PKNH_MYCTU
ID PKNH_MYCTU Reviewed; 626 AA.
AC P9WI71; L0T6C9; Q11053;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Serine/threonine-protein kinase PknH;
DE EC=2.7.11.1;
GN Name=pknH; OrderedLocusNames=Rv1266c; ORFNames=MTCY50.16;
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, PHOSPHORYLATION AT THR-170, AND MUTAGENESIS
RP OF LYS-45 AND THR-170.
RX PubMed=14690440; DOI=10.1021/bi035150b;
RA Molle V., Kremer L., Girard-Blanc C., Besra G.S., Cozzone A.J., Prost J.F.;
RT "An FHA phosphoprotein recognition domain mediates protein EmbR
RT phosphorylation by PknH, a Ser/Thr protein kinase from Mycobacterium
RT tuberculosis.";
RL Biochemistry 42:15300-15309(2003).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, INDUCTION, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-45.
RX PubMed=15043876; DOI=10.1016/j.femsle.2004.01.045;
RA Sharma K., Chandra H., Gupta P.K., Pathak M., Narayan A., Meena L.S.,
RA D'Souza R.C., Chopra P., Ramachandran S., Singh Y.;
RT "PknH, a transmembrane Hank's type serine/threonine kinase from
RT Mycobacterium tuberculosis is differentially expressed under stress
RT conditions.";
RL FEMS Microbiol. Lett. 233:107-113(2004).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16077122; DOI=10.1128/jb.187.16.5751-5760.2005;
RA Papavinasasundaram K.G., Chan B., Chung J.H., Colston M.J., Davis E.O.,
RA Av-Gay Y.;
RT "Deletion of the Mycobacterium tuberculosis pknH gene confers a higher
RT bacillary load during the chronic phase of infection in BALB/c mice.";
RL J. Bacteriol. 187:5751-5760(2005).
RN [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=16585755; DOI=10.1128/jb.188.8.2936-2944.2006;
RA Sharma K., Gupta M., Pathak M., Gupta N., Koul A., Sarangi S., Baweja R.,
RA Singh Y.;
RT "Transcriptional control of the mycobacterial embCAB operon by PknH through
RT a regulatory protein, EmbR, in vivo.";
RL J. Bacteriol. 188:2936-2944(2006).
RN [7]
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17286964; DOI=10.1016/j.bbrc.2007.01.122;
RA Zheng X., Papavinasasundaram K.G., Av-Gay Y.;
RT "Novel substrates of Mycobacterium tuberculosis PknH Ser/Thr kinase.";
RL Biochem. Biophys. Res. Commun. 355:162-168(2007).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20630871; DOI=10.1074/jbc.m110.132894;
RA Chao J.D., Papavinasasundaram K.G., Zheng X., Chavez-Steenbock A., Wang X.,
RA Lee G.Q., Av-Gay Y.;
RT "Convergence of Ser/Thr and two-component signaling to coordinate
RT expression of the dormancy regulon in Mycobacterium tuberculosis.";
RL J. Biol. Chem. 285:29239-29246(2010).
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).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 435-626, AND DISULFIDE BONDS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22727744; DOI=10.1016/j.jmb.2012.06.011;
RA Cavazos A., Prigozhin D.M., Alber T.;
RT "Structure of the sensor domain of Mycobacterium tuberculosis PknH receptor
RT kinase reveals a conserved binding cleft.";
RL J. Mol. Biol. 422:488-494(2012).
CC -!- FUNCTION: May regulate bacterial growth in response to external signals
CC to facilitate adaptation to the host environment. In vitro,
CC phosphorylates several substrates such as EmbR, DevR (DosR), DacB1 and
CC Rv0681. {ECO:0000269|PubMed:14690440, ECO:0000269|PubMed:15043876,
CC ECO:0000269|PubMed:16077122, ECO:0000269|PubMed:16585755,
CC ECO:0000269|PubMed:16817899, ECO:0000269|PubMed:17286964,
CC ECO:0000269|PubMed:20630871}.
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:14690440, ECO:0000269|PubMed:15043876,
CC ECO:0000269|PubMed:16585755, ECO:0000269|PubMed:17286964,
CC ECO:0000269|PubMed:20630871};
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:14690440,
CC ECO:0000269|PubMed:15043876, ECO:0000269|PubMed:16585755,
CC ECO:0000269|PubMed:17286964, ECO:0000269|PubMed:20630871};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:15043876};
CC -!- ACTIVITY REGULATION: Inhibited by the kinase inhibitors staurosporine
CC and H-7. {ECO:0000269|PubMed:15043876}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.597 uM for EmbR {ECO:0000269|PubMed:17286964};
CC KM=1.59 uM for DacB1 {ECO:0000269|PubMed:17286964};
CC KM=19.82 uM for Rv0681 {ECO:0000269|PubMed:17286964};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15043876};
CC Single-pass membrane protein {ECO:0000269|PubMed:15043876}.
CC -!- INDUCTION: Repressed by low pH and heat shock. Up-regulated inside the
CC host macrophages. {ECO:0000269|PubMed:15043876,
CC ECO:0000269|PubMed:16585755}.
CC -!- PTM: Autophosphorylated on threonine and serine residues.
CC Dephosphorylated by PstP. {ECO:0000269|PubMed:14690440}.
CC -!- DISRUPTION PHENOTYPE: Deletion causes hypervirulence during the chronic
CC phase of infection in BALB/c mice. Mutant displays increased resistance
CC to acidified nitrite stress. Does not affect sensitivity to ethambutol.
CC {ECO:0000269|PubMed:16077122}.
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; CCP44022.1; -; Genomic_DNA.
DR PIR; B70754; B70754.
DR RefSeq; NP_215782.1; NC_000962.3.
DR RefSeq; WP_010886110.1; NC_000962.3.
DR PDB; 4ESQ; X-ray; 1.70 A; A=435-626.
DR PDBsum; 4ESQ; -.
DR AlphaFoldDB; P9WI71; -.
DR SMR; P9WI71; -.
DR IntAct; P9WI71; 2.
DR STRING; 83332.Rv1266c; -.
DR iPTMnet; P9WI71; -.
DR PaxDb; P9WI71; -.
DR PRIDE; P9WI71; -.
DR DNASU; 887023; -.
DR GeneID; 887023; -.
DR KEGG; mtu:Rv1266c; -.
DR PATRIC; fig|83332.12.peg.1418; -.
DR TubercuList; Rv1266c; -.
DR eggNOG; COG0515; Bacteria.
DR OMA; MTTPYIV; -.
DR BRENDA; 2.7.11.1; 3445.
DR SABIO-RK; P9WI71; -.
DR PHI-base; PHI:3624; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
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:0045926; P:negative regulation of growth; IMP: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:0043388; P:positive regulation of DNA binding; IDA:MTBBASE.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:MTBBASE.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR GO; GO:0046890; P:regulation of lipid biosynthetic process; IMP:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IEP:MTBBASE.
DR Gene3D; 3.40.1000.70; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR026954; PknH-like_Extracell.
DR InterPro; IPR038232; PknH-like_Extracell_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF14032; PknH_C; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
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; ATP-binding; Cell membrane; Disulfide bond; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..626
FT /note="Serine/threonine-protein kinase PknH"
FT /id="PRO_0000171218"
FT TOPO_DOM 1..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..626
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 16..276
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 292..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..349
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 356..370
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 ECO:0000255|PROSITE-ProRule:PRU10027"
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 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:14690440"
FT DISULFID 482..545
FT /evidence="ECO:0000269|PubMed:22727744"
FT DISULFID 587..604
FT /evidence="ECO:0000269|PubMed:22727744"
FT MUTAGEN 45
FT /note="K->M: Abolished kinase activity."
FT /evidence="ECO:0000269|PubMed:14690440,
FT ECO:0000269|PubMed:15043876"
FT MUTAGEN 170
FT /note="T->A: Abolished autophosphorylation."
FT /evidence="ECO:0000269|PubMed:14690440"
FT HELIX 439..445
FT /evidence="ECO:0007829|PDB:4ESQ"
FT HELIX 449..456
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:4ESQ"
FT HELIX 480..482
FT /evidence="ECO:0007829|PDB:4ESQ"
FT HELIX 483..486
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 488..490
FT /evidence="ECO:0007829|PDB:4ESQ"
FT HELIX 491..494
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 501..508
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 515..524
FT /evidence="ECO:0007829|PDB:4ESQ"
FT HELIX 528..543
FT /evidence="ECO:0007829|PDB:4ESQ"
FT TURN 544..547
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 549..554
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 557..563
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 573..581
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 586..594
FT /evidence="ECO:0007829|PDB:4ESQ"
FT STRAND 597..607
FT /evidence="ECO:0007829|PDB:4ESQ"
FT HELIX 611..624
FT /evidence="ECO:0007829|PDB:4ESQ"
SQ SEQUENCE 626 AA; 66754 MW; 927C5D0A58605757 CRC64;
MSDAQDSRVG SMFGPYHLKR LLGRGGMGEV YEAEHTVKEW TVAVKLMTAE FSKDPVFRER
MKREARIAGR LQEPHVVPIH DYGEVDGQMF LEMRLVEGTD LDSVLKRFGP LTPPRAVAII
TQIASALDAA HADGVMHRDV KPQNILITRD DFAYLVDFGI ASATTDEKLT QLGTAVGTWK
YMAPERFSND EVTYRADIYA LACVLHECLT GAPPYRADSA GTLVSSHLMG PIPQPSAIRP
GIPKAFDAVV ARGMAKKPED RYASAGDLAL AAHEALSDPD QDHAADILRR SQESTLPAPP
KPVPPPTMPA TAMAPRQPPA PPVTPPGVQP APKPSYTPPA QPGPAGQRPG PTGQPSWAPN
SGPMPASGPT PTPQYYQGGG WGAPPSGGPS PWAQTPRKTN PWPLVAGAAA VVLVLVLGAI
GIWIAIRPKP VQPPQPVAEE RLSALLLNSS EVNAVMGSSS MQPGKPITSM DSSPVTVSLP
DCQGALYTSQ DPVYAGTGYT AINGLISSEP GDNYEHWVNQ AVVAFPTADK ARAFVQTSAD
KWKNCAGKTV TVTNKAKTYR WTFADVKGSP PTITVIDTQE GAEGWECQRA MSVANNVVVD
VNACGYRITN QAGQIAAKIV DKVNKE
