A0A5K1K8H0 · CDPK5_PLAF7
- ProteinCalcium-dependent protein kinase 5
- GeneCDPK5
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids568 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
Cofactor
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).
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 | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 131-139 | ATP (UniProtKB | ChEBI) | |||
Binding site | 154 | ATP (UniProtKB | ChEBI) | |||
Active site | 245 | Proton acceptor | |||
Binding site | 438 | Ca2+ 1 (UniProtKB | ChEBI) | |||
Binding site | 440 | Ca2+ 1 (UniProtKB | ChEBI) | |||
Binding site | 442 | Ca2+ 1 (UniProtKB | ChEBI) | |||
Binding site | 449 | Ca2+ 1 (UniProtKB | ChEBI) | |||
Binding site | 473 | Ca2+ 2 (UniProtKB | ChEBI) | |||
Binding site | 475 | Ca2+ 2 (UniProtKB | ChEBI) | |||
Binding site | 477 | Ca2+ 2 (UniProtKB | ChEBI) | |||
Binding site | 484 | Ca2+ 2 (UniProtKB | ChEBI) | |||
Binding site | 509 | Ca2+ 3 (UniProtKB | ChEBI) | |||
Binding site | 511 | Ca2+ 3 (UniProtKB | ChEBI) | |||
Binding site | 513 | Ca2+ 3 (UniProtKB | ChEBI) | |||
Binding site | 520 | Ca2+ 3 (UniProtKB | ChEBI) | |||
Binding site | 547 | Ca2+ 4 (UniProtKB | ChEBI) | |||
Binding site | 549 | Ca2+ 4 (UniProtKB | ChEBI) | |||
Binding site | 551 | Ca2+ 4 (UniProtKB | ChEBI) | |||
Binding site | 558 | Ca2+ 4 (UniProtKB | ChEBI) | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoplasmic vesicle | |
Cellular Component | extrinsic component of cytoplasmic side of plasma membrane | |
Cellular Component | extrinsic component of membrane | |
Cellular Component | microneme membrane | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | ATP binding | |
Molecular Function | calcium ion binding | |
Molecular Function | calcium-dependent protein serine/threonine kinase activity | |
Molecular Function | calcium/calmodulin-dependent protein kinase activity | |
Molecular Function | calmodulin binding | |
Molecular Function | histone H2AS1 kinase activity | |
Molecular Function | protein serine kinase activity | |
Biological Process | intracellular signal transduction | |
Biological Process | positive regulation of regulated secretory pathway | |
Biological Process | protein phosphorylation |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCalcium-dependent protein kinase 5
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)
Accessions
- Primary accessionA0A5K1K8H0
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
- Cellular component
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).
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 | ID | Position(s) | Source | Description | ||
---|---|---|---|---|---|---|
Chain | PRO_0000452845 | 1-568 | UniProt | Calcium-dependent protein kinase 5 | ||
Modified residue (large scale data) | 43 | PTMeXchange | Phosphoserine | |||
Modified residue (large scale data) | 51 | PTMeXchange | Phosphothreonine | |||
Modified residue (large scale data) | 54 | PTMeXchange | Phosphothreonine | |||
Modified residue (large scale data) | 281 | PTMeXchange | Phosphoserine | |||
Post-translational modification
May be palmitoylated.
Autophosphorylated in vitro.
Keywords
- PTM
Proteomic databases
Expression
Developmental stage
Expressed at the blood stage in schizonts (at protein level).
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, motif, region.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 125-379 | Protein kinase | |||
Motif | 400-408 | J domain autoinhibitory motif | |||
Region | 400-435 | J domain | |||
Motif | 409-418 | J domain EF-hand interaction motif | |||
Domain | 425-460 | EF-hand 1 | |||
Domain | 462-495 | EF-hand 2 | |||
Domain | 496-531 | EF-hand 3 | |||
Domain | 534-568 | EF-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).
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length568
- Mass (Da)66,248
- Last updated2019-12-11 v1
- ChecksumBE587C25EDE12E27
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL844509 EMBL· GenBank· DDBJ | VWP77689.1 EMBL· GenBank· DDBJ | Genomic DNA |