MACA_ECOLI
ID MACA_ECOLI Reviewed; 371 AA.
AC P75830;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Macrolide export protein MacA;
GN Name=macA; Synonyms=ybjY; OrderedLocusNames=b0878, JW0862;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=K12 / W3104 / ATCC 19020;
RX PubMed=11544226; DOI=10.1128/jb.183.19.5639-5644.2001;
RA Kobayashi N., Nishino K., Yamaguchi A.;
RT "Novel macrolide-specific ABC-type efflux transporter in Escherichia
RT coli.";
RL J. Bacteriol. 183:5639-5644(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP PROTEIN SEQUENCE OF 1-10, FUNCTION, SUBUNIT, INTERACTION WITH MACB,
RP SUBCELLULAR LOCATION, INDUCTION, AND DOMAIN.
RC STRAIN=K12;
RX PubMed=17214741; DOI=10.1111/j.1365-2958.2006.05549.x;
RA Tikhonova E.B., Devroy V.K., Lau S.Y., Zgurskaya H.I.;
RT "Reconstitution of the Escherichia coli macrolide transporter: the
RT periplasmic membrane fusion protein MacA stimulates the ATPase activity of
RT MacB.";
RL Mol. Microbiol. 63:895-910(2007).
RN [6]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH MACB AND TOLC.
RX PubMed=18955484; DOI=10.1074/jbc.m806964200;
RA Lin H.T., Bavro V.N., Barrera N.P., Frankish H.M., Velamakanni S.,
RA van Veen H.W., Robinson C.V., Borges-Walmsley M.I., Walmsley A.R.;
RT "MacB ABC transporter is a dimer whose ATPase activity and macrolide-
RT binding capacity are regulated by the membrane fusion protein MacA.";
RL J. Biol. Chem. 284:1145-1154(2009).
RN [7]
RP INTERACTION WITH TOLC.
RX PubMed=21325274; DOI=10.1074/jbc.m110.202598;
RA Xu Y., Song S., Moeller A., Kim N., Piao S., Sim S.H., Kang M., Yu W.,
RA Cho H.S., Chang I., Lee K., Ha N.C.;
RT "Functional implications of an intermeshing cogwheel-like interaction
RT between TolC and MacA in the action of macrolide-specific efflux pump
RT MacAB-TolC.";
RL J. Biol. Chem. 286:13541-13549(2011).
RN [8]
RP FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF GLY-353 AND GLY-357.
RX PubMed=21696464; DOI=10.1111/j.1365-2958.2011.07744.x;
RA Modali S.D., Zgurskaya H.I.;
RT "The periplasmic membrane proximal domain of MacA acts as a switch in
RT stimulation of ATP hydrolysis by MacB transporter.";
RL Mol. Microbiol. 81:937-951(2011).
RN [9]
RP FUNCTION, AND R-LPS-BINDING.
RX PubMed=23974027; DOI=10.1128/jb.00756-13;
RA Lu S., Zgurskaya H.I.;
RT "MacA, a periplasmic membrane fusion protein of the macrolide transporter
RT MacAB-TolC, binds lipopolysaccharide core specifically and with high
RT affinity.";
RL J. Bacteriol. 195:4865-4872(2013).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS) OF 31-371, AND SUBUNIT.
RX PubMed=19254725; DOI=10.1016/j.jmb.2009.02.048;
RA Yum S., Xu Y., Piao S., Sim S.H., Kim H.M., Jo W.S., Kim K.J., Kweon H.S.,
RA Jeong M.H., Jeon H., Lee K., Ha N.C.;
RT "Crystal structure of the periplasmic component of a tripartite macrolide-
RT specific efflux pump.";
RL J. Mol. Biol. 387:1286-1297(2009).
CC -!- FUNCTION: Part of the tripartite efflux system MacAB-TolC. MacA
CC stimulates the ATPase activity of MacB by promoting the closed ATP-
CC bound state of MacB, increases the capacity of MacB to bind macrolides
CC such as erythromycin, and provides a physical link between MacB and
CC TolC. When overexpressed, the system confers resistance against
CC macrolides composed of 14- and 15-membered lactones but no or weak
CC resistance against 16-membered ones. In addition, MacA binds tightly
CC rough-core lipopolysaccharide (R-LPS), suggesting that the system could
CC also transport R-LPS or a similar glycolipid.
CC {ECO:0000269|PubMed:11544226, ECO:0000269|PubMed:17214741,
CC ECO:0000269|PubMed:18955484, ECO:0000269|PubMed:21696464,
CC ECO:0000269|PubMed:23974027}.
CC -!- SUBUNIT: Homohexamer. Part of the tripartite efflux system MacAB-TolC,
CC which is composed of an inner membrane transporter, MacB, a periplasmic
CC membrane fusion protein, MacA, and an outer membrane component, TolC.
CC The complex forms a large protein conduit and can translocate molecules
CC across both the inner and outer membranes. MacA interacts with MacB and
CC TolC, and this interaction changes its conformation.
CC {ECO:0000269|PubMed:17214741, ECO:0000269|PubMed:18955484,
CC ECO:0000269|PubMed:19254725, ECO:0000269|PubMed:21325274,
CC ECO:0000269|PubMed:21696464}.
CC -!- INTERACTION:
CC P75830; P75830: macA; NbExp=4; IntAct=EBI-551961, EBI-551961;
CC P75830; P75831: macB; NbExp=3; IntAct=EBI-551961, EBI-1125580;
CC P75830; P02930: tolC; NbExp=3; IntAct=EBI-551961, EBI-875614;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:11544226,
CC ECO:0000269|PubMed:17214741}; Single-pass membrane protein
CC {ECO:0000269|PubMed:11544226, ECO:0000269|PubMed:17214741}; Periplasmic
CC side {ECO:0000269|PubMed:11544226, ECO:0000269|PubMed:17214741}.
CC -!- INDUCTION: Expressed at very low levels under standard laboratory
CC conditions. {ECO:0000269|PubMed:17214741}.
CC -!- DOMAIN: The periplasmic domain is sufficient to bind MacB. The membrane
CC proximal (MP) region plays a critical role in the stimulation of MacB
CC ATPase activity. {ECO:0000269|PubMed:17214741,
CC ECO:0000269|PubMed:21696464}.
CC -!- SIMILARITY: Belongs to the membrane fusion protein (MFP) (TC 8.A.1)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB64541.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB071145; BAB64541.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC73965.2; -; Genomic_DNA.
DR EMBL; AP009048; BAA35597.1; -; Genomic_DNA.
DR PIR; F64826; F64826.
DR RefSeq; NP_415399.4; NC_000913.3.
DR RefSeq; WP_000746442.1; NZ_LN832404.1.
DR PDB; 3FPP; X-ray; 2.99 A; A/B=31-371.
DR PDB; 5NIK; EM; 3.30 A; D/E/F/G/H/I=1-371.
DR PDB; 5NIL; EM; 5.30 A; D/E/F/G/H/I=1-371.
DR PDBsum; 3FPP; -.
DR PDBsum; 5NIK; -.
DR PDBsum; 5NIL; -.
DR AlphaFoldDB; P75830; -.
DR SMR; P75830; -.
DR BioGRID; 4260003; 406.
DR ComplexPortal; CPX-2107; MacAB-TolC ABC transporter complex.
DR DIP; DIP-11460N; -.
DR IntAct; P75830; 11.
DR STRING; 511145.b0878; -.
DR TCDB; 3.A.1.122.1; the atp-binding cassette (abc) superfamily.
DR jPOST; P75830; -.
DR PaxDb; P75830; -.
DR PRIDE; P75830; -.
DR EnsemblBacteria; AAC73965; AAC73965; b0878.
DR EnsemblBacteria; BAA35597; BAA35597; BAA35597.
DR GeneID; 947322; -.
DR KEGG; ecj:JW0862; -.
DR KEGG; eco:b0878; -.
DR PATRIC; fig|1411691.4.peg.1399; -.
DR EchoBASE; EB3458; -.
DR eggNOG; COG0845; Bacteria.
DR HOGENOM; CLU_018816_14_1_6; -.
DR InParanoid; P75830; -.
DR OMA; TGKIQPE; -.
DR PhylomeDB; P75830; -.
DR BioCyc; EcoCyc:MACA; -.
DR BioCyc; MetaCyc:MACA; -.
DR EvolutionaryTrace; P75830; -.
DR PRO; PR:P75830; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:1990281; C:efflux pump complex; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:EcoliWiki.
DR GO; GO:1990196; C:MacAB-TolC complex; IDA:EcoCyc.
DR GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IDA:ComplexPortal.
DR InterPro; IPR032317; HlyD_D23.
DR InterPro; IPR030190; MacA.
DR InterPro; IPR006143; RND_pump_MFP.
DR PANTHER; PTHR30469:SF34; PTHR30469:SF34; 1.
DR Pfam; PF16576; HlyD_D23; 1.
DR TIGRFAMs; TIGR01730; RND_mfp; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Cell inner membrane; Cell membrane;
KW Coiled coil; Direct protein sequencing; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..371
FT /note="Macrolide export protein MacA"
FT /id="PRO_0000018695"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..371
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT COILED 92..137
FT /evidence="ECO:0000255"
FT MUTAGEN 353
FT /note="G->A: 2-fold increase in susceptibility to
FT macrolides. Does not affect oligomerization and ability to
FT interact with MacB and TolC, but changes the structure of
FT the MP region. Does not stimulate MacB ATPase activity."
FT /evidence="ECO:0000269|PubMed:21696464"
FT MUTAGEN 353
FT /note="G->C: 4-fold increase in susceptibility to
FT macrolides. Does not stimulate MacB ATPase activity."
FT /evidence="ECO:0000269|PubMed:21696464"
FT MUTAGEN 353
FT /note="G->S: 2-fold increase in susceptibility to
FT macrolides."
FT /evidence="ECO:0000269|PubMed:21696464"
FT MUTAGEN 357
FT /note="G->A: 2-fold increase in susceptibility to
FT macrolides. Does not stimulate MacB ATPase activity."
FT /evidence="ECO:0000269|PubMed:21696464"
FT MUTAGEN 357
FT /note="G->C,S: Does not affect susceptibility to
FT macrolides."
FT /evidence="ECO:0000269|PubMed:21696464"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 49..63
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:3FPP"
FT HELIX 95..125
FT /evidence="ECO:0007829|PDB:3FPP"
FT HELIX 127..137
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:3FPP"
FT HELIX 144..155
FT /evidence="ECO:0007829|PDB:3FPP"
FT HELIX 157..169
FT /evidence="ECO:0007829|PDB:3FPP"
FT HELIX 171..174
FT /evidence="ECO:0007829|PDB:3FPP"
FT TURN 175..182
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 183..187
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 189..199
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 221..228
FT /evidence="ECO:0007829|PDB:3FPP"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 248..253
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 276..282
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 293..300
FT /evidence="ECO:0007829|PDB:3FPP"
FT STRAND 305..310
FT /evidence="ECO:0007829|PDB:5NIK"
FT TURN 311..313
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 323..327
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 345..354
FT /evidence="ECO:0007829|PDB:5NIK"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:5NIK"
SQ SEQUENCE 371 AA; 40624 MW; 8BF287DA03B92AF9 CRC64;
MKKRKTVKKR YVIALVIVIA GLITLWRILN APVPTYQTLI VRPGDLQQSV LATGKLDALR
KVDVGAQVSG QLKTLSVAIG DKVKKDQLLG VIDPEQAENQ IKEVEATLME LRAQRQQAEA
ELKLARVTYS RQQRLAQTKA VSQQDLDTAA TEMAVKQAQI GTIDAQIKRN QASLDTAKTN
LDYTRIVAPM AGEVTQITTL QGQTVIAAQQ APNILTLADM SAMLVKAQVS EADVIHLKPG
QKAWFTVLGD PLTRYEGQIK DVLPTPEKVN DAIFYYARFE VPNPNGLLRL DMTAQVHIQL
TDVKNVLTIP LSALGDPVGD NRYKVKLLRN GETREREVTI GARNDTDVEI VKGLEAGDEV
VIGEAKPGAA Q
