TETX_MYCA9
ID TETX_MYCA9 Reviewed; 475 AA.
AC B1MM05;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 1.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Flavin-dependent monooxygenase {ECO:0000305};
DE AltName: Full=TetX monooxygenase {ECO:0000303|PubMed:29632012};
DE Short=MabTetX {ECO:0000303|PubMed:29632012};
DE EC=1.14.13.231 {ECO:0000305|PubMed:29632012};
DE AltName: Full=Tetracycline destructase {ECO:0000303|PubMed:29632012};
GN Name=tetX {ECO:0000305}; OrderedLocusNames=MAB_1496c;
OS Mycobacteroides abscessus (strain ATCC 19977 / DSM 44196 / CIP 104536 / JCM
OS 13569 / NCTC 13031 / TMC 1543) (Mycobacterium abscessus).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacteroides; Mycobacteroides abscessus.
OX NCBI_TaxID=561007;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC
RC 1543;
RX PubMed=19543527; DOI=10.1371/journal.pone.0005660;
RA Ripoll F., Pasek S., Schenowitz C., Dossat C., Barbe V., Rottman M.,
RA Macheras E., Heym B., Herrmann J.L., Daffe M., Brosch R., Risler J.L.,
RA Gaillard J.L.;
RT "Non mycobacterial virulence genes in the genome of the emerging pathogen
RT Mycobacterium abscessus.";
RL PLoS ONE 4:E5660-E5660(2009).
RN [2]
RP FUNCTION IN INACTIVATING TETRACYCLINE, NO ACTIVITY WITH TIGECYCLINE,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, INDUCTION BY TETRACYCLINE, OPERON,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=29632012; DOI=10.1128/aac.00119-18;
RA Rudra P., Hurst-Hess K., Lappierre P., Ghosh P.;
RT "High Levels of Intrinsic Tetracycline Resistance in Mycobacterium
RT abscessus Are Conferred by a Tetracycline-Modifying Monooxygenase.";
RL Antimicrob. Agents Chemother. 62:0-0(2018).
CC -!- FUNCTION: An FAD-requiring monooxygenase active on some tetracycline
CC antibiotic derivatives, which leads to their inactivation. Hydroxylates
CC carbon 11a of tetracycline and some analogs (By similarity). Confers
CC resistance to tetracycline and doxycycline via an oxidoreductase
CC activity; probably monooxygenates the antibiotics. Does not act on
CC tigecycline (PubMed:29632012). {ECO:0000250|UniProtKB:Q93L51,
CC ECO:0000269|PubMed:29632012}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a tetracycline + H(+) + NADPH + O2 = an 11a-
CC hydroxytetracycline + H2O + NADP(+); Xref=Rhea:RHEA:61444,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:144644,
CC ChEBI:CHEBI:144645; Evidence={ECO:0000305|PubMed:29632012};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + tetracycline = 11a-hydroxytetracycline +
CC H2O + NADP(+); Xref=Rhea:RHEA:50004, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:77932, ChEBI:CHEBI:132727;
CC EC=1.14.13.231; Evidence={ECO:0000305|PubMed:29632012};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- ACTIVITY REGULATION: Inhibited by anhydrotetracycline.
CC {ECO:0000269|PubMed:29632012}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q01911}.
CC -!- INDUCTION: Expression increases >200-fold after exposure to
CC tetracycline, doxycycline or inhibitor anhydrotetracycline but not
CC tigecycline; expression is repressed by upstream TetR (MAB_1497c), is
CC not under control of whiB7. Probably part of the TetR-TetX operon.
CC {ECO:0000269|PubMed:29632012}.
CC -!- DISRUPTION PHENOTYPE: Cells are about 2-fold more sensitive to
CC tetracycline and doxycycline, but remain sensitive to tigecycline, a
CC broad spectrum glycylcycline antibiotic. {ECO:0000269|PubMed:29632012}.
CC -!- MISCELLANEOUS: Although it has a similar activity to Bacteroides TetX
CC it is phylogentically distinct and is thought to have evolved by
CC convergent evolution. {ECO:0000305|PubMed:29632012}.
CC -!- SIMILARITY: Belongs to the aromatic-ring hydroxylase family.
CC {ECO:0000305}.
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DR EMBL; CU458896; CAM61582.1; -; Genomic_DNA.
DR RefSeq; WP_005114138.1; NZ_MLCG01000002.1.
DR AlphaFoldDB; B1MM05; -.
DR SMR; B1MM05; -.
DR EnsemblBacteria; CAM61582; CAM61582; MAB_1496c.
DR GeneID; 66971881; -.
DR KEGG; mab:MAB_1496c; -.
DR OMA; PQWRTQE; -.
DR Proteomes; UP000007137; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Antibiotic resistance; Cytoplasm; FAD; Flavoprotein; Monooxygenase; NADP;
KW Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..475
FT /note="Flavin-dependent monooxygenase"
FT /id="PRO_0000448380"
SQ SEQUENCE 475 AA; 51510 MW; CEDABE832310FA9A CRC64;
MTVVIAGAGP TGLTLACELT RRGIACRVLD KAPDLFPGSR GKGLSPRTQE VFDDLGIAPA
INSGGMAMPP FRIYAGHEVV AERSLVEMLG TDIPSGPGIP YPGFWLVPQW RTDEILLDRL
RQFGGDVEFN CEVVGFTQRS DAVSVMVSQG GAPELLHASY LVGADGGRST VRKMLGVGFA
GETFERERTL IGDVRADGLE GSFCHVLTRD GQVSERFSLW NLPGSEHYQF VANMATEDVP
ALTLDAVQKL VVDRSGRDDI VLRDLRWISL YRVNARMVDR FRVGRVILAG DAAHVHSSAG
GQGLNTSVQD AYNLGWKLAA VIYGAPEKLL DTYEEERMPV AASVLGLSTD LHHRNFAPAK
GPAPQLHQMD ITYRGCSLAV DDRVFQGNLR AGDRAPDALL DNGVRLFDVL RGTHFTLLTF
GAQAPVIADV CIQQMTPSPD YDVTATTLVL VRPDGYIGVM TESGRTVLEY LARVV
