CSNK2A1 (casein kinase 2 alpha 1)

Gene

• Entrez ID: 1457
• Gene name: Casein kinase 2 alpha 1
• Gene symbol: CSNK2A1
• Synonyms: CK2A1, CKII, Cka1, Cka2, OCNDS
• Chromosome: 20
• Chromosome location: 20p13
• Summary: Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. It is involved in various cellular processes, including cell cycle control, apoptosis, and circadian rhythm. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. Multiple transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Apr 2018]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs869312840	T>C	Pathogenic	Missense variant, coding sequence variant
rs869312845	C>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs869312846	A>G	Pathogenic	Splice donor variant
rs869312848	T>C	Pathogenic	Missense variant, coding sequence variant
rs869312849	T>C,G	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs886041956	G>C	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs1057518092	C>T	Conflicting-interpretations-of-pathogenicity, not-provided, likely-pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs1057524708	C>A	Likely-pathogenic	Splice donor variant
rs1064795110	A>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1555762734	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1555762737	A>G	Pathogenic	Coding sequence variant, missense variant
rs1555763444	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1555764992	A>T	Likely-pathogenic	Coding sequence variant, 5 prime UTR variant, missense variant
rs1568512728	C>G	Pathogenic	Coding sequence variant, missense variant
rs1568532361	T>C	Pathogenic	Initiator codon variant, intron variant, missense variant
rs1600392059	T>-	Pathogenic	Intron variant, coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT007207	hsa-miR-216b-5p	Immunoblot, Luciferase reporter assay, qRT-PCR, Western blot	23137536
MIRT007208	hsa-miR-337-3p	Immunoblot, Luciferase reporter assay, qRT-PCR, Western blot	23137536
MIRT007209	hsa-miR-760	Immunoblot, Luciferase reporter assay, qRT-PCR, Western blot	23137536
MIRT007210	hsa-miR-186-5p	Immunoblot, Luciferase reporter assay, qRT-PCR, Western blot	23137536
MIRT030638	hsa-miR-22-3p	Sequencing	20371350
MIRT039530	hsa-miR-652-3p	CLASH	23622248
MIRT039801	hsa-miR-615-3p	CLASH	23622248
MIRT047136	hsa-miR-183-5p	CLASH	23622248
MIRT047431	hsa-miR-10b-5p	CLASH	23622248
MIRT047431	hsa-miR-10b-5p	PAR-CLIP	22012620
MIRT047540	hsa-miR-10a-5p	CLASH	23622248
MIRT047540	hsa-miR-10a-5p	PAR-CLIP	22012620
MIRT051854	hsa-let-7c-5p	CLASH	23622248
MIRT052272	hsa-let-7b-5p	CLASH	23622248
MIRT052591	hsa-let-7a-5p	CLASH	23622248
MIRT437426	hsa-miR-125b-5p	PAR-CLIP	22012620
MIRT437426	hsa-miR-125b-5p	Luciferase reporter assay, Western blot	24098452
MIRT513956	hsa-miR-4799-5p	PAR-CLIP	23446348
MIRT513956	hsa-miR-4799-5p	PAR-CLIP	26701625
MIRT513957	hsa-miR-6765-5p	PAR-CLIP	23446348
MIRT513958	hsa-miR-1304-5p	PAR-CLIP	23446348
MIRT513959	hsa-miR-107	PAR-CLIP	23446348
MIRT513959	hsa-miR-107	PAR-CLIP	26701625
MIRT513960	hsa-miR-103a-3p	PAR-CLIP	23446348
MIRT513960	hsa-miR-103a-3p	PAR-CLIP	26701625
MIRT513961	hsa-miR-3188	PAR-CLIP	23446348
MIRT513961	hsa-miR-3188	PAR-CLIP	22012620
MIRT513962	hsa-miR-2467-5p	PAR-CLIP	23446348
MIRT513963	hsa-miR-3975	PAR-CLIP	23446348
MIRT513964	hsa-miR-5009-3p	PAR-CLIP	23446348
MIRT513964	hsa-miR-5009-3p	PAR-CLIP	26701625
MIRT513965	hsa-miR-485-5p	PAR-CLIP	23446348
MIRT513966	hsa-miR-6884-5p	PAR-CLIP	23446348
MIRT538295	hsa-miR-4662a-5p	PAR-CLIP	22012620
MIRT538296	hsa-miR-3605-5p	PAR-CLIP	22012620
MIRT538297	hsa-miR-3679-5p	PAR-CLIP	22012620
MIRT538298	hsa-miR-1185-5p	PAR-CLIP	22012620
MIRT538299	hsa-miR-138-1-3p	PAR-CLIP	22012620
MIRT538300	hsa-miR-4319	PAR-CLIP	22012620
MIRT538301	hsa-miR-125a-5p	PAR-CLIP	22012620
MIRT538302	hsa-miR-625-3p	PAR-CLIP	22012620
MIRT538303	hsa-miR-504-5p	PAR-CLIP	22012620
MIRT538304	hsa-miR-580-3p	PAR-CLIP	22012620
MIRT538305	hsa-miR-6867-3p	PAR-CLIP	22012620
MIRT538306	hsa-miR-6852-3p	PAR-CLIP	22012620
MIRT538307	hsa-miR-3909	PAR-CLIP	22012620
MIRT538308	hsa-miR-6770-5p	PAR-CLIP	22012620
MIRT538309	hsa-miR-1253	PAR-CLIP	22012620
MIRT538310	hsa-miR-7706	PAR-CLIP	22012620
MIRT538311	hsa-miR-4685-3p	PAR-CLIP	22012620
MIRT538311	hsa-miR-4685-3p	HITS-CLIP	23824327
MIRT538312	hsa-miR-4287	PAR-CLIP	22012620
MIRT538312	hsa-miR-4287	HITS-CLIP	23824327
MIRT538313	hsa-miR-7113-3p	PAR-CLIP	22012620
MIRT538314	hsa-miR-4469	PAR-CLIP	22012620
MIRT538315	hsa-miR-3162-3p	PAR-CLIP	22012620
MIRT538316	hsa-miR-3163	PAR-CLIP	22012620
MIRT538317	hsa-miR-4695-5p	PAR-CLIP	22012620
MIRT538318	hsa-miR-6891-5p	PAR-CLIP	22012620
MIRT538319	hsa-miR-3173-3p	PAR-CLIP	22012620
MIRT538320	hsa-miR-518e-3p	PAR-CLIP	22012620
MIRT544554	hsa-miR-2110	PAR-CLIP	21572407
MIRT544555	hsa-miR-6780b-5p	PAR-CLIP	21572407
MIRT544556	hsa-miR-4271	PAR-CLIP	21572407
MIRT544557	hsa-miR-4725-3p	PAR-CLIP	21572407
MIRT544558	hsa-miR-6888-5p	PAR-CLIP	21572407
MIRT544559	hsa-miR-570-5p	PAR-CLIP	21572407
MIRT544560	hsa-miR-548ba	PAR-CLIP	21572407
MIRT544561	hsa-miR-548ai	PAR-CLIP	21572407
MIRT544562	hsa-miR-548ag	PAR-CLIP	21572407
MIRT624250	hsa-miR-6809-3p	HITS-CLIP	23824327
MIRT624250	hsa-miR-6809-3p	HITS-CLIP	19536157
MIRT624251	hsa-miR-6833-3p	HITS-CLIP	23824327
MIRT624251	hsa-miR-6833-3p	HITS-CLIP	19536157
MIRT624252	hsa-miR-4768-5p	HITS-CLIP	23824327
MIRT624252	hsa-miR-4768-5p	HITS-CLIP	19536157
MIRT624253	hsa-miR-6873-3p	HITS-CLIP	23824327
MIRT624253	hsa-miR-6873-3p	HITS-CLIP	19536157
MIRT624254	hsa-miR-5581-3p	HITS-CLIP	23824327
MIRT624254	hsa-miR-5581-3p	HITS-CLIP	19536157
MIRT624255	hsa-miR-103a-2-5p	HITS-CLIP	23824327
MIRT624256	hsa-miR-6499-3p	HITS-CLIP	23824327
MIRT624257	hsa-miR-1205	HITS-CLIP	23824327
MIRT624258	hsa-miR-1184	HITS-CLIP	23824327
MIRT624259	hsa-miR-3158-5p	HITS-CLIP	23824327
MIRT624260	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT624260	hsa-miR-6817-3p	HITS-CLIP	19536157
MIRT624261	hsa-miR-7110-3p	HITS-CLIP	23824327
MIRT624261	hsa-miR-7110-3p	HITS-CLIP	19536157
MIRT624262	hsa-miR-6845-3p	HITS-CLIP	23824327
MIRT624262	hsa-miR-6845-3p	HITS-CLIP	19536157
MIRT624263	hsa-miR-136-5p	HITS-CLIP	23824327
MIRT624263	hsa-miR-136-5p	HITS-CLIP	19536157
MIRT624264	hsa-miR-6872-3p	HITS-CLIP	23824327
MIRT624264	hsa-miR-6872-3p	HITS-CLIP	19536157
MIRT624265	hsa-miR-193a-5p	HITS-CLIP	23824327
MIRT659326	hsa-miR-4659b-3p	HITS-CLIP	23824327
MIRT659327	hsa-miR-4659a-3p	HITS-CLIP	23824327
MIRT659328	hsa-miR-6875-3p	HITS-CLIP	23824327
MIRT659329	hsa-miR-6868-3p	HITS-CLIP	23824327
MIRT659330	hsa-miR-6749-3p	HITS-CLIP	23824327
MIRT659331	hsa-miR-3124-3p	HITS-CLIP	23824327
MIRT659332	hsa-miR-1248	HITS-CLIP	23824327
MIRT659333	hsa-miR-1237-3p	HITS-CLIP	23824327
MIRT659334	hsa-miR-3667-3p	HITS-CLIP	23824327
MIRT659335	hsa-miR-6734-3p	HITS-CLIP	23824327
MIRT659336	hsa-miR-5088-3p	HITS-CLIP	23824327
MIRT704448	hsa-miR-1260b	HITS-CLIP	23313552
MIRT704449	hsa-miR-1260a	HITS-CLIP	23313552
MIRT704450	hsa-miR-188-3p	HITS-CLIP	23313552
MIRT704451	hsa-miR-4768-3p	HITS-CLIP	23313552
MIRT704452	hsa-miR-5690	HITS-CLIP	23313552
MIRT704453	hsa-miR-646	HITS-CLIP	23313552
MIRT704454	hsa-miR-1183	HITS-CLIP	23313552
MIRT736697	hsa-miR-1266-3p	PAR-CLIP	26701625
MIRT737289	hsa-miR-130a-3p	PAR-CLIP	26701625
MIRT737299	hsa-miR-130b-3p	PAR-CLIP	26701625
MIRT737666	hsa-miR-148a-3p	PAR-CLIP	26701625
MIRT737679	hsa-miR-148b-3p	PAR-CLIP	26701625
MIRT737868	hsa-miR-152-3p	PAR-CLIP	26701625
MIRT738057	hsa-miR-1825	PAR-CLIP	26701625
MIRT738728	hsa-miR-199a-5p	PAR-CLIP	26701625
MIRT738737	hsa-miR-199b-5p	PAR-CLIP	26701625
MIRT738744	hsa-miR-19a-3p	PAR-CLIP	26701625
MIRT738755	hsa-miR-19b-3p	PAR-CLIP	26701625
MIRT739609	hsa-miR-301a-3p	PAR-CLIP	26701625
MIRT739619	hsa-miR-301b-3p	PAR-CLIP	26701625
MIRT742071	hsa-miR-3666	PAR-CLIP	26701625
MIRT742095	hsa-miR-3671	PAR-CLIP	26701625
MIRT743784	hsa-miR-4295	PAR-CLIP	26701625
MIRT746138	hsa-miR-454-3p	PAR-CLIP	26701625
MIRT748508	hsa-miR-4762-5p	PAR-CLIP	26701625
MIRT751745	hsa-miR-607	PAR-CLIP	26701625

Transcription factors

Transcription factor	Regulation	Reference
ETS1	Unknown	19027835
NFKB1	Unknown	19027835
RELA	Unknown	19027835
SP1	Unknown	19027835

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	12700239, 15723517, 16193064, 20625391, 20864032, 23123191, 30699359
GO:0004674	Function	Protein serine/threonine kinase activity	IGI	28031292
GO:0004674	Function	Protein serine/threonine kinase activity	IMP	11035045
GO:0004674	Function	Protein serine/threonine kinase activity	TAS	2174700
GO:0005515	Function	Protein binding	IPI	10094392, 11574463, 12191471, 12769847, 14667819, 16873060, 18548200, 19011756, 19236849, 19294699, 19680552, 20439735, 20625391, 21075308, 21282530, 21516116, 21968188, 21988832, 22113938, 22317921, 22406621, 22975381, 23123191, 23455922, 23555304, 23752268, 24535599, 25241761, 254
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	21282530, 23123191
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	TAS	10799509
GO:0005956	Component	Protein kinase CK2 complex	IBA	21873635
GO:0005956	Component	Protein kinase CK2 complex	IDA	15723517
GO:0006457	Process	Protein folding	TAS
GO:0006468	Process	Protein phosphorylation	IDA	18548200, 20625391, 22406621
GO:0006656	Process	Phosphatidylcholine biosynthetic process	TAS
GO:0006915	Process	Apoptotic process	IEA
GO:0007049	Process	Cell cycle	IEA
GO:0007165	Process	Signal transduction	TAS	2174700
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	20625391
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016236	Process	Macroautophagy	TAS
GO:0016301	Function	Kinase activity	IDA	18548200
GO:0016580	Component	Sin3 complex	IDA	17827154
GO:0016581	Component	NuRD complex	IDA	17827154
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	28031292, 30699359
GO:0018107	Process	Peptidyl-threonine phosphorylation	IBA	21873635
GO:0018107	Process	Peptidyl-threonine phosphorylation	IDA	15723517
GO:0030177	Process	Positive regulation of Wnt signaling pathway	IMP	12700239
GO:0030307	Process	Positive regulation of cell growth	IDA	20625391
GO:0031519	Component	PcG protein complex	IDA	21282530
GO:0042802	Function	Identical protein binding	IPI	24013921, 32296183
GO:0043154	Process	Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP	16193064
GO:0045732	Process	Positive regulation of protein catabolic process	IDA	20625391
GO:0047485	Function	Protein N-terminus binding	IPI	11972058
GO:0048511	Process	Rhythmic process	IEA
GO:0051726	Process	Regulation of cell cycle	IBA	21873635
GO:0051879	Function	Hsp90 protein binding	TAS	19387550
GO:0061077	Process	Chaperone-mediated protein folding	TAS	19387550
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:1901796	Process	Regulation of signal transduction by p53 class mediator	TAS
GO:1905818	Process	Regulation of chromosome separation	IMP	11704824
GO:2000059	Process	Negative regulation of ubiquitin-dependent protein catabolic process	IGI	28031292
GO:2001234	Process	Negative regulation of apoptotic signaling pathway	TAS	28031292

Other IDs

• MIM: 115440
• HGNC: 2457
• e!Ensembl: ENSG00000101266

Protein

• UniProt ID: P68400
• Protein name: Casein kinase II subunit alpha (CK II alpha) (EC 2.7.11.1)
• Protein 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).
• PDB: 1JWH, 1NA7, 1PJK, 2PVR, 2ZJW, 3AMY, 3AT2, 3AT3, 3AT4, 3AXW, 3BQC, 3C13, 3FWQ, 3H30, 3JUH, 3MB6, 3MB7, 3NGA, 3NSZ, 3OWJ, 3OWK, 3OWL, 3PE1, 3PE2, 3PE4, 3Q04, 3Q9W, 3Q9X, 3Q9Y, 3Q9Z, 3QA0, 3R0T, 3RPS, 3TAX, 3U4U, 3U87, 3U9C, 3W8L, 3WAR, 3WIK, 3WIL, 3WOW, 4DGL, 4FBX, 4GRB, 4GUB, 4GYW, 4GYY, 4GZ3, 4IB5, 4KWP
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	39 → 324	Protein kinase domain	Domain

• Sequence:

  MSGPVPSRARVYTDVNTHRPREYWDYESHVVEWGNQDDYQLVRKLGRGKYSEVFEAINIT
  NNEKVVVKILKPVKKKKIKREIKILENLRGGPNIITLADIVKDPVSRTPALVFEHVNNTD
  FKQLYQTLTDYDIRFYMYEILKALDYCHSMGIMHRDVKPHNVMIDHEHRKLRLIDWGLAE
  FYHPGQEYNVRVASRYFKGPELLVDYQMYDYSLDMWSLGCMLASMIFRKEPFFHGHDNYD
  QLVRIAKVLGTEDLYDYIDKYNIELDPRFNDILGRHSRKRWERFVHSENQHLVSPEALDF
  LDKLLRYDHQSRLTAREAMEHPYFYTVVKDQARMGSSSMPGGSTPVSSANMMSGISSVPT
  PSPLGPLAGSPVIAAANPLGMPVPAAAGAQQ

• Sequence length: 391