CTKA_HELPJ
ID CTKA_HELPJ Reviewed; 325 AA.
AC Q9ZKJ5;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Serine/threonine-protein kinase CtkA;
DE Short=Ser/Thr-protein kinase CtkA;
DE EC=2.7.11.1;
DE AltName: Full=Cell-translocating kinase A;
GN Name=ctkA; OrderedLocusNames=jhp_0940;
OS Helicobacter pylori (strain J99 / ATCC 700824) (Campylobacter pylori J99).
OC Bacteria; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC Helicobacteraceae; Helicobacter.
OX NCBI_TaxID=85963;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=J99 / ATCC 700824;
RX PubMed=9923682; DOI=10.1038/16495;
RA Alm R.A., Ling L.-S.L., Moir D.T., King B.L., Brown E.D., Doig P.C.,
RA Smith D.R., Noonan B., Guild B.C., deJonge B.L., Carmel G., Tummino P.J.,
RA Caruso A., Uria-Nickelsen M., Mills D.M., Ives C., Gibson R., Merberg D.,
RA Mills S.D., Jiang Q., Taylor D.E., Vovis G.F., Trust T.J.;
RT "Genomic sequence comparison of two unrelated isolates of the human gastric
RT pathogen Helicobacter pylori.";
RL Nature 397:176-180(1999).
RN [2]
RP INDUCTION.
RC STRAIN=J99 / ATCC 700824;
RX PubMed=12404238; DOI=10.1053/gast.2002.36589;
RA Graham J.E., Peek R.M. Jr., Krishna U., Cover T.L.;
RT "Global analysis of Helicobacter pylori gene expression in human gastric
RT mucosa.";
RL Gastroenterology 123:1637-1648(2002).
RN [3]
RP FUNCTION.
RC STRAIN=J99 / ATCC 700824;
RX PubMed=17993522; DOI=10.1128/jb.01309-07;
RA Rizwan M., Alvi A., Ahmed N.;
RT "Novel protein antigen (JHP940) from the genomic plasticity region of
RT Helicobacter pylori induces tumor necrosis factor alpha and interleukin-8
RT secretion by human macrophages.";
RL J. Bacteriol. 190:1146-1151(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF APOPROEIN AND IN COMPLEX WITH
RP MG-ADP OR ATP ANALOG, FUNCTION, CATALYTIC ACTIVITY, GENE NAME,
RP PHOSPHORYLATION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ASP-155
RP AND ASP-179.
RC STRAIN=J99 / ATCC 700824;
RX PubMed=21098302; DOI=10.1073/pnas.1010153107;
RA Kim D.J., Park K.S., Kim J.H., Yang S.H., Yoon J.Y., Han B.G., Kim H.S.,
RA Lee S.J., Jang J.Y., Kim K.H., Kim M.J., Song J.S., Kim H.J., Park C.M.,
RA Lee S.K., Lee B.I., Suh S.W.;
RT "Helicobacter pylori proinflammatory protein up-regulates NF-kappaB as a
RT cell-translocating Ser/Thr kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:21418-21423(2010).
CC -!- FUNCTION: Virulence factor acting as a pro-inflammatory protein that
CC induces the secretion of the pro-inflammatory cytokines TNF-alpha
CC (tumor necrosis factor-alpha) and IL-8 (interleukin-8) from human
CC macrophages, as well as enhanced translocation of the transcription
CC factor NF-kappa-B complex in macrophages. Is a kinase capable of
CC autophosphorylating itself at a threonine residue near the N-terminus.
CC Also leads to enhanced phosphorylation of the NF-kappa-B p65 subunit
CC (RELA) at 'Ser-276' in human epithelial cancer cells; its kinase
CC activity is required for this enhanced phosphorylation that up-
CC regulates NF-kappa-B activity, but it does not directly phosphorylate
CC this protein. Thus, the kinase activity of CtkA may play an important
CC role in the induction of host inflammatory responses during H.pylori
CC infection. {ECO:0000269|PubMed:17993522, ECO:0000269|PubMed:21098302}.
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:21098302};
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:21098302};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21098302}. Host
CC cytoplasm, host cytosol {ECO:0000269|PubMed:21098302}. Host nucleus
CC {ECO:0000269|PubMed:21098302}. Note=Translocates into cultured human
CC cells. When examining the cellular location of the transiently
CC expressed CtkA after 0, 12, 24, and 48 hours of transfection, the
CC transiently expressed CtkA translocates from cytosol into nucleus in a
CC time-dependent manner.
CC -!- INDUCTION: Is strongly expressed in response to the interaction of
CC H.pylori with the mammalian gastric mucosa.
CC {ECO:0000269|PubMed:12404238}.
CC -!- DOMAIN: The C-terminal tail (residues 301-325) is not required for the
CC kinase activity and for translocation into human cells.
CC {ECO:0000269|PubMed:21098302}.
CC -!- PTM: Autophosphorylates on either Thr-3 or Thr-7.
CC {ECO:0000269|PubMed:21098302}.
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DR EMBL; AE001439; AAD06516.1; -; Genomic_DNA.
DR PIR; H71869; H71869.
DR RefSeq; WP_001142065.1; NZ_CP011330.1.
DR PDB; 3AKJ; X-ray; 2.00 A; A/B=1-325.
DR PDB; 3AKK; X-ray; 2.50 A; A/B/C/D=1-325.
DR PDB; 3AKL; X-ray; 2.90 A; A/B/C/D=1-325.
DR PDBsum; 3AKJ; -.
DR PDBsum; 3AKK; -.
DR PDBsum; 3AKL; -.
DR AlphaFoldDB; Q9ZKJ5; -.
DR SMR; Q9ZKJ5; -.
DR STRING; 85963.jhp_0940; -.
DR EnsemblBacteria; AAD06516; AAD06516; jhp_0940.
DR KEGG; hpj:jhp_0940; -.
DR PATRIC; fig|85963.30.peg.1656; -.
DR eggNOG; COG3550; Bacteria.
DR OMA; DRHNGNW; -.
DR EvolutionaryTrace; Q9ZKJ5; -.
DR Proteomes; UP000000804; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IDA:UniProtKB.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR InterPro; IPR012893; HipA-like_C.
DR Pfam; PF07804; HipA_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Host cytoplasm; Host nucleus; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Secreted;
KW Serine/threonine-protein kinase; Transferase; Virulence.
FT CHAIN 1..325
FT /note="Serine/threonine-protein kinase CtkA"
FT /id="PRO_0000423370"
FT REGION 296..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 296..315
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 21..24
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 88..90
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 160
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 179
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 179
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MUTAGEN 155
FT /note="D->Q: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:21098302"
FT MUTAGEN 179
FT /note="D->Q: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:21098302"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:3AKK"
FT STRAND 24..29
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 53..66
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 100..105
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:3AKK"
FT HELIX 119..128
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 134..151
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 162..170
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 190..197
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:3AKJ"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:3AKK"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:3AKL"
FT HELIX 225..231
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 235..244
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 245..247
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 250..258
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 265..281
FT /evidence="ECO:0007829|PDB:3AKJ"
FT HELIX 283..294
FT /evidence="ECO:0007829|PDB:3AKJ"
SQ SEQUENCE 325 AA; 37606 MW; 32DF158485F74DEE CRC64;
MPTIDFTFCE INPKKGFGGA NGNKISLFYN NELYMVKFPP KPSTHKEMSY TNGCFSEYVA
CHIVNSLGLK VQETLLGTYK NKIVVACKDF TTHQYELVDF LSLKNTMIEL EKSGKDTNLN
DVLYAIDNQH FIEPKVLKCF FWDMFVADTL LGNFDRHNGN WGFLRASNSK EYQIAPIFDC
GSCLYPQADD VVCQKVLSNI DELNARIYNF PQSILKDDND KKINYYDFLT QTNNKDCLDA
LLRIYPRIDM NKIHSIIDNT PFMSEIHKEF LHTMLDERKS KIIDVAHTRA IELSLQHKQA
HSNPYDNADD LDNSNEYTPT PKRRR
