CDPK5_PLABA
ID CDPK5_PLABA Reviewed; 562 AA.
AC A0A509AQE6;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=Calcium-dependent protein kinase 5 {ECO:0000303|PubMed:32866196};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:A0A5K1K8H0};
DE AltName: Full=PbCDPK5 {ECO:0000303|PubMed:32866196};
GN Name=CDPK5 {ECO:0000303|PubMed:32866196};
GN ORFNames=PBANKA_1351500 {ECO:0000312|EMBL:VUC57902.1};
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, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
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). Plays a central role in host
CC erythrocytes and hepatocytes infection cycles (PubMed:32866196). During
CC the liver stage, involved in sporozoite motility and thus in sporozoite
CC invasion of host hepatocytes, probably together with CDPK1 and CDPK4
CC (PubMed:32866196). Involved in merosome egress from host hepatocytes,
CC probably together with CDPK4 (PubMed:32866196). Required for the
CC release of hepatic merozoites from merosomes in the host blood stream
CC (PubMed:32866196). During the asexual blood stage, required for
CC merozoite egress from host erythrocytes by triggering microneme
CC secretion (By similarity). Phosphorylates transporter NPT1 at late
CC schizont stage (By similarity). {ECO:0000250|UniProtKB:A0A5K1K8H0,
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:A0A5K1K8H0};
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:A0A5K1K8H0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A0A5K1K8H0};
CC -!- ACTIVITY REGULATION: Activated by calcium (By similarity). Upon calcium
CC binding to the EF-hand domains, 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-278, which leads to
CC the kinase activation (By similarity).
CC {ECO:0000250|UniProtKB:A0A5K1K8H0, ECO:0000250|UniProtKB:Q8IBS5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A0A5K1K8H0}.
CC Cytoplasmic vesicle, secretory vesicle, microneme membrane
CC {ECO:0000250|UniProtKB:A0A5K1K8H0}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:A0A5K1K8H0}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:A0A5K1K8H0}. Cell membrane
CC {ECO:0000250|UniProtKB:A0A5K1K8H0}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:A0A5K1K8H0}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:A0A5K1K8H0}. Note=During the late stages of
CC schizogony, localizes to the cytoplasm in immature daughter merozoites,
CC co-localizes with AMA1 to a subset of micronemes and to the apical
CC region in maturing daughter merozoites, and near the plasma membrane in
CC mature daughter and free merozoites.
CC {ECO:0000250|UniProtKB:A0A5K1K8H0}.
CC -!- DEVELOPMENTAL STAGE: Expressed in sporozoites and in the late mature
CC liver stage (at protein level) (PubMed:32866196). Expressed in the
CC merosome, a membrane-surrounded vesicle which contains mature
CC merozoites and produced at the end of the liver stage (at protein
CC level) (PubMed:32866196). {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:Q8IBS5}.
CC -!- PTM: May be palmitoylated. {ECO:0000250|UniProtKB:A0A5K1K8H0}.
CC -!- PTM: Autophosphorylated in vitro. {ECO:0000250|UniProtKB:A0A5K1K8H0}.
CC -!- DISRUPTION PHENOTYPE: Sporozoite attachment to the substrate is normal
CC but sporozoite uninterrupted circular movement is impaired
CC (PubMed:32866196). No effect on cell traversal but reduces invasion of
CC host hepatocytes (PubMed:32866196). Reduces merosome release from
CC infected host hepatocytes (PubMed:32866196). Infection of mice with
CC knockout merosomes causes a severe delay in host erythrocytes infection
CC without affecting the asexual replication in host erythrocytes
CC (PubMed:32866196). {ECO:0000269|PubMed:32866196}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDPK subfamily. {ECO:0000305}.
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DR EMBL; LK023128; VUC57902.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A509AQE6; -.
DR SMR; A0A509AQE6; -.
DR STRING; 5821.PBANKA_135150; -.
DR VEuPathDB; PlasmoDB:PBANKA_1351500; -.
DR OMA; TCVAYQL; -.
DR Proteomes; UP000074855; Chromosome 13.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0033163; C:microneme membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma 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: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; 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; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Calcium; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Kinase; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Palmitate; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..562
FT /note="Calcium-dependent protein kinase 5"
FT /id="PRO_0000452846"
FT DOMAIN 118..372
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 419..453
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 454..489
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 490..525
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 528..562
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 394..429
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 394..402
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 403..412
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: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 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 434
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 436
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 443
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 503
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 505
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 507
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 514
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 541
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 543
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 545
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 547
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 552
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
SQ SEQUENCE 562 AA; 65108 MW; 1CFAB8802C6819B1 CRC64;
MCEHKANNKN DGEFVNLKEK NENNHCGNTK STIADCDDDY SIITLCTKCL STKTEVNKNK
IILDSKALKD SRTKRRSSVN INIDILNNNL NLSPYFDRSQ IVQETILMNN DDLEKLYELD
KYKLGKGSYG NVVKAINKKT GQAKAIKIID KKRINNIERL KREILIMKQM DHPNIIKLYE
VYEDNEKLYL VLELCTGGEL FDKIVKHGSF SEYETYKIMK QIFSALAYCH SKNIIHRDLK
PENILYVDSS DDSPIQIIDW GFASKCMNNH NLKSVVGTPY YIAPEILKGK YDKKCDIWSS
GVIMYILLCG YPPFNGKNND DILKKVKKGE FVFDSNYWSK ISLDAKELIC ECLNYNYKER
IDVHKIVNHK WFIKFKNYNH ITINKHLSKE LIEKFKKFHK LCKIKKLAIT CIAYQLNKKK
FGKMKKTFEA FDHNGDGVLT ISEIFQCLKV GDNEIDRDLY YLLKQLDTDG NGLIDYTEFL
AACLDHSILE QDAVCRNAFK IFDANGDGII TKDELLNVLS FSNDQMPFSK EIIENVIKEV
DANNDGYIDY DEFYKMMSGR QS
