RAAS_MYCTU
ID RAAS_MYCTU Reviewed; 212 AA.
AC O86312; F2GFW9; I6XXG2; Q7D8L0;
DT 05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=HTH-type transcriptional regulatory protein RaaS {ECO:0000305};
DE AltName: Full=Regulator of antimicrobial-assisted survival {ECO:0000303|PubMed:24590482};
GN Name=raaS {ECO:0000303|PubMed:24590482};
GN OrderedLocusNames=Rv1219c {ECO:0000312|EMBL:CCP43975.1};
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [3]
RP FUNCTION IN VIRULENCE, AND DISRUPTION PHENOTYPE.
RX PubMed=24590482; DOI=10.1128/aac.02774-13;
RA Turapov O., Waddell S.J., Burke B., Glenn S., Sarybaeva A.A., Tudo G.,
RA Labesse G., Young D.I., Young M., Andrew P.W., Butcher P.D.,
RA Cohen-Gonsaud M., Mukamolova G.V.;
RT "Antimicrobial treatment improves mycobacterial survival in nonpermissive
RT growth conditions.";
RL Antimicrob. Agents Chemother. 58:2798-2806(2014).
RN [4]
RP FUNCTION, DNA-BINDING, ACTIVITY REGULATION, SUBUNIT, INTERACTION WITH LONG
RP CHAIN ACYL-COA, AND MUTAGENESIS OF ARG-144 AND TYR-174.
RX PubMed=25012658; DOI=10.1074/jbc.m114.577338;
RA Turapov O., Waddell S.J., Burke B., Glenn S., Sarybaeva A.A., Tudo G.,
RA Labesse G., Young D.I., Young M., Andrew P.W., Butcher P.D.,
RA Cohen-Gonsaud M., Mukamolova G.V.;
RT "Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS
RT (Rv1219c) with DNA in mycobacteria.";
RL J. Biol. Chem. 289:25241-25249(2014).
RN [5] {ECO:0007744|PDB:4NN1}
RP X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS), FUNCTION, DNA-BINDING, SUBUNIT,
RP INTERACTION WITH DRUGS, INDUCTION, AND DOMAIN.
RC STRAIN=H37Rv;
RX PubMed=24424575; DOI=10.1002/pro.2424;
RA Kumar N., Radhakrishnan A., Wright C.C., Chou T.H., Lei H.T., Bolla J.R.,
RA Tringides M.L., Rajashankar K.R., Su C.C., Purdy G.E., Yu E.W.;
RT "Crystal structure of the transcriptional regulator Rv1219c of
RT Mycobacterium tuberculosis.";
RL Protein Sci. 23:423-432(2014).
CC -!- FUNCTION: Regulates the expression of the Rv1217c-Rv1218c multidrug
CC efflux system and its own expression. Acts by binding to promoter
CC regions of Rv1219c and upstream of the Rv1218c gene (PubMed:24424575).
CC Important for survival in prolonged stationary phase and during
CC macrophage infection (PubMed:24590482). May be used to eliminate non-
CC growing mycobacteria (PubMed:25012658). {ECO:0000269|PubMed:24424575,
CC ECO:0000269|PubMed:24590482, ECO:0000269|PubMed:25012658}.
CC -!- ACTIVITY REGULATION: Interaction with long chain acyl-CoA derivatives
CC (oleoyl-CoA and, to lesser extent, stearoyl-CoA) prevents binding to
CC DNA, leading to the expression of the target genes. Long chain acyl-CoA
CC derivatives may serve as biological indicators of the bacterial
CC metabolic state. {ECO:0000269|PubMed:25012658}.
CC -!- SUBUNIT: Homodimer (PubMed:24424575, PubMed:25012658). Interacts with
CC long chain acyl-CoA derivatives (PubMed:25012658). Interacts with
CC several drugs such rhodamine 6G, ethidium and safranin O
CC (PubMed:24424575). {ECO:0000269|PubMed:24424575,
CC ECO:0000269|PubMed:25012658}.
CC -!- INDUCTION: Expression is autoregulated. {ECO:0000269|PubMed:24424575}.
CC -!- DOMAIN: Contains an N-terminal DNA-binding domain and a C-terminal
CC ligand-binding domain, which can accommodate a variety of structurally
CC unrelated antimicrobial agents. The C-terminal domain is also involved
CC in dimerization. {ECO:0000269|PubMed:24424575}.
CC -!- DISRUPTION PHENOTYPE: Knockout mutant is impaired in long-term survival
CC at stationary phase and does not persist during macrophage infection.
CC {ECO:0000269|PubMed:24590482}.
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DR EMBL; AL123456; CCP43975.1; -; Genomic_DNA.
DR RefSeq; NP_215735.1; NC_000962.3.
DR RefSeq; WP_003406254.1; NZ_NVQJ01000039.1.
DR PDB; 4NN1; X-ray; 2.99 A; A=1-212.
DR PDBsum; 4NN1; -.
DR AlphaFoldDB; O86312; -.
DR SMR; O86312; -.
DR STRING; 83332.Rv1219c; -.
DR PaxDb; O86312; -.
DR PRIDE; O86312; -.
DR DNASU; 888582; -.
DR GeneID; 45425189; -.
DR GeneID; 888582; -.
DR KEGG; mtu:Rv1219c; -.
DR PATRIC; fig|83332.111.peg.1362; -.
DR TubercuList; Rv1219c; -.
DR eggNOG; COG1309; Bacteria.
DR OMA; IEQFGEH; -.
DR PhylomeDB; O86312; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001647; HTH_TetR.
DR InterPro; IPR036271; Tet_transcr_reg_TetR-rel_C_sf.
DR InterPro; IPR041484; TetR_C_25.
DR Pfam; PF17933; TetR_C_25; 1.
DR Pfam; PF00440; TetR_N; 1.
DR PRINTS; PR00455; HTHTETR.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF48498; SSF48498; 1.
DR PROSITE; PS50977; HTH_TETR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..212
FT /note="HTH-type transcriptional regulatory protein RaaS"
FT /id="PRO_0000447332"
FT DOMAIN 6..65
FT /note="HTH tetR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT DNA_BIND 28..47
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT MUTAGEN 144
FT /note="R->A: Reduces DNA binding affinity and ligand
FT binding."
FT /evidence="ECO:0000269|PubMed:25012658"
FT MUTAGEN 174
FT /note="Y->A: Reduces DNA binding affinity and ligand
FT binding."
FT /evidence="ECO:0000269|PubMed:25012658"
FT HELIX 7..23
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 29..36
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 40..47
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 50..74
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 79..86
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 87..91
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 107..129
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 139..159
FT /evidence="ECO:0007829|PDB:4NN1"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 179..188
FT /evidence="ECO:0007829|PDB:4NN1"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:4NN1"
FT HELIX 195..209
FT /evidence="ECO:0007829|PDB:4NN1"
SQ SEQUENCE 212 AA; 23181 MW; 8FBC03B909EA88C0 CRC64;
MRSADLTAHA RIREAAIEQF GRHGFGVGLR AIAEAAGVSA ALVIHHFGSK EGLRKACDDF
VAEEIRSSKA AALKSNDPTT WLAQMAEIES YAPLMAYLVR SMQSGGELAK MLWQKMIDNA
EEYLDEGVRA GTVKPSRDPR ARARFLAITG GGGFLLYLQM HENPTDLRAA LRDYAHDMVL
PSLEVYTEGL LADRAMYEAF LAEAQQGEAH VG
