CDPK3_PLABA
ID CDPK3_PLABA Reviewed; 554 AA.
AC A0A509AFG4;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Calcium-dependent protein kinase 3 {ECO:0000303|PubMed:16430692};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q8IBS5};
DE AltName: Full=PbCDPK3 {ECO:0000303|PubMed:16430692};
GN Name=CDPK3 {ECO:0000303|PubMed:16430692};
GN ORFNames=PBANKA_0408200 {ECO:0000312|EMBL:VUC54306.1};
OS Plasmodium berghei (strain Anka).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5823 {ECO:0000312|Proteomes:UP000074855};
RN [1] {ECO:0000312|Proteomes:UP000074855}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ANKA {ECO:0000312|Proteomes:UP000074855};
RX PubMed=25359557; DOI=10.1186/s12915-014-0086-0;
RA Otto T.D., Bohme U., Jackson A.P., Hunt M., Franke-Fayard B.,
RA Hoeijmakers W.A., Religa A.A., Robertson L., Sanders M., Ogun S.A.,
RA Cunningham D., Erhart A., Billker O., Khan S.M., Stunnenberg H.G.,
RA Langhorne J., Holder A.A., Waters A.P., Newbold C.I., Pain A., Berriman M.,
RA Janse C.J.;
RT "A comprehensive evaluation of rodent malaria parasite genomes and gene
RT expression.";
RL BMC Biol. 12:86-86(2014).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16430692; DOI=10.1111/j.1365-2958.2005.05014.x;
RA Ishino T., Orito Y., Chinzei Y., Yuda M.;
RT "A calcium-dependent protein kinase regulates Plasmodium ookinete access to
RT the midgut epithelial cell.";
RL Mol. Microbiol. 59:1175-1184(2006).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16796674; DOI=10.1111/j.1365-2958.2006.05189.x;
RA Siden-Kiamos I., Ecker A., Nybaeck S., Louis C., Sinden R.E., Billker O.;
RT "Plasmodium berghei calcium-dependent protein kinase 3 is required for
RT ookinete gliding motility and mosquito midgut invasion.";
RL Mol. Microbiol. 60:1355-1363(2006).
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 (PubMed:16796674).
CC However, another study showed that while required for ookinete invasion
CC of the midgut epithelium, is not required for ookinete gliding motility
CC (PubMed:16430692). {ECO:0000250|UniProtKB:Q8IBS5,
CC ECO:0000269|PubMed:16430692, ECO:0000269|PubMed:16796674}.
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 (By similarity). 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 (By similarity). This, in turn, may facilitate the
CC autophosphorylation of the activation loop at Thr-271, which leads to
CC the kinase activation (By similarity). {ECO:0000250|UniProtKB:Q8IBS5,
CC ECO:0000250|UniProtKB:Q9NJU9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16430692}.
CC -!- DEVELOPMENTAL STAGE: Expressed in ookinetes; expression increases
CC during ookinete maturation (at protein level).
CC {ECO:0000269|PubMed:16430692}.
CC -!- DOMAIN: The EF-hand domain 1 cannot bind calcium due to the presence of
CC a Lys instead of an Asp at position 427 and a Gln instead of a Glu at
CC position 434 preventing calcium binding (By similarity). The EF-hand
CC domains 3 and 4 probably bind calcium constitutively when calcium
CC levels are low, while the EF-hand domain 2 binds calcium following an
CC increase in calcium levels (By similarity).
CC {ECO:0000250|UniProtKB:Q9NJU9}.
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 -!- DISRUPTION PHENOTYPE: In the mosquito midgut, the number of oocysts are
CC reduced which is caused by a failure of ookinetes to migrate to and
CC transverse midgut epithelium (PubMed:16430692, PubMed:16796674).
CC Abnormal motility of ookinetes, characterized by frequent flexing,
CC bending, twirling, pendular motions and a failure to disperse
CC (PubMed:16796674). However, another study shows no defect in ookinete
CC motility (PubMed:16430692). Development and morphology of ookinetes are
CC normal (PubMed:16430692, PubMed:16796674). Sporozoite motility and
CC infectivity are normal (PubMed:16430692, PubMed:16796674). When
CC injected directly into the mosquito haemocoel, thus bypassing the
CC requirement to transverse the midgut epithelium, ookinetes mature
CC normally into oocysts (PubMed:16796674). {ECO:0000269|PubMed:16430692,
CC ECO:0000269|PubMed:16796674}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDPK subfamily. {ECO:0000305}.
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DR EMBL; LK023119; VUC54306.1; -; Genomic_DNA.
DR RefSeq; XP_675146.1; XM_670054.1.
DR AlphaFoldDB; A0A509AFG4; -.
DR SMR; A0A509AFG4; -.
DR STRING; 5823.A0A509AFG4; -.
DR VEuPathDB; PlasmoDB:PBANKA_0408200; -.
DR OMA; PWPRISH; -.
DR Proteomes; UP000074855; Chromosome 4.
DR GO; GO:0005737; C:cytoplasm; 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:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:2000147; P:positive regulation of cell motility; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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; 2.
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 ATP-binding; Calcium; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..554
FT /note="Calcium-dependent protein kinase 3"
FT /id="PRO_0000452963"
FT DOMAIN 110..365
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 410..445
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 448..479
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 480..515
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 521..554
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 30..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..420
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 385..393
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 394..403
FT /note="J domain EF-hand interaction motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT COMPBIAS 38..55
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 230
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 116..124
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 458
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 BINDING 460
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 BINDING 462
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 BINDING 464
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 BINDING 469
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 BINDING 493
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 BINDING 495
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 BINDING 497
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 BINDING 499
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 BINDING 504
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 BINDING 534
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 BINDING 536
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 BINDING 538
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 BINDING 540
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 BINDING 545
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"
SQ SEQUENCE 554 AA; 64328 MW; 8F19B0D81EADF9E7 CRC64;
MNQLCVERNL SISTAYIKSK PKKYIERIKK KKSSNKSIKS QHKFEGSKIA NKNNELKDIK
SKDPKHYENH INKNTKHKDI LLKSKRSDNF KFSRRGFILS FTGNLEDFYN LSEEPLGKGT
YGCVYKATDK LLKIQRAVKV VSKKKLKNIP RFRQEIDIMK NLDHPNVIKL LETFEDEEQI
YLIMDLCTGG ELFDKIIKKG SFVEMYASFI MKQIFSVLNY LHIRNICHRD IKPENFLFYD
KSTESLIKII DFGLAAYFND IDYEMKTKAG TPYYVAPQVL TGCYDYKCDL WSAGVLFYII
LCGYPPFYGE SDHEILSMVK KGKYNFKGKE WNNISEEAKD LIKRCLTIDS GKRINASEAL
KHPWFKKKKG SFNLDVKMDI HVLENFKNYA LLLKLQKLAM TIIAQQSNDY DLQQLKTVFL
YLDEDGKGNI TKNQLKKGLE NSGLKLPQNF DVLLDQIDSD GSGRIDYTEF LAAALDRKHL
SKKLIYCAFR VFDVDNDGEI TTAELAHILY NGNKKGSITQ KDVNQVKKMI QEVDKNNDGK
IDFYEFCEMM KLKY
