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 most 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 apparent 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, (4) 11TMS proteins in a 1 + 5 + 5 TMS arrangement and (5) 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.



Rafii, F. and M. Park. (2008). Detection and characterization of an ABC transporter in Clostridium hathewayi. Arch. Microbiol. 190: 417-426.


TC#NameOrganismal TypeExample

The putative two component ABC-4-type transporter (Rafii and Park, 2008).  It appears to transport multiple drugs including ethidium and fluoroquinolones. The membrane protein (Q83XH0) is N-terminally truncked and is missing 88 aas.  A full length protein is R5TMA6 with 451 aas and 10 TMSs in a 5 + 5 TMS arrangement. This membrane protein has replaced the former one in this TC entry.

Bacteria and archaea

The ABC-4 M/C-C transporter of Clostridium hathewayi (Q83XH0)


Putative transporter of 564 aas and 11 TMSs in a 1 + 5 + 5 TMS topology. Each of the 5 TMS domains appears to have a 3 + 2 TMS arrangment.  This protein hits proteins 9.B.28.2.6 and 2.7 in a TC BLAST search, which are DUF975/UPF6259 family proteins, with decent scores (e-10 and e-6, respectively). It is the first half of the 9.B.325.1.2 protein that resembles proteins of TC family 9.B.28 (particularly 9.B.325.2.6 and 7). This is the only member of family 9.B.325 that has this domain, and only its second 5 TMS domain is homolgous to other members of 9.B.325. Other 10 TMS members of the 9.B.325 family have two copies of the 5 TMS repeat unit. The N-terminal 5 TMS domain in protein 9.B.325.1.2 may be a protease domain that processes the transporter domain (see family 9.B.28 description).

Putative transporter of an uncultured Butyricicoccus sp.


Uncharacterized protein of 253 aas and 5 TMSs.

UP of Oceanispirochaeta sp. M1


Uncharacterized protein of 216 aas and 5 TMSs.

UP of Candidatus Borkfalki ceftriaxensis


Uncharacterized protein of 427 aas and 10 TMSs in a 5 + 5 TMS arrangement, where each of the two putative repeat units has a 3 + 2 TMS arrangement.

UP of Eubacterium sp. CAG:161


Uncharacterized protein of 436 aas and 10 TMSs in a 5 + 5 TMS arrangement where each 5 TMS domain has a 3 + 2 TMS arrangement.

UP of Bacteroides pectinophilus


Uncharacterized protein of 288 aas and 5 TMSs in a 3 + 3 TMS arrangement.

UP of Bifidobacterium animalis


Uncharacterized protein with 10 TMSs in a 5 + 5 TMS arrangement.  Its gene is adjacent to one encoding an ABC exporter (TC# 3.A.1.111.8), and could be a chaparone protein for insertion and folding of the ABC transporter (see also TC# 9.B.29.2.17 which appears to be a chaparone protein for the ABC exporter with TC# 3.A.1.122.2).

UP of Lachnospiraceae bacterium