ID STKP_STREE Reviewed; 659 AA.
AC Q8KY50;
DT 11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 27-MAR-2024, entry version 112.
DE RecName: Full=Serine/threonine-protein kinase StkP;
DE Short=Ser/Thr-protein kinase StkP;
DE EC=2.7.11.1 {ECO:0000269|PubMed:15720398};
DE AltName: Full=Eukaryotic-type Ser/Thr protein kinase;
DE Short=ESTPK;
GN Name=stkP;
OS Streptococcus pneumoniae.
OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=1313;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Rx / Cp1015;
RA Echenique J.R., Trombe M.C.;
RT "A serine/threonine kinase involved in competence regulation.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION OF TARGET SUBSTRATES, ACTIVITY
RP REGULATION, PHOSPHORYLATION, PTM, PH DEPENDENCE, SUBCELLULAR LOCATION,
RP OPERON STRUCTURE, AND MUTAGENESIS OF LYS-42.
RC STRAIN=Rx / Cp1015;
RX PubMed=15720398; DOI=10.1111/j.1742-4658.2005.04560.x;
RA Novakova L., Saskova L., Pallova P., Janecek J., Novotna J., Ulrych A.,
RA Echenique J., Trombe M.C., Branny P.;
RT "Characterization of a eukaryotic type serine/threonine protein kinase and
RT protein phosphatase of Streptococcus pneumoniae and identification of
RT kinase substrates.";
RL FEBS J. 272:1243-1254(2005).
RN [3]
RP SUBUNIT, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION ACTIVITY, AND DOMAIN.
RC STRAIN=Rx / Cp1015;
RX PubMed=17307148; DOI=10.1016/j.bbrc.2007.01.184;
RA Pallova P., Hercik K., Saskova L., Novakova L., Branny P.;
RT "A eukaryotic-type serine/threonine protein kinase StkP of Streptococcus
RT pneumoniae acts as a dimer in vivo.";
RL Biochem. Biophys. Res. Commun. 355:526-530(2007).
RN [4]
RP FUNCTION AS A GLOBAL TRANSCRIPTIONAL REGULATOR, AND DISRUPTION PHENOTYPE.
RC STRAIN=Rx / Cp1015;
RX PubMed=17416671; DOI=10.1128/jb.01616-06;
RA Saskova L., Novakova L., Basler M., Branny P.;
RT "Eukaryotic-type serine/threonine protein kinase StkP is a global regulator
RT of gene expression in Streptococcus pneumoniae.";
RL J. Bacteriol. 189:4168-4179(2007).
RN [5]
RP FUNCTION IN COMPETENCE, INTERACTION WITH PHPP, SUBCELLULAR LOCATION, AND
RP TOPOLOGY.
RC STRAIN=Rx / Cp1015;
RX PubMed=19502404; DOI=10.1128/jb.00196-09;
RA Osaki M., Arcondeguy T., Bastide A., Touriol C., Prats H., Trombe M.C.;
RT "The StkP/PhpP signaling couple in Streptococcus pneumoniae: cellular
RT organization and physiological characterization.";
RL J. Bacteriol. 191:4943-4950(2009).
RN [6]
RP FUNCTION, ROLE IN CELL DIVISION, IDENTIFICATION OF TARGET SUBSTRATES,
RP ACTIVITY REGULATION, DISRUPTION PHENOTYPE, DOMAIN, AND MUTAGENESIS OF
RP LYS-42.
RC STRAIN=Rx / Cp1015;
RX PubMed=20453092; DOI=10.1128/jb.01564-09;
RA Novakova L., Bezouskova S., Pompach P., Spidlova P., Saskova L., Weiser J.,
RA Branny P.;
RT "Identification of multiple substrates of the StkP Ser/Thr protein kinase
RT in Streptococcus pneumoniae.";
RL J. Bacteriol. 192:3629-3638(2010).
RN [7]
RP PEPTIDOGLYCAN-BINDING, 3D-STRUCTURE MODELING OF 363-659, AND DOMAIN.
RC STRAIN=Rx / Cp1015;
RX PubMed=21167155; DOI=10.1016/j.febslet.2010.12.016;
RA Maestro B., Novakova L., Hesek D., Lee M., Leyva E., Mobashery S.,
RA Sanz J.M., Branny P.;
RT "Recognition of peptidoglycan and beta-lactam antibiotics by the
RT extracellular domain of the Ser/Thr protein kinase StkP from Streptococcus
RT pneumoniae.";
RL FEBS Lett. 585:357-363(2011).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Rx1;
RX PubMed=22431591; DOI=10.1073/pnas.1119172109;
RA Beilharz K., Novakova L., Fadda D., Branny P., Massidda O., Veening J.W.;
RT "Control of cell division in Streptococcus pneumoniae by the conserved
RT Ser/Thr protein kinase StkP.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E905-E913(2012).
RN [9]
RP FUNCTION.
RC STRAIN=D39, R6, and Rx1;
RX PubMed=25550321; DOI=10.1128/mbio.01700-14;
RA Holeckova N., Doubravova L., Massidda O., Molle V., Buriankova K.,
RA Benada O., Kofronova O., Ulrych A., Branny P.;
RT "LocZ is a new cell division protein involved in proper septum placement in
RT Streptococcus pneumoniae.";
RL MBio 6:E01700-E01700(2015).
RN [10]
RP FUNCTION, SUBSTRATE, AND DISRUPTION PHENOTYPE.
RC STRAIN=Rx1;
RX PubMed=27776484; DOI=10.1186/s12866-016-0865-6;
RA Ulrych A., Holeckova N., Goldova J., Doubravova L., Benada O.,
RA Kofronova O., Halada P., Branny P.;
RT "Characterization of pneumococcal Ser/Thr protein phosphatase phpP mutant
RT and identification of a novel PhpP substrate, putative RNA binding protein
RT Jag.";
RL BMC Microbiol. 16:247-247(2016).
CC -!- FUNCTION: Protein kinase involved in signal transduction pathways that
CC regulate various cellular processes. Likely senses intracellular
CC peptidoglycan subunits present in the cell division septa of actively
CC growing cells; thus, intracellular unlinked peptidoglycan may serve as
CC the signal molecules that trigger StkP phosphorylation activity on a
CC set of substrates. Plays a crucial role in the regulation of cell shape
CC and cell division of S.pneumoniae through control of at least DivIVA
CC activity. Is involved in competence triggering, via the transduction of
CC signals culminating directly or indirectly in ComD activation. Is
CC important for the resistance of S.pneumoniae to various environmental
CC stress conditions. Appears to be a global regulator that positively
CC controls the transcription of a set of genes encoding functions
CC involved in cell wall metabolism, pyrimidine biosynthesis, DNA repair,
CC iron uptake, and oxidative stress response, and that seems to down-
CC regulate genes employed in competence. Since StkP is unlikely to
CC directly regulate transcription, the input signal must be transmitted
CC through an effector molecule. Identified target substrates that are
CC specifically phosphorylated by StkP in vivo, mainly on threonine
CC residues, are DivIVA, GlmM, PpaC, MapZ, KhpB (also called EloR/Jag) and
CC StkP itself. Autophosphorylated StkP is a substrate for the
CC cotranscribed protein phosphatase PhpP; PhpP and StkP appear to
CC constitute a functional signaling couple in vivo.
CC {ECO:0000269|PubMed:15720398, ECO:0000269|PubMed:17416671,
CC ECO:0000269|PubMed:19502404, ECO:0000269|PubMed:20453092,
CC ECO:0000269|PubMed:22431591, ECO:0000269|PubMed:25550321,
CC ECO:0000269|PubMed:27776484}.
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:15720398};
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:15720398};
CC -!- ACTIVITY REGULATION: StkP is activated continuously during growth and
CC its activity is inhibited upon growth arrest. Inhibited by
CC staurosporine, a known protein kinase inhibitor.
CC {ECO:0000269|PubMed:15720398, ECO:0000269|PubMed:20453092}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Active over the wide range of pH from 3 to 9.
CC {ECO:0000269|PubMed:15720398};
CC -!- SUBUNIT: Homodimer. StkP forms dimers through its transmembrane and
CC extracellular domains. Dimer formation likely promotes
CC autophosphorylation activity and might be necessary for targeting StkP
CC substrate. Interacts with PhpP via its kinase domain.
CC {ECO:0000269|PubMed:17307148, ECO:0000269|PubMed:19502404}.
CC -!- INTERACTION:
CC Q8KY50; Q8KY51: phpP; NbExp=2; IntAct=EBI-6405629, EBI-6405646;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15720398,
CC ECO:0000269|PubMed:17307148, ECO:0000269|PubMed:19502404,
CC ECO:0000269|PubMed:22431591}; Single-pass membrane protein
CC {ECO:0000269|PubMed:15720398, ECO:0000269|PubMed:17307148,
CC ECO:0000269|PubMed:19502404, ECO:0000269|PubMed:22431591}. Note=The C-
CC terminal PASTA domain is located in the periplasmic space, beneath the
CC peptidoglycan cell wall, and the kinase domain is located in the
CC cytoplasm. However, another study in the virulent strain TIGR4
CC (PubMed:20223804) showed that the C-terminal PASTA domain is exposed
CC extracellularly. Localizes to the midcell division sites.
CC -!- INDUCTION: The phpP and stkP genes form an operon.
CC {ECO:0000269|PubMed:15720398}.
CC -!- DOMAIN: Consists of an N-terminal kinase domain, a transmembrane
CC domain, and a C-terminal domain containing four repeats of the PASTA
CC signature sequence (Penicillin-binding protein and Ser/Thr protein
CC kinase associated domain). The C-terminal domain binds to synthetic and
CC native peptidoglycan (PGN) subunits and to beta-lactam antibiotics,
CC which mimic the terminal portions of the PGN stem peptide. Deletion of
CC both the transmembrane domain and the PASTA domain negatively affects
CC the stability of the core kinase domain. In contrast, the membrane
CC anchored kinase domain and the full-length form of StkP are stable and
CC capable of autophosphorylation. However, the membrane anchored kinase
CC domain (i.e. StkP lacking the C-terminal PASTA domain) is unable to
CC phosphorylate its substrates, which means that the PASTA domain is
CC essential for StkP activation and substrate phosphorylation. The PASTA
CC domain is also responsible for cellular targeting to midcell (shown in
CC the virulent strain D39). Both the transmembrane and extracellular
CC domains promote dimerization of StkP. {ECO:0000269|PubMed:17307148,
CC ECO:0000269|PubMed:20453092, ECO:0000269|PubMed:21167155}.
CC -!- PTM: Autophosphorylation occurs predominantly on threonine residue(s)
CC and weakly on serine residue(s). Dephosphorylated by PhpP.
CC {ECO:0000269|PubMed:15720398, ECO:0000305|PubMed:27776484}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene have a significantly
CC reduced growth rate in the early exponential phase, exhibit an
CC increased rate of autolysis at the stationary phase of growth and do
CC not achieve the same final optical density as the wild-type strain.
CC Their growth is almost completely impaired at 40 degrees Celsius, in
CC contrast to that of the wild-type strain which is unaffected at this
CC temperature. The mutant strain is also more susceptible to oxidative
CC stress, to osmotic stress, and is less tolerant to acidic pH. Moreover,
CC inactivation of stkP leads to morphological changes: a significant
CC number of cells do not have the typical ovoid shape but appear to be
CC longer with rather oval poles, and they exhibit an apparent cell
CC division defect. Complete loss of Thr-phosphorylation, competence is
CC decreased (PubMed:27776484). {ECO:0000269|PubMed:17416671,
CC ECO:0000269|PubMed:20453092, ECO:0000269|PubMed:27776484}.
CC -!- MISCELLANEOUS: Strain Rx1 is unencapsulated.
CC {ECO:0000305|PubMed:19502404, ECO:0000305|PubMed:27776484}.
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; AF285441; AAM47530.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8KY50; -.
DR SMR; Q8KY50; -.
DR IntAct; Q8KY50; 1.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0000917; P:division septum assembly; IEA:UniProtKB-KW.
DR GO; GO:0030420; P:establishment of competence for transformation; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010506; P:regulation of autophagy; IEA:InterPro.
DR GO; GO:0051302; P:regulation of cell division; IMP:CACAO.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR CDD; cd06577; PASTA_pknB; 3.
DR CDD; cd14014; STKc_PknB_like; 1.
DR Gene3D; 3.30.10.20; -; 4.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR045269; Atg1-like.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR005543; PASTA_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR NCBIfam; NF033483; PknB_PASTA_kin; 1.
DR PANTHER; PTHR24348:SF22; NON-SPECIFIC SERINE_THREONINE PROTEIN KINASE; 1.
DR PANTHER; PTHR24348; SERINE/THREONINE-PROTEIN KINASE UNC-51-RELATED; 1.
DR Pfam; PF03793; PASTA; 4.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00740; PASTA; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS51178; PASTA; 4.
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 ATP-binding; Cell cycle; Cell division; Cell membrane; Cell shape;
KW Competence; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Repeat;
KW Septation; Serine/threonine-protein kinase; Transcription;
KW Transcription regulation; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..659
FT /note="Serine/threonine-protein kinase StkP"
FT /id="PRO_0000418143"
FT TOPO_DOM 1..342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19502404"
FT TRANSMEM 343..363
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 364..659
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:19502404"
FT DOMAIN 12..273
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 366..433
FT /note="PASTA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT DOMAIN 434..505
FT /note="PASTA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT DOMAIN 506..577
FT /note="PASTA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT DOMAIN 578..651
FT /note="PASTA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00528"
FT REGION 541..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 136
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 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 42
FT /note="K->R: Dramatic reduction of phosphorylation."
FT /evidence="ECO:0000269|PubMed:15720398,
FT ECO:0000269|PubMed:20453092"
SQ SEQUENCE 659 AA; 72378 MW; F0146D420F2C565D CRC64;
MIQIGKIFAG RYRIVKQIGR GGMADVYLAK DLILDGEEVA VKVLRTNYQT DPIAVARFQR
EARAMADLDH PHIVRITDIG EEDGQQYLAM EYVAGLDLKR YIKEHYPLSN EEAVRIMRQI
LLAMRLAHTR GIVHRDLKPQ NILLTPDGTA KVTDFGIAVA FAETSLTQTN SMLGSVHYLS
PEQARGSKAT VQSDIYAMGI IFYEMLTGHI PYDGDSAVTI ALQHFQNPLP SVIAENSSVP
QALENVIIKA TAKKLTNRYR SVSEMYVDLS SSLSYNRRNE SKLIFDETSK ADTKTLPKVS
QSTLTSIPKV QAQTEHKSIK NPSQAVTEET YQPQAPKKHR FKMRYLILLA SLVLVAASLI
WILSRSPATI AIPDVAGQTV AEAKATLKKA NFEIGEEKTE ASEKVEEGRI IRTDPGAGTG
RKEGTKINLV VSSGKQSFQI SNYVGRKSSD VIAELKEKKV PDNLIKIEEE ESNESEAGTV
LKQSLPEGTT YDLSKATQIV LTVAKKATTI QLGNYIGRNS TEVISELKQK KVPENLIKIE
EEESSESEPG TIMKQSPGAG TTYDVSKPTQ IVLTVAKKVT SVAMPSYIGS SLEFTKNNLI
QIVGIKEANI EVVEVTTAPA GSVEGMVVEQ SPRAGEKVDL NKTRVKISIY KPKTTSATP
//
