Names & Taxonomy

Uniprot ID:
P68400
Entry Name:
CSK21_HUMAN
Status:
reviewed
Protein Names:
Casein kinase II subunit alpha (CK II alpha) (EC 2.7.11.1)
Gene Names:
CSNK2A1 CK2A1
Gene Names Primary:
CSNK2A1
Organism:
Homo sapiens (Human)

Structure

Length:
391
Sequence:
MSGPVPSRARVYTDVNTHRPREYWDYESHVVEWGNQDDYQLVRKLGRGKYSEVFEAINITNNEKVVVKILKPVKKKKIKREIKILENLRGGPNIITLADIVKDPVSRTPALVFEHVNNTDFKQLYQTLTDYDIRFYMYEILKALDYCHSMGIMHRDVKPHNVMIDHEHRKLRLIDWGLAEFYHPGQEYNVRVASRYFKGPELLVDYQMYDYSLDMWSLGCMLASMIFRKEPFFHGHDNYDQLVRIAKVLGTEDLYDYIDKYNIELDPRFNDILGRHSRKRWERFVHSENQHLVSPEALDFLDKLLRYDHQSRLTAREAMEHPYFYTVVKDQARMGSSSMPGGSTPVSSANMMSGISSVPTPSPLGPLAGSPVIAAANPLGMPVPAAAGAQQ
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus

Function

Function:
Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:
ENZYME REGULATION: Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization.
Active Site:
ACT_SITE 156 156 Proton acceptor.
Gene Ontology Go:
cytosol
nucleus
NuRD complex
plasma membrane
Sin3 complex
ATP binding
Hsp90 protein binding
protein N-terminus binding
protein phosphatase regulator activity
protein serine/threonine kinase activity
axon guidance
chaperone-mediated protein folding
mitotic cell cycle
mitotic spindle checkpoint
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of cell growth
positive regulation of cell proliferation
positive regulation of protein catabolic process
positive regulation of Wnt signaling pathway
protein autophosphorylation
protein phosphorylation
regulation of transcription, DNA-templated
rhythmic process
signal transduction
transcription, DNA-templated
Wnt signaling pathway
Gene Ontology Biological Process:
axon guidance
chaperone-mediated protein folding
mitotic cell cycle
mitotic spindle checkpoint
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of cell growth
positive regulation of cell proliferation
positive regulation of protein catabolic process
positive regulation of Wnt signaling pathway
protein autophosphorylation
protein phosphorylation
regulation of transcription, DNA-templated
rhythmic process
signal transduction
transcription, DNA-templated
Wnt signaling pathway
Gene Ontology Molecular Function:
ATP binding
Hsp90 protein binding
protein N-terminus binding
protein phosphatase regulator activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:
cytosol
nucleus
NuRD complex
plasma membrane
Sin3 complex
Keywords:
3D-structure
ATP-binding
Alternative splicing
Apoptosis
Biological rhythms
Cell cycle
Complete proteome
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Reference proteome
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Wnt signaling pathway
Interacts With:
O00257-3; P19784; P67870; O75822; Q13547; O60282; P43364-2; P23511; P29590; Q6ZNA4; Q96EB6; Q92504; Q08945; Q96MF2; Q9NVV9; P04637

Publication

PubMed ID:
2752008 2174700 8420794 14702039 19054851 11780052 15489334 7592773 11239457 11704824 12393879 16193064 15684395 18691976 19188443 12631575 19387553 19387552 19387551 19387550 19387549 19923321 20625391 20068231 21269460 22406621 24962073 11092945 11574463 14646071 12860116