Q9VT57 (CDK8_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 8
EC=2.7.11.22
EC=2.7.11.23

Alternative name(s):
Cell division protein kinase 8
Short name=DmCdk8
Mediator complex subunit Cdk8
Mediator of RNA polymerase II transcription subunit Cdk8

Gene names

Name:	Cdk8
ORF Names:	CG10572

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	454 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 preinitiation complex with RNA polymerase II and the general transcription factors. May phosphorylate 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. Required for leg and eye development and macrochaete specification or differentiation. Ref.1 Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1 UniProtKB P49336 ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
Cofactor	Magnesium By similarity. UniProtKB P49336
Subunit structure	Component of the Cdk8 module of the Mediator complex, composed of CycC, Cdk8, kto and skd.
Subcellular location	Nucleus Ref.1.
Developmental stage	Expressed both maternally and zygotically during developmental periods of maximal cell division; most abundant in early embryos and low levels in larvae, pupae and adults. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Activator Kinase Repressor Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from mutant phenotype Ref.1. Source: UniProtKB axon guidance Inferred from mutant phenotype PubMed 18516287. Source: FlyBase chaeta development Inferred from mutant phenotype Ref.5. Source: FlyBase imaginal disc-derived leg segmentation Inferred from mutant phenotype Ref.5. Source: FlyBase mitotic G2 DNA damage checkpoint Inferred from genetic interaction PubMed 21205937. Source: FlyBase sex comb development Inferred from mutant phenotype Ref.5. Source: FlyBase transcription initiation from RNA polymerase II promoter Inferred from sequence or structural similarity PubMed 11090137. Source: FlyBase
Cellular_component	mediator complex Inferred from direct assay PubMed 12556495. Source: FlyBase
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II carboxy-terminal domain kinase activity Inferred from electronic annotation. Source: EC RNA polymerase II transcription cofactor activity Inferred from sequence or structural similarity PubMed 11090137. Source: FlyBase cyclin-dependent protein serine/threonine kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Non-traceable author statement PubMed 10908587. Source: FlyBase
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CycC	P25008	2	EBI-163640,EBI-195485

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 454	454	Cyclin-dependent kinase 8		PRO_0000085798
Regions
	Domain	21 – 335	315	Protein kinase
	Nucleotide binding	27 – 35	9	ATP By similarity UniProtKB P49336
	Compositional bias	328 – 451	124	Gln-rich
Sites
	Active site	151	1	Proton acceptor By similarity UniProtKB P49336
	Binding site	52	1	ATP By similarity UniProtKB P49336
Experimental info
	Sequence conflict	9	1	T → A in AAB38385. Ref.1
	Sequence conflict	15	1	K → N in AAB38385. Ref.1
	Sequence conflict	37	1	K → R in AAB38385. Ref.1
	Sequence conflict	40	1	W → R in AAB38385. Ref.1
	Sequence conflict	70	1	L → W in AAB38385. Ref.1
	Sequence conflict	185	1	K → R in AAM50971. Ref.4
	Sequence conflict	321	1	N → I in AAB38385. Ref.1
	Sequence conflict	336	1	Q → R in AAB38385. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9VT57 [UniParc]. Last modified March 1, 2001. Version 2. Checksum: D73F6219E2A03C98	FASTA	454	53,682
	10 20 30 40 50 60 MDYDFKMKTQ IERTKVEDLF NYEGCKVGRG TYGHVYKAKW KETSDGKEYA LKQIDGTGLS 70 80 90 100 110 120 MSACREIALL RELKHQNVIT LIRVFLSHND RKVFLLIDYA EHDLWHIIKF HRAAKATKKQ 130 140 150 160 170 180 VVVPRGMVKS LLYQILDGIH YLHSNWVLHR DLKPANILVM GDGNERGRVK IADMGFARLF 190 200 210 220 230 240 NAPLKPLADL DPVVVTFWYR APELLLGARH YTKAIDIWAI GCIFAELLTS EPIFHCRQED 250 260 270 280 290 300 IKTSNPYHHD QLDRIFNVMG FPQDKDWEDI KKMPEHHTLT KDFKRSTYST CSLAKYMERH 310 320 330 340 350 360 KIKPDSKAFH LLQKLLLMDP NKRITSEQAM QDQYFQEEPQ PTQDVFAGCP IPYPKREFLT 370 380 390 400 410 420 DDDQEDKSDN KRQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ MNAEPNAKRV RLSGAGNQQD 430 440 450 FHHQQQQQQQ QQQQQQQQQQ QMMFNQQQNF QRFN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Drosophila Cdk8, a kinase partner of cyclin C that interacts with the large subunit of RNA polymerase II." Leclerc V., Tassan J.-P., O'Farrell P.H., Nigg E.A., Leopold P. Mol. Biol. Cell 7:505-513(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE. Tissue: Embryo.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[5]	"Distinct roles for Mediator Cdk8 module subunits in Drosophila development." Loncle N., Boube M., Joulia L., Boschiero C., Werner M., Cribbs D.L., Bourbon H.-M. EMBO J. 26:1045-1054(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CYCC; KTO AND SKD.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U33015 mRNA. Translation: AAB38385.1. AE014296 Genomic DNA. Translation: AAF50197.2. AY119111 mRNA. Translation: AAM50971.1.
RefSeq	NP_536735.2. NM_080487.3.
UniGene	Dm.5731.
3D structure databases
ProteinModelPortal	Q9VT57.
SMR	Q9VT57. Positions 1-353.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-38574N.
IntAct	Q9VT57. 3 interactions.
MINT	MINT-4329200.
STRING	7227.FBpp0076098.
Proteomic databases
PaxDb	Q9VT57.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0076369; FBpp0076098; FBgn0015618.
GeneID	39157.
KEGG	dme:Dmel_CG10572.
Organism-specific databases
CTD	1024.
FlyBase	FBgn0015618. Cdk8.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00530000064012.
InParanoid	Q9VT57.
KO	K02208.
OMA	NVITLIR.
OrthoDB	EOG4ZS7JJ.
PhylomeDB	Q9VT57.
Enzyme and pathway databases
SignaLink	Q9VT57.
Gene expression databases
Bgee	Q9VT57.
GermOnline	CG10572. Drosophila melanogaster.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	39157.
NextBio	812240.

Entry information

Entry name

CDK8_DROME

Accession

Primary (citable) accession number: Q9VT57
Secondary accession number(s): P91642, Q8MS41

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	March 1, 2001
Last modified:	May 29, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project