ESPR_MYCTU
ID ESPR_MYCTU Reviewed; 132 AA.
AC P9WJB7; L0TDR1; P96228; Q8VIS2;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Nucleoid-associated protein EspR {ECO:0000305};
DE AltName: Full=ESX-1 transcriptional regulatory protein EspR {ECO:0000305};
GN Name=espR; OrderedLocusNames=Rv3849;
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 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 [3]
RP FUNCTION AS AN ACTIVATOR, INDUCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=18685700; DOI=10.1038/nature07219;
RA Raghavan S., Manzanillo P., Chan K., Dovey C., Cox J.S.;
RT "Secreted transcription factor controls Mycobacterium tuberculosis
RT virulence.";
RL Nature 454:717-721(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 IN REGULATION OF THE ESPACD OPERON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22389481; DOI=10.1128/jb.00142-12;
RA Hunt D.M., Sweeney N.P., Mori L., Whalan R.H., Comas I., Norman L.,
RA Cortes T., Arnvig K.B., Davis E.O., Stapleton M.R., Green J., Buxton R.S.;
RT "Long-range transcriptional control of an operon necessary for virulence-
RT critical ESX-1 secretion in Mycobacterium tuberculosis.";
RL J. Bacteriol. 194:2307-2320(2012).
RN [6]
RP FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22479184; DOI=10.1371/journal.ppat.1002621;
RA Blasco B., Chen J.M., Hartkoorn R., Sala C., Uplekar S., Rougemont J.,
RA Pojer F., Cole S.T.;
RT "Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-
RT associated protein.";
RL PLoS Pathog. 8:E1002621-E1002621(2012).
RN [7]
RP FUNCTION, AND DNA-BINDING.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=23743602; DOI=10.1007/s00284-013-0404-8;
RA Cao G., Howard S.T., Zhang P., Hou G., Pang X.;
RT "Functional analysis of the EspR binding sites upstream of espR in
RT Mycobacterium tuberculosis.";
RL Curr. Microbiol. 67:572-579(2013).
RN [8]
RP MUTAGENESIS OF ARG-69; LYS-71; ARG-100; ARG-105; ASP-122; ARG-125 AND
RP ASP-131.
RC STRAIN=H37Rv;
RX PubMed=24633871; DOI=10.1128/jb.00039-14;
RA Blasco B., Japaridze A., Stenta M., Wicky B.I., Dietler G., Dal Peraro M.,
RA Pojer F., Cole S.T.;
RT "Functional dissection of intersubunit interactions in the EspR virulence
RT regulator of Mycobacterium tuberculosis.";
RL J. Bacteriol. 196:1889-1900(2014).
RN [9]
RP INDUCTION.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=25536998; DOI=10.1099/mic.0.000023;
RA Cao G., Howard S.T., Zhang P., Wang X., Chen X.L., Samten B., Pang X.;
RT "EspR, a regulator of the ESX-1 secretion system in Mycobacterium
RT tuberculosis, is directly regulated by the two-component systems MprAB and
RT PhoPR.";
RL Microbiology 161:477-489(2015).
RN [10]
RP CRYSTALLIZATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21206031; DOI=10.1107/s174430911004618x;
RA Gangwar S.P., Meena S.R., Saxena A.K.;
RT "Cloning, purification, crystallization and preliminary X-ray analysis of
RT ESX-1-secreted protein regulator (EspR) from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 67:83-86(2011).
RN [11] {ECO:0007744|PDB:3QF3, ECO:0007744|PDB:3QWG, ECO:0007744|PDB:3QYX}
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 2-122, FUNCTION, DNA-BINDING,
RP SUBUNIT, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21883526; DOI=10.1111/j.1365-2958.2011.07813.x;
RA Blasco B., Stenta M., Alonso-Sarduy L., Dietler G., Peraro M.D., Cole S.T.,
RA Pojer F.;
RT "Atypical DNA recognition mechanism used by the EspR virulence regulator of
RT Mycobacterium tuberculosis.";
RL Mol. Microbiol. 82:251-264(2011).
RN [12] {ECO:0007744|PDB:3R1F}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), SUBUNIT, DOMAIN, AND DNA-BINDING.
RX PubMed=21795602; DOI=10.1073/pnas.1110242108;
RA Rosenberg O.S., Dovey C., Tempesta M., Robbins R.A., Finer-Moore J.S.,
RA Stroud R.M., Cox J.S.;
RT "EspR, a key regulator of Mycobacterium tuberculosis virulence, adopts a
RT unique dimeric structure among helix-turn-helix proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:13450-13455(2011).
RN [13] {ECO:0007744|PDB:4NDW}
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS).
RX PubMed=24699733; DOI=10.1107/s2053230x14004166;
RA Gangwar S.P., Meena S.R., Saxena A.K.;
RT "Comparison of four different crystal forms of the Mycobacterium
RT tuberculosis ESX-1 secreted protein regulator EspR.";
RL Acta Crystallogr. F Struct. Biol. Commun. 70:433-437(2014).
CC -!- FUNCTION: Virulence regulator that has both architectural and
CC regulatory roles. Impacts cell wall functions and pathogenesis through
CC regulation of multiple genes, including the espACD operon, which is a
CC key ESX-1 component. Influences target gene expression positively or
CC negatively, depending on its binding position relative to the genes it
CC controls. Acts by binding directly to the DNA. May play a central role
CC in regulating virulence gene expression. {ECO:0000269|PubMed:18685700,
CC ECO:0000269|PubMed:21883526, ECO:0000269|PubMed:22389481,
CC ECO:0000269|PubMed:22479184, ECO:0000269|PubMed:23743602}.
CC -!- SUBUNIT: Homodimer. Binds DNA as a dimer of dimers.
CC {ECO:0000269|PubMed:21795602, ECO:0000269|PubMed:21883526}.
CC -!- INTERACTION:
CC P9WJB7; P9WJB7: espR; NbExp=3; IntAct=EBI-15937970, EBI-15937970;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, nucleoid
CC {ECO:0000269|PubMed:22479184}.
CC -!- INDUCTION: Negatively autoregulated (PubMed:22479184).
CC Transcriptionally regulated by the MprB/MprA and PhoP/PhoR two-
CC component systems (PubMed:25536998). Expression is growth phase-
CC dependent, peaking in the stationary phase (PubMed:22479184). Probably
CC induced upon phagocytosis (PubMed:18685700).
CC {ECO:0000269|PubMed:18685700, ECO:0000269|PubMed:22479184,
CC ECO:0000269|PubMed:25536998}.
CC -!- DOMAIN: The N-terminal domain binds DNA and the C-terminal domain is
CC involved in dimerization. Both domains are required for transcriptional
CC activity and for ESX-1 function. {ECO:0000269|PubMed:18685700,
CC ECO:0000269|PubMed:21795602, ECO:0000269|PubMed:21883526}.
CC -!- DISRUPTION PHENOTYPE: Mutants exhibit growth defect during infection of
CC mice. They establish a stable infection by three weeks, but the
CC bacterial burden is an order of magnitude less than the wild-type.
CC {ECO:0000269|PubMed:18685700}.
CC -!- CAUTION: Was originally thought to be secreted via the ESX-1 secretion
CC system, but it was probably released in the medium via cell lysis.
CC {ECO:0000305|PubMed:18685700, ECO:0000305|PubMed:22479184}.
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DR EMBL; AL123456; CCP46678.1; -; Genomic_DNA.
DR PIR; F70654; F70654.
DR RefSeq; NP_218366.1; NC_000962.3.
DR RefSeq; WP_003399759.1; NZ_NVQJ01000057.1.
DR PDB; 3QF3; X-ray; 2.41 A; A/B/C/D/E/F=2-132.
DR PDB; 3QWG; X-ray; 1.99 A; A/B=2-122.
DR PDB; 3QYX; X-ray; 3.75 A; A/B/C/D=2-132.
DR PDB; 3R1F; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=1-132.
DR PDB; 4NDW; X-ray; 3.30 A; A/B=1-132.
DR PDBsum; 3QF3; -.
DR PDBsum; 3QWG; -.
DR PDBsum; 3QYX; -.
DR PDBsum; 3R1F; -.
DR PDBsum; 4NDW; -.
DR AlphaFoldDB; P9WJB7; -.
DR SMR; P9WJB7; -.
DR STRING; 83332.Rv3849; -.
DR PaxDb; P9WJB7; -.
DR GeneID; 45427853; -.
DR GeneID; 886184; -.
DR KEGG; mtu:Rv3849; -.
DR TubercuList; Rv3849; -.
DR eggNOG; COG1476; Bacteria.
DR OMA; PAYFYDA; -.
DR Proteomes; UP000001584; Chromosome.
DR CollecTF; EXPREG_00000c30; -.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0009295; C:nucleoid; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003677; F:DNA binding; IDA:MTBBASE.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050708; P:regulation of protein secretion; IDA:MTBBASE.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IEP:MTBBASE.
DR Gene3D; 1.10.260.40; -; 1.
DR InterPro; IPR001387; Cro/C1-type_HTH.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; DNA-binding; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Virulence.
FT CHAIN 1..132
FT /note="Nucleoid-associated protein EspR"
FT /id="PRO_0000393905"
FT DNA_BIND 38..50
FT /note="H-T-H motif"
FT /evidence="ECO:0000255"
FT MUTAGEN 69
FT /note="R->A: Affects protein stability. Decreases affinity
FT for DNA and dimerization capacity."
FT /evidence="ECO:0000269|PubMed:24633871"
FT MUTAGEN 71
FT /note="K->A: Decreases affinity for DNA. Does not affect
FT dimerization."
FT /evidence="ECO:0000269|PubMed:24633871"
FT MUTAGEN 100
FT /note="R->A: Affects protein stability. Decreases affinity
FT for DNA. Does not affect dimerization."
FT /evidence="ECO:0000269|PubMed:24633871"
FT MUTAGEN 105
FT /note="R->A: Does not affect DNA binding."
FT /evidence="ECO:0000269|PubMed:24633871"
FT MUTAGEN 122
FT /note="D->A: Moderate impact on protein stability. Does not
FT affect DNA binding."
FT /evidence="ECO:0000269|PubMed:24633871"
FT MUTAGEN 125
FT /note="R->A: Moderate impact on protein stability. Does not
FT affect DNA binding."
FT /evidence="ECO:0000269|PubMed:24633871"
FT MUTAGEN 131
FT /note="D->A: Moderate impact on protein stability. Does not
FT affect DNA binding."
FT /evidence="ECO:0000269|PubMed:24633871"
FT HELIX 5..15
FT /evidence="ECO:0007829|PDB:3QWG"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:3QWG"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:3QWG"
FT HELIX 42..49
FT /evidence="ECO:0007829|PDB:3QWG"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:3QF3"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:3QWG"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:3QWG"
FT HELIX 78..94
FT /evidence="ECO:0007829|PDB:3QWG"
FT HELIX 97..106
FT /evidence="ECO:0007829|PDB:3QF3"
FT HELIX 111..127
FT /evidence="ECO:0007829|PDB:3QF3"
SQ SEQUENCE 132 AA; 14709 MW; 84EA0DB906D81996 CRC64;
MSTTFAARLN RLFDTVYPPG RGPHTSAEVI AALKAEGITM SAPYLSQLRS GNRTNPSGAT
MAALANFFRI KAAYFTDDEY YEKLDKELQW LCTMRDDGVR RIAQRAHGLP SAAQQKVLDR
IDELRRAEGI DA
