CDPK5_PLAF7
ID CDPK5_PLAF7 Reviewed; 568 AA.
AC A0A5K1K8H0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Calcium-dependent protein kinase 5 {ECO:0000303|PubMed:20466936};
DE EC=2.7.11.1 {ECO:0000269|PubMed:20466936, ECO:0000269|PubMed:31915223};
DE AltName: Full=PfCDPK5 {ECO:0000303|PubMed:20466936};
GN Name=CDPK5 {ECO:0000303|PubMed:20466936};
GN ORFNames=PF3D7_1337800 {ECO:0000312|EMBL:VWP77689.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
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 [2] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
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 [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND PHOSPHORYLATION.
RX PubMed=20466936; DOI=10.1126/science.1188191;
RA Dvorin J.D., Martyn D.C., Patel S.D., Grimley J.S., Collins C.R.,
RA Hopp C.S., Bright A.T., Westenberger S., Winzeler E., Blackman M.J.,
RA Baker D.A., Wandless T.J., Duraisingh M.T.;
RT "A plant-like kinase in Plasmodium falciparum regulates parasite egress
RT from erythrocytes.";
RL Science 328:910-912(2010).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=29487234; DOI=10.1128/mbio.00130-18;
RA Absalon S., Blomqvist K., Rudlaff R.M., DeLano T.J., Pollastri M.P.,
RA Dvorin J.D.;
RT "Calcium-Dependent Protein Kinase 5 Is Required for Release of Egress-
RT Specific Organelles in Plasmodium falciparum.";
RL MBio 9:0-0(2018).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=31915223; DOI=10.1128/msphere.00921-19;
RA Blomqvist K., Helmel M., Wang C., Absalon S., Labunska T., Rudlaff R.M.,
RA Adapa S., Jiang R., Steen H., Dvorin J.D.;
RT "Influence of Plasmodium falciparum Calcium-Dependent Protein Kinase 5
RT (PfCDPK5) on the Late Schizont Stage Phosphoproteome.";
RL MSphere 5:0-0(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 (PubMed:20466936, PubMed:31915223). Plays a
CC central role in host erythrocytes and hepatocytes infection cycles
CC (PubMed:20466936, PubMed:29487234). During the liver stage, involved in
CC sporozoite motility and thus in sporozoite invasion of host
CC hepatocytes, probably together with CDPK1 and CDPK4 (By similarity).
CC Involved in merosome egress from host hepatocytes, probably together
CC with CDPK4 (By similarity). Required for the release of hepatic
CC merozoites from merosomes in the host blood stream (By similarity).
CC During the asexual blood stage, required for merozoite egress from host
CC erythrocytes by triggering microneme secretion (PubMed:20466936,
CC PubMed:29487234). Phosphorylates transporter NPT1 at late schizont
CC stage (PubMed:31915223). {ECO:0000250|UniProtKB:A0A509AQE6,
CC ECO:0000269|PubMed:20466936, ECO:0000269|PubMed:29487234,
CC ECO:0000269|PubMed:31915223}.
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:20466936, ECO:0000269|PubMed:31915223};
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:20466936,
CC ECO:0000269|PubMed:31915223};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20466936};
CC -!- ACTIVITY REGULATION: Activated by calcium (PubMed:20466936). 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 (By similarity). This, in turn, may facilitate the
CC autophosphorylation of the activation loop at Thr-285, which leads to
CC the kinase activation (By similarity). {ECO:0000250|UniProtKB:Q8IBS5,
CC ECO:0000269|PubMed:20466936}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29487234}.
CC Cytoplasmic vesicle, secretory vesicle, microneme membrane
CC {ECO:0000269|PubMed:29487234}; Peripheral membrane protein
CC {ECO:0000269|PubMed:29487234}; Cytoplasmic side
CC {ECO:0000269|PubMed:29487234}. Cell membrane
CC {ECO:0000269|PubMed:20466936, ECO:0000269|PubMed:29487234,
CC ECO:0000269|PubMed:31915223}; Peripheral membrane protein
CC {ECO:0000303|PubMed:20466936}; Cytoplasmic side {ECO:0000305}.
CC Note=During the late stages of schizogony, localizes to the cytoplasm
CC in immature daughter merozoites, co-localizes with AMA1 to a subset of
CC micronemes and to the apical region in maturing daughter merozoites,
CC and near the plasma membrane in mature daughter and free merozoites.
CC {ECO:0000269|PubMed:29487234}.
CC -!- DEVELOPMENTAL STAGE: Expressed at the blood stage in schizonts (at
CC protein level). {ECO:0000269|PubMed:20466936}.
CC -!- DOMAIN: The junction domain (J domain) is composed of 2 motifs that
CC maintain the kinase inactive (By similarity). The N-terminal
CC autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic
CC domain while the C-terminal motif binds the EF-hand domains (By
CC similarity). {ECO:0000250|UniProtKB:Q8IBS5}.
CC -!- PTM: May be palmitoylated. {ECO:0000303|PubMed:12368867}.
CC -!- PTM: Autophosphorylated in vitro. {ECO:0000269|PubMed:20466936}.
CC -!- DISRUPTION PHENOTYPE: Impaired replication in host erythrocytes
CC (PubMed:20466936). Parasite development is arrested at the late
CC schizont stage before the rupture of the parasitophorous vacuole
CC membrane rupture, however, the daughter merozoites are fully mature and
CC their number per schizont is not affected (PubMed:20466936,
CC PubMed:29487234). Loss of secretion of AMA1-containing and EBA175-
CC containing micronemes (PubMed:29487234). SUB1-mediated processing of
CC AMA1 and SERA5, which is part of the protease cascade involved in
CC parasite egress, is reduced (PubMed:29487234). At the late schizont
CC stage, phosphorylation of several transmembrane- and membrane-
CC associated proteins and proteins associated with transport activity is
CC reduced (PubMed:31915223). {ECO:0000269|PubMed:20466936,
CC ECO:0000269|PubMed:29487234, ECO:0000269|PubMed:31915223}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDPK subfamily. {ECO:0000305}.
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DR EMBL; AL844509; VWP77689.1; -; Genomic_DNA.
DR RefSeq; XP_001350105.1; XM_001350069.1.
DR AlphaFoldDB; A0A5K1K8H0; -.
DR SMR; A0A5K1K8H0; -.
DR STRING; 5833.PF13_0211; -.
DR GeneID; 814178; -.
DR KEGG; pfa:PF3D7_1337800; -.
DR VEuPathDB; PlasmoDB:PF3D7_1337800; -.
DR OMA; TCVAYQL; -.
DR Reactome; R-PFA-5687128; MAPK6/MAPK4 signaling.
DR Proteomes; UP000001450; Chromosome 13.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0033163; C:microneme membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:1903307; P:positive regulation of regulated secretory pathway; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
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; 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 1: Evidence at protein level;
KW ATP-binding; Calcium; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Kinase; Lipoprotein; Membrane; Metal-binding; Nucleotide-binding;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..568
FT /note="Calcium-dependent protein kinase 5"
FT /id="PRO_0000452845"
FT DOMAIN 125..379
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 425..460
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 462..495
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 496..531
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 534..568
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 400..435
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 400..408
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT MOTIF 409..418
FT /note="J domain EF-hand interaction motif"
FT /evidence="ECO:0000250|UniProtKB:Q8IBS5"
FT ACT_SITE 245
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 131..139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 154
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 438
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 440
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 442
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 449
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 473
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 477
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 484
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 509
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 511
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 513
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 520
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
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 549
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 551
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 558
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
SQ SEQUENCE 568 AA; 66248 MW; BE587C25EDE12E27 CRC64;
MKETEVEDMD TNRKDGKIKK KEKIVNMKNE EVKSTTKSTL ADSDEDYSII TLCTKCLSKK
LEDNKNRIIL DSKAFKDNRL KGRCSVSSNE DPLDNKLNLS PYFDRSQIIQ EIILMNNDEL
SDVYEIDRYK LGKGSYGNVV KAVSKRTGQQ RAIKIIEKKK IHNIERLKRE ILIMKQMDHP
NIIKLYEVYE DNEKLYLVLE LCDGGELFDK IVKYGSFSEY EAYKIMKQIF SALYYCHSKN
IMHRDLKPEN ILYVDNTEDS PIQIIDWGFA SKCMNNHNLK SVVGTPYYIA PEILRGKYDK
RCDIWSSGVI MYILLCGYPP FNGKNNDEIL KKVEKGEFVF DSNYWARVSD DAKDLICQCL
NYNYKERIDV EQVLKHRWFK KFKSNNLIIN KTLNKTLIEK FKEFHKLCKI KKLAVTCIAY
QLNEKDIGKL KKTFEAFDHN GDGVLTISEI FQCLKVNDNE FDRELYFLLK QLDTDGNGLI
DYTEFLAACL DHSIFQQDVI CRNAFNVFDL DGDGVITKDE LFKILSFSAV QVSFSKEIIE
NLIKEVDSNN DGFIDYDEFY KMMTGVKE
