TAP_MYCTU
ID TAP_MYCTU Reviewed; 419 AA.
AC P9WJX9; L0T8U8; P64783; Q11060;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 39.
DE RecName: Full=Multidrug efflux pump Tap {ECO:0000305};
DE AltName: Full=Tetracycline/aminoglycoside resistance-like efflux pump {ECO:0000303|PubMed:20525733};
GN Name=tap {ECO:0000303|PubMed:9811639}; OrderedLocusNames=Rv1258c;
GN ORFNames=MTCY50.24;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION IN TETRACYCLINE RESISTANCE.
RC STRAIN=H37Rv;
RX PubMed=9811639; DOI=10.1128/jb.180.22.5836-5843.1998;
RA Ainsa J.A., Blokpoel M.C., Otal I., Young D.B., De Smet K.A., Martin C.;
RT "Molecular cloning and characterization of Tap, a putative multidrug efflux
RT pump present in Mycobacterium fortuitum and Mycobacterium tuberculosis.";
RL J. Bacteriol. 180:5836-5843(1998).
RN [3]
RP FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12520088;
RA De Rossi E., Arrigo P., Bellinzoni M., Silva P.A., Martin C., Ainsa J.A.,
RA Guglierame P., Riccardi G.;
RT "The multidrug transporters belonging to major facilitator superfamily in
RT Mycobacterium tuberculosis.";
RL Mol. Med. 8:714-724(2002).
RN [4]
RP INDUCTION.
RX PubMed=15057575; DOI=10.1007/s15010-004-3097-x;
RA Siddiqi N., Das R., Pathak N., Banerjee S., Ahmed N., Katoch V.M.,
RA Hasnain S.E.;
RT "Mycobacterium tuberculosis isolate with a distinct genomic identity
RT overexpresses a tap-like efflux pump.";
RL Infection 32:109-111(2004).
RN [5]
RP FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=20525733; DOI=10.1093/jac/dkq186;
RA Sharma S., Kumar M., Sharma S., Nargotra A., Koul S., Khan I.A.;
RT "Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of
RT Mycobacterium tuberculosis.";
RL J. Antimicrob. Chemother. 65:1694-1701(2010).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=24894561; DOI=10.1016/j.bmcl.2014.05.022;
RA Singh K., Kumar M., Pavadai E., Naran K., Warner D.F., Ruminski P.G.,
RA Chibale K.;
RT "Synthesis of new verapamil analogues and their evaluation in combination
RT with rifampicin against Mycobacterium tuberculosis and molecular docking
RT studies in the binding site of efflux protein Rv1258c.";
RL Bioorg. Med. Chem. Lett. 24:2985-2990(2014).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF VAL-219 AND SER-292.
RC STRAIN=H37Ra;
RX PubMed=30837962; DOI=10.3389/fmicb.2019.00216;
RA Liu J., Shi W., Zhang S., Hao X., Maslov D.A., Shur K.V., Bekker O.B.,
RA Danilenko V.N., Zhang Y.;
RT "Mutations in efflux pump Rv1258c (Tap) cause resistance to pyrazinamide,
RT isoniazid, and streptomycin in M. tuberculosis.";
RL Front. Microbiol. 10:216-216(2019).
RN [8]
RP 3D-STRUCTURE MODELING.
RX PubMed=30475855; DOI=10.1371/journal.pone.0207605;
RA Cloete R., Kapp E., Joubert J., Christoffels A., Malan S.F.;
RT "Molecular modelling and simulation studies of the Mycobacterium
RT tuberculosis multidrug efflux pump protein Rv1258c.";
RL PLoS ONE 13:E0207605-E0207605(2018).
CC -!- FUNCTION: Efflux pump that contributes to intrinsic antibiotic
CC resistance (PubMed:9811639, PubMed:12520088, PubMed:20525733,
CC PubMed:30837962). The pump uses the electrochemical gradient as a
CC source of energy (By similarity). Confers resistance to rifampicin
CC (PubMed:20525733). Confers low-level resistance to tetracycline and to
CC several aminoglycosides, including streptomycin, gentamicin, 2'-N-
CC ethylnetilmicin and 6'-N-ethylnetilmicin (PubMed:9811639,
CC PubMed:12520088). {ECO:0000250|UniProtKB:O32859,
CC ECO:0000269|PubMed:12520088, ECO:0000269|PubMed:20525733,
CC ECO:0000269|PubMed:30837962, ECO:0000269|PubMed:9811639}.
CC -!- ACTIVITY REGULATION: Inhibited by piperine, verapamil and verapamil
CC analogs. {ECO:0000269|PubMed:20525733, ECO:0000269|PubMed:24894561}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- INDUCTION: Induced by rifampicin and ofloxacin.
CC {ECO:0000269|PubMed:15057575}.
CC -!- MISCELLANEOUS: Point mutations found in this efflux pump in clinical
CC isolates can play an important role in conferring clinically relevant
CC resistance to multiple drugs, including pyrazinamide, and could explain
CC some previously unaccounted drug resistance in clinical strains.
CC {ECO:0000269|PubMed:30837962}.
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; AL123456; CCP44014.1; -; Genomic_DNA.
DR PIR; B70753; B70753.
DR RefSeq; NP_215774.1; NC_000962.3.
DR RefSeq; WP_003406359.1; NZ_NVQJ01000049.1.
DR AlphaFoldDB; P9WJX9; -.
DR SMR; P9WJX9; -.
DR STRING; 83332.Rv1258c; -.
DR PaxDb; P9WJX9; -.
DR DNASU; 887056; -.
DR GeneID; 887056; -.
DR KEGG; mtu:Rv1258c; -.
DR TubercuList; Rv1258c; -.
DR eggNOG; COG2271; Bacteria.
DR OMA; MVVNIPM; -.
DR PhylomeDB; P9WJX9; -.
DR PHI-base; PHI:7049; -.
DR Proteomes; UP000001584; 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:0015562; F:efflux transmembrane transporter activity; IMP:MTBBASE.
DR GO; GO:0046677; P:response to antibiotic; IEP:MTBBASE.
DR Gene3D; 1.20.1250.20; -; 2.
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 PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Antibiotic resistance; Cell inner membrane; Cell membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..419
FT /note="Multidrug efflux pump Tap"
FT /id="PRO_0000103772"
FT TRANSMEM 7..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 44..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..335
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 348..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MUTAGEN 219
FT /note="V->A: Shows higher efflux activity. Causes
FT clinically relevant low-level drug resistance to
FT pyrazinamide (PZA), isoniazid (INH) and streptomycin (SM)."
FT MUTAGEN 292
FT /note="S->L: Shows higher efflux activity. Causes
FT clinically relevant high-level drug resistance to
FT pyrazinamide (PZA), isoniazid (INH) and streptomycin (SM)."
SQ SEQUENCE 419 AA; 43287 MW; 69EA46BBFF653037 CRC64;
MRNSNRGPAF LILFATLMAA AGDGVSIVAF PWLVLQREGS AGQASIVASA TMLPLLFATL
VAGTAVDYFG RRRVSMVADA LSGAAVAGVP LVAWGYGGDA VNVLVLAVLA ALAAAFGPAG
MTARDSMLPE AAARAGWSLD RINGAYEAIL NLAFIVGPAI GGLMIATVGG ITTMWITATA
FGLSILAIAA LQLEGAGKPH HTSRPQGLVS GIAEGLRFVW NLRVLRTLGM IDLTVTALYL
PMESVLFPKY FTDHQQPVQL GWALMAIAGG GLVGALGYAV LAIRVPRRVT MSTAVLTLGL
ASMVIAFLPP LPVIMVLCAV VGLVYGPIQP IYNYVIQTRA AQHLRGRVVG VMTSLAYAAG
PLGLLLAGPL TDAAGLHATF LALALPIVCT GLVAIRLPAL RELDLAPQAD IDRPVGSAQ
