CDPK3_PLAF7
ID CDPK3_PLAF7 Reviewed; 562 AA.
AC Q9NJU9; O77333;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Calcium-dependent protein kinase 3 {ECO:0000303|PubMed:10760601};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q8IBS5};
DE AltName: Full=PfCDPK3 {ECO:0000303|PubMed:10760601};
GN Name=CDPK3 {ECO:0000303|PubMed:10760601}; Synonyms=CPK3;
GN ORFNames=MAL3P3.17, PF3D7_0310100, PFC0420w;
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 [GENOMIC DNA], AND 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=10448855; DOI=10.1038/22964;
RA Bowman S., Lawson D., Basham D., Brown D., Chillingworth T., Churcher C.M.,
RA Craig A., Davies R.M., Devlin K., Feltwell T., Gentles S., Gwilliam R.,
RA Hamlin N., Harris D., Holroyd S., Hornsby T., Horrocks P., Jagels K.,
RA Jassal B., Kyes S., McLean J., Moule S., Mungall K.L., Murphy L.,
RA Oliver K., Quail M.A., Rajandream M.A., Rutter S., Skelton J., Squares R.,
RA Squares S., Sulston J.E., Whitehead S., Woodward J.R., Newbold C.,
RA Barrell B.G.;
RT "The complete nucleotide sequence of chromosome 3 of Plasmodium
RT falciparum.";
RL Nature 400:532-538(1999).
RN [3]
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 [4]
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 [5]
RP ACTIVITY REGULATION, DOMAIN, AND CALCIUM-BINDING.
RX PubMed=28746405; DOI=10.1371/journal.pone.0181721;
RA Andresen C., Niklasson M., Cassman Ekloef S., Wallner B., Lundstroem P.;
RT "Biophysical characterization of the calmodulin-like domain of Plasmodium
RT falciparum calcium dependent protein kinase 3.";
RL PLoS ONE 12:e0181721-e0181721(2017).
RN [6] {ECO:0007744|PDB:3K21}
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 388-560 IN COMPLEX WITH CALCIUM,
RP ACTIVITY REGULATION, AND DOMAIN.
RX PubMed=21287613; DOI=10.1002/prot.22919;
RA Wernimont A.K., Amani M., Qiu W., Pizarro J.C., Artz J.D., Lin Y.H.,
RA Lew J., Hutchinson A., Hui R.;
RT "Structures of parasitic CDPK domains point to a common mechanism of
RT activation.";
RL Proteins 79:803-820(2011).
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 (By similarity). In the mosquito midgut,
CC regulates the gliding motility of the ookinete which is essential for
CC the ookinete to invade the midgut epithelium (By similarity). However,
CC another study showed that while required for ookinete invasion of the
CC midgut epithelium, is not required for ookinete gliding motility (By
CC similarity). {ECO:0000250|UniProtKB:A0A509AFG4,
CC ECO:0000250|UniProtKB:Q8IBS5}.
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:Q8IBS5};
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:Q8IBS5};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8IBS5};
CC -!- ACTIVITY REGULATION: Activated by calcium (Probable). Upon calcium
CC binding to the EF-hand domain 2, the C-terminus of the junction domain
CC (J domain) undergoes a conformational change which results in the
CC dissociation of the pseudo-substrate inhibitory motif from the
CC catalytic domain (Probable). This, in turn, may facilitate the
CC autophosphorylation of the activation loop at Thr-279, which leads to
CC the kinase activation (By similarity). {ECO:0000250|UniProtKB:Q8IBS5,
CC ECO:0000305|PubMed:21287613, ECO:0000305|PubMed:28746405}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A0A509AFG4}.
CC -!- DEVELOPMENTAL STAGE: Expressed in sexual stages, but not in asexual
CC stages. {ECO:0000269|PubMed:10760601}.
CC -!- DOMAIN: The EF-hand domain 1 cannot bind calcium due to the presence of
CC a Lys instead of an Asp at position 435 and a Gln instead of a Glu at
CC position 442 preventing calcium binding (PubMed:28746405,
CC PubMed:21287613). The EF-hand domains 3 and 4 probably bind calcium
CC constitutively when calcium levels are low, while the EF-hand domain 2
CC binds calcium following an increase in calcium levels
CC (PubMed:21287613). {ECO:0000269|PubMed:21287613,
CC ECO:0000269|PubMed:28746405}.
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 -!- 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; AF106064; AAF63154.1; -; Genomic_DNA.
DR EMBL; AL844502; CAB11118.4; -; Genomic_DNA.
DR PIR; T18445; T18445.
DR RefSeq; XP_001351174.1; XM_001351138.1.
DR PDB; 3K21; X-ray; 1.15 A; A=388-560.
DR PDBsum; 3K21; -.
DR AlphaFoldDB; Q9NJU9; -.
DR SMR; Q9NJU9; -.
DR STRING; 5833.PFC0420w; -.
DR PRIDE; Q9NJU9; -.
DR EnsemblProtists; CAB11118; CAB11118; PF3D7_0310100.
DR GeneID; 814416; -.
DR KEGG; pfa:PF3D7_0310100; -.
DR VEuPathDB; PlasmoDB:PF3D7_0310100; -.
DR HOGENOM; CLU_000288_37_4_1; -.
DR InParanoid; Q9NJU9; -.
DR OMA; CQSLGFC; -.
DR PhylomeDB; Q9NJU9; -.
DR BRENDA; 2.7.11.1; 4889.
DR Reactome; R-PFA-5687128; MAPK6/MAPK4 signaling.
DR EvolutionaryTrace; Q9NJU9; -.
DR Proteomes; UP000001450; Chromosome 3.
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; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:GeneDB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
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; ISS:GeneDB.
DR CDD; cd00051; EFh; 1.
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; Cytoplasm; Developmental protein;
KW Differentiation; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..562
FT /note="Calcium-dependent protein kinase 3"
FT /id="PRO_0000085839"
FT DOMAIN 118..373
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 418..453
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 453..487
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 488..523
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 529..562
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 393..428
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 393..401
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 402..411
FT /note="J domain EF-hand interaction motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT ACT_SITE 238
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 124..132
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 147
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 466
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 472
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 477
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 501
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 503
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 505
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 507
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 512
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 542
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 544
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 546
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 548
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT BINDING 553
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:21287613, ECO:0007744|PDB:3K21"
FT HELIX 388..414
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 418..430
FT /evidence="ECO:0007829|PDB:3K21"
FT STRAND 435..438
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 440..449
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 458..465
FT /evidence="ECO:0007829|PDB:3K21"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 475..482
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 485..487
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 490..500
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 510..519
FT /evidence="ECO:0007829|PDB:3K21"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 528..541
FT /evidence="ECO:0007829|PDB:3K21"
FT STRAND 543..549
FT /evidence="ECO:0007829|PDB:3K21"
FT HELIX 551..558
FT /evidence="ECO:0007829|PDB:3K21"
SQ SEQUENCE 562 AA; 65288 MW; 80DB5BA4194AC2E3 CRC64;
MNDLIIKNNK KGSCDVIIKY KCKKSDENIK RRKSSHKYIK NKSVVLGRSI MTNKKEKLKG
ALKYKGSKKE IKICNKKSMI KNDKDENTTL KSMKSDNFKF SRRGFILSFT GNLEDFYNLS
KEPLGKGTYG CVYKATDKLL KISRAVKVVS KKKLKNIPRF RQEIDIMKNL DHPNVVKLLE
TFEDSNQIYL VMELCTGGEL FDKIVKKGCF VETFASFIMK QIFSVLNYLH IRNICHRDIK
PENFLFYDMT PESLIKIIDF GLASYFTHNN YEMKTKAGTP YYVAPQVLTG SYNYKCDMWS
SGVLFYILLC GYPPFFGESD HEILSMVKKG KYQFKGKEWN NISEEAKDLI KRCLTMDADK
RICASEALQH PWFKKKKYAF NMDMKMDIHV LENFKNYGLL LKFQKLAMTI IAQQSNDYDV
EKLKSTFLVL DEDGKGYITK EQLKKGLEKD GLKLPYNFDL LLDQIDSDGS GKIDYTEFIA
AALDRKQLSK KLIYCAFRVF DVDNDGEITT AELAHILYNG NKKGNITQRD VNRVKRMIRD
VDKNNDGKID FHEFSEMMKL KF
