ID   MEFA_STRP6              Reviewed;         405 AA.
AC   Q5XBB2;
DT   31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   25-MAY-2022, entry version 96.
DE   RecName: Full=Macrolide efflux protein A {ECO:0000250|UniProtKB:P95827};
GN   Name=mefA {ECO:0000312|EMBL:AAR83188.1}; OrderedLocusNames=M6_Spy1166;
OS   Streptococcus pyogenes serotype M6 (strain ATCC BAA-946 / MGAS10394).
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC   Streptococcus.
OX   NCBI_TaxID=286636;
RN   [1] {ECO:0000312|EMBL:AAR83188.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC BAA-946 / MGAS10394;
RX   PubMed=14673771; DOI=10.1086/379897;
RA   Banks D.J., Porcella S.F., Barbian K.D., Martin J.M., Musser J.M.;
RT   "Structure and distribution of an unusual chimeric genetic element encoding
RT   macrolide resistance in phylogenetically diverse clones of group A
RT   Streptococcus.";
RL   J. Infect. Dis. 188:1898-1908(2003).
RN   [2] {ECO:0000312|EMBL:AAT87301.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-946 / MGAS10394;
RX   PubMed=15272401; DOI=10.1086/422697;
RA   Banks D.J., Porcella S.F., Barbian K.D., Beres S.B., Philips L.E.,
RA   Voyich J.M., DeLeo F.R., Martin J.M., Somerville G.A., Musser J.M.;
RT   "Progress toward characterization of the group A Streptococcus metagenome:
RT   complete genome sequence of a macrolide-resistant serotype M6 strain.";
RL   J. Infect. Dis. 190:727-738(2004).
CC   -!- FUNCTION: Confers resistance to 14-membered macrolides including
CC       erythromycin and to 15-membered macrolides but not to 16-membered
CC       macrolides, lincosamides or analogs of streptogramin B. May function as
CC       an efflux pump to regulate intracellular macrolide levels (By
CC       similarity). {ECO:0000250|UniProtKB:P95827}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the major facilitator superfamily. Drug:H(+)
CC       antiporter-3 (DHA3) (TC 2.A.1.21) family. {ECO:0000305}.
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DR   EMBL; AY445042; AAR83188.1; -; Genomic_DNA.
DR   EMBL; CP000003; AAT87301.1; -; Genomic_DNA.
DR   RefSeq; WP_000417517.1; NC_006086.1.
DR   AlphaFoldDB; Q5XBB2; -.
DR   SMR; Q5XBB2; -.
DR   EnsemblBacteria; AAT87301; AAT87301; M6_Spy1166.
DR   KEGG; spa:M6_Spy1166; -.
DR   HOGENOM; CLU_034180_16_0_9; -.
DR   OMA; TIWNQTI; -.
DR   Proteomes; UP000001167; Chromosome.
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:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR   Gene3D; 1.20.1250.20; -; 1.
DR   InterPro; IPR004751; Drug_antiport.
DR   InterPro; IPR011701; MFS.
DR   InterPro; IPR020846; MFS_dom.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   Pfam; PF07690; MFS_1; 1.
DR   SUPFAM; SSF103473; SSF103473; 1.
DR   TIGRFAMs; TIGR00900; 2A0121; 1.
DR   PROSITE; PS50850; MFS; 1.
PE   3: Inferred from homology;
KW   Antibiotic resistance; Cell membrane; Membrane; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..405
FT                   /note="Macrolide efflux protein A"
FT                   /id="PRO_0000408963"
FT   TRANSMEM        14..34
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        48..68
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        145..165
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        168..188
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        222..242
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        259..279
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        285..305
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        310..330
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        350..370
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        373..393
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   405 AA;  44279 MW;  52EC1EAAE3953011 CRC64;
     MEKYNNWKLK FYTIWAGQAV SLITSAILQM AIIFYLTEKT GSAMVLSMAS LLGFLPYAVF
     GPAIGVLVDR HDRKKIMIGA DLIIAAAGSV LTIVAFYMEL PVWMVMIVLF IRSIGTAFHT
     PALNAVTPLL VPEEQLTKCA GYSQSLQSIS YIVSPAVAAL LYSVWELNAI IAIDVLGAVI
     ASITVAIVRI PKLGDRVQSL DPNFIREMQE GMAVLRQNKG LFALLLVGTL YMFVYMPINA
     LFPLISMDYF NGTPVHISIT EISFASGMLI GGLLLGLFGN YQKRILLITA SIFMMGISLT
     ISGLLPQSGF FIFVVCCAIM GLSVPFYSGV QTALFQEKIK PEYLGRVFSL TGSIMSLAMP
     IGLILSALFA DRIGVNHWFL LSGTLIICIA IVCPMINEIR KLDLK