CDPK4_PLAYO
ID CDPK4_PLAYO Reviewed; 528 AA.
AC Q7RJG2;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Calcium-dependent protein kinase 4;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P62345};
GN Name=CDPK4; Synonyms=CPK4; ORFNames=PY03298;
OS Plasmodium yoelii yoelii.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=73239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17XNL;
RX PubMed=12368865; DOI=10.1038/nature01099;
RA Carlton J.M., Angiuoli S.V., Suh B.B., Kooij T.W., Pertea M., Silva J.C.,
RA Ermolaeva M.D., Allen J.E., Selengut J.D., Koo H.L., Peterson J.D., Pop M.,
RA Kosack D.S., Shumway M.F., Bidwell S.L., Shallom S.J., van Aken S.E.,
RA Riedmuller S.B., Feldblyum T.V., Cho J.K., Quackenbush J., Sedegah M.,
RA Shoaibi A., Cummings L.M., Florens L., Yates J.R. III, Raine J.D.,
RA Sinden R.E., Harris M.A., Cunningham D.A., Preiser P.R., Bergman L.W.,
RA Vaidya A.B., van Lin L.H., Janse C.J., Waters A.P., Smith H.O., White O.R.,
RA Salzberg S.L., Venter J.C., Fraser C.M., Hoffman S.L., Gardner M.J.,
RA Carucci D.J.;
RT "Genome sequence and comparative analysis of the model rodent malaria
RT parasite Plasmodium yoelii yoelii.";
RL Nature 419:512-519(2002).
CC -!- FUNCTION: Calcium-dependent protein kinase which acts as a sensor and
CC effector of intracellular Ca(2+) levels probably in part downstream of
CC cGMP-activated PKG kinase. Plays a central role in the host
CC erythrocytes and hepatocytes infection cycles, sexual reproduction and
CC mosquito transmission of the parasite. During the liver stage, involved
CC in sporozoite motility and thus in sporozoite invasion of host
CC hepatocytes, probably together with CDPK1 and CDPK5. Involved in
CC merosome egress from host hepatocytes, probably together with CDPK5.
CC During the asexual blood stage, involved in merozoite invasion of host
CC erythrocytes and motility by stabilizing the inner membrane complex, a
CC structure below the plasma membrane which acts as an anchor for the
CC glidosome, an acto-myosin motor. Required for cell cycle progression in
CC the male gametocyte. During male gametogenesis in the mosquito gut,
CC required to initiate the first round of DNA replication, probably by
CC facilitating the assembly of the pre-replicative MCM complex, to
CC assemble the first mitotic spindle and, at the end of gametogenesis, to
CC initiate axoneme motility, cytokinesis and subsequent exflagellation.
CC For each of these steps, may phosphorylate SOC1, SOC2 and SOC3,
CC respectively. Together with CDPK1, regulates ookinete gliding in the
CC mosquito host midgut. {ECO:0000250|UniProtKB:P62345}.
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:0000250|UniProtKB:P62345};
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:0000250|UniProtKB:P62345};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8IBS5};
CC -!- ACTIVITY REGULATION: Activated by calcium. Upon calcium binding to the
CC EF-hand domains, the C-terminus of the junction domain (J domain)
CC undergoes a conformational change which results in the dissociation of
CC the pseudo-substrate inhibitory motif from the catalytic domain. This,
CC in turn, may facilitate the autophosphorylation of the activation loop
CC at Thr-234, which leads to the kinase activation. Intracellular calcium
CC increase is triggered by xanthurenic acid (XA), a small mosquito
CC molecule that induces the differentiation of specialized transmission
CC stages, the gametocytes, into male and female gametes. Activated by a
CC decrease in temperature (20 degrees Celsius) and an increase in pH
CC (7.6) occurring when the parasite is ingested by in the mosquito.
CC {ECO:0000250|UniProtKB:Q8IBS5}.
CC -!- SUBUNIT: May interact with the pre-replication MCM complex prior male
CC gametogenesis activation. {ECO:0000250|UniProtKB:P62345}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P62345}. Cell
CC membrane {ECO:0000250|UniProtKB:Q8IBS5}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q8IBS5}.
CC -!- DOMAIN: The junction domain (J domain) is composed of 2 motifs that
CC maintain the kinase inactive. The N-terminal autoinhibitory motif acts
CC as a pseudosubstrate inhibiting the catalytic domain while the C-
CC terminal motif binds the EF-hand domains.
CC {ECO:0000250|UniProtKB:Q8IBS5}.
CC -!- PTM: Myristoylated; myristoylation may target it to different
CC subcellular compartments. During male gametogenesis, myristoylation is
CC required to initiate DNA replication but not for mitotic spindle
CC assembly or axoneme activation. {ECO:0000250|UniProtKB:P62345}.
CC -!- PTM: Not palmitoylated. {ECO:0000250|UniProtKB:P62345}.
CC -!- PTM: May be autophosphorylated on Thr-234 in vitro.
CC {ECO:0000250|UniProtKB:Q8IBS5}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDPK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AABL01000936; EAA22858.1; -; Genomic_DNA.
DR AlphaFoldDB; Q7RJG2; -.
DR SMR; Q7RJG2; -.
DR STRING; 73239.Q7RJG2; -.
DR EnsemblProtists; EAA22858; EAA22858; EAA22858.
DR InParanoid; Q7RJG2; -.
DR OMA; LEHEWIR; -.
DR Proteomes; UP000008553; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR CDD; cd00051; EFh; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF13499; EF-hand_7; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00054; EFh; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00018; EF_HAND_1; 4.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 3: Inferred from homology;
KW ATP-binding; Calcium; Cell membrane; Cytoplasm; Developmental protein;
KW Differentiation; Kinase; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Myristate; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..528
FT /note="Calcium-dependent protein kinase 4"
FT /id="PRO_0000085843"
FT DOMAIN 70..328
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 376..411
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 423..458
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 459..494
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 498..528
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 350..386
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 350..358
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 359..368
FT /note="J domain EF-hand interaction motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT ACT_SITE 193
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 76..84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 99
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 395
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 400
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 436
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 438
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 440
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 442
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 447
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 472
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 474
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 476
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 506
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 508
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 510
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 512
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 517
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P62345"
SQ SEQUENCE 528 AA; 60587 MW; 1F7C7D9ED162B066 CRC64;
MGQEMSTQSD IQNEDQKGNK RNLKGTQGKN GLKERSTSIS KEIVKNSFNN SKLRPGMFIQ
NSNVVFNEQY KGIKILGKGS FGEVILSKDK HTGHEYAIKV ISKKHVKRKT DKQSLLREVE
LLKMLDHINI MKLYEFFEDN NYYYLVSDVY SGGELFDEII SRKRFYEVDA ARIIKQVLSG
ITYMHKNNVV HRDLKPENIL LETKNKEDMI IKIIDFGLST HFEYSKKMKD KIGTAYYIAP
DVLHGTYDEK CDIWSCGVIL YILLSGCPPF NGSNEYDILK KVETGKYTFD LPQFKKISDK
AKDLIKKMLM YTSAVRISAR DALEHEWIRL MTSKDNVNID IPSLELSITN IKQFQSTQKL
AQAALLYMGS KLTTIDETKE LTKIFKKMDK NGDGQLDRNE LIIGYKELLK LKGDDTTDLD
NAAIEVEVDQ ILSSIDLDQN GYIEYSEFLT VAIDRKLLLS TERLEKAFKL FDKDGSGKIS
ANELAQLFGL GDVSSDCWKT VLKEVDQNND GEIDFKEFRD MLIKLCNY
