PKND_MYCTU
ID PKND_MYCTU Reviewed; 664 AA.
AC P9WI79; L0T6U6; O05871; P95308;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Serine/threonine-protein kinase PknD;
DE EC=2.7.11.1 {ECO:0000269|PubMed:17242402, ECO:0000269|PubMed:17411339, ECO:0000269|PubMed:24309377, ECO:0000269|PubMed:30642988};
GN Name=pknD; OrderedLocusNames=Rv0931c; ORFNames=MTCY08C9.08;
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 35801 / TMC 107 / Erdman;
RX PubMed=9119030; DOI=10.1111/j.1432-1033.1997.00604.x;
RA Peirs P., De Wit L., Braibant M., Huygen K., Content J.;
RT "A serine/threonine protein kinase from Mycobacterium tuberculosis.";
RL Eur. J. Biochem. 244:604-612(1997).
RN [2]
RP SEQUENCE REVISION.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RA Content J.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP PHOSPHORYLATION AT THR-135; THR-169; THR-171; THR-173 AND THR-209, 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 [5]
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 [6]
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS
RP OF HIS-79 AND TYR-81.
RX PubMed=17242402; DOI=10.1074/jbc.m610193200;
RA Greenstein A.E., Echols N., Lombana T.N., King D.S., Alber T.;
RT "Allosteric activation by dimerization of the PknD receptor Ser/Thr protein
RT kinase from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 282:11427-11435(2007).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-138.
RX PubMed=17411339; DOI=10.1371/journal.ppat.0030049;
RA Greenstein A.E., MacGurn J.A., Baer C.E., Falick A.M., Cox J.S., Alber T.;
RT "M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma
RT factor homolog.";
RL PLoS Pathog. 3:E49-E49(2007).
RN [9]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=20933472; DOI=10.1016/j.tube.2010.09.004;
RA Vanzembergh F., Peirs P., Lefevre P., Celio N., Mathys V., Content J.,
RA Kalai M.;
RT "Effect of PstS sub-units or PknD deficiency on the survival of
RT Mycobacterium tuberculosis.";
RL Tuberculosis 90:338-345(2010).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-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 [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24309377; DOI=10.1073/pnas.1321205110;
RA Hatzios S.K., Baer C.E., Rustad T.R., Siegrist M.S., Pang J.M., Ortega C.,
RA Alber T., Grundner C., Sherman D.R., Bertozzi C.R.;
RT "Osmosensory signaling in Mycobacterium tuberculosis mediated by a
RT eukaryotic-like Ser/Thr protein kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E5069-E5077(2013).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30642988; DOI=10.1128/jb.00725-18;
RA Misra R., Menon D., Arora G., Virmani R., Gaur M., Naz S., Jaisinghani N.,
RA Bhaduri A., Bothra A., Maji A., Singhal A., Karwal P., Hentschker C.,
RA Becher D., Rao V., Nandicoori V.K., Gandotra S., Singh Y.;
RT "Tuning the Mycobacterium tuberculosis alternative sigma factor SigF
RT through the multidomain regulator Rv1364c and osmosensory kinase protein
RT kinase D.";
RL J. Bacteriol. 201:0-0(2019).
RN [13] {ECO:0007744|PDB:1RWI, ECO:0007744|PDB:1RWL}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 403-664.
RX PubMed=15136047; DOI=10.1016/j.jmb.2004.03.063;
RA Good M.C., Greenstein A.E., Young T.A., Ng H.L., Alber T.;
RT "Sensor domain of the Mycobacterium tuberculosis receptor Ser/Thr protein
RT kinase, PknD, forms a highly symmetric beta propeller.";
RL J. Mol. Biol. 339:459-469(2004).
CC -!- FUNCTION: Part of a signaling pathway that enables adaptation to
CC osmotic stress through cell wall remodeling and virulence factor
CC production (PubMed:24309377). Phosphorylates the osmosensory protein
CC OprA, which inhibits binding of OprA to Rv2638, leading to the
CC regulation of osmotically regulated genes, including the ESX-1-
CC associated virulence factor espA (PubMed:17411339, PubMed:17242402,
CC PubMed:24309377). In addition, directly phosphorylates the alternative
CC sigma factor SigF and its regulator, Rv1364c, which regulates the SigF-
CC Rv1364c interaction (PubMed:30642988). Can also phosphorylate the FHA
CC domain of Rv1747 (PubMed:15987910). {ECO:0000269|PubMed:15987910,
CC ECO:0000269|PubMed:17242402, ECO:0000269|PubMed:17411339,
CC ECO:0000269|PubMed:24309377, ECO:0000269|PubMed:30642988}.
CC -!- FUNCTION: Key microbial factor required for central nervous system
CC tuberculosis. Required for invasion of host brain endothelia, but not
CC macrophages, lung epithelia or other endothelia.
CC {ECO:0000250|UniProtKB:P9WI78}.
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:17242402, ECO:0000269|PubMed:17411339,
CC ECO:0000269|PubMed:30642988};
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:17242402,
CC ECO:0000269|PubMed:17411339, ECO:0000269|PubMed:24309377,
CC ECO:0000269|PubMed:30642988};
CC -!- ACTIVITY REGULATION: Dimerization activates the kinase domain of
CC unphosphorylated PknD via an allosteric mechanism, triggering
CC autophosphorylation and phosphorylation of target proteins.
CC Phosphorylated PknD is fully active even in the absence of
CC dimerization. {ECO:0000269|PubMed:17242402}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17242402}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- INDUCTION: Increased expression after 3 hours of phosphate starvation,
CC no protein detected after 24 hours phosphate starvation (at protein
CC level). Part of the pstS2-pknD operon. {ECO:0000269|PubMed:20933472}.
CC -!- PTM: Autophosphorylated (PubMed:15967413, PubMed:16739134,
CC PubMed:17242402). Dephosphorylated by PstP (PubMed:15967413).
CC {ECO:0000269|PubMed:15967413, ECO:0000269|PubMed:16739134,
CC ECO:0000269|PubMed:17242402}.
CC -!- DISRUPTION PHENOTYPE: No growth phenotype in phosphate-rich medium (3.6
CC mM Pi), in restricted medium (Sauton) grows better than wild-type but
CC in phosphate-free Sauton medium dies faster than wild-type when pre-
CC exposed to starvation. {ECO:0000269|PubMed:20933472}.
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; X99618; CAA67929.2; -; Genomic_DNA.
DR EMBL; AL123456; CCP43679.1; -; Genomic_DNA.
DR PIR; C70584; C70584.
DR RefSeq; NP_215446.1; NC_000962.3.
DR RefSeq; WP_003404782.1; NZ_NVQJ01000001.1.
DR PDB; 1RWI; X-ray; 1.80 A; A/B=403-664.
DR PDB; 1RWL; X-ray; 1.90 A; A=403-664.
DR PDBsum; 1RWI; -.
DR PDBsum; 1RWL; -.
DR AlphaFoldDB; P9WI79; -.
DR SMR; P9WI79; -.
DR IntAct; P9WI79; 2.
DR STRING; 83332.Rv0931c; -.
DR iPTMnet; P9WI79; -.
DR PaxDb; P9WI79; -.
DR DNASU; 885607; -.
DR GeneID; 45424897; -.
DR GeneID; 885607; -.
DR KEGG; mtu:Rv0931c; -.
DR TubercuList; Rv0931c; -.
DR eggNOG; COG0515; Bacteria.
DR eggNOG; COG3391; Bacteria.
DR OMA; FFVEMRL; -.
DR BRENDA; 2.7.11.1; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0005887; C:integral component of plasma membrane; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0016036; P:cellular response to phosphate starvation; 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:0032091; P:negative regulation of protein binding; 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 CDD; cd14952; NHL_PKND_like; 1.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035016; NHL_PKND.
DR InterPro; IPR001258; NHL_repeat.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR013658; SGL.
DR Pfam; PF01436; NHL; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF08450; SGL; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51125; NHL; 6.
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; Kinase; Membrane;
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:0007744|PubMed:21969609"
FT CHAIN 2..664
FT /note="Serine/threonine-protein kinase PknD"
FT /id="PRO_0000171209"
FT TOPO_DOM 2..381
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..664
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 15..276
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 414..456
FT /note="NHL 1"
FT REPEAT 457..497
FT /note="NHL 2"
FT REPEAT 498..539
FT /note="NHL 3"
FT REPEAT 540..581
FT /note="NHL 4"
FT REPEAT 582..623
FT /note="NHL 5"
FT REPEAT 624..664
FT /note="NHL 6"
FT REGION 303..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 138
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 21..29
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 135
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 169
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 171
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 173
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 209
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MUTAGEN 79
FT /note="H->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:17242402"
FT MUTAGEN 81
FT /note="Y->A: Decreases activity and alters substrate
FT specificity."
FT /evidence="ECO:0000269|PubMed:17242402"
FT MUTAGEN 138
FT /note="D->N: 2600-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:17411339"
FT STRAND 428..433
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 439..443
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 445..447
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 449..453
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:1RWL"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 482..486
FT /evidence="ECO:0007829|PDB:1RWI"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 490..494
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 510..517
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 523..527
FT /evidence="ECO:0007829|PDB:1RWI"
FT HELIX 528..530
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 532..536
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 565..569
FT /evidence="ECO:0007829|PDB:1RWI"
FT HELIX 570..572
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 574..578
FT /evidence="ECO:0007829|PDB:1RWI"
FT TURN 580..582
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 585..587
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 595..601
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 607..611
FT /evidence="ECO:0007829|PDB:1RWI"
FT TURN 612..614
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 617..620
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 638..643
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 649..653
FT /evidence="ECO:0007829|PDB:1RWI"
FT HELIX 654..656
FT /evidence="ECO:0007829|PDB:1RWI"
FT STRAND 658..662
FT /evidence="ECO:0007829|PDB:1RWI"
SQ SEQUENCE 664 AA; 69545 MW; FE39716825A41CC1 CRC64;
MSDAVPQVGS QFGPYQLLRL LGRGGMGEVY EAEDTRKHRV VALKLISPQY SDNAVFRARM
QREADTAGRL TEPHIVPIHD YGEINGQFFV EMRMIDGTSL RALLKQYGPL TPARAVAIVR
QIAAALDAAH ANGVTHRDVK PENILVTASD FAYLVDFGIA RAASDPGLTQ TGTAVGTYNY
MAPERFTGDE VTYRADIYAL ACVLGECLTG APPYRADSVE RLIAAHLMDP APQPSQLRPG
RVPPALDQVI AKGMAKNPAE RFMSAGDLAI AAHDALTTSE QHQATTILRR GDNATLLATP
ADTGLSQSES GIAGAGTGPP TPGAARWSPG DSATVAGPLA ADSRGGNWPS QTGHSPAVPN
ALQASLGHAV PPAGNKRKVW AVVGAAAIVL VAIVAAAGYL VLRPSWSPTQ ASGQTVLPFT
GIDFRLSPSG VAVDSAGNVY VTSEGMYGRV VKLATGSTGT TVLPFNGLYQ PQGLAVDGAG
TVYVTDFNNR VVTLAAGSNN QTVLPFDGLN YPEGLAVDTQ GAVYVADRGN NRVVKLAAGS
KTQTVLPFTG LNDPDGVAVD NSGNVYVTDT DNNRVVKLEA ESNNQVVLPF TDITAPWGIA
VDEAGTVYVT EHNTNQVVKL LAGSTTSTVL PFTGLNTPLA VAVDSDRTVY VADRGNDRVV
KLTS
