Reactome | UniProt:P49336 CDK8

chain	chain:1-464
checksum	00CBAB6CE354605F
comment	FUNCTION Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)CATALYTIC ACTIVITY [DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H(+)COFACTOR Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II. Interacts with CTNNB1, GLI3 and MAML1.INTERACTION The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
crossReference	[DatabaseIdentifier:11780866] Guide to Pharmacology - Targets:1980 [DatabaseIdentifier:12818475] ZINC - World Drugs:CDK8_HUMAN [DatabaseIdentifier:12815620] ZINC target:P49336 [DatabaseIdentifier:12812261] ZINC - Substances:CDK8_HUMAN [DatabaseIdentifier:12810454] ZINC - Predictions - Purchasable:CDK8_HUMAN [DatabaseIdentifier:12806946] ZINC - Investigational:CDK8_HUMAN [DatabaseIdentifier:12805858] ZINC - FDA approved:CDK8_HUMAN [DatabaseIdentifier:12804763] ZINC - Biogenic:CDK8_HUMAN [DatabaseIdentifier:12454840] RefSeq:NP_001305297.1 [DatabaseIdentifier:12454841] RefSeq:NP_001251.1 [DatabaseIdentifier:12285215] Pharos - Targets:P49336 [DatabaseIdentifier:12264202] PRO:P49336 [DatabaseIdentifier:12175442] PDB:5HBE [DatabaseIdentifier:12175438] PDB:5IDN [DatabaseIdentifier:12175435] PDB:5I5Z [DatabaseIdentifier:12139978] PDB:8TQW [DatabaseIdentifier:12175448] PDB:4F6S [DatabaseIdentifier:12175446] PDB:4F70 [DatabaseIdentifier:12175445] PDB:4G6L [DatabaseIdentifier:12175431] PDB:5XS2 [DatabaseIdentifier:12175437] PDB:5HBJ [DatabaseIdentifier:12175432] PDB:4F7J [DatabaseIdentifier:12175444] PDB:5BNJ [DatabaseIdentifier:12175436] PDB:9H8C [DatabaseIdentifier:12175440] PDB:4F6W [DatabaseIdentifier:12175434] PDB:5HBH [DatabaseIdentifier:12175430] PDB:5IDP [DatabaseIdentifier:12156735] PDB:8TQC [DatabaseIdentifier:12175439] PDB:4F6U [DatabaseIdentifier:12175429] PDB:6QTG [DatabaseIdentifier:12175441] PDB:6Y0A [DatabaseIdentifier:12175428] PDB:6TPA [DatabaseIdentifier:12175447] PDB:5XQX [DatabaseIdentifier:12175450] PDB:5HNB [DatabaseIdentifier:12175443] PDB:5HVY [DatabaseIdentifier:12175449] PDB:5ICP [DatabaseIdentifier:12175433] PDB:4F7L [DatabaseIdentifier:12175426] PDB:4F7N [DatabaseIdentifier:12175425] PDB:4CRL [DatabaseIdentifier:12175427] PDB:4F7S [DatabaseIdentifier:12156736] PDB:8TQ2 [DatabaseIdentifier:12175418] PDB:6T41 [DatabaseIdentifier:12175424] PDB:9H8S [DatabaseIdentifier:12175423] PDB:5FGK [DatabaseIdentifier:12175422] PDB:5CEI [DatabaseIdentifier:12175420] PDB:3RGF [DatabaseIdentifier:12175419] PDB:6R3S [DatabaseIdentifier:12175421] PDB:6QTJ [DatabaseIdentifier:12124906] OpenTargets:ENSG00000132964 [DatabaseIdentifier:11840371] HPA:ENSG00000132964-CDK8 [DatabaseIdentifier:11831330] HMDB Protein:HMDBP01191 [DatabaseIdentifier:11802740] GlyGen:P49336 [DatabaseIdentifier:11787296] GeneCards:CDK8 [DatabaseIdentifier:11513053] ENSEMBL:ENSG00000132964 [DatabaseIdentifier:11628856] ENSEMBL:ENSP00000370938 [DatabaseIdentifier:11751555] ENSEMBL:ENST00000381527
databaseName	UniProt
dbId	69456
description	recommendedName: Cyclin-dependent kinase 8 ecNumber: 2.7.11.22 ecNumber: 2.7.11.23 alternativeName: Cell division protein kinase 8 alternativeName: Mediator complex subunit CDK8 alternativeName: Mediator of RNA polymerase II transcription subunit CDK8 alternativeName: Protein kinase K35
displayName	UniProt:P49336 CDK8
geneName	CDK8
identifier	P49336
isSequenceChanged	false
keyword	3D-structure Activator Alternative splicing ATP-binding Autism spectrum disorder Disease variant Intellectual disability Kinase Nucleotide-binding Nucleus Proteomics identification Reference proteome Repressor Serine/threonine-protein kinase Transcription Transcription regulation Transferase
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	CDK8
otherIdentifier	1024 11745882_s_at 11763387_s_at 1189_at 1553112_PM_s_at 1553112_s_at 1553113_PM_s_at 1553113_s_at 16773430 204831_PM_at 204831_at 3482502 3482503 3482504 3482505 3482506 3482507 3482508 3482509 3482510 3482511 3482512 3482522 3482523 3482524 3482536 3482537 3482539 3482540 3482542 3482543 3482544 3482546 3482548 3482550 3482553 3482554 3482571 35140_at 7968199 A_14_P128762 A_23_P139958 GE576844 GE60102 GE855583 GO:0000166 GO:0000307 GO:0003824 GO:0004672 GO:0004674 GO:0004693 GO:0005515 GO:0005524 GO:0005634 GO:0005654 GO:0005730 GO:0006355 GO:0006468 GO:0008353 GO:0016301 GO:0016592 GO:0016740 GO:0032991 GO:0045944 GO:0051726 GO:0106310 GO:0140096 GO:1990508 HMNXSV003011355 HMNXSV003014489 Hs.25283.0.S2_3p_at Hs2.397734.1.S1_3p_s_at Hs2.397734.1.S2_3p_s_at ILMN_1777913 ILMN_1816527 PH_hs_0019005 TC13000068.hg TC13000974.hg X85753_at p26666
physicalEntity	[EntityWithAccessionedSequence:R-HSA-212440] CDK8 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000132964] ENSEMBL:ENSG00000132964 CDK8 [ReferenceDNASequence:12763963] UCSC:P49336 CDK8 [ReferenceDNASequence:12110269] OMIM:603184 CDK8 [ReferenceDNASequence:12091509] NCBI Gene:1024 CDK8 [ReferenceDNASequence:12007416] Monarch:1024 CDK8 [ReferenceDNASequence:11914990] KEGG:hsa:1024 CDK8 [ReferenceDNASequence:11818935] HGNC:1779 CDK8 [ReferenceDNASequence:11377627] BioGPS Gene:1024 CDK8 [ReferenceDNASequence:11403323] COSMIC - genes:CDK8 CDK8 [ReferenceDNASequence:11412929] CTD Gene:1024 CDK8 [ReferenceDNASequence:11440925] dbSNP Gene:1024 CDK8
referenceTranscript	[ReferenceRNASequence:12636346] RefSeq:NM_001318368.2 CDK8 [ReferenceRNASequence:12636345] RefSeq:NM_001260.3 CDK8
schemaClass	ReferenceGeneProduct
secondaryIdentifier	CDK8_HUMAN Q5VUF3 Q6ISB5
sequenceLength	464
species	[Species:48887] Homo sapiens
stId	uniprot:P49336
url	http://purl.uniprot.org/uniprot/P49336

UniProt:P49336 CDK8 Show undefined attributes

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