MTRB_MYCTU
ID MTRB_MYCTU Reviewed; 567 AA.
AC P9WGK9; L0TF19; O05890; Q50496;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 41.
DE RecName: Full=Sensor histidine kinase MtrB;
DE EC=2.7.13.3;
GN Name=mtrB; OrderedLocusNames=Rv3245c; ORFNames=MTCY20B11.20c;
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 [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=8655513; DOI=10.1128/jb.178.11.3314-3321.1996;
RA Via L.E., Curcic R., Mudd M.H., Dhandayuthapani S., Ulmer R.J., Deretic V.;
RT "Elements of signal transduction in Mycobacterium tuberculosis: in vitro
RT phosphorylation and in vivo expression of the response regulator MtrA.";
RL J. Bacteriol. 178:3314-3321(1996).
RN [2]
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 [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10851001; DOI=10.1128/jb.182.13.3832-3838.2000;
RA Zahrt T.C., Deretic V.;
RT "An essential two-component signal transduction system in Mycobacterium
RT tuberculosis.";
RL J. Bacteriol. 182:3832-3838(2000).
RN [4]
RP CHARACTERIZATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16629667; DOI=10.1111/j.1365-2958.2006.05137.x;
RA Fol M., Chauhan A., Nair N.K., Maloney E., Moomey M., Jagannath C.,
RA Madiraju M.V., Rajagopalan M.;
RT "Modulation of Mycobacterium tuberculosis proliferation by MtrA, an
RT essential two-component response regulator.";
RL Mol. Microbiol. 60:643-657(2006).
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 SUBCELLULAR LOCATION, AND INTERACTION WITH LPQB.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20233304; DOI=10.1111/j.1365-2958.2010.07110.x;
RA Nguyen H.T., Wolff K.A., Cartabuke R.H., Ogwang S., Nguyen L.;
RT "A lipoprotein modulates activity of the MtrAB two-component system to
RT provide intrinsic multidrug resistance, cytokinetic control and cell wall
RT homeostasis in Mycobacterium.";
RL Mol. Microbiol. 76:348-364(2010).
RN [7]
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 [8]
RP FUNCTION, INTERACTION WITH MTRA, AUTOPHOSPHORYLATION, COFACTOR, AND
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21295603; DOI=10.1016/j.plasmid.2011.01.002;
RA Al Zayer M., Stankowska D., Dziedzic R., Sarva K., Madiraju M.V.,
RA Rajagopalan M.;
RT "Mycobacterium tuberculosis mtrA merodiploid strains with point mutations
RT in the signal-receiving domain of MtrA exhibit growth defects in nutrient
RT broth.";
RL Plasmid 65:210-218(2011).
RN [9]
RP FUNCTION, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-305.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22610443; DOI=10.1074/jbc.m112.346544;
RA Plocinska R., Purushotham G., Sarva K., Vadrevu I.S., Pandeeti E.V.,
RA Arora N., Plocinski P., Madiraju M.V., Rajagopalan M.;
RT "Septal localization of the Mycobacterium tuberculosis MtrB sensor kinase
RT promotes MtrA regulon expression.";
RL J. Biol. Chem. 287:23887-23899(2012).
CC -!- FUNCTION: Member of the two-component regulatory system MtrA/MtrB.
CC Probably functions as a membrane-associated protein kinase that
CC phosphorylates MtrA in response to environmental signals.
CC Autophosphorylates and transfers phosphate to MtrA in vitro.
CC Overexpression of MtrA alone decreases bacterial virulence in mouse
CC infection; co-expression of MtrA and MtrB restores normal bacterial
CC growth, suggesting that bacterial growth in macrophages requires an
CC optimal ratio of MtrB to MtrA. Probably plays a role in cell division.
CC {ECO:0000269|PubMed:21295603, ECO:0000269|PubMed:22610443}.
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:21295603};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:21295603};
CC Note=Autophosphorylates in the presence of Mg(2+) and/or Ca(2+), but
CC only Mg(2+) ions promote phosphotransfer to MtrA.
CC {ECO:0000269|PubMed:21295603};
CC -!- ACTIVITY REGULATION: Ca(2+) ions inhibit the phosphotransfer from MtrB
CC to MtrA. {ECO:0000269|PubMed:21295603}.
CC -!- SUBUNIT: Interacts with MrtA. Interacts with LpqB, probably
CC extracytoplasmically via MtrB's sensor domain.
CC {ECO:0000269|PubMed:20233304, ECO:0000269|PubMed:21295603}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20233304,
CC ECO:0000269|PubMed:22610443}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:20233304, ECO:0000269|PubMed:22610443}. Note=Found
CC at the septa or mid-cell, independent of phosphorylation state.
CC -!- PTM: The C-terminal domain (residues 234-567) autophosphorylates.
CC -!- DISRUPTION PHENOTYPE: Not essential for growth in liquid culture.
CC {ECO:0000269|PubMed:10851001}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
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DR EMBL; U14909; AAB07807.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46064.1; -; Genomic_DNA.
DR PIR; G70592; G70592.
DR RefSeq; NP_217762.1; NC_000962.3.
DR RefSeq; WP_003917137.1; NZ_NVQJ01000003.1.
DR AlphaFoldDB; P9WGK9; -.
DR SMR; P9WGK9; -.
DR STRING; 83332.Rv3245c; -.
DR PaxDb; P9WGK9; -.
DR DNASU; 888719; -.
DR GeneID; 888719; -.
DR KEGG; mtu:Rv3245c; -.
DR TubercuList; Rv3245c; -.
DR eggNOG; COG5000; Bacteria.
DR eggNOG; COG5002; Bacteria.
DR OMA; NRFWRSD; -.
DR PhylomeDB; P9WGK9; -.
DR BRENDA; 2.7.13.3; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IBA:GO_Central.
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; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Two-component regulatory system.
FT CHAIN 1..567
FT /note="Sensor histidine kinase MtrB"
FT /id="PRO_0000074809"
FT TRANSMEM 42..62
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 235..287
FT /note="HAMP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00102"
FT DOMAIN 302..519
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 529..552
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 553..567
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 305
FT /note="Phosphohistidine; by autocatalysis"
FT /evidence="ECO:0000305"
FT MUTAGEN 305
FT /note="H->D,Y: Loss of autophosphorylation. Partially
FT complements an M.smegmatis mtrB disruption, cells are still
FT filamentous and bulged but the protein targets to septa."
FT /evidence="ECO:0000269|PubMed:22610443"
FT CONFLICT 308
FT /note="R -> G (in Ref. 1; AAB07807)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 567 AA; 61637 MW; B4C73C330DF1764E CRC64;
MIFGSRRRIR GRRGRSGPMT RGLSALSRAV AVAWRRSLQL RVVALTLGLS LAVILALGFV
LTSQVTNRVL DIKVRAAIDQ IERARTTVSG IVNGEETRSL DSSLQLARNT LTSKTDPASG
AGLAGAFDAV LMVPGDGPRA ASTAGPVDQV PNALRGFVKA GQAAYQYATV QTEGFSGPAL
IIGTPTLSRV ANLELYLIFP LASEQATITL VRGTMATGGL VLLVLLAGIA LLVSRQVVVP
VRSASRIAER FAEGHLSERM PVRGEDDMAR LAVSFNDMAE SLSRQIAQLE EFGNLQRRFT
SDVSHELRTP LTTVRMAADL IYDHSADLDP TLRRSTELMV SELDRFETLL NDLLEISRHD
AGVAELSVEA VDLRTTVNNA LGNVGHLAEE AGIELLVDLP AEQVIAEVDA RRVERILRNL
IANAIDHAEH KPVRIRMAAD EDTVAVTVRD YGVGLRPGEE KLVFSRFWRS DPSRVRRSGG
TGLGLAISVE DARLHQGRLE AWGEPGEGAC FRLTLPMVRG HKVTTSPLPM KPIPQPVLQP
VAQPNPQPMP PEYKERQRPR EHAEWSG
