PACE_ACIBT
ID PACE_ACIBT Reviewed; 144 AA.
AC P0DUT9;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 1.
DT 25-MAY-2022, entry version 3.
DE RecName: Full=Short-chain diamines transporter {ECO:0000305};
DE AltName: Full=Acinetobacter chlorhexidine efflux protein I {ECO:0000303|PubMed:24277845};
GN Name=aceI {ECO:0000303|PubMed:24277845};
GN OrderedLocusNames=A1S_2063 {ECO:0000312|EMBL:ABO12490.2};
OS Acinetobacter baumannii (strain ATCC 17978 / CIP 53.77 / LMG 1025 / NCDC
OS KC755 / 5377).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Moraxellales; Moraxellaceae;
OC Acinetobacter; Acinetobacter calcoaceticus/baumannii complex.
OX NCBI_TaxID=400667;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 17978 / CIP 53.77 / LMG 1025 / NCDC KC755 / 5377;
RX PubMed=17344419; DOI=10.1101/gad.1510307;
RA Smith M.G., Gianoulis T.A., Pukatzki S., Mekalanos J.J., Ornston L.N.,
RA Gerstein M., Snyder M.;
RT "New insights into Acinetobacter baumannii pathogenesis revealed by high-
RT density pyrosequencing and transposon mutagenesis.";
RL Genes Dev. 21:601-614(2007).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND MUTAGENESIS OF GLU-15.
RC STRAIN=ATCC 17978 / CIP 53.77 / LMG 1025 / NCDC KC755 / 5377;
RX PubMed=24277845; DOI=10.1073/pnas.1317052110;
RA Hassan K.A., Jackson S.M., Penesyan A., Patching S.G., Tetu S.G.,
RA Eijkelkamp B.A., Brown M.H., Henderson P.J., Paulsen I.T.;
RT "Transcriptomic and biochemical analyses identify a family of chlorhexidine
RT efflux proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:20254-20259(2013).
RN [3]
RP FUNCTION, NOMENCLATURE, AND GENE FAMILY.
RX PubMed=25670776; DOI=10.1128/mbio.01982-14;
RA Hassan K.A., Liu Q., Henderson P.J., Paulsen I.T.;
RT "Homologs of the Acinetobacter baumannii AceI transporter represent a new
RT family of bacterial multidrug efflux systems.";
RL MBio 6:0-0(2015).
RN [4]
RP NOMENCLATURE, AND GENE FAMILY.
RX PubMed=25954261; DOI=10.3389/fmicb.2015.00333;
RA Hassan K.A., Elbourne L.D., Li L., Gamage H.K., Liu Q., Jackson S.M.,
RA Sharples D., Kolstoe A.B., Henderson P.J., Paulsen I.T.;
RT "An ace up their sleeve: a transcriptomic approach exposes the AceI efflux
RT protein of Acinetobacter baumannii and reveals the drug efflux potential
RT hidden in many microbial pathogens.";
RL Front. Microbiol. 6:333-333(2015).
RN [5]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 17978 / CIP 53.77 / LMG 1025 / NCDC KC755 / 5377;
RX PubMed=29481596; DOI=10.1093/jac/dky034;
RA Liu Q., Hassan K.A., Ashwood H.E., Gamage H.K.A.H., Li L., Mabbutt B.C.,
RA Paulsen I.T.;
RT "Regulation of the aceI multidrug efflux pump gene in Acinetobacter
RT baumannii.";
RL J. Antimicrob. Chemother. 73:1492-1500(2018).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, INDUCTION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-15.
RX PubMed=31416917; DOI=10.1073/pnas.1901591116;
RA Hassan K.A., Naidu V., Edgerton J.R., Mettrick K.A., Liu Q., Fahmy L.,
RA Li L., Jackson S.M., Ahmad I., Sharples D., Henderson P.J.F., Paulsen I.T.;
RT "Short-chain diamines are the physiological substrates of PACE family
RT efflux pumps.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:18015-18020(2019).
RN [7]
RP ACTIVITY REGULATION, SUBUNIT, INDUCTION, AND MUTAGENESIS OF GLU-15.
RX PubMed=32636271; DOI=10.1073/pnas.2003271117;
RA Bolla J.R., Howes A.C., Fiorentino F., Robinson C.V.;
RT "Assembly and regulation of the chlorhexidine-specific efflux pump AceI.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:17011-17018(2020).
CC -!- FUNCTION: Mediates the efflux of short-chain diamines when energized by
CC an electrochemical gradient (PubMed:31416917). Recognizes specifically
CC the short-chain diamines cadaverine and putrescine as substrates, and
CC promotes the active transport of these substrates in exchange for a
CC cation (PubMed:31416917). Protons are probably the primary source of
CC energy for transport, however it was not possible to conclude with
CC complete certainty that protons, rather than alternative cations such
CC as Na(+) ions, are exchanged for substrates by AceI (PubMed:31416917).
CC In addition, is involved in resistance to the synthetic biocide
CC chlorhexidine, a widely used antiseptic and disinfectant in both
CC hospital and community settings (PubMed:24277845, PubMed:25670776).
CC Interacts directly with chlorhexidine and mediates its efflux via an
CC energy-dependent mechanism (PubMed:24277845).
CC {ECO:0000269|PubMed:24277845, ECO:0000269|PubMed:25670776,
CC ECO:0000269|PubMed:31416917}.
CC -!- ACTIVITY REGULATION: Protonation/deprotonation of Glu-15 may play an
CC important role in transporter function (PubMed:32636271). Cadaverin
CC transport is inhibited in the presence of CCCP (PubMed:31416917).
CC {ECO:0000269|PubMed:31416917, ECO:0000269|PubMed:32636271}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.65 mM for cadaverine {ECO:0000269|PubMed:31416917};
CC -!- SUBUNIT: Exists in a monomer-homodimer equilibrium. The dimer is
CC probably the functional form of the protein, and the assembly of the
CC dimer is mediated by binding of chlorhexidine and promoted by high pH
CC conditions. {ECO:0000269|PubMed:32636271}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:24277845}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Transcriptionally regulated by the AceR regulator
CC (PubMed:29481596, PubMed:32636271). Strongly induced by the short-chain
CC diamines cadaverine and putrescine. Only moderately induced by the
CC triamine spermidine and weakly induced by the tetraamine spermine
CC (PubMed:31416917). Expression is also induced by more than 10-fold in
CC response to chlorhexidine exposure (PubMed:24277845, PubMed:29481596).
CC {ECO:0000269|PubMed:24277845, ECO:0000269|PubMed:29481596,
CC ECO:0000269|PubMed:31416917, ECO:0000269|PubMed:32636271}.
CC -!- DISRUPTION PHENOTYPE: Inactivation of the gene results in at least 8-
CC fold reduction in tolerance to cadaverine and putrescine but no change
CC in tolerance to spermidine or spermine (PubMed:31416917). Deletion
CC mutant also shows decreased chlorhexidine resistance (PubMed:29481596).
CC {ECO:0000269|PubMed:29481596, ECO:0000269|PubMed:31416917}.
CC -!- SIMILARITY: Belongs to the proteobacterial antimicrobial compound
CC efflux (PACE) (TC 2.A.117) family. {ECO:0000305|PubMed:25670776,
CC ECO:0000305|PubMed:25954261}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABO12490.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CP000521; ABO12490.2; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_005135057.1; NZ_CP053098.1.
DR GeneID; 56377069; -.
DR KEGG; acb:A1S_2063; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR InterPro; IPR007896; BTP_bacteria.
DR Pfam; PF05232; BTP; 2.
PE 1: Evidence at protein level;
KW Antiport; Cell inner membrane; Cell membrane; Membrane; Stress response;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..144
FT /note="Short-chain diamines transporter"
FT /id="PRO_0000453611"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 35..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MUTAGEN 15
FT /note="E->Q: Loss of activity. Mutant accumulates
FT cadaverine. Retains affinity for chlorhexidine, but does
FT not confer resistance to chlorhexidine. Favors the
FT monomeric form at both low pH and high pH."
FT /evidence="ECO:0000269|PubMed:24277845,
FT ECO:0000269|PubMed:31416917, ECO:0000269|PubMed:32636271"
SQ SEQUENCE 144 AA; 16639 MW; 522A28CA383ABD9A CRC64;
MLISKRRLIH AISYEGILLV IIAIALSFIF NMPMEVTGTL GVFMAVVSVF WNMIFNHYFE
KVEHKYNWER TIPVRILHAI GFEGGLLIAT VPMIAYMMQM TVIDAFILDI GLTLCILVYT
FIFQWCYDHI EDKFFPNAKA ASLH
