Ser1619
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Home > Phosphorylation Site Page: > Ser1619  -  POLR2A (human)

Site Information
SPSysPtsPsYSPTS   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447616

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 41 ) , flow cytometry ( 1 , 8 ) , immunoprecipitation ( 2 , 3 , 6 , 8 , 9 , 17 , 18 , 22 , 25 , 26 , 29 , 30 , 31 , 33 , 36 , 39 , 41 ) , mass spectrometry ( 4 , 6 , 14 ) , mutation of modification site ( 17 , 40 , 41 ) , peptide sequencing ( 15 , 18 , 41 ) , phospho-antibody ( 1 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 16 , 17 , 20 , 21 , 22 , 26 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 , 44 , 46 , 47 , 48 , 49 , 50 , 51 , 54 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 20 , 22 , 29 , 30 , 31 , 32 , 34 , 35 , 37 , 41 , 42 , 43 , 46 , 47 , 48 , 54 )
Disease tissue studied:
breast cancer ( 3 , 35 , 36 , 47 ) , cervical cancer ( 10 , 18 ) , cervical adenocarcinoma ( 10 , 18 ) , colorectal cancer ( 5 , 8 , 9 , 20 , 26 , 43 ) , colorectal carcinoma ( 5 , 8 , 9 , 20 , 26 , 43 ) , T cell leukemia ( 1 ) , liver cancer ( 3 ) , lung cancer ( 30 , 31 , 54 ) , mesothelioma ( 30 ) , non-small cell lung cancer ( 31 ) , lymphoma ( 4 , 34 , 41 , 46 ) , Burkitt's lymphoma ( 4 , 34 , 41 ) , T cell lymphoma ( 1 ) , ovarian cancer ( 16 ) , prostate cancer ( 3 , 39 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 2 , 15 , 17 , 21 , 25 , 40 , 48 ) , A2780 (ovarian) ( 16 ) , A549 (pulmonary) ( 54 ) , B5/589 (epithelial) ( 9 ) , BHK-21 (fibroblast) ( 42 ) , CV ( 39 ) , dendritic cell ( 29 ) , GH4C1 (pituitary cell) ( 44 ) , HCT116 (intestinal) ( 5 , 8 , 9 , 20 , 26 , 43 ) , HEK293T (epithelial) ( 32 ) , HeLa (cervical) ( 6 , 17 , 21 , 22 , 31 , 33 , 37 , 42 , 47 , 50 , 51 ) , HeLa S3 (cervical) ( 10 , 18 ) , HepG2 (hepatic) ( 3 ) , HL60 (myeloid) ( 46 ) , Jurkat (T lymphocyte) ( 46 ) , LNCaP (prostate cell) ( 3 , 39 ) , lymphocyte ( 1 ) , mammary gland [HEXIM1 (human), genetic knockin] ( 35 ) , MCF-7 (breast cell) ( 3 , 35 , 36 , 47 ) , MES (pulmonary) ( 30 ) , NCI-H1299 (pulmonary) ( 31 ) , neuron ( 7 ) , prostate ( 39 ) , Raji (B lymphocyte) ( 4 , 34 , 41 ) , Sf21 ( 14 ) , SF9 ( 5 ) , T lymphocyte-blood ( 38 ) , T-ALL (T lymphocyte) ( 1 ) , U-937 (myeloid) ( 46 )

Upstream Regulation
Regulatory protein:
ASH2L (human) ( 9 ) , BRCA2 (human) ( 47 ) , C1QBP (human) ( 48 ) , CDK7 (human) ( 43 ) , EBNA2 (herpesvirus) ( 49 ) , NSD1 (human) ( 26 ) , p57Kip2 (human) ( 31 ) , p57Kip2 (mouse) ( 31 ) , PKN1 (human) ( 39 ) , POLR2A (human) ( 25 ) , RPAP2 (human) ( 17 ) , Tax (retrovirus) ( 42 ) , TLR8 (human) ( 29 )
Putative in vivo kinases:
CDK7 (human) ( 7 ) , CDK9 (human) ( 44 ) , DYRK1A (human) ( 13 )
Kinases, in vitro:
CDK12 (human) ( 5 , 11 , 14 ) , CDK13 (human) ( 5 , 11 ) , CDK7 (human) ( 31 , 33 , 34 , 51 , 56 ) , CDK9 (human) ( 5 , 11 , 14 , 33 , 55 , 57 ) , DYRK1A (human) ( 13 )
Putative upstream phosphatases:
SSU72 (human) ( 7 )
Phosphatases, in vitro:
CDC14A (human) ( 19 ) , CTDSP1 (human) ( 28 , 45 , 52 ) , RPAP2 (human) ( 17 ) , SSU72 (human) ( 23 )
Treatments:
10058-F4 ( 30 ) , alvocidib ( 5 , 10 , 12 , 46 ) , anti-TCR ( 38 ) , BAY_1143572 ( 1 ) , CdkI-83 ( 16 ) , dexamethasone ( 31 , 54 ) , dinaciclib ( 12 ) , DRB ( 44 , 50 ) , estradiol ( 36 ) , flavopiridol ( 4 ) , H2O2 ( 50 ) , IFN-gamma ( 51 ) , metribolone ( 39 ) , NAC ( 46 ) , Ro31-8220 ( 39 ) , SB203580 ( 50 ) , seliciclib ( 33 ) , siRNA ( 39 , 47 ) , SP600125 ( 50 ) , SU9516 ( 46 ) , TNF ( 54 ) , triptolide ( 37 ) , U0126 ( 50 ) , UV ( 50 )

Downstream Regulation
Effects of modification on POLR2A:
enzymatic activity, induced ( 44 , 45 ) , intracellular localization ( 30 ) , molecular association, regulation ( 2 , 18 , 44 , 45 ) , protein degradation ( 2 )
Effects of modification on biological processes:
apoptosis, induced ( 9 ) , transcription, altered ( 7 , 24 , 33 ) , transcription, induced ( 2 , 9 , 11 , 13 , 23 , 30 , 39 , 40 , 44 , 48 , 54 , 56 ) , transcription, inhibited ( 45 )
Induce interaction with:
CABIN1 (human) ( 18 ) , CTDSP1 (human) ( 45 ) , DNA ( 44 ) , HIRA (human) ( 18 ) , UBN1 (human) ( 18 )

References 

1

Narita T, et al. (2017) Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma. Blood 130, 1114-1124
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2

Martínez-Alonso M, Hengrung N, Fodor E (2016) RNA-Free and Ribonucleoprotein-Associated Influenza Virus Polymerases Directly Bind the Serine-5-Phosphorylated Carboxyl-Terminal Domain of Host RNA Polymerase II. J Virol 90, 6014-21
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3

Zhao Y, et al. (2016) Activation of P-TEFb by Androgen Receptor-Regulated Enhancer RNAs in Castration-Resistant Prostate Cancer. Cell Rep 15, 599-610
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4

Schüller R, et al. (2016) Heptad-Specific Phosphorylation of RNA Polymerase II CTD. Mol Cell 61, 305-14
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5

Greifenberg AK, et al. (2016) Structural and Functional Analysis of the Cdk13/Cyclin K Complex. Cell Rep 14, 320-31
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6

Jaenicke LA, et al. (2016) Ubiquitin-Dependent Turnover of MYC Antagonizes MYC/PAF1C Complex Accumulation to Drive Transcriptional Elongation. Mol Cell 61, 54-67
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7

Chen F, et al. (2015) Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development. Genes Dev 29, 2377-90
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8

Liang K, et al. (2015) Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis. Mol Cell 60, 435-45
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9

Mungamuri SK, et al. (2015) Ash2L enables P53-dependent apoptosis by favoring stable transcription pre-initiation complex formation on its pro-apoptotic target promoters. Oncogene 34, 2461-70
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10

Mayer A, et al. (2015) Native elongating transcript sequencing reveals human transcriptional activity at nucleotide resolution. Cell 161, 541-54
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11

Liang K, et al. (2015) Characterization of Human Cyclin-Dependent Kinase 12 (CDK12) and CDK13 Complexes in C-Terminal Domain Phosphorylation, Gene Transcription, and RNA Processing. Mol Cell Biol 35, 928-38
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12

Yeh YY, et al. (2015) Up-regulation of CDK9 kinase activity and Mcl-1 stability contributes to the acquired resistance to cyclin-dependent kinase inhibitors in leukemia. Oncotarget 6, 2667-79
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13

Di Vona C, et al. (2015) Chromatin-wide Profiling of DYRK1A Reveals a Role as a Gene-Specific RNA Polymerase II CTD Kinase. Mol Cell 57, 506-20
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14

Bösken CA, et al. (2014) The structure and substrate specificity of human Cdk12/Cyclin K. Nat Commun 5, 3505
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15

Schwartz JC, et al. (2012) FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2. Genes Dev 26, 2690-5
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16

Liu X, et al. (2012) In vitro antitumor mechanism of a novel cyclin-dependent kinase inhibitor CDKI-83. Invest New Drugs 30, 889-97
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17

Egloff S, et al. (2012) Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA genes. Mol Cell 45, 111-22
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18

Ray-Gallet D, et al. (2011) Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity. Mol Cell 44, 928-41
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19

Clemente-Blanco A, et al. (2011) Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription. Nat Cell Biol 13, 1450-6
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20

Blazek D, et al. (2011) The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev 25, 2158-72
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21

Preker P, et al. (2011) PROMoter uPstream Transcripts share characteristics with mRNAs and are produced upstream of all three major types of mammalian promoters. Nucleic Acids Res 39, 7179-93
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22

Lenasi T, Peterlin BM, Barboric M (2011) Cap-binding protein complex links pre-mRNA capping to transcription elongation and alternative splicing through positive transcription elongation factor b (P-TEFb). J Biol Chem 286, 22758-68
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23

Werner-Allen JW, et al. (2011) cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72. J Biol Chem 286, 5717-26
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24

Tran K, Gralla JD (2010) The TFIIB tip domain couples transcription initiation to events involved in RNA processing. J Biol Chem 285, 39580-7
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25

Mapendano CK, et al. (2010) Crosstalk between mRNA 3' end processing and transcription initiation. Mol Cell 40, 410-22
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26

Lucio-Eterovic AK, et al. (2010) Role for the nuclear receptor-binding SET domain protein 1 (NSD1) methyltransferase in coordinating lysine 36 methylation at histone 3 with RNA polymerase II function. Proc Natl Acad Sci U S A 107, 16952-7
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27

Egloff S, et al. (2010) The integrator complex recognizes a new double mark on the RNA polymerase II carboxyl-terminal domain. J Biol Chem 285, 20564-9
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28

Zhang M, et al. (2010) Structural and functional analysis of the phosphoryl transfer reaction mediated by the human small C-terminal domain phosphatase, Scp1. Protein Sci 19, 974-86
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29

Gringhuis SI, et al. (2010) HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat Immunol 11, 419-26
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30

Rahl PB, et al. (2010) c-Myc regulates transcriptional pause release. Cell 141, 432-45
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31

Ma Y, et al. (2010) CDKN1C negatively regulates RNA polymerase II C-terminal domain phosphorylation in an E2F1-dependent manner. J Biol Chem 285, 9813-22
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32

Wang Y, Fairley JA, Roberts SG (2010) Phosphorylation of TFIIB links transcription initiation and termination. Curr Biol 20, 548-53
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33

Boeing S, et al. (2010) RNA polymerase II C-terminal heptarepeat domain Ser-7 phosphorylation is established in a mediator-dependent fashion. J Biol Chem 285, 188-96
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34

Akhtar MS, et al. (2009) TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA polymerase II. Mol Cell 34, 387-93
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35

Ogba N, et al. (2008) HEXIM1 regulates 17beta-estradiol/estrogen receptor-alpha-mediated expression of cyclin D1 in mammary cells via modulation of P-TEFb. Cancer Res 68, 7015-24
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36

Bittencourt D, et al. (2008) Cotranscriptional splicing potentiates the mRNA production from a subset of estradiol-stimulated genes. Mol Cell Biol 28, 5811-24
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37

Leuenroth SJ, Crews CM (2008) Triptolide-induced transcriptional arrest is associated with changes in nuclear substructure. Cancer Res 68, 5257-66
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38

Schones DE, et al. (2008) Dynamic regulation of nucleosome positioning in the human genome. Cell 132, 887-98
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39

Metzger E, et al. (2008) Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation. Nat Cell Biol 10, 53-60
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40

Egloff S, et al. (2007) Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene expression. Science 318, 1777-9
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41

Chapman RD, et al. (2007) Transcribing RNA polymerase II is phosphorylated at CTD residue serine-7. Science 318, 1780-2
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42

Cho WK, et al. (2007) Modulation of the Brd4/P-TEFb interaction by the human T-lymphotropic virus type 1 tax protein. J Virol 81, 11179-86
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43

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44

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45

Zhang Y, et al. (2006) Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1. Mol Cell 24, 759-70
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46

Gao N, et al. (2006) The three-substituted indolinone cyclin-dependent kinase 2 inhibitor 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516) kills human leukemia cells via down-regulation of Mcl-1 through a transcriptional mechanism. Mol Pharmacol 70, 645-55
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47

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48

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49

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50

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51

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52

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53

Comer FI, Hart GW (2001) Reciprocity between O-GlcNAc and O-phosphate on the carboxyl terminal domain of RNA polymerase II. Biochemistry 40, 7845-52
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54

Nissen RM, Yamamoto KR (2000) The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 14, 2314-29
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55

Garber ME, et al. (2000) CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA. Mol Cell Biol 20, 6958-69
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56

Watanabe Y, et al. (2000) Modulation of TFIIH-associated kinase activity by complex formation and its relationship with CTD phosphorylation of RNA polymerase II. Genes Cells 5, 407-23
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57

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