A0A5K1K8H0 · CDPK5_PLAF7

Function

function

Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca2+ levels probably in part downstream of cGMP-activated PKG kinase (PubMed:20466936, PubMed:31915223).
Plays a central role in host erythrocytes and hepatocytes infection cycles (PubMed:20466936, PubMed:29487234).
During the liver stage, involved in sporozoite motility and thus in sporozoite invasion of host hepatocytes, probably together with CDPK1 and CDPK4 (By similarity).
Involved in merosome egress from host hepatocytes, probably together with CDPK4 (By similarity).
Required for the release of hepatic merozoites from merosomes in the host blood stream (By similarity).
During the asexual blood stage, required for merozoite egress from host erythrocytes by triggering microneme secretion (PubMed:20466936, PubMed:29487234).
Phosphorylates transporter NPT1 at late schizont stage (PubMed:31915223).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Activity regulation

Activated by calcium (PubMed:20466936).
Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity).
This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-285, which leads to the kinase activation (By similarity).

Features

Showing features for binding site, active site.

Type
IDPosition(s)Description
Binding site131-139ATP (UniProtKB | ChEBI)
Binding site154ATP (UniProtKB | ChEBI)
Active site245Proton acceptor
Binding site438Ca2+ 1 (UniProtKB | ChEBI)
Binding site440Ca2+ 1 (UniProtKB | ChEBI)
Binding site442Ca2+ 1 (UniProtKB | ChEBI)
Binding site449Ca2+ 1 (UniProtKB | ChEBI)
Binding site473Ca2+ 2 (UniProtKB | ChEBI)
Binding site475Ca2+ 2 (UniProtKB | ChEBI)
Binding site477Ca2+ 2 (UniProtKB | ChEBI)
Binding site484Ca2+ 2 (UniProtKB | ChEBI)
Binding site509Ca2+ 3 (UniProtKB | ChEBI)
Binding site511Ca2+ 3 (UniProtKB | ChEBI)
Binding site513Ca2+ 3 (UniProtKB | ChEBI)
Binding site520Ca2+ 3 (UniProtKB | ChEBI)
Binding site547Ca2+ 4 (UniProtKB | ChEBI)
Binding site549Ca2+ 4 (UniProtKB | ChEBI)
Binding site551Ca2+ 4 (UniProtKB | ChEBI)
Binding site558Ca2+ 4 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytoplasmic vesicle
Cellular Componentextrinsic component of cytoplasmic side of plasma membrane
Cellular Componentextrinsic component of membrane
Cellular Componentmicroneme membrane
Cellular Componentnucleus
Cellular Componentplasma membrane
Molecular FunctionATP binding
Molecular Functioncalcium ion binding
Molecular Functioncalcium-dependent protein serine/threonine kinase activity
Molecular Functioncalcium/calmodulin-dependent protein kinase activity
Molecular Functioncalmodulin binding
Molecular Functionhistone H2AS1 kinase activity
Molecular Functionprotein serine kinase activity
Biological Processintracellular signal transduction
Biological Processpositive regulation of regulated secretory pathway
Biological Processprotein phosphorylation

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Calcium-dependent protein kinase 5
  • EC number
  • Alternative names
    • PfCDPK5

Gene names

    • Name
      CDPK5
    • ORF names
      PF3D7_1337800

Organism names

  • Taxonomic identifier
  • Strain
    • 3D7
  • Taxonomic lineage
    Eukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)

Accessions

  • Primary accession
    A0A5K1K8H0

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Cytoplasmic vesicle, secretory vesicle, microneme membrane
; Peripheral membrane protein
Cell membrane
; Peripheral membrane protein
Note: During the late stages of schizogony, localizes to the cytoplasm in immature daughter merozoites, co-localizes with AMA1 to a subset of micronemes and to the apical region in maturing daughter merozoites, and near the plasma membrane in mature daughter and free merozoites.

Keywords

Phenotypes & Variants

Disruption phenotype

Impaired replication in host erythrocytes (PubMed:20466936).
Parasite development is arrested at the late schizont stage before the rupture of the parasitophorous vacuole membrane rupture, however, the daughter merozoites are fully mature and their number per schizont is not affected (PubMed:20466936, PubMed:29487234).
Loss of secretion of AMA1-containing and EBA175-containing micronemes (PubMed:29487234).
SUB1-mediated processing of AMA1 and SERA5, which is part of the protease cascade involved in parasite egress, is reduced (PubMed:29487234).
At the late schizont stage, phosphorylation of several transmembrane- and membrane-associated proteins and proteins associated with transport activity is reduced (PubMed:31915223).

PTM/Processing

Features

Showing features for chain, modified residue (large scale data).

Type
IDPosition(s)Source
Description
ChainPRO_00004528451-568UniProtCalcium-dependent protein kinase 5
Modified residue (large scale data)43PTMeXchangePhosphoserine
Modified residue (large scale data)51PTMeXchangePhosphothreonine
Modified residue (large scale data)54PTMeXchangePhosphothreonine
Modified residue (large scale data)281PTMeXchangePhosphoserine

Post-translational modification

May be palmitoylated.
Autophosphorylated in vitro.

Keywords

Proteomic databases

Expression

Developmental stage

Expressed at the blood stage in schizonts (at protein level).

Interaction

Protein-protein interaction databases

Family & Domains

Features

Showing features for domain, motif, region.

Type
IDPosition(s)Description
Domain125-379Protein kinase
Motif400-408J domain autoinhibitory motif
Region400-435J domain
Motif409-418J domain EF-hand interaction motif
Domain425-460EF-hand 1
Domain462-495EF-hand 2
Domain496-531EF-hand 3
Domain534-568EF-hand 4

Domain

The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (By similarity).
The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (By similarity).

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    568
  • Mass (Da)
    66,248
  • Last updated
    2019-12-11 v1
  • Checksum
    BE587C25EDE12E27
MKETEVEDMDTNRKDGKIKKKEKIVNMKNEEVKSTTKSTLADSDEDYSIITLCTKCLSKKLEDNKNRIILDSKAFKDNRLKGRCSVSSNEDPLDNKLNLSPYFDRSQIIQEIILMNNDELSDVYEIDRYKLGKGSYGNVVKAVSKRTGQQRAIKIIEKKKIHNIERLKREILIMKQMDHPNIIKLYEVYEDNEKLYLVLELCDGGELFDKIVKYGSFSEYEAYKIMKQIFSALYYCHSKNIMHRDLKPENILYVDNTEDSPIQIIDWGFASKCMNNHNLKSVVGTPYYIAPEILRGKYDKRCDIWSSGVIMYILLCGYPPFNGKNNDEILKKVEKGEFVFDSNYWARVSDDAKDLICQCLNYNYKERIDVEQVLKHRWFKKFKSNNLIINKTLNKTLIEKFKEFHKLCKIKKLAVTCIAYQLNEKDIGKLKKTFEAFDHNGDGVLTISEIFQCLKVNDNEFDRELYFLLKQLDTDGNGLIDYTEFLAACLDHSIFQQDVICRNAFNVFDLDGDGVITKDELFKILSFSAVQVSFSKEIIENLIKEVDSNNDGFIDYDEFYKMMTGVKE

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AL844509
EMBL· GenBank· DDBJ
VWP77689.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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