2.A.86 The Autoinducer-2 Exporter (AI-2E) Family (formerly the PerM Family, TC #9.B.22)

  The AI-2E family (UPF0118) is a large family of prokaryotic proteins derived from a variety of bacteria and archaea. Those examined are about 350 residues in length, and the couple that have been examined exhibit 7 putative transmembrane α-helical spanners (TMSs) (Rettner and Saier, 2010). E. coli, B. subtilis and several other prokaryotes have multiple paralogues encoded within their genomes. Herzberg et al. (2006) have presented strong evidence for a role of a AI-2E family homologue, YdgG (renamed TqsA), as an exporter of the E. coli autoinducer-2 (AI-2) (Camilli and Bassler, 2006; Chen et al., 2002). AT-2 is a proposed signalling molecule for interspecies communication in bacteria. It is a furanosyl borate diester (Chen et al., 2002). It is induced in Bacillus subtilis by exposure to rice seedlings (Xie et al. 2015). 

   More recently, it has been reported that this family includes a member of the
UPF0118 family (which is the former designation for the AI-2E family), and this transmembrane protein with 7 TMSs, exhibits pH-dependent Na+ or Li+/H+ antiport activity. Phylogenetic analyses were reported (Dong et al. 2017).  Thus, it appears that different members of the family may have very different transport functions.


The transport reactions catalyzed by membeers of the AI-2E family are:

AI-2 (in) ⇌ AI-2 (out)

Na+ or Li+ (out) + H+ (in) → Na+ or Li+ (in) + H+ (out)

This family belongs to the .



Besse A., Peduzzi J., Rebuffat S. and Carre-Mlouka A. (2015). Antimicrobial peptides and proteins in the face of extremes: Lessons from archaeocins. Biochimie. 118:344-55.

Camilli, A. and Bassler, B.L. (2006). Bacterial small-molecule signaling pathways. Science 311: 1113-1116.

Chen, X., S. Schauder, N. Potier, A. Van Dorsselaer, I. Pelczer, B.L. Bassler, and F.M. Hughson. (2002). Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415: 488-489.

Dong, P., L. Wang, N. Song, L. Yang, J. Chen, M. Yan, H. Chen, R. Zhang, J. Li, H. Abdel-Motaal, and J. Jiang. (2017). A UPF0118 family protein with uncharacterized function from the moderate halophile Halobacillus andaensis represents a novel class of Na(Li)/H antiporter. Sci Rep 7: 45936.

Eichenberger, P., S.T. Jensen, E.M. Conlon, C. van Ooij, J. Silvaggi, J.E. González-Pastor, M. Fujita, S. Ben-Yehuda, P. Stragier, J.S. Liu, and R. Losick. (2003). The sigmaE regulon and the identification of additional sporulation genes in Bacillus subtilis. J. Mol. Biol. 327: 945-972.

Herzberg, M., I.K. Kaye, W. Peti, and T.K. Wood. (2006). YdgG (TqsA) controls biofilm formation in Escherichia coli K-12 through autoinducer 2 transport. J. Bacteriol. 188: 587-598.

Kociolek, L.K., D.N. Gerding, D.W. Hecht, and E.A. Ozer. (2018). Comparative genomics analysis of Clostridium difficile epidemic strain DH/NAP11/106. Microbes Infect 20: 245-253.

Nobre, L.S., F. Al-Shahrour, J. Dopazo, and L.M. Saraiva. (2009). Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli. Microbiology 155: 813-824.

Ravcheev, D.A., M.S. Gel'fand, A.A. Mironov, and A.B. Rakhmaninova. (2002). [Purine regulon of γ-proteobacteria: a detailed description]. Genetika 38: 1203-1214.

Rettner, R.E. and M.H. Saier, Jr. (2010). The autoinducer-2 exporter superfamily. J. Mol. Microbiol. Biotechnol. 18: 195-205.

Turner, M.S. and J.D. Helmann. (2000). Mutations in multidrug efflux homologs, sugar isomerases, and antimicrobial biosynthesis genes differentially elevate activity of the σX and σW factors in Bacillus subtilis. J. Bacteriol. 182: 5202-5210.

Xie, S., H. Wu, L. Chen, H. Zang, Y. Xie, and X. Gao. (2015). Transcriptome profiling of Bacillus subtilis OKB105 in response to rice seedlings. BMC Microbiol 15: 21.


TC#NameOrganismal TypeExample
2.A.86.1.1Putative permease, PerMBacteria and archaeaPerM of E. coli (P0AFI9)

Uncharacterized protein of 502 aas and 8 TMSs

Red algae

UP of Galdieria sulphuraria


7 TMS permease which is encoded by a gene adjacent to a spore germination receptor (2.A.3.9.5) and an ABC exporter (TC# 3.A.1.147.2).


Permease of Paenibacillus mucilaginosus


Putative permease of 322 aas and 6 TMSs, HalU (Besse et al. 2015).

HalU of Halobacterium sp. (strain AS7092)


Uncharacterized protein of361 aas and 7 TMSs in a 2 + 5 TMS arrangement.

UP of Entamoeba histolytica



The sodium-lithium/proton antiporter; Na+ or Li+/H+ antiporter, UPF0118 or YtvI of 352 aas and 7 TMSs (Dong et al. 2017).

Na+ or Li+/H+ antiporter of Halobacillus andaensis


YtvI putative porter, of 363 aas and 8-10 TMSs in a 3 + 1, 2 or 3 + 3 + 1 arrangement. It is involved in virulence (Kociolek et al. 2018).

YtvI of Peptoclostridium difficile (Clostridium difficile)


Putative permease, YhhT (member of the PurR purine regulon)

Bacteria and archaea

YhhT of E. coli (P0AGM0)

2.A.86.1.3Putative permease, Yct2, encoded near the cta operonBacteria and archaeaYct2 of Bacillus firmus (spQ04454)

Autoinducer-2 (AI-2) exporter, TqsA (YdgG).  Plays a role in biofilm formation (Nobre et al. 2009).


TqsA of E. coli (POAFS5)


Permease (residues 1-380) fused to an ATP/GTP P-loop NTPase (AAA) superfamily domain (420-658) (Walker B motif; IstB-like)


Fused permease-ATPase protein of Brucella abortus (C9VRY8)


Putative aldose-1-epimerase (N-terminus) fusion protein with 7-8 TMS C-terminal transporter domain. Probable Aldose transporter.


Aldose-1-epimerase-transporter fusion protein of Micrococcus luteus (D3LPG3) 


Rv0205 (UFP0118) protein (376 aas, 8 putative TMSs) (may function with a heme uptake transporter) (TC# 2.A.6.5.5)


Rv0205 of Mycobacterium tuberculosis (O53656)


Putative transporter, YueF. Negatively regulates the sigW gene that encode the extra cytoplasmic sigma factor, sigma W, that activates genes which function in detoxification and the production of antimicrobial compounds (Turner and Helmann, 2000). SigW controls genes involved in transport and detoxification.


YueF of Bacillus subtilis (O32095)


Sporulation protein, YtvI of 371 aas and 6 - 8 TMSs. It is expressed under sigma E control, and null mutants are defective in spore formation (Eichenberger et al. 2003)). In Clostridium difficile, the orthologous ytvI gene is a virulence gene (Kociolek et al. 2018).


YtvI of Bacillus subtilis


TC#NameOrganismal TypeExample

Purine regulon gene product, YdiK (under PurR control (Ravcheev et al., 2002)).


YdiK of E. coli (B1LE48)


AI-2E homologue


AI-2E homologue of Myxococcus xanthus


Putative transporter


Putative transporter of Natronomonas pharaonis


TC#NameOrganismal TypeExample