Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 2.7.11.23 - [RNA-polymerase]-subunit kinase and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC2.7.11.23
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
The enzyme appears to be distinct from other protein kinases. It brings about multiple phosphorylations of the unique C-terminal repeat domain of the largest subunit of eukaryotic DNA-directed RNA polymerase (EC 2.7.7.6). The enzyme does not phosphorylate casein, phosvitin or histone.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Synonyms
dna-pk, tfiih, p-tefb, dna-dependent protein kinase, positive transcription elongation factor b, ctd kinase, kin28, srb10, ctdk-i, tfiih kinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C-terminal repeat domain kinase
-
-
-
-
Cdk1
-
-
CTD kinase
DNA-dependent protein kinase
-
-
DNA-PK
-
-
Down syndrome-associated kinase
-
-
DYRK1A
-
-
glycogen synthase kinase 3
-
-
GSK-3
-
-
GSK-3beta
-
isoform
kinase, ribonucleate nucleotidyltransferase II C-terminal domain (phosphorylating)
-
-
-
-
kinase, ribonucleate nucleotidyltransferase isozyme II IIa subunit (phosphorylating)
-
-
-
-
MAPK
-
-
pol II CTD kinase
-
-
positive transcription elongation factor b
-
RNA polymerase II carboxyl-terminal domain kinase
-
-
RNA polymerase II CTD kinase
-
-
-
-
RNA polymerase II phospho-CTD kinase
-
-
RNAPII phospho-CTD kinase
-
-
TFIIH
-
-
additional information
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[DNA-directed RNA polymerase] phosphotransferase
The enzyme appears to be distinct from other protein kinases. It brings about multiple phosphorylations of the unique C-terminal repeat domain of the largest subunit of eukaryotic DNA-directed RNA polymerase (EC 2.7.7.6). The enzyme does not phosphorylate casein, phosvitin or histone.
CAS REGISTRY NUMBER
COMMENTARY hide
122097-00-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + casein
ADP + phosphocasein
show the reaction diagram
-
phosphorylated at about 30% the rate of RNA-polymerase II subunit
-
-
?
ATP + CTD-containing fusion proteins
ADP + ?
show the reaction diagram
ATP + DYRKtide
ADP + phospho-DYRKtide
show the reaction diagram
-
-
-
-
?
ATP + GST-tagged yCTD fusion protein
?
show the reaction diagram
hCDK13 purified from nuclear extracts displays CTD kinase activity in vitro with recombinant GST-tagged yeast CTD fusion proteins as substrate, hyperphosphorylation of the CTD by hCDK13 kinase
-
-
?
ATP + histone H1
ADP + phosphohistone H1
show the reaction diagram
-
-
-
-
?
ATP + HIV Tat
ADP + phosphorylated HIV-Tat
show the reaction diagram
ATP + RNA polymerase II
?
show the reaction diagram
ATP + RNA polymerase II C-terminal subunit
ADP + phosphoylated RNA polymerase II C-terminal subunit
show the reaction diagram
ATP + synthetic peptide
ADP + phosphorylated synthetic peptide
show the reaction diagram
-
-
-
-
?
ATP + synthetic peptides
ADP + ?
show the reaction diagram
ATP + [carboxy terminal domain of RNA polymerase II]
ADP + phospho-[carboxy terminal domain of RNA polymerase II]
show the reaction diagram
-
the enzyme GSK-3 phosphorylates the carboxy terminal domain of RNA polymerase II in vitro, but preferentially when the substrate is previously phosphorylated, consistently with the requirement of a priming phosphorylation reported for GSK-3 efficacy
-
-
?
ATP + [DNA-directed eukaryotic RNA polymerase II subunit IIa]
ADP + phospho-[DNA-directed RNA polymerase II subunit IIa]
show the reaction diagram
ATP + [DNA-directed RNA polymerase II]
ADP + phospho-[DNA-directed RNA polymerase II]
show the reaction diagram
ATP + [DNA-directed RNA polymerase]
ADP + phospho-[DNA-directed RNA polymerase]
show the reaction diagram
ATP + [RNA polymerase II]
ADP + phospho-[RNA polymerase II]
show the reaction diagram
the CDK9 subunit of positive transcription elongation factor b phosphorylates RNA polymerase II at its Ser-2 carboxy-terminal domain repeat
-
-
?
dATP + [DNA-directed eukaryotic RNA polymerase II subunit IIa]
dADP + ?
show the reaction diagram
-
-
-
-
?
GTP + [DNA-directed eukaryotic RNA polymerase II subunit IIa]
GDP + ?
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + HIV Tat
ADP + phosphorylated HIV-Tat
show the reaction diagram
-
-
-
-
?
ATP + RNA polymerase II C-terminal subunit
ADP + phosphoylated RNA polymerase II C-terminal subunit
show the reaction diagram
ATP + [DNA-directed eukaryotic RNA polymerase II subunit IIa]
ADP + phospho-[DNA-directed RNA polymerase II subunit IIa]
show the reaction diagram
ATP + [DNA-directed RNA polymerase II]
ADP + phospho-[DNA-directed RNA polymerase II]
show the reaction diagram
only Rpb1, the largest subunit of RNAPII evolved a unique, highly repetitive carboxy-terminal domain, termed CTD. Dynamic phosphorylation patterns of serine residues in the CTD during gene transcription. Also phosphorylation of threonine 4 and tyrosine 1 in the CTD. CTD is composed of multiple tandem heptapeptides with the evolutionary conserved consensus motif Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7
-
-
?
ATP + [DNA-directed RNA polymerase]
ADP + phospho-[DNA-directed RNA polymerase]
show the reaction diagram
ATP + [RNA polymerase II]
ADP + phospho-[RNA polymerase II]
show the reaction diagram
the CDK9 subunit of positive transcription elongation factor b phosphorylates RNA polymerase II at its Ser-2 carboxy-terminal domain repeat
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
-
1 mM used in assay conditions
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-(5-isoquinolinesulfonyl)-2-methylpiperazine
5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole
6-[(2-[[4-(2,4-dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-yl]amino]ethyl)amino]pyridine-3-carbonitrile
-
-
8-(methylthio)-4,5-dihydrothieno[3',4':5,6]benzoisoxazole-6-carboamide
-
KM05283, CTD kinase inhibitor
GW779439X
-
21% inhibition at 0.0001 mM
-
GW801372X
-
33% inhibition at 0.0001 mM
-
GW805758X
-
36% inhibition at 0.0001 mM
-
GW806290X
-
22% inhibition at 0.0001 mM
-
GW810578X
-
26% inhibition at 0.0001 mM
-
harmine
-
-
N-(4-methoxybenzyl)-2-(5-nitro-1,3-thiazol-2-yl)acetamide
-
-
roscovitine
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cyclin H
-
required by Cdk7
-
cyclin T1
-
DNA
-
activation
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.03 - 0.06
ATP
0.15
Synthetic peptide
-
27°C, pH 7.5
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
27 - 28
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
foreskin fibroblasts
Manually annotated by BRENDA team
-
fibrosarcoma cell line
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the human orthologue of Saccharomyces cerevisiae Ctk1 is one or both of the isozyme pair, hCDK12-hCDK13
malfunction
metabolism
-
DYRK1A is a dosage-sensitive protein kinase that fulfills key roles during development and in tissue homeostasis. DYRK1A-bound promoters show a higher occurrence of activating chromatin modifications when compared with genes that do not associate with DYRK1A, including high levels of H3K4me3 and H3K4me2 surrounding TSSs or elevated H3K36me3 in the gene body
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CDK1_HUMAN
297
0
34095
Swiss-Prot
other Location (Reliability: 1)
CDK7_HUMAN
346
0
39038
Swiss-Prot
other Location (Reliability: 2)
CDK8_HUMAN
464
0
53284
Swiss-Prot
other Location (Reliability: 1)
CDK9_HUMAN
372
0
42778
Swiss-Prot
other Location (Reliability: 1)
CDK12_HUMAN
1490
0
164155
Swiss-Prot
other Location (Reliability: 1)
CDK13_HUMAN
1512
0
164923
Swiss-Prot
other Location (Reliability: 2)
D6R9G1_HUMAN
253
0
28502
TrEMBL
other Location (Reliability: 2)
D6REC6_HUMAN
149
0
17001
TrEMBL
other Location (Reliability: 2)
A0A0S2Z3F9_HUMAN
346
0
39038
TrEMBL
other Location (Reliability: 2)
PLK3_HUMAN
646
0
71629
Swiss-Prot
-
CDK2_HUMAN
298
0
33930
Swiss-Prot
-
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
180000
-
gel filtration, enzyme component B
340000
-
gel filtration, enzyme component A
67000
-
1 * 67000 + 1 * 83000, component B, SDS-PAGE
83000
-
1 * 67000 + 1 * 83000, component B, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
1 * 67000 + 1 * 83000, component B, SDS-PAGE
additional information
-
the three CTD kinase isozymes possess CDK-cyclin pairs, and TFIIH additionally forms a preinitiation complex, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D167N
-
dominant-negative mutant of CDK9, inhibits transcriptional activation by EBNA 2
D173A
-
CDK8 mutant, shows no effect on basal or EBNA 2-activated transcription
K41M
-
CDK7 mutant, both EBNA 2-activated and basal transcription from Cp reporter construct are not particularly dependent on CDK7 kinase activity with only small effects observed in the presence of high levels of mutant K41M
K85A
-
kinase-dead mutant of isoform GSK-3beta
additional information
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, glycerol, 20% v/v
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native hCDK13 from nuclear extracts of HeLa cells by Ion exchange chromatography and affinity chromatography, recombinant His-tagged chimeric mutant Ctk1/13 kinase from Saccharomyces cerevisiae strain FY23 by cation exchange chromatography and nickel affinity chromatography
recombinant His-tagged chimeric mutant Ctk1/12 kinase from Saccharomyces cerevisiae strain FY23 by cation exchange chromatographyand nickel affinity chromatography
two components: A and B
-
two kinases: CDTK1 and CDTK2
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cDNA copy of cdk9HA placed into a lentiviral vector where its transcription is driven by an EF1alpha promoter, overexpression in HFF cells
DG75 cells transfected with pcDNA3-K41M, pFLAG-CMV2-D173A or pFLAG-CMV2-D167N
-
hCDK12, recombinant expression of the His-tagged chimeric mutant Ctk1/12 kinase in Saccharomyces cerevisiae strain FY23
hCDK13, recombinant expression of the His-tagged chimeric mutant Ctk1/13 kinase in Saccharomyces cerevisiae strain FY23
overexpression of HA-tagged cdk9 in 293FT cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
IE2 and multiple cellular factors needed for viral RNA synthesis accumulate within the first 8 h at the viral transcriptosome, functional cdk activity is required for the specific recruitment of cdk7 and cdk9 during this time interval
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Cisek, L.J.; Corden, J.L.
Purification of protein kinases that phosphorylate the repetitive carboxyl-terminal domain of eukaryotic RNA polymerase II
Methods Enzymol.
200
301-325
1991
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Triticum aestivum
Manually annotated by BRENDA team
Lee, J.M.; Greenleaf, A.L.
A protein kinase that phosphorylates the C-terminal repeat domain of the largest subunit of RNA polymerase II
Proc. Natl. Acad. Sci. USA
86
3624-3628
1989
Saccharomyces cerevisiae, Drosophila sp. (in: flies), Homo sapiens, Drosophila sp. (in: flies) Kc
Manually annotated by BRENDA team
Stevens, A.; Maupin, M.K.
5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits a HeLa protein kinase that phosphorylates an RNA polymerase II-derived peptide
Biochem. Biophys. Res. Commun.
159
508-515
1989
Homo sapiens
Manually annotated by BRENDA team
Payne, J.M.; Dahmus, M.E.
Partial purification and characterization of two distinct protein kinases that differentially phosphorylate the carboxyl-terminal domain of RNA polymerase subunit IIa
J. Biol. Chem.
268
80-87
1993
Homo sapiens
Manually annotated by BRENDA team
Dvir, A.; Stein, L.Y.; Calore, B.L.; Dynan, W.S.
Purification and characterization of a template-associated protein kinase that phosphorylates RNA polymerase II
J. Biol. Chem.
268
10440-10447
1993
Homo sapiens
Manually annotated by BRENDA team
Medlin, J.E.; Uguen, P.; Taylor, A.; Bentley, D.L.; Murphy, S.
The C-terminal domain of pol II and a DRB-sensitive kinase are required for 3' processing of U2 snRNA
EMBO J.
22
925-934
2003
Homo sapiens
Manually annotated by BRENDA team
Palancade, B.; Bensaude, O.
Investigating RNA polymerase II carboxyl-terminal domain (CTD) phosphorylation
Eur. J. Biochem.
270
3859-3870
2003
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Schizosaccharomyces pombe
Manually annotated by BRENDA team
Tamrakar, S.; Kapasi, A.J.; Spector, D.H.
Human cytomegalovirus infection induces specific hyperphosphorylation of the carboxyl-terminal domain of the large subunit of RNA polymerase II that is associated with changes in the abundance, activity, and localization of cdk9 and cdk7
J. Virol.
79
15477-15493
2005
Homo sapiens
Manually annotated by BRENDA team
Jacobs, E.Y.; Ogiwara, I.; Weiner, A.M.
Role of the C-terminal domain of RNA polymerase II in U2 snRNA transcription and 3' processing
Mol. Cell. Biol.
24
846-855
2004
Homo sapiens
Manually annotated by BRENDA team
Hirose, Y.; Ohkuma, Y.
Phosphorylation of the C-terminal domain of RNA polymerase II plays central roles in the integrated events of eucaryotic gene expression
J. Biochem.
141
601-608
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Xenopus laevis
Manually annotated by BRENDA team
Kapasi, A.J.; Spector, D.H.
Inhibition of the cyclin-dependent kinases at the beginning of the human cytomegalovirus infection specifically alters the levels and localization of the RNA polymerase II carboxyl-terminal domain kinases cdk9 and cdk7 at the viral transcriptosome
J. Virol.
82
394-407
2007
Homo sapiens, Homo sapiens (P50613), Homo sapiens (P50750)
Manually annotated by BRENDA team
Bark-Jones, S.J.; Webb, H.M.; West, M.J.
EBV EBNA 2 stimulates CDK9-dependent transcription and RNA polymerase II phosphorylation on serine 5
Oncogene
25
1775-1785
2006
Homo sapiens
Manually annotated by BRENDA team
Heidemann, M.; Hintermair, C.; Vo, K.; Eick, D.
Dynamic phosphorylation patterns of RNA polymerase II CTD during transcription
Biochim. Biophys. Acta
1829
55-62
2013
Schizosaccharomyces pombe (O14098), Schizosaccharomyces pombe (Q12126), Schizosaccharomyces pombe (Q96WV9), Saccharomyces cerevisiae (P06242), Saccharomyces cerevisiae (P23293), Saccharomyces cerevisiae (P39073), Saccharomyces cerevisiae (Q03957), Homo sapiens (P49336), Homo sapiens (P50613), Homo sapiens (P50750), Homo sapiens (Q9H4B4), Drosophila melanogaster (Q24216), Drosophila melanogaster (Q9VT57), Schizosaccharomyces pombe ATCC 24843 (O14098), Schizosaccharomyces pombe ATCC 24843 (Q12126), Schizosaccharomyces pombe ATCC 24843 (Q96WV9)
Manually annotated by BRENDA team
Bartkowiak, B.; Liu, P.; Phatnani, H.P.; Fuda, N.J.; Cooper, J.J.; Price, D.H.; Adelman, K.; Lis, J.T.; Greenleaf, A.L.
CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1
Genes Dev.
24
2303-2316
2010
Homo sapiens (Q14004), Homo sapiens (Q9NYV4), Homo sapiens, Drosophila melanogaster (Q9VP22)
Manually annotated by BRENDA team
Tyagi, S.; Ochem, A.; Tyagi, M.
DNA-dependent protein kinase interacts functionally with the RNA polymerase II complex recruited at the human immunodeficiency virus (HIV) long terminal repeat and plays an important role in HIV gene expression
J. Gen. Virol.
92
1710-1720
2011
Homo sapiens
Manually annotated by BRENDA team
Di Vona, C.; Bezdan, D.; Islam, A.B.; Salichs, E.; Lopez-Bigas, N.; Ossowski, S.; de la Luna, S.
Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase
Mol. Cell
57
506-520
2015
Homo sapiens
Manually annotated by BRENDA team
Donnio, L.M.; Lagarou, A.; Sueur, G.; Mari, P.O.; Giglia-Mari, G.
CSB-dependent cyclin-dependent kinase 9 degradation and RNA polymerase II phosphorylation during transcription-coupled repair
Mol. Cell. Biol.
39
e00225-18
2019
Homo sapiens (P50750)
Manually annotated by BRENDA team
Nieto Moreno, N.; Villafanez, F.; Giono, L.E.; Cuenca, C.; Soria, G.; Munoz, M.J.; Kornblihtt, A.R.
GSK-3 is an RNA polymerase II phospho-CTD kinase
Nucleic Acids Res.
48
6068-6080
2020
Homo sapiens
Manually annotated by BRENDA team