PKNE_MYCTU
ID PKNE_MYCTU Reviewed; 566 AA.
AC P9WI77; L0TA94; O08149; P72001;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Serine/threonine-protein kinase PknE;
DE EC=2.7.11.1;
GN Name=pknE; OrderedLocusNames=Rv1743; ORFNames=MTCY28.05;
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 CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY, AUTOPHOSPHORYLATION,
RP AND MUTAGENESIS OF LYS-45.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12927792; DOI=10.1016/s0006-291x(03)01476-1;
RA Molle V., Girard-Blanc C., Kremer L., Doublet P., Cozzone A.J., Prost J.F.;
RT "Protein PknE, a novel transmembrane eukaryotic-like serine/threonine
RT kinase from Mycobacterium tuberculosis.";
RL Biochem. Biophys. Res. Commun. 308:820-825(2003).
RN [3]
RP PHOSPHORYLATION AT SER-7; THR-11; THR-50; THR-59; THR-170; THR-175 AND
RP THR-178, AND 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 [4]
RP FUNCTION.
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 [5]
RP AUTOPHOSPHORYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16739134; DOI=10.1002/pmic.200500900;
RA Molle V., Zanella-Cleon I., Robin J.P., Mallejac S., Cozzone A.J.,
RA Becchi M.;
RT "Characterization of the phosphorylation sites of Mycobacterium
RT tuberculosis serine/threonine protein kinases, PknA, PknD, PknE, and PknH
RT by mass spectrometry.";
RL Proteomics 6:3754-3766(2006).
RN [6]
RP FUNCTION IN VIRULENCE, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17892498; DOI=10.1111/j.1462-5822.2007.01049.x;
RA Jayakumar D., Jacobs W.R. Jr., Narayanan S.;
RT "Protein kinase E of Mycobacterium tuberculosis has a role in the nitric
RT oxide stress response and apoptosis in a human macrophage model of
RT infection.";
RL Cell. Microbiol. 10:365-374(2008).
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 IN VIRULENCE, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23108860; DOI=10.1007/s00203-012-0848-4;
RA Kumar D., Palaniyandi K., Challu V.K., Kumar P., Narayanan S.;
RT "PknE, a serine/threonine protein kinase from Mycobacterium tuberculosis
RT has a role in adaptive responses.";
RL Arch. Microbiol. 195:75-80(2013).
RN [9]
RP FUNCTION IN VIRULENCE, AND DISRUPTION PHENOTYPE.
RX PubMed=21945589; DOI=10.1016/j.meegid.2011.09.008;
RA Kumar D., Narayanan S.;
RT "pknE, a serine/threonine kinase of Mycobacterium tuberculosis modulates
RT multiple apoptotic paradigms.";
RL Infect. Genet. Evol. 12:737-747(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-289, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16762364; DOI=10.1016/j.jmb.2006.05.015;
RA Gay L.M., Ng H.L., Alber T.;
RT "A conserved dimer and global conformational changes in the structure of
RT apo-PknE Ser/Thr protein kinase from Mycobacterium tuberculosis.";
RL J. Mol. Biol. 360:409-420(2006).
CC -!- FUNCTION: Important for survival of the bacterium in the host during
CC infection. Promotes the survival of infected macrophages by activating
CC multiple signaling responses and suppressing apoptosis of macrophages
CC during nitrate stress. May contribute to the adaptation of
CC M.tuberculosis during stress conditions by maintaining the cellular
CC integrity. Can phosphorylate the FHA domain of Rv1747.
CC {ECO:0000269|PubMed:15987910, ECO:0000269|PubMed:17892498,
CC ECO:0000269|PubMed:21945589, ECO:0000269|PubMed:23108860}.
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:12927792};
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:12927792};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16762364}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12927792};
CC Single-pass membrane protein {ECO:0000269|PubMed:12927792}.
CC -!- INDUCTION: Induced by nitric oxide stress. Repressed under oxidative
CC stress. {ECO:0000269|PubMed:17892498}.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC Dephosphorylated by PstP. {ECO:0000269|PubMed:15967413}.
CC -!- DISRUPTION PHENOTYPE: Mutants show increased resistance to nitric oxide
CC donors, increased sensitivity to reducing agents, and growth reduction
CC at pH 7.0 and in the presence of lysozyme. They increase macrophage
CC apoptosis, and exhibit lower rates of survival and multiplication in an
CC in vitro macrophage model of infection. {ECO:0000269|PubMed:17892498,
CC ECO:0000269|PubMed:21945589, ECO:0000269|PubMed:23108860}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AL123456; CCP44509.1; -; Genomic_DNA.
DR PIR; H70985; H70985.
DR RefSeq; NP_216259.1; NC_000962.3.
DR RefSeq; WP_003898998.1; NZ_NVQJ01000010.1.
DR PDB; 2H34; X-ray; 2.80 A; A/B=1-289.
DR PDBsum; 2H34; -.
DR AlphaFoldDB; P9WI77; -.
DR SMR; P9WI77; -.
DR IntAct; P9WI77; 2.
DR STRING; 83332.Rv1743; -.
DR iPTMnet; P9WI77; -.
DR PaxDb; P9WI77; -.
DR DNASU; 885284; -.
DR GeneID; 885284; -.
DR KEGG; mtu:Rv1743; -.
DR TubercuList; Rv1743; -.
DR eggNOG; COG0515; Bacteria.
DR eggNOG; COG1651; Bacteria.
DR OMA; ITIFDFG; -.
DR PhylomeDB; P9WI77; -.
DR BRENDA; 2.7.11.1; 3445.
DR PHI-base; PHI:3625; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; 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: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:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IDA:MTBBASE.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MTBBASE.
DR GO; GO:0051409; P:response to nitrosative stress; IMP:MTBBASE.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF13462; Thioredoxin_4; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1..566
FT /note="Serine/threonine-protein kinase PknE"
FT /id="PRO_0000171211"
FT TOPO_DOM 1..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..566
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 16..275
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 296..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..330
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 139
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 22..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 45
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 7
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 11
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 50
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 59
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 170
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 175
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 178
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MUTAGEN 45
FT /note="K->M: Lack of kinase activity."
FT /evidence="ECO:0000269|PubMed:12927792"
FT STRAND 18..24
FT /evidence="ECO:0007829|PDB:2H34"
FT STRAND 26..35
FT /evidence="ECO:0007829|PDB:2H34"
FT TURN 36..39
FT /evidence="ECO:0007829|PDB:2H34"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 48..53
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:2H34"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:2H34"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 101..108
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 113..132
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:2H34"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2H34"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 197..210
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 244..252
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:2H34"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:2H34"
SQ SEQUENCE 566 AA; 60512 MW; C31534068DE60FE4 CRC64;
MDGTAESREG TQFGPYRLRR LVGRGGMGDV YEAEDTVRER IVALKLMSET LSSDPVFRTR
MQREARTAGR LQEPHVVPIH DFGEIDGQLY VDMRLINGVD LAAMLRRQGP LAPPRAVAIV
RQIGSALDAA HAAGATHRDV KPENILVSAD DFAYLVDFGI ASATTDEKLT QLGNTVGTLY
YMAPERFSES HATYRADIYA LTCVLYECLT GSPPYQGDQL SVMGAHINQA IPRPSTVRPG
IPVAFDAVIA RGMAKNPEDR YVTCGDLSAA AHAALATADQ DRATDILRRS QVAKLPVPST
HPVSPGTRWP QPTPWAGGAP PWGPPSSPLP RSARQPWLWV GVAVAVVVAL AGGLGIALAH
PWRSSGPRTS APPPPPPADA VELRVLNDGV FVGSSVAPTT IDIFNEPICP PCGSFIRSYA
SDIDTAVADK QLAVRYHLLN FLDDQSHSKN YSTRAVAASY CVAGQNDPKL YASFYSALFG
SDFQPQENAA SDRTDAELAH LAQTVGAEPT AISCIKSGAD LGTAQTKATN ASETLAGFNA
SGTPFVWDGS MVVNYQDPSW LARLIG
