STKP_STRPN
ID STKP_STRPN Reviewed; 659 AA.
AC Q97PA9;
DT 11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Serine/threonine-protein kinase StkP;
DE Short=Ser/Thr-protein kinase StkP;
DE EC=2.7.11.1;
DE AltName: Full=Eukaryotic-type Ser/Thr protein kinase;
DE Short=ESTPK;
GN Name=stkP; OrderedLocusNames=SP_1732;
OS Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=170187;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=11463916; DOI=10.1126/science.1061217;
RA Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D.,
RA Peterson S.N., Heidelberg J.F., DeBoy R.T., Haft D.H., Dodson R.J.,
RA Durkin A.S., Gwinn M.L., Kolonay J.F., Nelson W.C., Peterson J.D.,
RA Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D.,
RA Holtzapple E.K., Khouri H.M., Wolf A.M., Utterback T.R., Hansen C.L.,
RA McDonald L.A., Feldblyum T.V., Angiuoli S.V., Dickinson T., Hickey E.K.,
RA Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A.,
RA Morrison D.A., Hollingshead S.K., Fraser C.M.;
RT "Complete genome sequence of a virulent isolate of Streptococcus
RT pneumoniae.";
RL Science 293:498-506(2001).
RN [2]
RP IDENTIFICATION AS A VACCINE ANTIGEN, BIOTECHNOLOGY, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=18166586; DOI=10.1084/jem.20071168;
RA Giefing C., Meinke A.L., Hanner M., Henics T., Bui M.D., Gelbmann D.,
RA Lundberg U., Senn B.M., Schunn M., Habel A., Henriques-Normark B.,
RA Ortqvist A., Kalin M., von Gabain A., Nagy E.;
RT "Discovery of a novel class of highly conserved vaccine antigens using
RT genomic scale antigenic fingerprinting of pneumococcus with human
RT antibodies.";
RL J. Exp. Med. 205:117-131(2008).
RN [3]
RP FUNCTION, ROLE IN CELL DIVISION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION
RP ACTIVITY, INTERACTION WITH FTSZ, SUBCELLULAR LOCATION, TOPOLOGY, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-334 / TIGR4, and PJ1324 / Serotype 6B;
RX PubMed=20223804; DOI=10.1099/mic.0.036335-0;
RA Giefing C., Jelencsics K.E., Gelbmann D., Senn B.M., Nagy E.;
RT "The pneumococcal eukaryotic-type serine/threonine protein kinase StkP co-
RT localizes with the cell division apparatus and interacts with FtsZ in
RT vitro.";
RL Microbiology 156:1697-1707(2010).
RN [4]
RP BIOTECHNOLOGY.
RC STRAIN=ATCC BAA-334 / TIGR4;
RX PubMed=22538529; DOI=10.1002/jps.23175;
RA Iyer V., Hu L., Liyanage M.R., Esfandiary R., Reinisch C., Meinke A.,
RA Maisonneuve J., Volkin D.B., Joshi S.B., Middaugh C.R.;
RT "Preformulation characterization of an aluminum salt-adjuvanted trivalent
RT recombinant protein-based vaccine candidate against Streptococcus
RT pneumoniae.";
RL J. Pharm. Sci. 101:3078-3090(2012).
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. StkP also plays an important role for bacterial survival in
CC vivo. Identified target substrates that are specifically phosphorylated
CC by StkP in vivo, mainly on threonine residues, are DivIVA, GlmM, PpaC,
CC MapZ (shown in the avirulent strain Rx / Cp1015), KhpB (also called
CC EloR/Jag, shown in strains R6 and Rx1) and StkP itself. Also able to
CC phosphorylate FtsZ in vitro, however FtsZ may not be a target of StkP
CC in vivo. Autophosphorylated StkP is a substrate for the cotranscribed
CC protein phosphatase PhpP (shown in the avirulent strain Rx / Cp1015);
CC PhpP and StkP appear to constitute a functional signaling couple in
CC vivo. {ECO:0000269|PubMed:20223804}.
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:20223804};
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:20223804};
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 (By similarity). Interacts with FtsZ in vitro via its kinase
CC domain. {ECO:0000250, ECO:0000269|PubMed:20223804}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20223804};
CC Single-pass membrane protein {ECO:0000269|PubMed:20223804}. Note=The
CC kinase domain is located intracellularly, while the C-terminal PASTA
CC domain is exposed extracellularly, being surface accessible in vivo and
CC recognized by the immune system (PubMed:20223804). However, another
CC study in an avirulent strain (PubMed:19502404) showed that the C-
CC terminal PASTA domain is located in the periplasmic space, beneath the
CC peptidoglycan cell wall. Localizes to the midcell division sites in
CC dividing cells of growing cultures but in the stationary phase, the
CC characteristic midcell localization of StkP disappears and StkP shows a
CC diffuse membrane localization. Displays a temporal colocalization with
CC FtsZ. {ECO:0000269|PubMed:20223804}.
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 PASTA domain binds to peptidoglycan
CC (PGN) subunits, is essential for StkP activation and substrate
CC phosphorylation, and is responsible for cellular targeting to midcell
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylation occurs predominantly at the threonine residue
CC and weakly at the serine residue. Dephosphorylated by PhpP (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Disruption of this gene results in a strong
CC reduction of bacterial growth, and increased antibiotic sensitivity to
CC penicillin, cephalosporins (e.g. ceftazidime), and vancomycin in vitro.
CC Cells lacking this gene are highly attenuated in virulence, and
CC demonstrate an elongated shape and very few division septa separating
CC the daughter cells. The lack of StkP does not disturb FtsZ ring
CC formation and does not affect the expression level and the
CC phosphorylation status of FtsZ. {ECO:0000269|PubMed:18166586,
CC ECO:0000269|PubMed:20223804}.
CC -!- BIOTECHNOLOGY: Was identified as an important pneumococcal antigen that
CC provides significant cross-protection in models of pneumococcal sepsis
CC and pneumonia. Was selected as one of the lead candidates for
CC development of a new pneumococcus protein-based vaccine. Is a component
CC of a trivalent recombinant protein-based vaccine candidate for
CC protection against S.pneumoniae, whose initial formulation development
CC evaluations are described in PubMed:22538529.
CC {ECO:0000269|PubMed:18166586, ECO:0000269|PubMed:22538529}.
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; AE005672; AAK75808.1; -; Genomic_DNA.
DR PIR; G95201; G95201.
DR RefSeq; WP_000614538.1; NZ_AKVY01000001.1.
DR AlphaFoldDB; Q97PA9; -.
DR SMR; Q97PA9; -.
DR STRING; 170187.SP_1732; -.
DR EnsemblBacteria; AAK75808; AAK75808; SP_1732.
DR KEGG; spn:SP_1732; -.
DR eggNOG; COG0515; Bacteria.
DR eggNOG; COG2815; Bacteria.
DR OMA; DPDYRYQ; -.
DR PhylomeDB; Q97PA9; -.
DR BioCyc; SPNE170187:G1FZB-1755-MON; -.
DR Proteomes; UP000000585; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
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 Pfam; PF03793; PASTA; 4.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00740; PASTA; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Repeat; Septation;
KW Serine/threonine-protein kinase; Transferase; Transmembrane;
KW Transmembrane helix; Virulence.
FT CHAIN 1..659
FT /note="Serine/threonine-protein kinase StkP"
FT /id="PRO_0000418144"
FT TOPO_DOM 1..342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 343..363
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 364..659
FT /note="Extracellular"
FT /evidence="ECO:0000250"
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"
SQ SEQUENCE 659 AA; 72289 MW; 4723AE1001BCE4CF CRC64;
MIQIGKIFAG RYRIVKQIGR GGMADVYLAK DLILDGEEVA VKVLRTNYQT DPIAVARFQR
EARAMADLDH PHIVRITDIG EEDGQQYLAM EYVAGLDLKR YIKEHYPLSN EEAVRIMGQI
LLAMRLAHTR GIVHRDLKPQ NILLTPDGTA KVTDFGIAVA FAETSLTQTN SMLGSVHYLS
PEQARGSKAT VQSDIYAMGI IFYEMLTGHI PYDGDSAVTI ALQHFQKPLP SVIAENPSVP
QALENVIIKA TAKKLTNRYR SVSEMYVDLS SSLSYNRRNE SKLIFDETSK ADTKTLPKVS
QSTLTSIPKV QAQTEHKSIK NPSQAVTEET YQPQAPKKHR FKMRYLILLA SLVLVAASLI
WILSRTPATI 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 GSAEGMVVEQ SPRAGEKVDL NKTRVKISIY KPKTTSATP
