CDPK2_PLAF7
ID CDPK2_PLAF7 Reviewed; 513 AA.
AC Q8ICR0;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 4.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Calcium-dependent protein kinase 2 {ECO:0000303|PubMed:23792132};
DE EC=2.7.11.1 {ECO:0000269|PubMed:23792132};
DE AltName: Full=PfCDPK2 {ECO:0000303|PubMed:23792132};
GN Name=CDPK2 {ECO:0000303|PubMed:23792132}; Synonyms=CPK2;
GN ORFNames=MAL6P1.108, PF3D7_0610600, PFF0520w;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [3]
RP DEVELOPMENTAL STAGE.
RX PubMed=10760601; DOI=10.1016/s0167-4781(00)00032-4;
RA Li J.-L., Baker D.A., Cox L.S.;
RT "Sexual stage-specific expression of a third calcium-dependent protein
RT kinase from Plasmodium falciparum.";
RL Biochim. Biophys. Acta 1491:341-349(2000).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND PHOSPHORYLATION.
RX PubMed=23792132; DOI=10.1016/j.pep.2013.06.006;
RA Lauciello L., Kappes B., Scapozza L., Perozzo R.;
RT "Expression, purification and biochemical characterization of recombinant
RT Ca-dependent protein kinase 2 of the malaria parasite Plasmodium
RT falciparum.";
RL Protein Expr. Purif. 90:170-177(2013).
RN [5]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=29042501; DOI=10.1128/mbio.01656-17;
RA Bansal A., Molina-Cruz A., Brzostowski J., Mu J., Miller L.H.;
RT "Plasmodium falciparum Calcium-Dependent Protein Kinase 2 Is Critical for
RT Male Gametocyte Exflagellation but Not Essential for Asexual
RT Proliferation.";
RL MBio 8:0-0(2017).
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 (PubMed:23792132). During male gametogenesis
CC in the mosquito gut, required for male exflagellation, possibly by
CC regulating male gamete exit from the host erythrocytes
CC (PubMed:29042501). Not required for asexual blood stage proliferation
CC (PubMed:29042501). {ECO:0000269|PubMed:23792132,
CC ECO:0000269|PubMed:29042501}.
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:23792132};
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:23792132};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:23792132};
CC -!- ACTIVITY REGULATION: Activated by calcium (PubMed:23792132). Upon
CC calcium binding to the EF-hand domains, the C-terminus of the junction
CC domain (J domain) undergoes a conformational change which results in
CC the dissociation of the pseudo-substrate inhibitory motif from the
CC catalytic domain (By similarity). This, in turn, may facilitate the
CC autophosphorylation of the activation loop at Thr-232, which leads to
CC the kinase activation (By similarity). {ECO:0000250|UniProtKB:Q8IBS5,
CC ECO:0000269|PubMed:23792132}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=76.4 uM for ATP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:23792132};
CC Vmax=1.88 pmol/min/ug enzyme toward ATP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:23792132};
CC Note=kcat is 0.002 sec(-1) with ATP as substrate (at 30 degrees
CC Celsius). {ECO:0000269|PubMed:23792132};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23792132}.
CC -!- DEVELOPMENTAL STAGE: During the asexual blood stage, expressed in
CC schizonts and to a lower extend in trophozoites (at protein level)
CC (PubMed:29042501). Expressed in gametocytes during the sexual blood
CC stage (at protein level) (PubMed:10760601, PubMed:29042501).
CC {ECO:0000269|PubMed:10760601, ECO:0000269|PubMed:29042501}.
CC -!- DOMAIN: The EF-hand domain 2 appears to lack a functional calcium
CC binding site. {ECO:0000250|UniProtKB:O15865}.
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. {ECO:0000250|UniProtKB:P62344}.
CC -!- PTM: Autophosphorylated in vitro. {ECO:0000269|PubMed:23792132}.
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; AL844505; CAG25347.2; -; Genomic_DNA.
DR RefSeq; XP_966095.1; XM_961002.1.
DR AlphaFoldDB; Q8ICR0; -.
DR SMR; Q8ICR0; -.
DR STRING; 5833.PFF0520w; -.
DR PRIDE; Q8ICR0; -.
DR EnsemblProtists; CAG25347; CAG25347; PF3D7_0610600.
DR HOGENOM; CLU_000288_37_4_1; -.
DR InParanoid; Q8ICR0; -.
DR OMA; FEINPWP; -.
DR PhylomeDB; Q8ICR0; -.
DR Reactome; R-PFA-5687128; MAPK6/MAPK4 signaling.
DR Proteomes; UP000001450; Chromosome 6.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0048232; P:male gamete generation; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
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; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
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; Calcium; Kinase; Lipoprotein; Magnesium; 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:0000250|UniProtKB:P62344"
FT CHAIN 2..513
FT /note="Calcium-dependent protein kinase 2"
FT /id="PRO_0000085837"
FT DOMAIN 72..326
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 370..405
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 406..441
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 442..477
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 480..513
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 345..380
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 345..353
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 354..363
FT /note="J domain EF-hand interaction motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT ACT_SITE 192
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 78..86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 383
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 394
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 455
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 457
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 459
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 461
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 466
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 493
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 495
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 497
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 499
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 504
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
SQ SEQUENCE 513 AA; 59048 MW; EB61F256FDF602C3 CRC64;
MGNHLSVNKL KRKKKKKSFL NIYGKNTNEN TSKQSNDYKY DINTSCISRE GTTTLERKNL
ILCHSGKLED KYIIDEKLGQ GTYGCVYKGI DKVTNQLYAI KEEKKDRLKN INRFFQEIEI
MKKLDHPNIV KLYETYENDN YIYLIMELCS GRELFDSIIE NGSFTEKNAA TIMKQIFSAI
FYLHSLNIVH RDLKPENFLF QSENKDSLLK IIDFGLSKNL GTGEFTTTKA GTPYYVAPQV
LDGKYDKKCD IWSSGVIMYT LLCGYPPFYG DTDNEVLKKV KKGEFCFYEN DWGSISSDAK
NLITKLLTYN PNERCTIEEA LNHPWITQMT KSHEHVELSS TLLKNLKNFK KENELKKIAL
TIIAKHLCDV EINNLRNIFI ALDVDNSGTL SSQEILDGLK KIGYQKIPPD IHQVLRDIDS
NASGQIHYTD FLAATIDKQT YLKKEVCLIP FKFFDIDGNG KISVEELKRI FGRDDIENPL
IDKAIDSLLQ EVDLNGDGEI DFHEFMLMMS KKK
