MPRA_MYCTU
ID MPRA_MYCTU Reviewed; 230 AA.
AC P9WGM9; L0T5H1; O53894; Q7D914;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Response regulator MprA;
DE AltName: Full=Mycobacterial persistence regulator A;
GN Name=mprA; OrderedLocusNames=Rv0981;
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 INDUCTION SIGE-DEPENDENT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11489128; DOI=10.1046/j.1365-2958.2001.02525.x;
RA Manganelli R., Voskuil M.I., Schoolnik G.K., Smith I.;
RT "The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global
RT gene expression and survival in macrophages.";
RL Mol. Microbiol. 41:423-437(2001).
RN [3]
RP FUNCTION DURING STAGES OF PERSISTENT INFECTION, AND INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11675502; DOI=10.1073/pnas.221272198;
RA Zahrt T.C., Deretic V.;
RT "Mycobacterium tuberculosis signal transduction system required for
RT persistent infections.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12706-12711(2001).
RN [4]
RP FUNCTION AS A TRANSCRIPTIONAL REGULATOR, PHOSPHORYLATION AT ASP-48 BY MPRB,
RP AND MUTAGENESIS OF ASP-48 AND ASP-53.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14638785; DOI=10.1128/iai.71.12.6962-6970.2003;
RA Zahrt T.C., Wozniak C., Jones D., Trevett A.;
RT "Functional analysis of the Mycobacterium tuberculosis MprAB two-component
RT signal transduction system.";
RL Infect. Immun. 71:6962-6970(2003).
RN [5]
RP FUNCTION AS A TRANSCRIPTIONAL REGULATOR, SUBUNIT, AUTOREGULATION,
RP DNA-BINDING, AND MUTAGENESIS OF ASP-48.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15601704; DOI=10.1128/jb.187.1.202-212.2005;
RA He H., Zahrt T.C.;
RT "Identification and characterization of a regulatory sequence recognized by
RT Mycobacterium tuberculosis persistence regulator MprA.";
RL J. Bacteriol. 187:202-212(2005).
RN [6]
RP FUNCTION IN STRESS RESPONSE, INDUCTION, DNA-BINDING, AND MUTAGENESIS OF
RP ASP-48.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16513743; DOI=10.1128/jb.188.6.2134-2143.2006;
RA He H., Hovey R., Kane J., Singh V., Zahrt T.C.;
RT "MprAB is a stress-responsive two-component system that directly regulates
RT expression of sigma factors SigB and SigE in Mycobacterium tuberculosis.";
RL J. Bacteriol. 188:2134-2143(2006).
RN [7]
RP FUNCTION DURING NORMAL GROWTH CONDITION AND UNDER STRESS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17379732; DOI=10.1099/mic.0.29281-0;
RA Pang X., Vu P., Byrd T.F., Ghanny S., Soteropoulos P., Mukamolova G.V.,
RA Wu S., Samten B., Howard S.T.;
RT "Evidence for complex interactions of stress-associated regulons in an
RT mprAB deletion mutant of Mycobacterium tuberculosis.";
RL Microbiology 153:1229-1242(2007).
RN [8]
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).
CC -!- FUNCTION: Member of the two-component regulatory system MprB/MprA which
CC contributes to maintaining a balance among several systems involved in
CC stress resistance and is required for establishment and maintenance of
CC persistent infection in the host. Functions as a transcriptional
CC regulator that recognizes a 19-bp nucleotide motif comprizing two
CC loosely conserved 8-bp direct DNA-binding motif repeats separated by a
CC 3-bp spacer region. MprB/MprA is involved in regulation of numerous
CC stress-responsive genes, including up-regulation of two sigma factors,
CC sigE and sigB as well as pepD and mprA, and repression of multiple
CC genes from regulons associated with hypoxia, starvation and iron
CC metabolism. The majority of genes regulated by MprB/MprA under a
CC particular stress condition are different from those induced during
CC normal growth, but several genes are commonly regulated under more than
CC one condition. {ECO:0000269|PubMed:11675502,
CC ECO:0000269|PubMed:14638785, ECO:0000269|PubMed:15601704,
CC ECO:0000269|PubMed:16513743, ECO:0000269|PubMed:17379732}.
CC -!- SUBUNIT: Monomer. Interaction with each conserved 8-bp repeat requires
CC tandem binding by two protein monomers (Probable).
CC {ECO:0000305|PubMed:15601704}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- INDUCTION: Autoregulated. Differentially up-regulated under different
CC stress conditions, such as low concentrations of detergents and
CC alkaline pH. Induced by low concentrations of sodium dodecyl sulfate
CC (SDS) in a SigE-dependent manner. In strain ATCC 25618 / H37Rv,
CC repressed during growth in macrophages. {ECO:0000269|PubMed:11489128,
CC ECO:0000269|PubMed:11675502, ECO:0000269|PubMed:16513743}.
CC -!- PTM: Phosphorylated and dephosphorylated by MprB.
CC {ECO:0000269|PubMed:14638785}.
CC -!- MISCELLANEOUS: Phosphorylation is not required for binding to DNA in
CC vitro. However, phosphorylation enhances DNA binding and is required
CC for activity in vivo.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP43731.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL123456; CCP43731.1; ALT_INIT; Genomic_DNA.
DR PIR; A70821; A70821.
DR RefSeq; NP_215496.2; NC_000962.3.
DR AlphaFoldDB; P9WGM9; -.
DR SMR; P9WGM9; -.
DR STRING; 83332.Rv0981; -.
DR PaxDb; P9WGM9; -.
DR DNASU; 885038; -.
DR GeneID; 885038; -.
DR KEGG; mtu:Rv0981; -.
DR TubercuList; Rv0981; -.
DR eggNOG; COG0745; Bacteria.
DR OMA; NYEFFGD; -.
DR PhylomeDB; P9WGM9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0032993; C:protein-DNA complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:MTBBASE.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IBA:GO_Central.
DR GO; GO:0000156; F:phosphorelay response regulator activity; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0000160; P:phosphorelay signal transduction system; IDA:MTBBASE.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0010446; P:response to alkaline pH; IEP:UniProtKB.
DR CDD; cd00383; trans_reg_C; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR001867; OmpR/PhoB-type_DNA-bd.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR InterPro; IPR039420; WalR-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR48111; PTHR48111; 1.
DR Pfam; PF00072; Response_reg; 1.
DR Pfam; PF00486; Trans_reg_C; 1.
DR SMART; SM00448; REC; 1.
DR SMART; SM00862; Trans_reg_C; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS51755; OMPR_PHOB; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; DNA-binding; Phosphoprotein; Reference proteome;
KW Repressor; Stress response; Transcription; Transcription regulation;
KW Two-component regulatory system; Virulence.
FT CHAIN 1..230
FT /note="Response regulator MprA"
FT /id="PRO_0000308427"
FT DOMAIN 4..118
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DNA_BIND 129..227
FT /note="OmpR/PhoB-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01091"
FT MOD_RES 48
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000305|PubMed:14638785"
FT MUTAGEN 48
FT /note="D->A: Abolishes phosphorylation. No loss of DNA-
FT binding activity in vitro."
FT /evidence="ECO:0000269|PubMed:14638785,
FT ECO:0000269|PubMed:15601704, ECO:0000269|PubMed:16513743"
FT MUTAGEN 53
FT /note="D->A: No loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:14638785"
SQ SEQUENCE 230 AA; 25894 MW; 7A159FED949BE001 CRC64;
MSVRILVVDD DRAVRESLRR SLSFNGYSVE LAHDGVEALD MIASDRPDAL VLDVMMPRLD
GLEVCRQLRG TGDDLPILVL TARDSVSERV AGLDAGADDY LPKPFALEEL LARMRALLRR
TKPEDAAESM AMRFSDLTLD PVTREVNRGQ RRISLTRTEF ALLEMLIANP RRVLTRSRIL
EEVWGFDFPT SGNALEVYVG YLRRKTEADG EPRLIHTVRG VGYVLRETPP
