to ciprofloxacin (Rafii and Park 2008). The fact that CCCP inhibited ethidium efflux from these cells led to the possibility that the pmf rather than ATP hydrolysis provided the energy for transport. Thus, there is some doubt that these proteins function as ABC-type porters.