CDPK2_PLAFK
ID CDPK2_PLAFK Reviewed; 513 AA.
AC O15865;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Calcium-dependent protein kinase 2 {ECO:0000303|PubMed:9247932};
DE EC=2.7.11.1 {ECO:0000269|PubMed:9247932};
DE AltName: Full=PfCDPK2 {ECO:0000303|PubMed:9247932};
GN Name=CDPK2 {ECO:0000303|PubMed:9247932}; Synonyms=CPK2;
OS Plasmodium falciparum (isolate K1 / Thailand).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5839;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RX PubMed=9247932; DOI=10.1016/s0166-6851(97)00052-2;
RA Faerber P.M., Graeser R., Franklin R.M., Kappes R.;
RT "Molecular cloning and characterization of a second calcium-dependent
RT protein kinase of Plasmodium falciparum.";
RL Mol. Biochem. Parasitol. 87:211-216(1997).
RN [2] {ECO:0007744|PDB:3PM8}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 335-513 IN COMPLEX WITH CALCIUM.
RA Wernimont A.K., Hutchinson A., Lew J., Chamberlain K., MacKenzie F.,
RA Loppnau P., Cossar D., Crombet L., Arrowsmith C.H., Edwards A.M.,
RA Bountra C., Weigelt J., Hui R., Amani M.;
RT "CAD domain of PFF0520w, Calcium dependent protein kinase.";
RL Submitted (NOV-2010) to the PDB data bank.
RN [3] {ECO:0007744|PDB:4MVF}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 30-511 IN COMPLEX WITH CALCIUM.
RA Lauciello L., Pernot L., Bottegoni G., Bisson W., Scapozza L., Perozzo R.;
RT "P. falciparum Calcium-Dependent Protein Kinase 2 (PfCDPK2): First Crystal
RT Structure and Virtual Ligand Screening.";
RL Submitted (SEP-2013) to the PDB data bank.
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:9247932). During male gametogenesis
CC in the mosquito gut, required for male exflagellation, possibly by
CC regulating male gamete exit from the host erythrocytes. Not required
CC for asexual blood stage proliferation (By similarity).
CC {ECO:0000250|UniProtKB:Q8ICR0, ECO:0000269|PubMed:9247932}.
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:9247932};
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:9247932};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8ICR0};
CC -!- ACTIVITY REGULATION: Activated by calcium (PubMed:9247932). 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. This, in turn, may facilitate the autophosphorylation
CC of the activation loop at Thr-232, which leads to the kinase activation
CC (By similarity). {ECO:0000250|UniProtKB:Q8IBS5,
CC ECO:0000269|PubMed:9247932}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q8ICR0}.
CC -!- DEVELOPMENTAL STAGE: Expressed in ring, trophozoite, schizont and
CC segmenter stages. {ECO:0000269|PubMed:9247932}.
CC -!- DOMAIN: The EF-hand domain 2 appears to lack a functional calcium
CC binding site. {ECO:0000305|Ref.2, ECO:0000305|Ref.3}.
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:9247932}.
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; X99763; CAA68090.1; -; Genomic_DNA.
DR PDB; 3PM8; X-ray; 2.00 A; A/B=335-513.
DR PDB; 4MVF; X-ray; 2.00 A; A=30-511.
DR PDBsum; 3PM8; -.
DR PDBsum; 4MVF; -.
DR AlphaFoldDB; O15865; -.
DR SMR; O15865; -.
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; IEA:UniProt.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
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; 3.
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 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Calcium; Kinase; Lipoprotein; Magnesium;
KW Metal-binding; Myristate; Nucleotide-binding; Phosphoprotein; 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_0000085838"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.3, ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.3, ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.3, ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.3, ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.3, ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
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 ECO:0000269|Ref.2, ECO:0000269|Ref.3, ECO:0007744|PDB:3PM8,
FT ECO:0007744|PDB:4MVF"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:4MVF"
FT STRAND 72..80
FT /evidence="ECO:0007829|PDB:4MVF"
FT STRAND 82..91
FT /evidence="ECO:0007829|PDB:4MVF"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:4MVF"
FT STRAND 97..104
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 108..121
FT /evidence="ECO:0007829|PDB:4MVF"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:4MVF"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 156..161
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 166..185
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:4MVF"
FT STRAND 198..204
FT /evidence="ECO:0007829|PDB:4MVF"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 245..263
FT /evidence="ECO:0007829|PDB:4MVF"
FT TURN 290..294
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 297..306
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 317..321
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 324..329
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 342..348
FT /evidence="ECO:0007829|PDB:3PM8"
FT TURN 349..351
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 354..366
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 369..382
FT /evidence="ECO:0007829|PDB:3PM8"
FT STRAND 387..390
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 392..402
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 409..416
FT /evidence="ECO:0007829|PDB:3PM8"
FT STRAND 421..427
FT /evidence="ECO:0007829|PDB:4MVF"
FT HELIX 428..433
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 438..441
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 444..454
FT /evidence="ECO:0007829|PDB:3PM8"
FT STRAND 459..462
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 464..471
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 479..492
FT /evidence="ECO:0007829|PDB:3PM8"
FT STRAND 497..501
FT /evidence="ECO:0007829|PDB:3PM8"
FT HELIX 502..510
FT /evidence="ECO:0007829|PDB:3PM8"
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
