PKNB_MYCTU
ID PKNB_MYCTU Reviewed; 626 AA.
AC P9WI81; L0T5F6; P0A5S4; P71584;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Serine/threonine-protein kinase PknB;
DE EC=2.7.11.1;
GN Name=pknB; OrderedLocusNames=Rv0014c; ORFNames=MTCY10H4.14c;
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 PROTEIN SEQUENCE OF 2-29.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2022).
RN [3]
RP PROTEIN SEQUENCE OF 162-189, CATALYTIC ACTIVITY, PHOSPHORYLATION AT THR-171
RP AND THR-173, MUTAGENESIS OF THR-171 AND THR-173, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12950916; DOI=10.1046/j.1365-2958.2003.03657.x;
RA Boitel B., Ortiz-Lombardia M., Duran R., Pompeo F., Cole S.T.,
RA Cervenansky C., Alzari P.M.;
RT "PknB kinase activity is regulated by phosphorylation in two Thr residues
RT and dephosphorylation by PstP, the cognate phospho-Ser/Thr phosphatase, in
RT Mycobacterium tuberculosis.";
RL Mol. Microbiol. 49:1493-1508(2003).
RN [4]
RP CATALYTIC ACTIVITY, AND AUTOPHOSPHORYLATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10531215; DOI=10.1128/iai.67.11.5676-5682.1999;
RA Av-Gay Y., Jamil S., Drews S.J.;
RT "Expression and characterization of the Mycobacterium tuberculosis
RT serine/threonine protein kinase PknB.";
RL Infect. Immun. 67:5676-5682(1999).
RN [5]
RP PHOSPHORYLATION AT SER-166; THR-171; THR-173; THR-294 AND THR-309, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15967413; DOI=10.1016/j.bbrc.2005.05.173;
RA Duran R., Villarino A., Bellinzoni M., Wehenkel A., Fernandez P.,
RA Boitel B., Cole S.T., Alzari P.M., Cervenansky C.;
RT "Conserved autophosphorylation pattern in activation loops and
RT juxtamembrane regions of Mycobacterium tuberculosis Ser/Thr protein
RT kinases.";
RL Biochem. Biophys. Res. Commun. 333:858-867(2005).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, PHOSPHORYLATION AT THR-171 AND
RP THR-173, OVEREXPRESSION, AND MUTAGENESIS OF LYS-40.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15985609; DOI=10.1101/gad.1311105;
RA Kang C.M., Abbott D.W., Park S.T., Dascher C.C., Cantley L.C., Husson R.N.;
RT "The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB:
RT substrate identification and regulation of cell shape.";
RL Genes Dev. 19:1692-1704(2005).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH GARA, AND MUTAGENESIS OF
RP THR-171 AND THR-173.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15978616; DOI=10.1016/j.jmb.2005.05.049;
RA Villarino A., Duran R., Wehenkel A., Fernandez P., England P., Brodin P.,
RA Cole S.T., Zimny-Arndt U., Jungblut P.R., Cervenansky C., Alzari P.M.;
RT "Proteomic identification of M. tuberculosis protein kinase substrates:
RT PknB recruits GarA, a FHA domain-containing protein, through activation
RT loop-mediated interactions.";
RL J. Mol. Biol. 350:953-963(2005).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15987910; DOI=10.1110/ps.051413405;
RA Grundner C., Gay L.M., Alber T.;
RT "Mycobacterium tuberculosis serine/threonine kinases PknB, PknD, PknE, and
RT PknF phosphorylate multiple FHA domains.";
RL Protein Sci. 14:1918-1921(2005).
RN [9]
RP FUNCTION AS A KINASE WITH EMBR AS SUBSTRATE, AND DEPHOSPHORYLATION BY PSTP.
RX PubMed=16817899; DOI=10.1111/j.1742-4658.2006.05289.x;
RA Sharma K., Gupta M., Krupa A., Srinivasan N., Singh Y.;
RT "EmbR, a regulatory protein with ATPase activity, is a substrate of
RT multiple serine/threonine kinases and phosphatase in Mycobacterium
RT tuberculosis.";
RL FEBS J. 273:2711-2721(2006).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16980473; DOI=10.1128/jb.00963-06;
RA Fernandez P., Saint-Joanis B., Barilone N., Jackson M., Gicquel B.,
RA Cole S.T., Alzari P.M.;
RT "The Ser/Thr protein kinase PknB is essential for sustaining mycobacterial
RT growth.";
RL J. Bacteriol. 188:7778-7784(2006).
RN [11]
RP RETRACTED PAPER.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16436437; DOI=10.1099/mic.0.28630-0;
RA Dasgupta A., Datta P., Kundu M., Basu J.;
RT "The serine/threonine kinase PknB of Mycobacterium tuberculosis
RT phosphorylates PBPA, a penicillin-binding protein required for cell
RT division.";
RL Microbiology 152:493-504(2006).
RN [12]
RP RETRACTION NOTICE OF PUBMED:16436437.
RX PubMed=26231854; DOI=10.1099/mic.0.000110;
RA Dasgupta A., Datta P., Kundu M., Basu J.;
RL Microbiology 161:1537-1537(2015).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH FHAB, AND MUTAGENESIS OF
RP LYS-40; THR-171; THR-173; THR-294 AND THR-309.
RX PubMed=19826007; DOI=10.1074/jbc.m109.058834;
RA Gupta M., Sajid A., Arora G., Tandon V., Singh Y.;
RT "Forkhead-associated domain-containing protein Rv0019c and polyketide-
RT associated protein PapA5, from substrates of serine/threonine protein
RT kinase PknB to interacting proteins of Mycobacterium tuberculosis.";
RL J. Biol. Chem. 284:34723-34734(2009).
RN [14]
RP FUNCTION AS A KINASE WITH GLMU AS SUBSTRATE.
RX PubMed=19121323; DOI=10.1016/j.jmb.2008.12.031;
RA Parikh A., Verma S.K., Khan S., Prakash B., Nandicoori V.K.;
RT "PknB-mediated phosphorylation of a novel substrate, N-acetylglucosamine-1-
RT phosphate uridyltransferase, modulates its acetyltransferase activity.";
RL J. Mol. Biol. 386:451-464(2009).
RN [15]
RP FUNCTION AS A KINASE WITH RSEA AS A SUBSTRATE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20025669; DOI=10.1111/j.1365-2958.2009.07008.x;
RA Barik S., Sureka K., Mukherjee P., Basu J., Kundu M.;
RT "RseA, the SigE specific anti-sigma factor of Mycobacterium tuberculosis,
RT is inactivated by phosphorylation-dependent ClpC1P2 proteolysis.";
RL Mol. Microbiol. 75:592-606(2010).
RN [16]
RP ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF ARG-10; LEU-33; ASP-76 AND
RP ASP-138.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21134645; DOI=10.1016/j.str.2010.09.019;
RA Lombana T.N., Echols N., Good M.C., Thomsen N.D., Ng H.L., Greenstein A.E.,
RA Falick A.M., King D.S., Alber T.;
RT "Allosteric activation mechanism of the Mycobacterium tuberculosis receptor
RT Ser/Thr protein kinase, PknB.";
RL Structure 18:1667-1677(2010).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [18]
RP FUNCTION AS A KINASE WITH PSTP AS SUBSTRATE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21423706; DOI=10.1371/journal.pone.0017871;
RA Sajid A., Arora G., Gupta M., Upadhyay S., Nandicoori V.K., Singh Y.;
RT "Phosphorylation of Mycobacterium tuberculosis Ser/Thr phosphatase by PknA
RT and PknB.";
RL PLoS ONE 6:E17871-E17871(2011).
RN [19]
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=21829358; DOI=10.1371/journal.ppat.1002182;
RA Mir M., Asong J., Li X., Cardot J., Boons G.J., Husson R.N.;
RT "The extracytoplasmic domain of the Mycobacterium tuberculosis Ser/Thr
RT kinase PknB binds specific muropeptides and is required for PknB
RT localization.";
RL PLoS Pathog. 7:E1002182-E1002182(2011).
RN [20]
RP INTERACTION WITH FHAA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22000520; DOI=10.1016/j.str.2011.07.011;
RA Roumestand C., Leiba J., Galophe N., Margeat E., Padilla A., Bessin Y.,
RA Barthe P., Molle V., Cohen-Gonsaud M.;
RT "Structural insight into the Mycobacterium tuberculosis Rv0020c protein and
RT its interaction with the PknB kinase.";
RL Structure 19:1525-1534(2011).
RN [21]
RP FUNCTION.
RX PubMed=22275220; DOI=10.1126/scisignal.2002525;
RA Gee C.L., Papavinasasundaram K.G., Blair S.R., Baer C.E., Falick A.M.,
RA King D.S., Griffin J.E., Venghatakrishnan H., Zukauskas A., Wei J.R.,
RA Dhiman R.K., Crick D.C., Rubin E.J., Sassetti C.M., Alber T.;
RT "A phosphorylated pseudokinase complex controls cell wall synthesis in
RT mycobacteria.";
RL Sci. Signal. 5:RA7-RA7(2012).
RN [22]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DOMAIN.
RC STRAIN=H37Rv;
RX PubMed=24706757; DOI=10.1074/jbc.m114.563536;
RA Chawla Y., Upadhyay S., Khan S., Nagarajan S.N., Forti F., Nandicoori V.K.;
RT "Protein kinase B (PknB) of Mycobacterium tuberculosis is essential for
RT growth of the pathogen in vitro as well as for survival within the host.";
RL J. Biol. Chem. 289:13858-13875(2014).
RN [23]
RP FUNCTION, AND IDENTIFICATION OF PRCA AS SUBSTRATE.
RC STRAIN=H37Rv;
RX PubMed=25224505; DOI=10.1007/s12275-014-4416-2;
RA Anandan T., Han J., Baun H., Nyayapathy S., Brown J.T., Dial R.L.,
RA Moltalvo J.A., Kim M.S., Yang S.H., Ronning D.R., Husson R.N., Suh J.,
RA Kang C.M.;
RT "Phosphorylation regulates mycobacterial proteasome.";
RL J. Microbiol. 52:743-754(2014).
RN [24]
RP FUNCTION, AND INDUCTION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=24409094; DOI=10.1371/journal.pbio.1001746;
RA Ortega C., Liao R., Anderson L.N., Rustad T., Ollodart A.R., Wright A.T.,
RA Sherman D.R., Grundner C.;
RT "Mycobacterium tuberculosis Ser/Thr protein kinase B mediates an oxygen-
RT dependent replication switch.";
RL PLoS Biol. 12:E1001746-E1001746(2014).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-279 IN COMPLEX WITH ATP.
RX PubMed=12551895; DOI=10.1074/jbc.m300660200;
RA Ortiz-Lombardia M., Pompeo F., Boitel B., Alzari P.M.;
RT "Crystal structure of the catalytic domain of the PknB serine/threonine
RT kinase from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 278:13094-13100(2003).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-308 IN COMPLEX WITH ATP,
RP CATALYTIC ACTIVITY, METAL BINDING AT ASN-143 AND ASP-156, ATP BINDING AT
RP LYS-40, PHOSPHORYLATION AT SER-166; SER-169; THR-171; THR-173; THR-294 AND
RP SER-295, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12548283; DOI=10.1038/nsb897;
RA Young T.A., Delagoutte B., Endrizzi J.A., Falick A.M., Alber T.;
RT "Structure of Mycobacterium tuberculosis PknB supports a universal
RT activation mechanism for Ser/Thr protein kinases.";
RL Nat. Struct. Biol. 10:168-174(2003).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 1-279 IN COMPLEX WITH
RP MITOXANTRONE, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=16674948; DOI=10.1016/j.febslet.2006.04.046;
RA Wehenkel A., Fernandez P., Bellinzoni M., Catherinot V., Barilone N.,
RA Labesse G., Jackson M., Alzari P.M.;
RT "The structure of PknB in complex with mitoxantrone, an ATP-competitive
RT inhibitor, suggests a mode of protein kinase regulation in mycobacteria.";
RL FEBS Lett. 580:3018-3022(2006).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-308 IN COMPLEX WITH ADP, AND
RP PHOSPHORYLATION AT THR-171.
RX PubMed=19008858; DOI=10.1038/emboj.2008.236;
RA Mieczkowski C., Iavarone A.T., Alber T.;
RT "Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor
RT Ser/Thr kinase.";
RL EMBO J. 27:3186-3197(2008).
RN [29]
RP STRUCTURE BY NMR OF 355-491, AND ACTIVITY REGULATION.
RX PubMed=20462494; DOI=10.1016/j.str.2010.02.013;
RA Barthe P., Mukamolova G.V., Roumestand C., Cohen-Gonsaud M.;
RT "The structure of PknB extracellular PASTA domain from mycobacterium
RT tuberculosis suggests a ligand-dependent kinase activation.";
RL Structure 18:606-615(2010).
CC -!- FUNCTION: Protein kinase that regulates many aspects of mycobacterial
CC physiology, and is critical for growth in vitro and survival of the
CC pathogen in the host (PubMed:24706757). Is a key component of a signal
CC transduction pathway that regulates cell growth, cell shape and cell
CC division via phosphorylation of target proteins such as GarA, GlmU,
CC PapA5, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747
CC and RseA (PubMed:15978616, PubMed:15985609, PubMed:15987910,
CC PubMed:16817899, PubMed:16980473, PubMed:19121323, PubMed:19826007,
CC PubMed:20025669, PubMed:21423706, PubMed:22275220). Also catalyzes the
CC phosphorylation of the core proteasome alpha-subunit (PrcA), and
CC thereby regulates the proteolytic activity of the proteasome
CC (PubMed:25224505). Is a major regulator of the oxygen-dependent
CC replication switch since PknB activity is necessary for reactivation of
CC cells from the hypoxic state (PubMed:24409094). Shows a strong
CC preference for Thr versus Ser as the phosphoacceptor. Overexpression of
CC PknB alters cell morphology and leads to cell death (PubMed:24706757)
CC (PubMed:24409094). {ECO:0000269|PubMed:15978616,
CC ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:15987910,
CC ECO:0000269|PubMed:16817899, ECO:0000269|PubMed:16980473,
CC ECO:0000269|PubMed:19121323, ECO:0000269|PubMed:19826007,
CC ECO:0000269|PubMed:20025669, ECO:0000269|PubMed:21423706,
CC ECO:0000269|PubMed:22275220, ECO:0000269|PubMed:24409094,
CC ECO:0000269|PubMed:24706757, ECO:0000269|PubMed:25224505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:10531215, ECO:0000269|PubMed:12548283,
CC ECO:0000269|PubMed:12950916, ECO:0000269|PubMed:15978616,
CC ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:15987910,
CC ECO:0000269|PubMed:19826007};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:10531215,
CC ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12950916,
CC ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:15985609,
CC ECO:0000269|PubMed:15987910, ECO:0000269|PubMed:19826007};
CC -!- ACTIVITY REGULATION: Interaction of the PASTA domains with
CC peptidoglycan leads to septal and polar localization of PknB, and
CC dimerization of the intracellular kinase domain. Dimerization activates
CC the kinase domain via an allosteric mechanism, triggering
CC autophosphorylation and phosphorylation of target proteins. Inhibited
CC by mitoxantrone. Inhibition prevents mycobacterial growth.
CC {ECO:0000269|PubMed:16674948, ECO:0000269|PubMed:20462494,
CC ECO:0000269|PubMed:21134645, ECO:0000269|PubMed:21829358}.
CC -!- SUBUNIT: Homodimer. Interacts with the FHA domain of GarA, FhaB and
CC FhaA. {ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12551895,
CC ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:16674948,
CC ECO:0000269|PubMed:19008858, ECO:0000269|PubMed:19826007,
CC ECO:0000269|PubMed:21134645, ECO:0000269|PubMed:22000520}.
CC -!- INTERACTION:
CC P9WI81; P71590: fhaA; NbExp=4; IntAct=EBI-2946037, EBI-15896562;
CC P9WI81; P9WJA9: garA; NbExp=2; IntAct=EBI-2946037, EBI-6405522;
CC P9WI81; P9WI81: pknB; NbExp=12; IntAct=EBI-2946037, EBI-2946037;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21829358};
CC Single-pass membrane protein {ECO:0000269|PubMed:21829358}.
CC Note=Localizes to septum and cell poles (PubMed:21829358). The
CC localization of PknB to the cell membrane is essential for cell
CC survival (PubMed:24706757). {ECO:0000269|PubMed:21829358,
CC ECO:0000269|PubMed:24706757}.
CC -!- INDUCTION: Expressed predominantly in exponential phase
CC (PubMed:15985609). PknB levels are regulated in response to hypoxia;
CC its expression is down-regulated during hypoxia and recovers to aerated
CC levels upon reaeration (at mRNA and protein level) (PubMed:24409094).
CC {ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:24409094}.
CC -!- DOMAIN: The intracellular kinase domain and all four extracytoplasmic
CC PASTA domains are essential for PknB function and cell survival
CC (PubMed:24706757). The PASTA domains interact with peptidoglycans and
CC are required for PknB localization (PubMed:21829358).
CC {ECO:0000269|PubMed:21829358, ECO:0000269|PubMed:24706757}.
CC -!- PTM: Autophosphorylated. Dephosphorylated by PstP.
CC {ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12950916,
CC ECO:0000269|PubMed:15967413, ECO:0000269|PubMed:15985609,
CC ECO:0000269|PubMed:19008858}.
CC -!- DISRUPTION PHENOTYPE: Essential for growth, it cannot be disrupted
CC (PubMed:16980473). PknB depletion in M.tuberculosis results in cell
CC death and aberrant cell morphology, and leads to complete clearance of
CC the pathogen from the host tissues using the murine infection model
CC (PubMed:24706757). {ECO:0000269|PubMed:16980473,
CC ECO:0000269|PubMed:24706757}.
CC -!- MISCELLANEOUS: Overexpression causes major growth and morphological
CC changes that indicate defects in cell wall synthesis and possibly in
CC cell division. {ECO:0000305|PubMed:15985609}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- CAUTION: An article reported the role of PknB in phosphorylation of
CC PbpA, but this paper was later retracted as some figures were modified
CC prior to publication. {ECO:0000305|PubMed:16436437,
CC ECO:0000305|PubMed:26231854}.
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DR EMBL; AL123456; CCP42736.1; -; Genomic_DNA.
DR PIR; D70699; D70699.
DR RefSeq; NP_214528.1; NC_000962.3.
DR RefSeq; WP_003400356.1; NZ_NVQJ01000005.1.
DR PDB; 1MRU; X-ray; 3.00 A; A/B=1-308.
DR PDB; 1O6Y; X-ray; 2.20 A; A=1-279.
DR PDB; 2FUM; X-ray; 2.89 A; A/B/C/D=1-279.
DR PDB; 2KUD; NMR; -; A=355-491.
DR PDB; 2KUE; NMR; -; A=423-557.
DR PDB; 2KUF; NMR; -; A=491-626.
DR PDB; 2KUI; NMR; -; A=355-626.
DR PDB; 3F61; X-ray; 1.80 A; A=1-308.
DR PDB; 3F69; X-ray; 2.80 A; A/B=1-308.
DR PDB; 3ORI; X-ray; 2.00 A; A/B/C/D=1-308.
DR PDB; 3ORO; X-ray; 1.90 A; A=1-308.
DR PDB; 5E0Y; X-ray; 2.00 A; A=558-626.
DR PDB; 5E0Z; X-ray; 2.00 A; A=491-626.
DR PDB; 5E10; X-ray; 1.80 A; A=360-491.
DR PDB; 5E12; X-ray; 2.21 A; A/B=423-626.
DR PDB; 5U94; X-ray; 2.20 A; A=1-280.
DR PDB; 6B2P; X-ray; 3.01 A; A=1-279.
DR PDB; 6I2P; X-ray; 2.37 A; A/B=1-279.
DR PDBsum; 1MRU; -.
DR PDBsum; 1O6Y; -.
DR PDBsum; 2FUM; -.
DR PDBsum; 2KUD; -.
DR PDBsum; 2KUE; -.
DR PDBsum; 2KUF; -.
DR PDBsum; 2KUI; -.
DR PDBsum; 3F61; -.
DR PDBsum; 3F69; -.
DR PDBsum; 3ORI; -.
DR PDBsum; 3ORO; -.
DR PDBsum; 5E0Y; -.
DR PDBsum; 5E0Z; -.
DR PDBsum; 5E10; -.
DR PDBsum; 5E12; -.
DR PDBsum; 5U94; -.
DR PDBsum; 6B2P; -.
DR PDBsum; 6I2P; -.
DR AlphaFoldDB; P9WI81; -.
DR SMR; P9WI81; -.
DR IntAct; P9WI81; 4.
DR MINT; P9WI81; -.
DR STRING; 83332.Rv0014c; -.
DR BindingDB; P9WI81; -.
DR ChEMBL; CHEMBL1908385; -.
DR DrugBank; DB02930; Adenosine 5'-[gamma-thio]triphosphate.
DR DrugBank; DB03909; Adenosine-5'-[Beta, Gamma-Methylene]Triphosphate.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P9WI81; -.
DR iPTMnet; P9WI81; -.
DR PaxDb; P9WI81; -.
DR GeneID; 45423973; -.
DR GeneID; 887072; -.
DR KEGG; mtu:Rv0014c; -.
DR TubercuList; Rv0014c; -.
DR eggNOG; COG0515; Bacteria.
DR eggNOG; COG2815; Bacteria.
DR OMA; DPDYRYQ; -.
DR PhylomeDB; P9WI81; -.
DR PRO; PR:P9WI81; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010698; F:acetyltransferase activator activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0004672; F:protein kinase activity; IDA:MTBBASE.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MTBBASE.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:MTBBASE.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0045967; P:negative regulation of growth rate; IMP:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:MTBBASE.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IDA:MTBBASE.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:MTBBASE.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IDA:MTBBASE.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR005543; PASTA_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF03793; PASTA; 4.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00740; PASTA; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51178; PASTA; 4.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell membrane;
KW Direct protein sequencing; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Transmembrane;
KW Transmembrane helix; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:34915127,
FT ECO:0007744|PubMed:21969609"
FT CHAIN 2..626
FT /note="Serine/threonine-protein kinase PknB"
FT /id="PRO_0000171208"
FT TOPO_DOM 2..332
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 333..353
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 354..626
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 11..274
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 356..422
FT /note="PASTA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT DOMAIN 423..490
FT /note="PASTA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT DOMAIN 491..557
FT /note="PASTA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT DOMAIN 558..626
FT /note="PASTA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT REGION 299..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 138
FT /note="Proton acceptor"
FT BINDING 17..25
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12551895"
FT BINDING 40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12551895"
FT BINDING 93..95
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12551895"
FT BINDING 140..143
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12551895"
FT BINDING 143
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 156
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12551895"
FT BINDING 156
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 166
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12548283,
FT ECO:0000269|PubMed:15967413"
FT MOD_RES 169
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12548283"
FT MOD_RES 171
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12548283,
FT ECO:0000269|PubMed:12950916, ECO:0000269|PubMed:15967413,
FT ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:19008858"
FT MOD_RES 173
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12548283,
FT ECO:0000269|PubMed:12950916, ECO:0000269|PubMed:15967413,
FT ECO:0000269|PubMed:15985609"
FT MOD_RES 294
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12548283,
FT ECO:0000269|PubMed:15967413"
FT MOD_RES 295
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12548283"
FT MOD_RES 309
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MUTAGEN 10
FT /note="R->A: Impairs kinase activity."
FT /evidence="ECO:0000269|PubMed:21134645"
FT MUTAGEN 33
FT /note="L->D: Impairs kinase activity."
FT /evidence="ECO:0000269|PubMed:21134645"
FT MUTAGEN 40
FT /note="K->M: Lack of autophosphorylation. Decreases
FT affinity for FhaB."
FT /evidence="ECO:0000269|PubMed:15985609,
FT ECO:0000269|PubMed:19826007"
FT MUTAGEN 76
FT /note="D->A: Impairs kinase activity."
FT /evidence="ECO:0000269|PubMed:21134645"
FT MUTAGEN 138
FT /note="D->N: Impairs kinase activity."
FT /evidence="ECO:0000269|PubMed:21134645"
FT MUTAGEN 171
FT /note="T->A: Reduces activity and autophosphorylation.
FT Decreases interaction with GarA."
FT /evidence="ECO:0000269|PubMed:12950916,
FT ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:19826007"
FT MUTAGEN 173
FT /note="T->A: Reduces activity and autophosphorylation.
FT Decreases interaction with GarA."
FT /evidence="ECO:0000269|PubMed:12950916,
FT ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:19826007"
FT MUTAGEN 294
FT /note="T->A: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:19826007"
FT MUTAGEN 309
FT /note="T->A: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:19826007"
FT STRAND 5..7
FT /evidence="ECO:0007829|PDB:3F61"
FT TURN 8..10
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 11..19
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 21..30
FT /evidence="ECO:0007829|PDB:3F61"
FT TURN 31..34
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 35..42
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 50..60
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 74..82
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 85..93
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 112..131
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:3F69"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:3ORO"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:5U94"
FT HELIX 185..189
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 195..211
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 221..230
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 236..239
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1O6Y"
FT HELIX 245..254
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:3F61"
FT HELIX 266..277
FT /evidence="ECO:0007829|PDB:3F61"
FT STRAND 358..361
FT /evidence="ECO:0007829|PDB:2KUI"
FT HELIX 370..379
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 383..389
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 398..404
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:2KUI"
FT STRAND 415..421
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:5E10"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:2KUD"
FT HELIX 437..446
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 452..458
FT /evidence="ECO:0007829|PDB:5E10"
FT HELIX 461..463
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 466..472
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 484..490
FT /evidence="ECO:0007829|PDB:5E10"
FT STRAND 494..496
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:2KUF"
FT HELIX 505..515
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 520..525
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 533..539
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 544..546
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 551..556
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 560..562
FT /evidence="ECO:0007829|PDB:5E0Z"
FT HELIX 571..579
FT /evidence="ECO:0007829|PDB:5E0Z"
FT TURN 580..582
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:5E0Z"
FT HELIX 597..599
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 602..608
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 613..615
FT /evidence="ECO:0007829|PDB:5E0Z"
FT STRAND 620..625
FT /evidence="ECO:0007829|PDB:5E0Z"
SQ SEQUENCE 626 AA; 66510 MW; 6C27EEBE9D5A453B CRC64;
MTTPSHLSDR YELGEILGFG GMSEVHLARD LRLHRDVAVK VLRADLARDP SFYLRFRREA
QNAAALNHPA IVAVYDTGEA ETPAGPLPYI VMEYVDGVTL RDIVHTEGPM TPKRAIEVIA
DACQALNFSH QNGIIHRDVK PANIMISATN AVKVMDFGIA RAIADSGNSV TQTAAVIGTA
QYLSPEQARG DSVDARSDVY SLGCVLYEVL TGEPPFTGDS PVSVAYQHVR EDPIPPSARH
EGLSADLDAV VLKALAKNPE NRYQTAAEMR ADLVRVHNGE PPEAPKVLTD AERTSLLSSA
AGNLSGPRTD PLPRQDLDDT DRDRSIGSVG RWVAVVAVLA VLTVVVTIAI NTFGGITRDV
QVPDVRGQSS ADAIATLQNR GFKIRTLQKP DSTIPPDHVI GTDPAANTSV SAGDEITVNV
STGPEQREIP DVSTLTYAEA VKKLTAAGFG RFKQANSPST PELVGKVIGT NPPANQTSAI
TNVVIIIVGS GPATKDIPDV AGQTVDVAQK NLNVYGFTKF SQASVDSPRP AGEVTGTNPP
AGTTVPVDSV IELQVSKGNQ FVMPDLSGMF WVDAEPRLRA LGWTGMLDKG ADVDAGGSQH
NRVVYQNPPA GTGVNRDGII TLRFGQ
