PKNK_MYCTU
ID PKNK_MYCTU Reviewed; 1110 AA.
AC P9WI65; L0TEA2; P95078;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Serine/threonine-protein kinase PknK;
DE EC=2.7.11.1;
DE AltName: Full=Protein kinase K;
GN Name=pknK; OrderedLocusNames=Rv3080c; ORFNames=MTCY22D7.01, MTV013.01c;
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 FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP THR-179 AND THR-181, AND MUTAGENESIS OF LYS-55; THR-179 AND THR-181.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19251699; DOI=10.1074/jbc.m808705200;
RA Kumar P., Kumar D., Parikh A., Rananaware D., Gupta M., Singh Y.,
RA Nandicoori V.K.;
RT "The Mycobacterium tuberculosis protein kinase K modulates activation of
RT transcription from the promoter of mycobacterial monooxygenase operon
RT through phosphorylation of the transcriptional regulator VirS.";
RL J. Biol. Chem. 284:11090-11099(2009).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20522497; DOI=10.1099/mic.0.040675-0;
RA Malhotra V., Arteaga-Cortes L.T., Clay G., Clark-Curtiss J.E.;
RT "Mycobacterium tuberculosis protein kinase K confers survival advantage
RT during early infection in mice and regulates growth in culture and during
RT persistent infection: implications for immune modulation.";
RL Microbiology 156:2829-2841(2010).
RN [4]
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 [5]
RP FUNCTION, SUBUNIT, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22661693; DOI=10.1128/jb.00585-12;
RA Malhotra V., Okon B.P., Clark-Curtiss J.E.;
RT "Mycobacterium tuberculosis protein kinase K enables growth adaptation
RT through translation control.";
RL J. Bacteriol. 194:4184-4196(2012).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=22740025; DOI=10.1007/s11010-012-1369-9;
RA Kumari R., Singh S.K., Singh D.K., Singh P.K., Chaurasiya S.K.,
RA Srivastava K.K.;
RT "Functional characterization delineates that a Mycobacterium tuberculosis
RT specific protein kinase (Rv3080c) is responsible for the growth,
RT phagocytosis and intracellular survival of avirulent mycobacteria.";
RL Mol. Cell. Biochem. 369:67-74(2012).
CC -!- FUNCTION: Key microbial factor involved in regulation of early and late
CC events in tuberculosis infection, and in host-pathogen interactions.
CC Modulates host immunity during early infection. Slows mycobacterial
CC growth during chronic infection in host and during a variety of stress
CC conditions in vitro. Regulates the expression of a large subset of tRNA
CC genes as a means to facilitate adaptation to changing growth
CC environments. In vitro, directs the inhibition of transcription and
CC translation processes in a phosphorylation-dependent manner.
CC Phosphorylates the transcriptional regulator VirS, thereby increasing
CC the affinity of VirS for the mycobacterial monooxygenase (mymA)
CC promoter. In vitro, can also phosphorylate the mycobacterial
CC monooxygenase operon products Rv3083 (MymA), Rv3084 (LipR), Rv3085 and
CC Rv3088. {ECO:0000269|PubMed:19251699, ECO:0000269|PubMed:20522497,
CC ECO:0000269|PubMed:22661693, ECO:0000269|PubMed:22740025}.
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:19251699};
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:19251699};
CC -!- SUBUNIT: Forms oligomeric complexes in solution.
CC {ECO:0000269|PubMed:22661693}.
CC -!- INTERACTION:
CC P9WI65; P9WI65: pknK; NbExp=2; IntAct=EBI-6418825, EBI-6418825;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Secreted, cell wall.
CC Note=Probably attached to the cell membrane through interactions
CC mediated by its C-terminal region. May be secreted during infection.
CC -!- INDUCTION: Induced during early infection in human macrophages.
CC {ECO:0000269|PubMed:20522497, ECO:0000269|PubMed:22740025}.
CC -!- DOMAIN: The C-terminal region exerts intrasteric control that
CC autoregulates kinase activity. {ECO:0000269|PubMed:22661693}.
CC -!- PTM: Can autophosphorylate the carboxyl terminal region in addition to
CC Thr-179 and Thr-181. {ECO:0000269|PubMed:19251699}.
CC -!- DISRUPTION PHENOTYPE: Deletion affects cell size and cell wall
CC composition, increases survival during persistent infection in mice,
CC and increases resistance to acidic pH, hypoxia, oxidative and
CC stationary-phase stresses in vitro. {ECO:0000269|PubMed:20522497}.
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; CCP45889.1; -; Genomic_DNA.
DR PIR; A70652; A70652.
DR RefSeq; NP_217596.1; NC_000962.3.
DR RefSeq; WP_003899905.1; NZ_NVQJ01000011.1.
DR AlphaFoldDB; P9WI65; -.
DR SMR; P9WI65; -.
DR STRING; 83332.Rv3080c; -.
DR iPTMnet; P9WI65; -.
DR PaxDb; P9WI65; -.
DR PRIDE; P9WI65; -.
DR GeneID; 888659; -.
DR KEGG; mtu:Rv3080c; -.
DR TubercuList; Rv3080c; -.
DR eggNOG; COG0515; Bacteria.
DR eggNOG; COG2909; Bacteria.
DR OMA; SITERTC; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion 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:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IDA:MTBBASE.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR041664; AAA_16.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016236; Ser/Thr_kinase_PknK_prd.
DR Pfam; PF13191; AAA_16; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000574; Ser/Thr_PK_PknK_prd; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF52540; SSF52540; 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 ATP-binding; Cell membrane; Cell wall; Cytoplasm; Kinase; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Secreted; Serine/threonine-protein kinase; Transferase;
KW Virulence.
FT CHAIN 1..1110
FT /note="Serine/threonine-protein kinase PknK"
FT /id="PRO_0000171224"
FT DOMAIN 26..283
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 308..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 32..40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 154
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 179
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19251699"
FT MOD_RES 181
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19251699"
FT MUTAGEN 55
FT /note="K->M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19251699"
FT MUTAGEN 179
FT /note="T->A: Loss of activity; when associated with A-181."
FT /evidence="ECO:0000269|PubMed:19251699"
FT MUTAGEN 181
FT /note="T->A: Loss of activity; when associated with A-179."
FT /evidence="ECO:0000269|PubMed:19251699"
SQ SEQUENCE 1110 AA; 119418 MW; 2F81BF18BCD3E472 CRC64;
MTDVDPHATR RDLVPNIPAE LLEAGFDNVE EIGRGGFGVV YRCVQPSLDR AVAVKVLSTD
LDRDNLERFL REQRAMGRLS GHPHIVTVLQ VGVLAGGRPF IVMPYHAKNS LETLIRRHGP
LDWRETLSIG VKLAGALEAA HRVGTLHRDV KPGNILLTDY GEPQLTDFGI ARIAGGFETA
TGVIAGSPAF TAPEVLEGAS PTPASDVYSL GATLFCALTG HAAYERRSGE RVIAQFLRIT
SQPIPDLRKQ GLPADVAAAI ERAMARHPAD RPATAADVGE ELRDVQRRNG VSVDEMPLPV
ELGVERRRSP EAHAAHRHTG GGTPTVPTPP TPATKYRPSV PTGSLVTRSR LTDILRAGGR
RRLILIHAPS GFGKSTLAAQ WREELSRDGA AVAWLTIDND DNNEVWFLSH LLESIRRVRP
TLAESLGHVL EEHGDDAGRY VLTSLIDEIH ENDDRIAVVI DDWHRVSDSR TQAALGFLLD
NGCHHLQLIV TSWSRAGLPV GRLRIGDELA EIDSAALRFD TDEAAALLND AGGLRLPRAD
VQALTTSTDG WAAALRLAAL SLRGGGDATQ LLRGLSGASD VIHEFLSENV LDTLEPELRE
FLLVASVTER TCGGLASALA GITNGRAMLE EAEHRGLFLQ RTEDDPNWFR FHQMFADFLH
RRLERGGSHR VAELHRRASA WFAENGYLHE AVDHALAAGD PARAVDLVEQ DETNLPEQSK
MTTLLAIVQK LPTSMVVSRA RLQLAIAWAN ILLQRPAPAT GALNRFETAL GRAELPEATQ
ADLRAEADVL RAVAEVFADR VERVDDLLAE AMSRPDTLPP RVPGTAGNTA ALAAICRFEF
AEVYPLLDWA APYQEMMGPF GTVYAQCLRG MAARNRLDIV AALQNFRTAF EVGTAVGAHS
HAARLAGSLL AELLYETGDL AGAGRLMDES YLLGSEGGAV DYLAARYVIG ARVKAAQGDH
EGAADRLSTG GDTAVQLGLP RLAARINNER IRLGIALPAA VAADLLAPRT IPRDNGIATM
TAELDEDSAV RLLSAGDSAD RDQACQRAGA LAAAIDGTRR PLAALQAQIL HIETLAATGR
ESDARNELAP VATKCAELGL SRLLVDAGLA
