PKNF_MYCTU
ID PKNF_MYCTU Reviewed; 476 AA.
AC P9WI75; L0T7T0; O08151; P72003;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Serine/threonine-protein kinase PknF;
DE EC=2.7.11.1;
GN Name=pknF; OrderedLocusNames=Rv1746; ORFNames=MTCY28.09;
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, AND MUTAGENESIS OF LYS-41.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11496007; DOI=10.1099/00221287-147-8-2307;
RA Koul A., Choidas A., Tyagi A.K., Drlica K., Singh Y., Ullrich A.;
RT "Serine/threonine protein kinases PknF and PknG of Mycobacterium
RT tuberculosis: characterization and localization.";
RL Microbiology 147:2307-2314(2001).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15135525; DOI=10.1111/j.1574-6968.2004.tb09536.x;
RA Molle V., Soulat D., Jault J.M., Grangeasse C., Cozzone A.J., Prost J.F.;
RT "Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation
RT by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis.";
RL FEMS Microbiol. Lett. 234:215-223(2004).
RN [4]
RP PHOSPHORYLATION AT THR-8; THR-13; THR-173; THR-175; THR-287 AND SER-290,
RP 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 [5]
RP INTERACTION WITH RV1747, AND MUTAGENESIS OF LYS-41; THR-173; THR-175 AND
RP THR-178.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16040957; DOI=10.1128/iai.73.8.4471-4477.2005;
RA Curry J.M., Whalan R., Hunt D.M., Gohil K., Strom M., Rickman L.,
RA Colston M.J., Smerdon S.J., Buxton R.S.;
RT "An ABC transporter containing a forkhead-associated domain interacts with
RT a serine-threonine protein kinase and is required for growth of
RT Mycobacterium tuberculosis in mice.";
RL Infect. Immun. 73:4471-4477(2005).
RN [6]
RP FUNCTION.
RX PubMed=15866927; DOI=10.1128/jb.187.10.3415-3420.2005;
RA Deol P., Vohra R., Saini A.K., Singh A., Chandra H., Chopra P., Das T.K.,
RA Tyagi A.K., Singh Y.;
RT "Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in
RT glucose transport and cell division.";
RL J. Bacteriol. 187:3415-3420(2005).
RN [7]
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-41; THR-173 AND
RP THR-175.
RX PubMed=19201798; DOI=10.1128/jb.01569-08;
RA Canova M.J., Kremer L., Molle V.;
RT "The Mycobacterium tuberculosis GroEL1 chaperone is a substrate of Ser/Thr
RT protein kinases.";
RL J. Bacteriol. 191:2876-2883(2009).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21622570; DOI=10.1074/jbc.m111.246132;
RA Spivey V.L., Molle V., Whalan R.H., Rodgers A., Leiba J., Stach L.,
RA Walker K.B., Smerdon S.J., Buxton R.S.;
RT "Forkhead-associated (FHA) domain containing ABC transporter Rv1747 is
RT positively regulated by Ser/Thr phosphorylation in Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 286:26198-26209(2011).
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).
CC -!- FUNCTION: Phosphorylates the FHA domains of the ABC transporter Rv1747,
CC the heat-shock protein GroEL 1, and Rv0020c. May play a role in the
CC regulation of glucose transport, cell growth and septum formation.
CC {ECO:0000269|PubMed:15135525, ECO:0000269|PubMed:15866927,
CC ECO:0000269|PubMed:15987910, ECO:0000269|PubMed:19201798,
CC ECO:0000269|PubMed:21622570}.
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:11496007, ECO:0000269|PubMed:15135525,
CC ECO:0000269|PubMed:19201798, ECO:0000269|PubMed:21622570};
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:11496007,
CC ECO:0000269|PubMed:15135525, ECO:0000269|PubMed:19201798,
CC ECO:0000269|PubMed:21622570};
CC -!- SUBUNIT: Interacts with Rv1747. {ECO:0000269|PubMed:16040957}.
CC -!- INTERACTION:
CC P9WI75; P9WPE7: groEL2; NbExp=3; IntAct=EBI-2945875, EBI-2945826;
CC P9WI75; P9WMK1: hspX; NbExp=2; IntAct=EBI-2945875, EBI-2945921;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11496007};
CC Single-pass membrane protein {ECO:0000269|PubMed:11496007}.
CC -!- PTM: Autophosphorylated. Dephosphorylated by PstP.
CC {ECO:0000269|PubMed:15967413}.
CC -!- DISRUPTION PHENOTYPE: Disruption does not attenuate growth in
CC macrophages. {ECO:0000269|PubMed:21622570}.
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; CCP44512.1; -; Genomic_DNA.
DR PIR; C70986; C70986.
DR RefSeq; NP_216262.1; NC_000962.3.
DR RefSeq; WP_003899000.1; NZ_NVQJ01000010.1.
DR PDB; 7NAA; X-ray; 2.75 A; A/B/C/D=1-278.
DR PDBsum; 7NAA; -.
DR AlphaFoldDB; P9WI75; -.
DR SMR; P9WI75; -.
DR IntAct; P9WI75; 2.
DR STRING; 83332.Rv1746; -.
DR ChEMBL; CHEMBL2016432; -.
DR iPTMnet; P9WI75; -.
DR PaxDb; P9WI75; -.
DR DNASU; 885275; -.
DR GeneID; 45425719; -.
DR GeneID; 885275; -.
DR KEGG; mtu:Rv1746; -.
DR TubercuList; Rv1746; -.
DR eggNOG; COG0515; Bacteria.
DR OMA; IHDAGYL; -.
DR PhylomeDB; P9WI75; -.
DR PRO; PR:P9WI75; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA: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:0051055; P:negative regulation of lipid 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:0001558; P:regulation of cell growth; IMP:MTBBASE.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; IMP:MTBBASE.
DR GO; GO:0000921; P:septin ring assembly; IMP:MTBBASE.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..476
FT /note="Serine/threonine-protein kinase PknF"
FT /id="PRO_0000171213"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 12..279
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 332..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..376
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 137
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 18..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 8
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 13
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 175
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 287
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MOD_RES 290
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15967413"
FT MUTAGEN 41
FT /note="K->M: Loss of kinase activity. Abolishes interaction
FT with Rv1747."
FT /evidence="ECO:0000269|PubMed:11496007,
FT ECO:0000269|PubMed:16040957, ECO:0000269|PubMed:19201798"
FT MUTAGEN 173
FT /note="T->A: Abolishes interaction with Rv1747. Impairs
FT autokinase activity."
FT /evidence="ECO:0000269|PubMed:16040957,
FT ECO:0000269|PubMed:19201798"
FT MUTAGEN 175
FT /note="T->A: Decreases interaction with Rv1747. Decreases
FT autokinase activity."
FT /evidence="ECO:0000269|PubMed:16040957,
FT ECO:0000269|PubMed:19201798"
FT MUTAGEN 178
FT /note="T->A: Decreases interaction with Rv1747."
FT /evidence="ECO:0000269|PubMed:16040957"
SQ SEQUENCE 476 AA; 50668 MW; 8A9C755F912D4776 CRC64;
MPLAEGSTFA GFTIVRQLGS GGMGEVYLAR HPRLPRQDAL KVLRADVSAD GEYRARFNRE
ADAAASLWHP HIVAVHDRGE FDGQLWIDMD FVDGTDTVSL LRDRYPNGMP GPEVTEIITA
VAEALDYAHE RRLLHRDVKP ANILIANPDS PDRRIMLADF GIAGWVDDPS GLTATNMTVG
TVSYAAPEQL MGNELDGRAD QYALAATAFH LLTGSPPFQH ANPAVVISQH LSASPPAIGD
RVPELTPLDP VFAKALAKQP KDRYQRCVDF ARALGHRLGG AGDPDDTRVS QPVAVAAPAK
RSLLRTAVIV PAVLAMLLVM AVAVAVREFQ RADDERAAQP ARTRTTTSAG TTTSVAPAST
TRPAPTTPTT TGAADTATAS PTAAVVAIGA LCFPLGSTGT TKTGATAYCS TLQGTNTTIW
SLTEDTVASP TVTATADPTE APLPIEQESP IRVCMQQTGQ TRRECREEIR RSNGWP
