Y3131_MYCTU
ID Y3131_MYCTU Reviewed; 344 AA.
AC P9WIZ7; L0TD88; P95195; Q7D627;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 2.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Putative NAD(P)H nitroreductase Rv3131 {ECO:0000305};
GN OrderedLocusNames=Rv3131;
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 PROTEIN SEQUENCE OF 2-24, AND SEQUENCE REVISION TO N-TERMINUS.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2022).
RN [3]
RP INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11416222; DOI=10.1073/pnas.121172498;
RA Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I.,
RA Schoolnik G.K.;
RT "Regulation of the Mycobacterium tuberculosis hypoxic response gene
RT encoding alpha -crystallin.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001).
RN [4]
RP INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, AND DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12953092; DOI=10.1084/jem.20030205;
RA Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., Dolganov G.M.,
RA Sherman D.R., Schoolnik G.K.;
RT "Inhibition of respiration by nitric oxide induces a Mycobacterium
RT tuberculosis dormancy program.";
RL J. Exp. Med. 198:705-713(2003).
RN [5]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [6]
RP INDUCTION BY CARBON MONOXIDE (CO).
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007;
RA Shiloh M.U., Manzanillo P., Cox J.S.;
RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during
RT macrophage infection.";
RL Cell Host Microbe 3:323-330(2008).
RN [7]
RP INDUCTION BY CARBON MONOXIDE (CO), AND DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18400743; DOI=10.1074/jbc.m802274200;
RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I.,
RA Agarwal A., Steyn A.J.;
RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium
RT tuberculosis dormancy regulon.";
RL J. Biol. Chem. 283:18032-18039(2008).
RN [8]
RP BIOTECHNOLOGY.
RX PubMed=19553548; DOI=10.1128/cvi.00111-09;
RA Black G.F., Thiel B.A., Ota M.O., Parida S.K., Adegbola R., Boom W.H.,
RA Dockrell H.M., Franken K.L., Friggen A.H., Hill P.C., Klein M.R.,
RA Lalor M.K., Mayanja H., Schoolnik G., Stanley K., Weldingh K.,
RA Kaufmann S.H., Walzl G., Ottenhoff T.H.;
RT "Immunogenicity of novel DosR regulon-encoded candidate antigens of
RT Mycobacterium tuberculosis in three high-burden populations in Africa.";
RL Clin. Vaccine Immunol. 16:1203-1212(2009).
RN [9]
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 [10]
RP FUNCTION, AND INTERACTION WITH TLR2.
RC STRAIN=H37Rv;
RX PubMed=27094446; DOI=10.1038/srep24535;
RA Peddireddy V., Doddam S.N., Qureshi I.A., Yerra P., Ahmed N.;
RT "A putative nitroreductase from the DosR regulon of Mycobacterium
RT tuberculosis induces pro-inflammatory cytokine expression via TLR2
RT signaling pathway.";
RL Sci. Rep. 6:24535-24535(2016).
CC -!- FUNCTION: Stimulates pro-inflammatory cytokine expression via TLR2
CC signaling pathway. Activation of TLR2 results in the phosphorylation
CC and activation of NF-kappa-B. Also induces TLR2 expression. May
CC influence the innate immune responses to facilitate the survival of
CC M.tuberculosis in the granulomatous microenvironment.
CC {ECO:0000269|PubMed:27094446}.
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000305};
CC -!- SUBUNIT: Interacts with human TLR2. {ECO:0000269|PubMed:27094446}.
CC -!- INDUCTION: A member of the dormancy regulon. Induced in response to
CC reduced oxygen tension (hypoxia), low levels of nitric oxide (NO) and
CC carbon monoxide (CO). It is hoped that this regulon will give insight
CC into the latent, or dormant phase of infection.
CC {ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:12953092,
CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359}.
CC -!- BIOTECHNOLOGY: This protein serves as an immunogenic antigen, inducing
CC gamma-interferon responses in whole-blood cultures from M.tuberculosis-
CC exposed adults in Uganda, and The Gambia but not from South Africa,
CC indicating this might be a good vaccine candidate.
CC {ECO:0000269|PubMed:19553548}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP45941.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000269|PubMed:34915127};
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DR EMBL; AL123456; CCP45941.1; ALT_INIT; Genomic_DNA.
DR PIR; D70645; D70645.
DR RefSeq; NP_217647.3; NC_000962.3.
DR AlphaFoldDB; P9WIZ7; -.
DR SMR; P9WIZ7; -.
DR STRING; 83332.Rv3131; -.
DR PaxDb; P9WIZ7; -.
DR DNASU; 888838; -.
DR GeneID; 888838; -.
DR KEGG; mtu:Rv3131; -.
DR TubercuList; Rv3131; -.
DR eggNOG; COG0778; Bacteria.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR Gene3D; 3.40.109.10; -; 2.
DR InterPro; IPR000415; Nitroreductase-like.
DR SUPFAM; SSF55469; SSF55469; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Flavoprotein; FMN; NAD; NADP; Oxidoreductase;
KW Reference proteome; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:34915127"
FT CHAIN 2..344
FT /note="Putative NAD(P)H nitroreductase Rv3131"
FT /id="PRO_0000392943"
FT BINDING 40..44
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255"
FT BINDING 326
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255"
SQ SEQUENCE 344 AA; 37049 MW; 6ACAD2A4C05DCB49 CRC64;
MTAAVDGKGP AAMNTHFPDA ETVRTVLTLA VRAPSIHNTQ PWRWRVCPTS LELFSRPDMQ
LRSTDPDGRE LILSCGVALH HCVVALASLG WQAKVNRFPD PKDRCHLATI GVQPLVPDQA
DVALAAAIPR RRTDRRAYSC WPVPGGDIAL MAARAARGGV MLRQVSALDR MKAIVAQAVL
DHVTDEEYLR ELTIWSGRYG SVAGVPARNE PPSDPSAPIP GRLFAGPGLS QPSDVLPADD
GAAILALGTE TDDRLARLRA GEAASIVLLT ATAMGLACCP ITEPLEIAKT RDAVRAEVFG
AGGYPQMLLR VGWAPINADP LPPTPRRELS QVVEWPEELL RQRC
