Q9VP22 (CDK12_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 12
EC=2.7.11.22
EC=2.7.11.23

Alternative name(s):
Cell division protein kinase 12
Short name=dCdk12

Gene names

Name:	Cdk12
ORF Names:	CG7597

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	1157 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cyclin-dependent kinase which displays CTD kinase activity: hyperphosphorylates the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit, thereby acting as a key regulator of transcription elongation. Ref.7
Catalytic activity	ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate. Ref.7 ATP + a protein = ADP + a phosphoprotein. Ref.7
Subunit structure	Interacts with cyclin CycK. Ref.7
Subcellular location	Nucleus. Chromosome. Note: Localizes to active genes. Ref.7
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAL28383.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Chromosome Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	neurogenesis Inferred from mutant phenotype PubMed 21549331. Source: FlyBase phagocytosis, engulfment Inferred from mutant phenotype PubMed 16336044. Source: FlyBase phosphorylation of RNA polymerase II C-terminal domain Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	nuclear chromosome Inferred from direct assay Ref.7. Source: UniProtKB nuclear cyclin-dependent protein kinase holoenzyme complex Inferred from direct assay Ref.7. Source: UniProtKB polytene chromosome puff Inferred from direct assay Ref.7. Source: FlyBase
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II carboxy-terminal domain kinase activity Inferred from direct assay Ref.7. Source: UniProtKB cyclin-dependent protein serine/threonine kinase activity Inferred from sequence or structural similarity PubMed 10889219. Source: FlyBase
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1157	1157	Cyclin-dependent kinase 12		PRO_0000372859
Regions
	Domain	804 – 1098	295	Protein kinase
	Nucleotide binding	810 – 818	9	ATP By similarity
Sites
	Active site	936	1	Proton acceptor By similarity
	Binding site	833	1	ATP By similarity
Amino acid modifications
	Modified residue	106	1	Phosphothreonine Ref.5
	Modified residue	184	1	Phosphothreonine Ref.5
	Modified residue	190	1	Phosphoserine Ref.5
	Modified residue	192	1	Phosphoserine Ref.5
	Modified residue	217	1	Phosphothreonine Ref.5
	Modified residue	280	1	Phosphoserine Ref.5
	Modified residue	283	1	Phosphothreonine Ref.5
	Modified residue	291	1	Phosphoserine Ref.5
	Modified residue	301	1	Phosphoserine Ref.5
	Modified residue	314	1	Phosphoserine Ref.5
	Modified residue	353	1	Phosphoserine Ref.5
	Modified residue	365	1	Phosphothreonine Ref.5
	Modified residue	487	1	Phosphoserine Ref.5
	Modified residue	492	1	Phosphoserine Ref.5
	Modified residue	553	1	Phosphoserine Ref.6
	Modified residue	730	1	Phosphoserine Ref.5
	Modified residue	743	1	Phosphoserine Ref.5
	Modified residue	747	1	Phosphoserine Ref.5
	Modified residue	755	1	Phosphoserine Ref.5
Experimental info
	Sequence conflict	188	1	A → V in AAL39951. Ref.3
	Sequence conflict	1099	1	R → K in AAL28383. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9VP22 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: B37ADCFBCAB4E9F3	FASTA	1,157	128,333
	10 20 30 40 50 60 MHASSAAATA LVEYSDVSSE DFSDQEAGDL DADAGKGAGN IKKPKPAPDN QFSKGRLDAK 70 80 90 100 110 120 PDKEGYDNYR SRRAEDSSDP VAAGSRQTSS SEATNPREEP SQASNTSKDE LWGREIYMSS 130 140 150 160 170 180 DSIDTDELEA EMKRQKRKKQ KKEKHKHKSK KKSKKRKKKR AKSYSSIDSM SDNDINALLD 190 200 210 220 230 240 RRYTPPTAPS KSNERTVSAA PSSFTPHNLK ESSSPATPPP VRRPNTNSNY YGESSLETAN 250 260 270 280 290 300 SALGSNLQVT VTNKQSISNR LRSPPPSSRS SGNGPRFGNS PRTPPPSHYS SSGGGGVGSG 310 320 330 340 350 360 SVVRDSRSSR YVNSPHKEDV SAHHRSSHDH GYQGRYSGAG SSSHDTRKVK RLSPELDRYN 370 380 390 400 410 420 HQPSTPPHKR RKFSDGREVG LGNFEHSRHH SGKYERYSRD RYSRRSSRSP SVQHSRSRQS 430 440 450 460 470 480 PSGGLSSGSN AFRHGGSHKH KYGTTVSSTP SHTTRTSKRA SGTGTSGDRY SRSPRTSSRY 490 500 510 520 530 540 MESSPPSPVG ASGSHHYHHR RSPRMRQRTR GDSRRRSPSS ASSESSASRS RSPTSRDLKH 550 560 570 580 590 600 KREEYIKKIS ETSLFAELVK DRHKRQKALK EIIERQEENS NSNSNGALTI NDNSSSVDGN 610 620 630 640 650 660 TPNAADGRSA PGSGTPAAAS TTSNGLQALG SKPDLDLNNI PMPNKQNDSV VSNPASNADV 670 680 690 700 710 720 PDSVAQLKQP LLVPPFSASK NNIKPKSLTS LPLPPGMNVL DLAGARSPSP GQKKESDEKN 730 740 750 760 770 780 VTSSGSANKS VLNLPMPPVI PGSEELSGDD DVIDSPEDFD APAVGTVHGH GGGPGTTRQR 790 800 810 820 830 840 PVILNRRDSR NNVRDWGERC VDVFEMIAQI GEGTYGQVYK ARDHHTNDMV ALKKVRLEHE 850 860 870 880 890 900 KEGFPITAVR EIKILRQLNH RNIVNLHEIV TDKQDAVEFR KDKGSFYLVF EYMDHDLMGL 910 920 930 940 950 960 LESGMVDFNE ENNASIMKQL LDGLNYCHKK NFLHRDIKCS NILMNNRGKV KLADFGLARL 970 980 990 1000 1010 1020 YNADDRERPY TNKVITLWYR PPELLLGEER YGPSIDVWSC GCILGELFVK RPLFQANAEM 1030 1040 1050 1060 1070 1080 AQLETISKIC GSPVPAVWPN VIKLPLFHTL KQKKTHRRRL REDFEFMPAP ALDLLDKMLD 1090 1100 1110 1120 1130 1140 LDPDKRITAE DALRSPWLRK INPDEMPTPQ LPTWQDCHEL WSKKRRRQMR EQQESLPPTV 1150 IASTKYQQHG ATMVGDA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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.
[2]	"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.
[3]	"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 and Ovary.
[4]	Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E. Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley.
[5]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-106; THR-184; SER-190; SER-192; THR-217; SER-280; THR-283; SER-291; SER-301; SER-314; SER-353; THR-365; SER-487; SER-492; SER-730; SER-743; SER-747 AND SER-755, MASS SPECTROMETRY. Tissue: Embryo.
[6]	"An integrated chemical, mass spectrometric and computational strategy for (quantitative) phosphoproteomics: application to Drosophila melanogaster Kc167 cells." Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A., Eng J.K., Aebersold R., Tao W.A. Mol. Biosyst. 3:275-286(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553, MASS SPECTROMETRY.
[7]	"CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1." Bartkowiak B., Liu P., Phatnani H.P., Fuda N.J., Cooper J.J., Price D.H., Adelman K., Lis J.T., Greenleaf A.L. Genes Dev. 24:2303-2316(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH CYCK.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AE014296 Genomic DNA. Translation: AAF51738.1. AE014296 Genomic DNA. Translation: AAN12171.1. AY060835 mRNA. Translation: AAL28383.1. Different initiation. AY069806 mRNA. Translation: AAL39951.1. BT058001 mRNA. Translation: ACM16711.1.
RefSeq	NP_001262167.1. NM_001275238.1. NP_649325.2. NM_141068.3. NP_730643.1. NM_168912.2.
UniGene	Dm.1943.
3D structure databases
ProteinModelPortal	Q9VP22.
SMR	Q9VP22. Positions 777-1143.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9VP22. 7 interactions.
STRING	7227.FBpp0078013.
Proteomic databases
PaxDb	Q9VP22.
PRIDE	Q9VP22.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0078357; FBpp0078013; FBgn0037093. FBtr0078358; FBpp0078014; FBgn0037093. FBtr0332716; FBpp0304962; FBgn0037093.
GeneID	40385.
KEGG	dme:Dmel_CG7597.
UCSC	CG7597-RA. d. melanogaster.
Organism-specific databases
CTD	51755.
FlyBase	FBgn0037093. Cdk12.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00690000102025.
InParanoid	Q8T9E1.
KO	K08819.
OMA	TISKICG.
OrthoDB	EOG45QFV6.
PhylomeDB	Q9VP22.
Enzyme and pathway databases
SignaLink	Q9VP22.
Gene expression databases
Bgee	Q9VP22.
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	40385.
NextBio	818504.

Entry information

Entry name

CDK12_DROME

Accession

Primary (citable) accession number: Q9VP22
Secondary accession number(s): Q8T9E1, Q95SE1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 26, 2009
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project