CDPK1_PLABA
ID CDPK1_PLABA Reviewed; 523 AA.
AC A0A509AHB6;
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 1 {ECO:0000303|PubMed:22817984};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P62344};
DE AltName: Full=PbCDPK1 {ECO:0000303|PubMed:22817984};
GN Name=CDPK1 {ECO:0000303|PubMed:22817984};
GN ORFNames=PBANKA_0314200 {ECO:0000312|EMBL:VUC54180.1};
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=22817984; DOI=10.1016/j.chom.2012.05.014;
RA Sebastian S., Brochet M., Collins M.O., Schwach F., Jones M.L.,
RA Goulding D., Rayner J.C., Choudhary J.S., Billker O.;
RT "A Plasmodium calcium-dependent protein kinase controls zygote development
RT and transmission by translationally activating repressed mRNAs.";
RL Cell Host Microbe 12:9-19(2012).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24265753; DOI=10.1371/journal.pone.0079171;
RA Jebiwott S., Govindaswamy K., Mbugua A., Bhanot P.;
RT "Plasmodium berghei calcium dependent protein kinase 1 is not required for
RT host cell invasion.";
RL PLoS ONE 8:e79171-e79171(2013).
RN [4] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=32866196; DOI=10.1371/journal.ppat.1008131;
RA Govindasamy K., Bhanot P.;
RT "Overlapping and distinct roles of CDPK family members in the pre-
RT erythrocytic stages of the rodent malaria parasite, Plasmodium berghei.";
RL PLoS Pathog. 16:e1008131-e1008131(2020).
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). During the liver stage,
CC involved in sporozoite motility and thus in sporozoite invasion of host
CC hepatocytes, probably together with CDPK4 and CDPK5 (PubMed:32866196).
CC In the mosquito midgut and during the last stage of male gamete
CC exflagellation, may play a role in the rupture of the host erythrocyte
CC membrane (PubMed:22817984). In the mosquito midgut, required for the
CC differentiation of the zygote into the ookinete by promoting the
CC translational activation of a subset of repressed mRNAs; these mRNAs
CC are kept repressed in the zygote by the DOZI- or CITH-containing mRNP
CC complexes (PubMed:22817984, PubMed:24265753). Dispensable during the
CC asexual blood stage (PubMed:24265753). {ECO:0000250|UniProtKB:P62344,
CC ECO:0000269|PubMed:22817984, ECO:0000269|PubMed:24265753,
CC ECO:0000269|PubMed:32866196}.
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:P62344};
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:P62344};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P62344};
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-230, which leads to the kinase activation.
CC {ECO:0000250|UniProtKB:P62344}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P62344}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P62344}; Lipid-
CC anchor {ECO:0000250|UniProtKB:P62344}. Cell membrane
CC {ECO:0000269|PubMed:22817984}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62344}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P62344}. Parasitophorous vacuole membrane
CC {ECO:0000250|UniProtKB:P62344}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62344}. Cytoplasm
CC {ECO:0000250|UniProtKB:A0A2I0BVG8}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:A0A2I0BVG8}. Host cell membrane
CC {ECO:0000250|UniProtKB:P62344}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62344}. Note=Calcium and/or autophosphorylation
CC does not affect membrane localization. {ECO:0000250|UniProtKB:P62344}.
CC -!- DEVELOPMENTAL STAGE: During the asexual blood stage, expressed in
CC schizonts (PubMed:22817984). Expressed in gametocytes
CC (PubMed:22817984). Expressed in ookinetes and oocyst early stages
CC (PubMed:22817984). Expressed in sporozoites (PubMed:22817984,
CC PubMed:32866196). Not expressed during the liver stage
CC (PubMed:32866196). {ECO:0000269|PubMed:22817984,
CC ECO:0000269|PubMed:32866196}.
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:P62344}.
CC -!- PTM: Myristoylated. Myristoylation and palmitoylation are required for
CC the localization to the parasitophorous vacuole membrane.
CC {ECO:0000250|UniProtKB:P62344}.
CC -!- PTM: Palmitoylated. Palmitoylation increases in merozoites in response
CC to low level of extracellular K(+) in the host blood. Myristoylation
CC and palmitoylation are required for the localization to the
CC parasitophorous vacuole membrane. {ECO:0000250|UniProtKB:P62344}.
CC -!- PTM: Phosphorylation at Thr-230 may regulate CDPK1 kinase activity.
CC Phosphorylation increases in response to an increase in intracellular
CC Ca(2+) levels. Autophosphorylated in vitro. Autophosphorylation does
CC not affect membrane localization in vitro.
CC {ECO:0000250|UniProtKB:P62344}.
CC -!- DISRUPTION PHENOTYPE: In the mosquito midgut, male gametocyte
CC exflagellation is normal; however, the rupture of the host erythrocyte
CC cell membrane is delayed (PubMed:22817984). Fertilization is normal,
CC however zygote development into ookinetes is arrested at the retort
CC stage where ookinetes are still immotile (PubMed:22817984,
CC PubMed:24265753). In arrested ookinetes, protein levels, but not mRNA
CC levels, of a subset of proteins including MyoA and MTIP, two components
CC of the motor complex, CTRP and SOAP are strongly reduced
CC (PubMed:22817984). In arrested ookinetes, apical complex including
CC collar, apical rings and micronemes and the pellicle, consisting of the
CC plasma membrane, the inner membrane complex and the subpellicular
CC microtubules are normally assembled (PubMed:22817984). During host
CC liver invasion, sporozoite attachment to the substrate is normal but
CC sporozoite uninterrupted circular movement is impaired
CC (PubMed:32866196). No effect on cell traversal but reduces invasion of
CC host hepatocytes (PubMed:32866196). No defect in the asexual
CC erythrocyte stage; infection, development and egress from host
CC erythrocytes are normal (PubMed:24265753). Conditional knockout in
CC sporozoites, does not affect sporozoite invasion of the mosquito
CC salivary gland or invasion of host hepatocytes (PubMed:22817984).
CC {ECO:0000269|PubMed:22817984, ECO:0000269|PubMed:24265753,
CC ECO:0000269|PubMed:32866196}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDPK subfamily. {ECO:0000305}.
CC -!- CAUTION: Unlike P.falciparum CDPK1, appears not to be involved in the
CC asexual blood stage and in male gamete exflagellation prior host
CC erythrocyte membrane rupture. {ECO:0000305|PubMed:22817984,
CC ECO:0000305|PubMed:32866196}.
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DR EMBL; LK023118; VUC54180.1; -; Genomic_DNA.
DR RefSeq; XP_675880.1; XM_670788.1.
DR AlphaFoldDB; A0A509AHB6; -.
DR SMR; A0A509AHB6; -.
DR STRING; 5823.A0A509AHB6; -.
DR VEuPathDB; PlasmoDB:PBANKA_0314200; -.
DR OMA; KFDECDA; -.
DR Proteomes; UP000074855; Chromosome 3.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0020005; C:symbiont-containing vacuole 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:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:2000147; P:positive regulation of cell motility; IMP:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
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 2: Evidence at transcript level;
KW ATP-binding; Calcium; Cell membrane; Cell projection; Cilium; Cytoplasm;
KW Flagellum; Host cell membrane; Host membrane; Kinase; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Myristate; Nucleotide-binding;
KW Palmitate; 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..523
FT /note="Calcium-dependent protein kinase 1"
FT /id="PRO_0000453002"
FT DOMAIN 57..324
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 371..406
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 415..450
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 451..486
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 487..520
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 345..363
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOTIF 345..352
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOTIF 353..363
FT /note="J domain interacts with the EF-hand domains"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 190
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 63..71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 90
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10141"
FT BINDING 384
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 386
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 390
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 428
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 430
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 434
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 439
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 464
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 466
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 498
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 500
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 502
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 504
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 509
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 230
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
SQ SEQUENCE 523 AA; 60809 MW; 5BE6EF6702C358F5 CRC64;
MGCNQSKSAN DVRGNKVNHV NSKKKNNKRE DTNDGEEIAI NPGMYVRKKE GKIGESYFKV
RKLGSGAYGE VLLCKEKNGH SEKAIKVIKK SQFDKGRYSD DNKNIEKFHE EIYNEISLLK
SLDHPNIIKL FDVFEDKKYF YLVTEFYEGG ELFEQIINRH KFDECDAANI MKQILSGICY
LHKHNIVHRD IKPENILLEN KNSLLNIKIV DFGLSSFFSK DYKLRDRLGT AYYIAPEVLK
KKYNEKCDVW SCGVIMYILL CGYPPFGGQN DQDIIKKVEK GKYYFDFNDW KNISDEAKEL
IKLMLTYDYN KRCTAEEALN SRWIKKYANN INKSDQKTLC GALSNMRKFE GSQKLAQAAI
LFIGSKLTTL EERKELTDIF KKLDKNGDGQ LDKKELIEGY NVLRNFKNEL GELKNVEEEV
DNILKEVDFD KNGYIEYSEF ISVCMDKQIL FSEERLRRAF NLFDTDKSGK ITKEELANLF
GLTSISEKTW NDVLGEADQN KDNMIDFDEF VSMMHKICDH KTF
