NARL_MYCTU
ID NARL_MYCTU Reviewed; 216 AA.
AC P9WGM5; L0T7W4; O53856; Q7D965;
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=Probable transcriptional regulatory protein NarL;
GN Name=narL; OrderedLocusNames=Rv0844c;
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, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12595424; DOI=10.1128/iai.71.3.1134-1140.2003;
RA Parish T., Smith D.A., Kendall S., Casali N., Bancroft G.J., Stoker N.G.;
RT "Deletion of two-component regulatory systems increases the virulence of
RT Mycobacterium tuberculosis.";
RL Infect. Immun. 71:1134-1140(2003).
RN [3]
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 [4]
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 [5]
RP FUNCTION, PHOSPHORYLATION AT ASP-61, INTERACTION WITH DEVR, AND MUTAGENESIS
RP OF ASP-61.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=25659431; DOI=10.1074/jbc.m114.591800;
RA Malhotra V., Agrawal R., Duncan T.R., Saini D.K., Clark-Curtiss J.E.;
RT "Mycobacterium tuberculosis response regulators, DevR and NarL, interact in
RT vivo and co-regulate gene expression during aerobic nitrate metabolism.";
RL J. Biol. Chem. 290:8294-8309(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-145, AND SUBUNIT.
RX PubMed=19052358; DOI=10.1107/s1744309108035203;
RA Schnell R., Agren D., Schneider G.;
RT "1.9 A structure of the signal receiver domain of the putative response
RT regulator NarL from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 64:1096-1100(2008).
CC -!- FUNCTION: Member of the two-component regulatory system NarS/NarL that
CC regulates genes involved in aerobic nitrate metabolism
CC (PubMed:25659431). Upon phosphorylation by NarS, functions as a
CC transcription regulator by direct binding to promoter regions of target
CC genes together with DevR to regulate their expression during aerobic
CC nitrate metabolism (PubMed:25659431). {ECO:0000269|PubMed:25659431}.
CC -!- SUBUNIT: Monomer in solution (PubMed:19052358). Interacts with DevR
CC (PubMed:25659431). {ECO:0000269|PubMed:19052358,
CC ECO:0000269|PubMed:25659431}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- PTM: Phosphorylated by NarS. {ECO:0000269|PubMed:25659431}.
CC -!- DISRUPTION PHENOTYPE: Mutants show no change in virulence in mouse
CC model of infection. {ECO:0000269|PubMed:12595424}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
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DR EMBL; AL123456; CCP43592.1; -; Genomic_DNA.
DR PIR; D70813; D70813.
DR RefSeq; NP_215359.1; NC_000962.3.
DR RefSeq; WP_003404388.1; NZ_NVQJ01000040.1.
DR PDB; 3EUL; X-ray; 1.90 A; A/B/C/D=1-145.
DR PDBsum; 3EUL; -.
DR AlphaFoldDB; P9WGM5; -.
DR SMR; P9WGM5; -.
DR STRING; 83332.Rv0844c; -.
DR PaxDb; P9WGM5; -.
DR DNASU; 885603; -.
DR GeneID; 45424810; -.
DR GeneID; 885603; -.
DR KEGG; mtu:Rv0844c; -.
DR TubercuList; Rv0844c; -.
DR eggNOG; COG2197; Bacteria.
DR OMA; QHENKEY; -.
DR PhylomeDB; P9WGM5; -.
DR PHI-base; PHI:3620; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000160; P:phosphorelay signal transduction system; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR CDD; cd06170; LuxR_C_like; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR016032; Sig_transdc_resp-reg_C-effctor.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR InterPro; IPR000792; Tscrpt_reg_LuxR_C.
DR Pfam; PF00196; GerE; 1.
DR Pfam; PF00072; Response_reg; 1.
DR PRINTS; PR00038; HTHLUXR.
DR SMART; SM00421; HTH_LUXR; 1.
DR SMART; SM00448; REC; 1.
DR SUPFAM; SSF46894; SSF46894; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS50043; HTH_LUXR_2; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; DNA-binding; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Two-component regulatory system.
FT CHAIN 1..216
FT /note="Probable transcriptional regulatory protein NarL"
FT /id="PRO_0000401134"
FT DOMAIN 10..126
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DOMAIN 148..213
FT /note="HTH luxR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00411"
FT DNA_BIND 172..191
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00411"
FT MOD_RES 61
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169,
FT ECO:0000269|PubMed:25659431"
FT MUTAGEN 61
FT /note="D->N: Complete loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:25659431"
FT STRAND 9..14
FT /evidence="ECO:0007829|PDB:3EUL"
FT HELIX 18..30
FT /evidence="ECO:0007829|PDB:3EUL"
FT STRAND 32..42
FT /evidence="ECO:0007829|PDB:3EUL"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:3EUL"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:3EUL"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3EUL"
FT HELIX 69..78
FT /evidence="ECO:0007829|PDB:3EUL"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:3EUL"
FT HELIX 94..102
FT /evidence="ECO:0007829|PDB:3EUL"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:3EUL"
FT HELIX 115..127
FT /evidence="ECO:0007829|PDB:3EUL"
SQ SEQUENCE 216 AA; 22916 MW; 4604E6D7C8D132E5 CRC64;
MSNPQPEKVR VVVGDDHPLF REGVVRALSL SGSVNVVGEA DDGAAALELI KAHLPDVALL
DYRMPGMDGA QVAAAVRSYE LPTRVLLISA HDEPAIVYQA LQQGAAGFLL KDSTRTEIVK
AVLDCAKGRD VVAPSLVGGL AGEIRQRAAP VAPVLSARER EVLNRIACGQ SIPAIAAELY
VAPSTVKTHV QRLYEKLGVS DRAAAVAEAM RQRLLD
