DegronMD - P68400(CSNK2A1)

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 (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621, PubMed:24962073). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (PubMed:12631575, PubMed:19387552, PubMed:19387551). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (PubMed:12631575, PubMed:19387552, PubMed:19387551). 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 (PubMed:11704824, PubMed:19188443). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis (PubMed:11239457). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:16193064). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:16193064). 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, ATF4, SRF, MAX, JUN, FOS, MYC and MYB (PubMed:19387550, PubMed:12631575, PubMed:19387552, PubMed:19387551, PubMed:23123191). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (PubMed:19387550). Mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, leading to activate both kinase and non-kinase client proteins of Hsp90 (PubMed:30699359). Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 (PubMed:19387549). Acts as an ectokinase that phosphorylates several extracellular proteins (PubMed:19387550, PubMed:12631575, PubMed:19387552, PubMed:19387551). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (PubMed:19387550, PubMed:12631575, PubMed:19387552, PubMed:19387551). Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation (PubMed:20625391, PubMed:22406621). 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 (By similarity). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073). {ECO:0000250|UniProtKB:P19139, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:11704824, ECO:0000269|PubMed:16193064, ECO:0000269|PubMed:19188443, ECO:0000269|PubMed:20625391, ECO:0000269|PubMed:22406621, ECO:0000269|PubMed:23123191, ECO:0000269|PubMed:24962073, ECO:0000269|PubMed:30699359, ECO:0000303|PubMed:12631575, ECO:0000303|PubMed:19387549, ECO:0000303|PubMed:19387550, ECO:0000303|PubMed:19387551, ECO:0000303|PubMed:19387552}. View more >>

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GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E22Q	TCGA-85-A4CL	LUSC	TCGA	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation rewiring degron network	0.1111
p.E22Q	DO45454	LUSC	ICGC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation rewiring degron network	0.1111
p.A9D	TCGA-HU-A4GU	STAD	TCGA	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation altering degron motif	0.6682
p.A9D	DO47849	STAD	ICGC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation altering degron motif	0.6682
p.H18Q	DO228974	LICA	ICGC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation rewiring degron network	0.2222
p.D9E	DO41199	UCEC	ICGC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation altering degron motif	0.6758
p.T13I	SIDM01016	T-Lymphoblastic Leukemia	GDSC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation altering degron motif	0.7078
p.T13I	SIDM01263	T-Lymphoblastic Leukemia	GDSC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation altering degron motif	0.7078
p.T13I	ACH-000995	Leukemia	CCLE	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation altering degron motif	0.7078
p.T13I	Jurkat	haematopoietic and lymphoid tissue	COSMIC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation altering degron motif	0.7078
p.R21G	SIDM00771	Non-Small Cell Lung Carcinoma	GDSC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation rewiring degron network	0.1389
p.R21G	ACH-000496	Lung Cancer	CCLE	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation rewiring degron network	0.1389
p.R21G	NCI-H1792	lung	COSMIC	RARVYTD	LIG_APCC_ABBAyCdc20_2	8:14	Mutation rewiring degron network	0.1389

DegronMD: protein-targeted degradation, mutation and drug response to degrons

CSNK2A1

UniProt ID: P68400

Entrez ID: 1457

Protein name: Casein kinase II subunit alpha (CK II alpha) (EC 2.7.11.1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for CSNK2A1 in