MPRB_MYCTU
ID MPRB_MYCTU Reviewed; 504 AA.
AC P9WGL1; L0T8A3; O53895; Q7D913;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 43.
DE RecName: Full=Signal transduction histidine-protein kinase/phosphatase MprB;
DE EC=2.7.13.3;
DE EC=3.1.3.-;
DE AltName: Full=Mycobacterial persistence regulator B;
GN Name=mprB; OrderedLocusNames=Rv0982;
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 IN SIGNAL TRANSDUCTION, AUTOPHOSPHORYLATION, COFACTOR, AND
RP MUTAGENESIS OF HIS-249.
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 IN MPRA-MEDIATED TRANSCRIPTIONAL REGULATION, AND INDUCTION.
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, AND TOPOLOGY.
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 INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16586367; DOI=10.1086/502631;
RA Jain S.K., Paul-Satyaseela M., Lamichhane G., Kim K.S., Bishai W.R.;
RT "Mycobacterium tuberculosis invasion and traversal across an in vitro human
RT blood-brain barrier as a pathogenic mechanism for central nervous system
RT tuberculosis.";
RL J. Infect. Dis. 193:1287-1295(2006).
RN [8]
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 [9]
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 [10]
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. In response to environmental signals
CC MprB acts as both a membrane-associated protein kinase that undergoes
CC autophosphorylation and subsequently transfers the phosphate to MprA,
CC and a protein phosphatase that dephosphorylates phospho-MprA. MprB/MprA
CC is involved in regulation of numerous stress-responsive genes,
CC including up-regulation of two sigma factors, sigE and sigB as well as
CC pepD and mprA, and repression of multiple genes from regulons
CC associated with hypoxia, starvation and iron metabolism. The majority
CC of genes regulated by MprB/MprA under a particular stress condition are
CC different from those induced during normal growth, but several genes
CC are commonly regulated under more than one condition.
CC {ECO:0000269|PubMed:11675502, ECO:0000269|PubMed:14638785,
CC ECO:0000269|PubMed:15601704, ECO:0000269|PubMed:16513743,
CC ECO:0000269|PubMed:17379732}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-
CC histidine.; EC=2.7.13.3;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:14638785};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:14638785};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- INDUCTION: Induced by MprA. 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. Highly up-regulated during the
CC early stages of invasion of the human blood-brain barrier.
CC {ECO:0000269|PubMed:11489128, ECO:0000269|PubMed:11675502,
CC ECO:0000269|PubMed:15601704, ECO:0000269|PubMed:16513743,
CC ECO:0000269|PubMed:16586367}.
CC -!- PTM: Autophosphorylated.
CC -!- MISCELLANEOUS: Deletion experiments show that amino acids 95-133 are
CC required for activation of MprA.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
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DR EMBL; AL123456; CCP43732.1; -; Genomic_DNA.
DR PIR; B70821; B70821.
DR RefSeq; NP_215497.1; NC_000962.3.
DR RefSeq; WP_003911317.1; NZ_NVQJ01000018.1.
DR AlphaFoldDB; P9WGL1; -.
DR SMR; P9WGL1; -.
DR STRING; 83332.Rv0982; -.
DR PaxDb; P9WGL1; -.
DR DNASU; 885062; -.
DR GeneID; 885062; -.
DR KEGG; mtu:Rv0982; -.
DR TubercuList; Rv0982; -.
DR eggNOG; COG2205; Bacteria.
DR eggNOG; COG2972; Bacteria.
DR OMA; VKAQMTE; -.
DR PhylomeDB; P9WGL1; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IDA:MTBBASE.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:MTBBASE.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IBA:GO_Central.
DR GO; GO:0018106; P:peptidyl-histidine phosphorylation; IDA:MTBBASE.
DR GO; GO:0000160; P:phosphorelay signal transduction system; IDA:MTBBASE.
DR CDD; cd00082; HisKA; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR003660; HAMP_dom.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR InterPro; IPR003661; HisK_dim/P.
DR InterPro; IPR036097; HisK_dim/P_sf.
DR InterPro; IPR004358; Sig_transdc_His_kin-like_C.
DR Pfam; PF00672; HAMP; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00512; HisKA; 1.
DR PRINTS; PR00344; BCTRLSENSOR.
DR SMART; SM00304; HAMP; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SMART; SM00388; HisKA; 1.
DR SUPFAM; SSF47384; SSF47384; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS50885; HAMP; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Hydrolase; Kinase; Magnesium; Manganese;
KW Membrane; Nucleotide-binding; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Stress response; Transferase; Transmembrane;
KW Transmembrane helix; Two-component regulatory system; Virulence.
FT CHAIN 1..504
FT /note="Signal transduction histidine-protein
FT kinase/phosphatase MprB"
FT /id="PRO_0000308440"
FT TOPO_DOM 1..26
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..163
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..504
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 186..238
FT /note="HAMP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00102"
FT DOMAIN 246..466
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT REGION 471..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..504
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 249
FT /note="Phosphohistidine; by autocatalysis"
FT /evidence="ECO:0000305"
FT MUTAGEN 249
FT /note="H->Q: Abolishes autophosphorylation as well as
FT dephosphorylation of phospho-MprA."
FT /evidence="ECO:0000269|PubMed:14638785"
SQ SEQUENCE 504 AA; 54408 MW; 26792A71AC432232 CRC64;
MWWFRRRDRA PLRATSSLSL RWRVMLLAMS MVAMVVVLMS FAVYAVISAA LYSDIDNQLQ
SRAQLLIASG SLAADPGKAI EGTAYSDVNA MLVNPGQSIY TAQQPGQTLP VGAAEKAVIR
GELFMSRRTT ADQRVLAIRL TNGSSLLISK SLKPTEAVMN KLRWVLLIVG GIGVAVAAVA
GGMVTRAGLR PVGRLTEAAE RVARTDDLRP IPVFGSDELA RLTEAFNLML RALAESRERQ
ARLVTDAGHE LRTPLTSLRT NVELLMASMA PGAPRLPKQE MVDLRADVLA QIEELSTLVG
DLVDLSRGDA GEVVHEPVDM ADVVDRSLER VRRRRNDILF DVEVIGWQVY GDTAGLSRMA
LNLMDNAAKW SPPGGHVGVR LSQLDASHAE LVVSDRGPGI PVQERRLVFE RFYRSASARA
LPGSGLGLAI VKQVVLNHGG LLRIEDTDPG GQPPGTSIYV LLPGRRMPIP QLPGATAGAR
STDIENSRGS ANVISVESQS TRAT
