ID RPB1_HUMAN Reviewed; 1970 AA. AC P24928; A6NN93; B9EH88; Q6NX41; DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-2009, sequence version 2. DT 27-MAR-2024, entry version 240. DE RecName: Full=DNA-directed RNA polymerase II subunit RPB1 {ECO:0000305}; DE Short=RNA polymerase II subunit B1; DE EC=2.7.7.6 {ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:30190596, ECO:0000269|PubMed:9852112}; DE AltName: Full=3'-5' exoribonuclease; DE EC=3.1.13.- {ECO:0000269|PubMed:8381534}; DE AltName: Full=DNA-directed RNA polymerase II subunit A; DE AltName: Full=DNA-directed RNA polymerase III largest subunit; DE AltName: Full=RNA-directed RNA polymerase II subunit RPB1; DE EC=2.7.7.48 {ECO:0000269|PubMed:23395899}; GN Name=POLR2A {ECO:0000312|HGNC:HGNC:9187}; Synonyms=POLR2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1542581; DOI=10.1093/nar/20.4.910; RA Wintzerith M., Acker J., Vicaire S., Vigneron M., Kedinger C.; RT "Complete sequence of the human RNA polymerase II largest subunit."; RL Nucleic Acids Res. 20:910-910(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7622068; DOI=10.1016/0378-1119(95)00081-g; RA Mita K., Tsuji H., Morimyo M., Takahashi E., Nenoi M., Ichimura S., RA Yamauchi M., Hongo E., Hayashi A.; RT "The human gene encoding the largest subunit of RNA polymerase II."; RL Gene 159:285-286(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=8381534; DOI=10.1073/pnas.90.3.843; RA Wang D., Hawley D.K.; RT "Identification of a 3'-->5' exonuclease activity associated with human RNA RT polymerase II."; RL Proc. Natl. Acad. Sci. U.S.A. 90:843-847(1993). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE RNA POLYMERASE II RP CORE-COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=9852112; DOI=10.1074/jbc.273.51.34444; RA Kershnar E., Wu S.-Y., Chiang C.-M.; RT "Immunoaffinity purification and functional characterization of human RT transcription factor IIH and RNA polymerase II from clonal cell lines that RT conditionally express epitope-tagged subunits of the multiprotein RT complexes."; RL J. Biol. Chem. 273:34444-34453(1998). RN [8] RP INTERACTION WITH SAFB. RX PubMed=9671816; DOI=10.1093/nar/26.15.3542; RA Nayler O., Straetling W., Bourquin J.-P., Stagljar I., Lindemann L., RA Jasper H., Hartmann A.M., Fackelmeyer F.O., Ullrich A., Stamm S.; RT "SAF-B couples transcription and pre-mRNA splicing to SAR/MAR elements."; RL Nucleic Acids Res. 26:3542-3549(1998). RN [9] RP IDENTIFICATION IN A COMPLEX WITH HTATSF1; CCNT1; NCL; SUPT5H AND CDK9. RX PubMed=10393184; DOI=10.1093/emboj/18.13.3688; RA Parada C.A., Roeder R.G.; RT "A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV- RT 1 transcription."; RL EMBO J. 18:3688-3701(1999). RN [10] RP INTERACTION WITH HTATSF1. RX PubMed=10454543; DOI=10.1128/mcb.19.9.5960; RA Kim J.B., Yamaguchi Y., Wada T., Handa H., Sharp P.A.; RT "Tat-SF1 protein associates with RAP30 and human SPT5 proteins."; RL Mol. Cell. Biol. 19:5960-5968(1999). RN [11] RP INTERACTION WITH FNBP3. RX PubMed=12381297; DOI=10.1016/s0022-2836(02)00968-3; RA Allen M., Friedler A., Schon O., Bycroft M.; RT "The structure of an FF domain from human HYPA/FBP11."; RL J. Mol. Biol. 323:411-416(2002). RN [12] RP INTERACTION WITH SYNCRIP. RX PubMed=12376575; DOI=10.1074/mcp.m200029-mcp200; RA Carty S.M., Greenleaf A.L.; RT "Hyperphosphorylated C-terminal repeat domain-associating proteins in the RT nuclear proteome link transcription to DNA/chromatin modification and RNA RT processing."; RL Mol. Cell. Proteomics 1:598-610(2002). RN [13] RP INTERACTION WITH DDX5. RX PubMed=12527917; DOI=10.1038/sj.onc.1206067; RA Rossow K.L., Janknecht R.; RT "Synergism between p68 RNA helicase and the transcriptional coactivators RT CBP and p300."; RL Oncogene 22:151-156(2003). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [15] RP INTERACTION WITH CCNT2. RX PubMed=15563843; DOI=10.1016/j.gene.2004.08.027; RA Kurosu T., Zhang F., Peterlin B.M.; RT "Transcriptional activity and substrate recognition of cyclin T2 from P- RT TEFb."; RL Gene 343:173-179(2004). RN [16] RP INTERACTION WITH CCNL2. RX PubMed=14684736; DOI=10.1074/jbc.m312895200; RA Yang L., Li N., Wang C., Yu Y., Yuan L., Zhang M., Cao X.; RT "Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in RT pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma RT cells."; RL J. Biol. Chem. 279:11639-11648(2004). RN [17] RP INTERACTION WITH MEN1. RX PubMed=14992727; DOI=10.1016/s1097-2765(04)00081-4; RA Hughes C.M., Rozenblatt-Rosen O., Milne T.A., Copeland T.D., Levine S.S., RA Lee J.C., Hayes D.N., Shanmugam K.S., Bhattacharjee A., Biondi C.A., RA Kay G.F., Hayward N.K., Hess J.L., Meyerson M.; RT "Menin associates with a trithorax family histone methyltransferase complex RT and with the hoxc8 locus."; RL Mol. Cell 13:587-597(2004). RN [18] RP INTERACTION WITH SFRS19. RX PubMed=15992770; DOI=10.1016/j.bbrc.2005.06.053; RA Katsarou M.E., Papakyriakou A., Katsaros N., Scorilas A.; RT "Expression of the C-terminal domain of novel human SR-A1 protein: RT interaction with the CTD domain of RNA polymerase II."; RL Biochem. Biophys. Res. Commun. 334:61-68(2005). RN [19] RP INTERACTION WITH SETD2. RX PubMed=16118227; DOI=10.1074/jbc.m504012200; RA Sun X.-J., Wei J., Wu X.-Y., Hu M., Wang L., Wang H.-H., Zhang Q.-H., RA Chen S.-J., Huang Q.-H., Chen Z.; RT "Identification and characterization of a novel human histone H3 lysine 36 RT specific methyltransferase."; RL J. Biol. Chem. 280:35261-35271(2005). RN [20] RP INTERACTION WITH SETD2. RX PubMed=16314571; DOI=10.1073/pnas.0506350102; RA Li M., Phatnani H.P., Guan Z., Sage H., Greenleaf A.L., Zhou P.; RT "Solution structure of the Set2-Rpb1 interacting domain of human Set2 and RT its interaction with the hyperphosphorylated C-terminal domain of Rpb1."; RL Proc. Natl. Acad. Sci. U.S.A. 102:17636-17641(2005). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1909 AND TYR-1923, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [22] RP INTERACTION WITH PAF1 IN PAF1/RNA POLYMERASE II. RC TISSUE=Fetal pancreas; RX PubMed=16491129; DOI=10.1038/sj.onc.1209353; RA Moniaux N., Nemos C., Schmied B.M., Chauhan S.C., Deb S., Morikane K., RA Choudhury A., Vanlith M., Sutherlin M., Sikela J.M., Hollingsworth M.A., RA Batra S.K.; RT "The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), RT localized on the 19q13 amplicon, is associated with tumorigenesis."; RL Oncogene 25:3247-3257(2006). RN [23] RP INTERACTION WITH SUPT6H, AND PHOSPHORYLATION. RX PubMed=17234882; DOI=10.1101/gad.1503107; RA Yoh S.M., Cho H., Pickle L., Evans R.M., Jones K.A.; RT "The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA RT splicing and export."; RL Genes Dev. 21:160-174(2007). RN [24] RP INTERACTION WITH CMTR1. RX PubMed=18533109; DOI=10.1016/j.bbrc.2008.05.137; RA Haline-Vaz T., Silva T.C.L., Zanchin N.I.T.; RT "The human interferon-regulated ISG95 protein interacts with RNA polymerase RT II and shows methyltransferase activity."; RL Biochem. Biophys. Res. Commun. 372:719-724(2008). RN [25] RP INTERACTION WITH SCAF8. RX PubMed=18550522; DOI=10.1074/jbc.m803540200; RA Becker R., Loll B., Meinhart A.; RT "Snapshots of the RNA processing factor SCAF8 bound to different RT phosphorylated forms of the carboxyl-terminal domain of RNA polymerase RT II."; RL J. Biol. Chem. 283:22659-22669(2008). RN [26] RP FUNCTION AS RNA-DIRECTED RNA POLYMERASE (MICROBIAL INFECTION). RX PubMed=18032511; DOI=10.1128/jvi.01758-07; RA Chang J., Nie X., Chang H.E., Han Z., Taylor J.; RT "Transcription of hepatitis delta virus RNA by RNA polymerase II."; RL J. Virol. 82:1118-1127(2008). RN [27] RP INTERACTION WITH SETD1A; SETD1B AND WDR82. RX PubMed=17998332; DOI=10.1128/mcb.01356-07; RA Lee J.H., Skalnik D.G.; RT "Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A RT Histone H3-Lys4 methyltransferase complex to transcription start sites of RT transcribed human genes."; RL Mol. Cell. Biol. 28:609-618(2008). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1849; TYR-1874; SER-1896; RP TYR-1909; SER-1913; SER-1920; TYR-1923; SER-1927 AND SER-1934, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [30] RP INTERACTION WITH ATF7IP. RX PubMed=19106100; DOI=10.1074/jbc.m807098200; RA Liu L., Ishihara K., Ichimura T., Fujita N., Hino S., Tomita S., RA Watanabe S., Saitoh N., Ito T., Nakao M.; RT "MCAF1/AM is involved in Sp1-mediated maintenance of cancer-associated RT telomerase activity."; RL J. Biol. Chem. 284:5165-5174(2009). RN [31] RP PHOSPHORYLATION BY CDK7. RX PubMed=19450536; DOI=10.1016/j.molcel.2009.04.016; RA Akhtar M.S., Heidemann M., Tietjen J.R., Zhang D.W., Chapman R.D., Eick D., RA Ansari A.Z.; RT "TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA RT polymerase II."; RL Mol. Cell 34:387-393(2009). RN [32] RP PHOSPHORYLATION BY CDK7 AND CDK9. RX PubMed=19667075; DOI=10.1128/mcb.00637-09; RA Glover-Cutter K., Larochelle S., Erickson B., Zhang C., Shokat K., RA Fisher R.P., Bentley D.L.; RT "TFIIH-associated Cdk7 kinase functions in phosphorylation of C-terminal RT domain Ser7 residues, promoter-proximal pausing, and termination by RNA RT polymerase II."; RL Mol. Cell. Biol. 29:5455-5464(2009). RN [33] RP PHOSPHORYLATION BY CDK7. RX PubMed=19136461; DOI=10.1093/nar/gkn1061; RA Lolli G.; RT "Binding to DNA of the RNA-polymerase II C-terminal domain allows RT discrimination between Cdk7 and Cdk9 phosphorylation."; RL Nucleic Acids Res. 37:1260-1268(2009). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1843; THR-1854; SER-1878; RP SER-1882; SER-1899; SER-1913; SER-1917; SER-1920; SER-1927; SER-1931 AND RP SER-1934, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [35] RP INTERACTION WITH RECQL5R. RX PubMed=20231364; DOI=10.1128/mcb.01583-09; RA Islam M.N., Fox D. III, Guo R., Enomoto T., Wang W.; RT "RecQL5 promotes genome stabilization through two parallel RT mechanisms--interacting with RNA polymerase II and acting as a helicase."; RL Mol. Cell. Biol. 30:2460-2472(2010). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [38] RP INTERACTION WITH U2AF2. RX PubMed=21536736; DOI=10.1101/gad.2038011; RA David C.J., Boyne A.R., Millhouse S.R., Manley J.L.; RT "The RNA polymerase II C-terminal domain promotes splicing activation RT through recruitment of a U2AF65-Prp19 complex."; RL Genes Dev. 25:972-983(2011). RN [39] RP PHOSPHORYLATION BY CDK9. RX PubMed=21127351; DOI=10.1074/jbc.m110.176628; RA Cojocaru M., Bouchard A., Cloutier P., Cooper J.J., Varzavand K., RA Price D.H., Coulombe B.; RT "Transcription factor IIS cooperates with the E3 ligase UBR5 to RT ubiquitinate the CDK9 subunit of the positive transcription elongation RT factor B."; RL J. Biol. Chem. 286:5012-5022(2011). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1917 AND SER-1931, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [41] RP METHYLATION AT ARG-1810 BY CARM1, AND MUTAGENESIS OF ARG-1810. RX PubMed=21454787; DOI=10.1126/science.1202663; RA Sims R.J. III, Rojas L.A., Beck D., Bonasio R., Schuller R., RA Drury W.J. III, Eick D., Reinberg D.; RT "The C-terminal domain of RNA polymerase II is modified by site-specific RT methylation."; RL Science 332:99-103(2011). RN [42] RP PHOSPHORYLATION, AND DOMAIN. RX PubMed=22137580; DOI=10.1016/j.molcel.2011.11.006; RA Egloff S., Zaborowska J., Laitem C., Kiss T., Murphy S.; RT "Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to RT snRNA genes."; RL Mol. Cell 45:111-122(2012). RN [43] RP UBIQUITINATION. RX PubMed=22466610; DOI=10.1038/ng.2229; RA Nakazawa Y., Sasaki K., Mitsutake N., Matsuse M., Shimada M., Nardo T., RA Takahashi Y., Ohyama K., Ito K., Mishima H., Nomura M., Kinoshita A., RA Ono S., Takenaka K., Masuyama R., Kudo T., Slor H., Utani A., Tateishi S., RA Yamashita S., Stefanini M., Lehmann A.R., Yoshiura K.I., Ogi T.; RT "Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase RT IIo processing in transcription-coupled nucleotide-excision repair."; RL Nat. Genet. 44:586-592(2012). RN [44] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN ICP22 (MICROBIAL RP INFECTION). RX PubMed=23029222; DOI=10.1371/journal.pone.0045749; RA Guo L., Wu W.J., Liu L.D., Wang L.C., Zhang Y., Wu L.Q., Guan Y., Li Q.H.; RT "Herpes simplex virus 1 ICP22 inhibits the transcription of viral gene RT promoters by binding to and blocking the recruitment of P-TEFb."; RL PLoS ONE 7:E45749-E45749(2012). RN [45] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23395899; DOI=10.1038/emboj.2013.18; RA Wagner S.D., Yakovchuk P., Gilman B., Ponicsan S.L., Drullinger L.F., RA Kugel J.F., Goodrich J.A.; RT "RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and RT destabilize a non-coding RNA."; RL EMBO J. 32:781-790(2013). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27; SER-217; SER-1850; RP SER-1864; SER-1868; SER-1878; SER-1882; THR-1885; SER-1899; SER-1913; RP SER-1920; SER-1927 AND SER-1934, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [47] RP FUNCTION, CATALYTIC ACTIVITY, ACETYLATION, AND MUTAGENESIS OF LYS-1838; RP LYS-1859; LYS-1866; LYS-1873; LYS-1887; LYS-1908; LYS-1922 AND LYS-1936. RX PubMed=24207025; DOI=10.1016/j.molcel.2013.10.009; RA Schroeder S., Herker E., Itzen F., He D., Thomas S., Gilchrist D.A., RA Kaehlcke K., Cho S., Pollard K.S., Capra J.A., Schnoelzer M., Cole P.A., RA Geyer M., Bruneau B.G., Adelman K., Ott M.; RT "Acetylation of RNA polymerase II regulates growth-factor-induced gene RT transcription in mammalian cells."; RL Mol. Cell 52:314-324(2013). RN [48] RP INTERACTION WITH SETX. RX PubMed=23149945; DOI=10.1128/mcb.01195-12; RA Yuce O., West S.C.; RT "Senataxin, defective in the neurodegenerative disorder ataxia with RT oculomotor apraxia 2, lies at the interface of transcription and the DNA RT damage response."; RL Mol. Cell. Biol. 33:406-417(2013). RN [49] RP INTERACTION WITH MCM3AP. RX PubMed=23652018; DOI=10.1038/ncomms2823; RA Singh S.K., Maeda K., Eid M.M., Almofty S.A., Ono M., Pham P., RA Goodman M.F., Sakaguchi N.; RT "GANP regulates recruitment of AID to immunoglobulin variable regions by RT modulating transcription and nucleosome occupancy."; RL Nat. Commun. 4:1830-1830(2013). RN [50] RP INTERACTION WITH PIH1D1. RX PubMed=24656813; DOI=10.1016/j.celrep.2014.03.013; RA Horejsi Z., Stach L., Flower T.G., Joshi D., Flynn H., Skehel J.M., RA O'Reilly N.J., Ogrodowicz R.W., Smerdon S.J., Boulton S.J.; RT "Phosphorylation-dependent PIH1D1 interactions define substrate specificity RT of the R2TP cochaperone complex."; RL Cell Rep. 7:19-26(2014). RN [51] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1874; SER-1906; TYR-1909 AND RP TYR-1923, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [52] RP METHYLATION, AND ACETYLATION. RX PubMed=26687004; DOI=10.7554/elife.11215; RA Dias J.D., Rito T., Torlai Triglia E., Kukalev A., Ferrai C., Chotalia M., RA Brookes E., Kimura H., Pombo A.; RT "Methylation of RNA polymerase II non-consensus Lysine residues marks early RT transcription in mammalian cells."; RL Elife 4:0-0(2015). RN [53] RP SUBCELLULAR LOCATION, ACETYLATION AT LYS-1866; LYS-1887; LYS-1922 AND RP LYS-1936, METHYLATION AT LYS-1859; LYS-1866; LYS-1873; LYS-1887; LYS-1922 RP AND LYS-1936, AND PHOSPHORYLATION AT THR-1840; SER-1843; SER-1845; RP SER-1849; SER-1850; SER-1857; TYR-1860; SER-1861; THR-1863; SER-1864; RP TYR-1867; THR-1870; TYR-1874; SER-1875; THR-1877; SER-1878; TYR-1881; RP SER-1882; TYR-1909; THR-1912; SER-1913; THR-1915; TYR-1916; SER-1917; RP THR-1919; SER-1920; TYR-1923; THR-1926; SER-1927; THR-1929; TYR-1930; RP SER-1931; THR-1933 AND SER-1934. RX PubMed=26566685; DOI=10.1080/21541264.2015.1114983; RA Voss K., Forne I., Descostes N., Hintermair C., Schueller R., Maqbool M.A., RA Heidemann M., Flatley A., Imhof A., Gut M., Gut I., Kremmer E., RA Andrau J.C., Eick D.; RT "Site-specific methylation and acetylation of lysine residues in the C- RT terminal domain (CTD) of RNA polymerase II."; RL Transcription 6:91-101(2015). RN [54] RP INTERACTION WITH FUS, AND FUNCTION. RX PubMed=26124092; DOI=10.1073/pnas.1506282112; RA Yu Y., Reed R.; RT "FUS functions in coupling transcription to splicing by mediating an RT interaction between RNAP II and U1 snRNP."; RL Proc. Natl. Acad. Sci. U.S.A. 112:8608-8613(2015). RN [55] RP INTERACTION WITH ZMYND8. RX PubMed=26655721; DOI=10.1074/jbc.m115.679985; RA Adhikary S., Sanyal S., Basu M., Sengupta I., Sen S., Srivastava D.K., RA Roy S., Das C.; RT "Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation RT Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive RT Genes by Putative Chromatin Reader ZMYND8."; RL J. Biol. Chem. 291:2664-2681(2016). RN [56] RP INTERACTION WITH TDRD3; PRMT5; SETX; SMN1 AND XRN2, METHYLATION AT ARG-1603 RP AND ARG-1810, AND MUTAGENESIS OF ARG-1810. RX PubMed=26700805; DOI=10.1038/nature16469; RA Yanling Zhao D., Gish G., Braunschweig U., Li Y., Ni Z., Schmitges F.W., RA Zhong G., Liu K., Li W., Moffat J., Vedadi M., Min J., Pawson T.J., RA Blencowe B.J., Greenblatt J.F.; RT "SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal RT domain control termination."; RL Nature 529:48-53(2016). RN [57] RP INTERACTION WITH SRPK2, SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=28076779; DOI=10.1016/j.celrep.2016.12.050; RA Sridhara S.C., Carvalho S., Grosso A.R., Gallego-Paez L.M., RA Carmo-Fonseca M., de Almeida S.F.; RT "Transcription Dynamics Prevent RNA-Mediated Genomic Instability through RT SRPK2-Dependent DDX23 Phosphorylation."; RL Cell Rep. 18:334-343(2017). RN [58] RP FUNCTION. RX PubMed=28108474; DOI=10.1101/gad.293837.116; RA Vo Ngoc L., Cassidy C.J., Huang C.Y., Duttke S.H., Kadonaga J.T.; RT "The human initiator is a distinct and abundant element that is precisely RT positioned in focused core promoters."; RL Genes Dev. 31:6-11(2017). RN [59] RP INTERACTION WITH UVSSA; ERCCC6 AND THE TFIIH COMPLEX, IDENTIFICATION BY RP MASS SPECTROMETRY, UBIQUITINATION AT LYS-1268, AND MUTAGENESIS OF LYS-1268. RX PubMed=32142649; DOI=10.1016/j.cell.2020.02.010; RA Nakazawa Y., Hara Y., Oka Y., Komine O., van den Heuvel D., Guo C., RA Daigaku Y., Isono M., He Y., Shimada M., Kato K., Jia N., Hashimoto S., RA Kotani Y., Miyoshi Y., Tanaka M., Sobue A., Mitsutake N., Suganami T., RA Masuda A., Ohno K., Nakada S., Mashimo T., Yamanaka K., Luijsterburg M.S., RA Ogi T.; RT "Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled RT Repair."; RL Cell 180:1228-1244(2020). RN [60] RP PHOSPHORYLATION, UBIQUITINATION AT LYS-1268, AND MUTAGENESIS OF LYS-1268. RX PubMed=32142654; DOI=10.1016/j.cell.2020.02.009; RA Tufegdzic Vidakovic A., Mitter R., Kelly G.P., Neumann M., Harreman M., RA Rodriguez-Martinez M., Herlihy A., Weems J.C., Boeing S., Encheva V., RA Gaul L., Milligan L., Tollervey D., Conaway R.C., Conaway J.W., RA Snijders A.P., Stewart A., Svejstrup J.Q.; RT "Regulation of the RNAPII Pool Is Integral to the DNA Damage Response."; RL Cell 180:1245-1261(2020). RN [61] RP UBIQUITINATION. RX PubMed=35633597; DOI=10.1016/j.dnarep.2022.103343; RA Herlihy A.E., Boeing S., Weems J.C., Walker J., Dirac-Svejstrup A.B., RA Lehner M.H., Conaway R.C., Conaway J.W., Svejstrup J.Q.; RT "UBAP2/UBAP2L regulate UV-induced ubiquitylation of RNA polymerase II and RT are the human orthologues of yeast Def1."; RL DNA Repair 115:103343-103343(2022). RN [62] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1796-1803 IN COMPLEX WITH CTDSP1, RP AND DEPHOSPHORYLATION. RX PubMed=17157258; DOI=10.1016/j.molcel.2006.10.027; RA Zhang Y., Kim Y., Genoud N., Gao J., Kelly J.W., Pfaff S.L., Gill G.N., RA Dixon J.E., Noel J.P.; RT "Determinants for dephosphorylation of the RNA polymerase II C-terminal RT domain by Scp1."; RL Mol. Cell 24:759-770(2006). RN [63] RP STRUCTURE BY ELECTRON MICROSCOPY IN COMPLEX WITH RECQL5, INTERACTION WITH RP RECQL5 AND TCEA1, SUBUNIT, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23748380; DOI=10.1038/nsmb.2596; RA Kassube S.A., Jinek M., Fang J., Tsutakawa S., Nogales E.; RT "Structural mimicry in transcription regulation of human RNA polymerase II RT by the DNA helicase RECQL5."; RL Nat. Struct. Mol. Biol. 20:892-899(2013). RN [64] RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) IN COMPLEX WITH ZN(2+) RP AND MG(2+), FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBUNIT. RX PubMed=27193682; DOI=10.1038/nature17970; RA He Y., Yan C., Fang J., Inouye C., Tjian R., Ivanov I., Nogales E.; RT "Near-atomic resolution visualization of human transcription promoter RT opening."; RL Nature 533:359-365(2016). RN [65] RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS), FUNCTION, CATALYTIC RP ACTIVITY, AND SUBUNIT. RX PubMed=30190596; DOI=10.1038/s41594-018-0118-5; RA Jishage M., Yu X., Shi Y., Ganesan S.J., Chen W.Y., Sali A., Chait B.T., RA Asturias F.J., Roeder R.G.; RT "Architecture of Pol II(G) and molecular mechanism of transcription RT regulation by Gdown1."; RL Nat. Struct. Mol. Biol. 25:859-867(2018). RN [66] RP INVOLVEMENT IN NEDHIB, VARIANTS NEDHIB LEU-371; THR-457; SER-531; TYR-669 RP DEL; 700-GLN--ASN-1970 DEL; 735-GLN--ASN-1970 DEL; MET-736; SER-755 DEL; RP THR-769; THR-848; HIS-1109; PRO-1124; LYS-1125 DEL; SER-1251 AND HIS-1603, RP CHARACTERIZATION OF VARIANTS NEDHIB THR-457; SER-531; MET-736; SER-755 DEL; RP PRO-1124; SER-1251 AND HIS-1603, AND MUTAGENESIS OF 812-LYS--ASN-1970. RX PubMed=31353023; DOI=10.1016/j.ajhg.2019.06.016; RA Haijes H.A., Koster M.J.E., Rehmann H., Li D., Hakonarson H., Cappuccio G., RA Hancarova M., Lehalle D., Reardon W., Schaefer G.B., Lehman A., RA van de Laar I.M.B.H., Tesselaar C.D., Turner C., Goldenberg A., Patrier S., RA Thevenon J., Pinelli M., Brunetti-Pierri N., Prchalova D., Havlovicova M., RA Vlckova M., Sedlacek Z., Lopez E., Ragoussis V., Pagnamenta A.T., Kini U., RA Vos H.R., van Es R.M., van Schaik R.F.M.A., van Essen T.A.J., Kibaek M., RA Taylor J.C., Sullivan J., Shashi V., Petrovski S., Fagerberg C., RA Martin D.M., van Gassen K.L.I., Pfundt R., Falk M.J., McCormick E.M., RA Timmers H.T.M., van Hasselt P.M.; RT "De Novo Heterozygous POLR2A Variants Cause a Neurodevelopmental Syndrome RT with Profound Infantile-Onset Hypotonia."; RL Am. J. Hum. Genet. 105:283-301(2019). CC -!- FUNCTION: Catalytic core component of RNA polymerase II (Pol II), a CC DNA-dependent RNA polymerase which synthesizes mRNA precursors and many CC functional non-coding RNAs using the four ribonucleoside triphosphates CC as substrates (PubMed:9852112, PubMed:23748380, PubMed:27193682, CC PubMed:30190596) (By similarity). Pol II-mediated transcription cycle CC proceeds through transcription initiation, transcription elongation and CC transcription termination stages. During transcription initiation, Pol CC II pre-initiation complex (PIC) is recruited to DNA promoters, with CC focused-type promoters containing either the initiator (Inr) element, CC or the TATA-box found in cell-type specific genes and dispersed-type CC promoters that often contain hypomethylated CpG islands usually found CC in housekeeping genes. Once the polymerase has escaped from the CC promoter it enters the elongation phase during which RNA is actively CC polymerized, based on complementarity with the template DNA strand. CC Transcription termination involves the release of the RNA transcript CC and polymerase from the DNA (PubMed:9852112, PubMed:23748380, CC PubMed:27193682, PubMed:30190596, PubMed:28108474) (By similarity). CC Forms Pol II active center together with the second largest subunit CC POLR2B/RPB2. Appends one nucleotide at a time to the 3' end of the CC nascent RNA, with POLR2A/RPB1 most likely contributing a Mg(2+)- CC coordinating DxDGD motif, and POLR2B/RPB2 participating in the CC coordination of a second Mg(2+) ion and providing lysine residues CC believed to facilitate Watson-Crick base pairing between the incoming CC nucleotide and template base. Typically, Mg(2+) ions direct a 5' CC nucleoside triphosphate to form a phosphodiester bond with the 3' CC hydroxyl of the preceding nucleotide of the nascent RNA, with the CC elimination of pyrophosphate. The reversible pyrophosphorolysis can CC occur at high pyrophosphate concentrations (PubMed:9852112, CC PubMed:30190596, PubMed:8381534) (By similarity). Can proofread the CC nascent RNA transcript by means of a 3' -> 5' exonuclease activity. If CC a ribonucleotide is mis-incorporated, backtracks along the template DNA CC and cleaves the phosphodiester bond releasing the mis-incorporated 5'- CC ribonucleotide (PubMed:8381534) (By similarity). Through its unique C- CC terminal domain (CTD, 52 heptapeptide tandem repeats) serves as a CC platform for assembly of factors that regulate transcription CC initiation, elongation and termination. CTD phosphorylation on Ser-5 CC mediates Pol II promoter escape, whereas phosphorylation on Ser-2 is CC required for Pol II pause release during transcription elongation and CC further pre-mRNA processing. Additionally, the regulation of gene CC expression levels depends on the balance between methylation and CC acetylation levels of the CTD-lysines. Initiation or early elongation CC steps of transcription of growth-factor-induced immediate early genes CC are regulated by the acetylation status of the CTD. Methylation and CC dimethylation have a repressive effect on target genes expression. CC Cooperates with mRNA splicing machinery in co-transcriptional 5'-end CC capping and co-transcriptional splicing of pre-mRNA (PubMed:24207025, CC PubMed:26124092) (By similarity). {ECO:0000250|UniProtKB:G3MZY8, CC ECO:0000250|UniProtKB:P08775, ECO:0000269|PubMed:23748380, CC ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26124092, CC ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:28108474, CC ECO:0000269|PubMed:30190596, ECO:0000269|PubMed:8381534, CC ECO:0000269|PubMed:9852112}. CC -!- FUNCTION: RNA-dependent RNA polymerase that catalyzes the extension of CC a non-coding RNA (ncRNA) at the 3'-end using the four ribonucleoside CC triphosphates as substrates. An internal ncRNA sequence near the 3'-end CC serves as a template in a single-round Pol II-mediated RNA CC polymerization reaction. May decrease the stability of ncRNAs that CC repress Pol II-mediated gene transcription. CC {ECO:0000269|PubMed:23395899}. CC -!- FUNCTION: (Microbial infection) Acts as an RNA-dependent RNA polymerase CC when associated with small delta antigen of Hepatitis delta virus, CC acting both as a replicase and transcriptase for the viral RNA circular CC genome. {ECO:0000269|PubMed:18032511}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA- CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; CC EC=2.7.7.6; Evidence={ECO:0000269|PubMed:23748380, CC ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:30190596, CC ECO:0000269|PubMed:9852112}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21249; CC Evidence={ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:24207025, CC ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:30190596, CC ECO:0000269|PubMed:9852112}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21250; CC Evidence={ECO:0000305|PubMed:8381534}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA- CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; CC EC=2.7.7.48; Evidence={ECO:0000269|PubMed:23395899}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21249; CC Evidence={ECO:0000269|PubMed:23395899}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 3'-end ribonucleotidyl-ribonucleotide-RNA + H2O = a 3'-end CC ribonucleotide-RNA + a ribonucleoside 5'-phosphate + H(+); CC Xref=Rhea:RHEA:77763, Rhea:RHEA-COMP:17428, Rhea:RHEA-COMP:18982, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58043, CC ChEBI:CHEBI:74896, ChEBI:CHEBI:197502; CC Evidence={ECO:0000269|PubMed:8381534}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77764; CC Evidence={ECO:0000269|PubMed:8381534}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:27193682}; CC Note=Two Mg(2+) ions are coordinated by both the catalytic residues and CC the nucleic acid substrate to enhance substrate recognition and CC catalytic efficiency. {ECO:0000269|PubMed:27193682}; CC -!- ACTIVITY REGULATION: Pol II enzymatic activities are inhibited by CC alpha-amanitin. 3'->5' exonuclease activity is stimulated by CC TCEA1/TFIIS, whereas pyrophosphorolysis is enhanced by TFIIF. CC {ECO:0000269|PubMed:8381534}. CC -!- SUBUNIT: Component of the RNA polymerase II (Pol II) core complex CC consisting of 12 subunits: a ten-subunit catalytic core composed of CC POLR2A/RPB1, POLR2B/RPB2, POLR2C/RPB3, POLR2I/RPB9, POLR2J/RPB11, CC POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and CC POLR2L/RPABC5 and a mobile stalk composed of two subunits POLR2D/RPB4 CC and POLR2G/RPB7, protruding from the core and functioning primarily in CC transcription initiation. Part of Pol II(G) complex, in which Pol II CC core associates with an additional subunit POLR2M; unlike conventional CC Pol II, Pol II(G) functions as a transcriptional repressor. Part of CC TBP-based Pol II pre-initiation complex (PIC), in which Pol II core CC assembles with general transcription factors and other specific CC initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, CC ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and CC TBP; this large multi-subunit PIC complex mediates DNA unwinding and CC targets Pol II core to the transcription start site where the first CC phosphodiester bond forms (PubMed:9852112, PubMed:27193682, CC PubMed:30190596). Component of a complex which is at least composed of CC HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, Pol II, CC SUPT5H, and NCL/nucleolin (PubMed:10454543, PubMed:10393184, CC PubMed:17234882). The large PER complex involved in the repression of CC transcriptional termination is composed of at least PER2, CDK9, DDX5, CC DHX9, NCBP1 and POLR2A (active) (PubMed:28076779). Interacts (via the CC C-terminal domain (CTD)) with U2AF2; recruits PRPF19 and the Prp19 CC complex to the pre-mRNA and may couple transcription to pre-mRNA CC splicing (PubMed:21536736). Interacts (via the C-terminal domain (CTD)) CC with SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes CC (PubMed:26700805). Interacts via the phosphorylated C-terminal domain CC with WDR82 and with SETD1A and SETD1B only in the presence of WDR82 CC (PubMed:17998332). When phosphorylated at 'Ser-5', interacts with MEN1; CC the unphosphorylated form, or phosphorylated at 'Ser-2' does not CC interact (PubMed:14992727). When phosphorylated at 'Ser-5', interacts CC with ZMYND8; the form phosphorylated at 'Ser-2' does not interact CC (PubMed:26700805). When phosphorylated at 'Ser-2', interacts with CC SUPT6H (via SH2 domain) (PubMed:17234882). Interacts with RECQL5 and CC TCEA1; binding of RECQL5 prevents TCEA1 binding (PubMed:20231364, CC PubMed:23748380). The phosphorylated C-terminal domain interacts with CC FNBP3 (PubMed:12381297). The phosphorylated C-terminal domain interacts CC with SYNCRIP (PubMed:12376575). Interacts with ATF7IP CC (PubMed:19106100). Interacts with DDX5 (PubMed:12527917). Interacts CC with WWP2 (By similarity). Interacts with SETX (PubMed:23149945, CC PubMed:26700805). Interacts (phosphorylated) with PIH1D1 CC (PubMed:24656813). Interacts (via the C-terminal domain (CTD)) with CC TDRD3 (PubMed:26700805). Interacts with PRMT5 (PubMed:26700805). CC Interacts with XRN2 (PubMed:26700805). Interacts with SAFB/SAFB1 CC (PubMed:9671816). Interacts with CCNL1 (Probable). Interacts with CCNL2 CC (PubMed:14684736). Interacts with MYO1C (By similarity). Interacts with CC PAF1 (PubMed:16491129). Interacts with SFRS19 (PubMed:15992770). CC Interacts (via C-terminus) with CMTR1 (PubMed:18533109). Interacts (via CC C-terminus) with CTDSP1 (PubMed:17157258). Interacts (via C-terminus) CC with SCAF8 (PubMed:18550522). Interacts (via the C-terminal domain CC (CTD)) with CCNT2 (PubMed:15563843). Interacts with FUS CC (PubMed:26124092). Interacts with MCM3AP isoform GANP CC (PubMed:23652018). Interacts with kinase SRPK2; the interaction occurs CC during the co-transcriptional formation of inappropriate R-loops CC (PubMed:28076779). Interacts with SETD2 (PubMed:16118227, CC PubMed:16314571). Interacts with UVSSA (PubMed:32142649). Interacts CC with ERCC6 (PubMed:32142649). Interacts with the TFIIH complex CC (PubMed:32142649). {ECO:0000250|UniProtKB:P08775, CC ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10454543, CC ECO:0000269|PubMed:12376575, ECO:0000269|PubMed:12381297, CC ECO:0000269|PubMed:12527917, ECO:0000269|PubMed:14684736, CC ECO:0000269|PubMed:14992727, ECO:0000269|PubMed:15563843, CC ECO:0000269|PubMed:15992770, ECO:0000269|PubMed:16118227, CC ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:16491129, CC ECO:0000269|PubMed:17157258, ECO:0000269|PubMed:17234882, CC ECO:0000269|PubMed:17998332, ECO:0000269|PubMed:18533109, CC ECO:0000269|PubMed:18550522, ECO:0000269|PubMed:19106100, CC ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:21536736, CC ECO:0000269|PubMed:23149945, ECO:0000269|PubMed:23652018, CC ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:24656813, CC ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:26700805, CC ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:28076779, CC ECO:0000269|PubMed:30190596, ECO:0000269|PubMed:32142649, CC ECO:0000269|PubMed:9671816, ECO:0000269|PubMed:9852112, ECO:0000305}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1 CC protein ICP22; this interaction causes loss of CTD 'Ser-2' CC phosphorylation from Pol II engaged in transcription (PubMed:23029222). CC {ECO:0000269|PubMed:23029222}. CC -!- INTERACTION: CC P24928; Q9NWX5: ASB6; NbExp=4; IntAct=EBI-295301, EBI-6425205; CC P24928; Q6P1J9: CDC73; NbExp=6; IntAct=EBI-295301, EBI-930143; CC P24928; P17844: DDX5; NbExp=3; IntAct=EBI-295301, EBI-351962; CC P24928; Q9UPY3-1: DICER1; NbExp=3; IntAct=EBI-295301, EBI-15569571; CC P24928; Q8N108-16: MIER1; NbExp=3; IntAct=EBI-295301, EBI-25830642; CC P24928; Q8N7H5: PAF1; NbExp=5; IntAct=EBI-295301, EBI-2607770; CC P24928; O14744: PRMT5; NbExp=6; IntAct=EBI-295301, EBI-351098; CC P24928; O94762-1: RECQL5; NbExp=8; IntAct=EBI-295301, EBI-15710057; CC P24928; Q96P16: RPRD1A; NbExp=3; IntAct=EBI-295301, EBI-1053506; CC P24928; Q9NQG5: RPRD1B; NbExp=10; IntAct=EBI-295301, EBI-747925; CC P24928; Q7Z333: SETX; NbExp=7; IntAct=EBI-295301, EBI-1220123; CC P24928; Q16637: SMN2; NbExp=12; IntAct=EBI-295301, EBI-395421; CC P24928; Q96H20: SNF8; NbExp=2; IntAct=EBI-295301, EBI-747719; CC P24928; O00267: SUPT5H; NbExp=5; IntAct=EBI-295301, EBI-710464; CC P24928; P23193: TCEA1; NbExp=5; IntAct=EBI-295301, EBI-2608271; CC P24928; Q9H7E2: TDRD3; NbExp=6; IntAct=EBI-295301, EBI-3938232; CC P24928; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-295301, EBI-17438286; CC P24928; Q9HCS7: XAB2; NbExp=2; IntAct=EBI-295301, EBI-295232; CC P24928; Q98140: ORF24; Xeno; NbExp=2; IntAct=EBI-295301, EBI-14033488; CC P24928; L8B1Q7: ORF6; Xeno; NbExp=3; IntAct=EBI-295301, EBI-11712334; CC P24928; Q67020: PA; Xeno; NbExp=2; IntAct=EBI-295301, EBI-11514477; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26566685, CC ECO:0000269|PubMed:28076779, ECO:0000269|PubMed:9852112}. Cytoplasm CC {ECO:0000269|PubMed:26566685}. Chromosome CC {ECO:0000269|PubMed:28076779}. Note=Hypophosphorylated form is mainly CC found in the cytoplasm, while the hyperphosphorylated and active form CC is nuclear (PubMed:26566685). Co-localizes with kinase SRPK2 and CC helicase DDX23 at chromatin loci where unscheduled R-loops form CC (PubMed:28076779). {ECO:0000269|PubMed:26566685, CC ECO:0000269|PubMed:28076779}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P24928-1; Sequence=Displayed; CC Name=2; CC IsoId=P24928-2; Sequence=VSP_056184, VSP_056185; CC -!- DOMAIN: The C-terminal domain (CTD) serves as a platform for assembly CC of factors that regulate transcription initiation, elongation, CC termination and mRNA processing. {ECO:0000303|PubMed:22137580}. CC -!- DOMAIN: The trigger loop allows entry of NTPs into the active site, CC switching between an open and closed state with each NTP addition CC cycle. {ECO:0000250|UniProtKB:G3MZY8}. CC -!- DOMAIN: The bridging helix crosses the cleft near the catalytic site CC and is thought to promote polymerase translocation by acting as a CC ratchet that moves the DNA-RNA hybrid through the active site. CC {ECO:0000250|UniProtKB:G3MZY8}. CC -!- PTM: The tandem heptapeptide repeats in the C-terminal domain (CTD) can CC be highly phosphorylated (PubMed:28076779). The phosphorylation CC activates Pol II. Phosphorylation occurs mainly at residues 'Ser-2' and CC 'Ser-5' of the heptapeptide repeat and is mediated, at least, by CDK7 CC and CDK9. CDK7 phosphorylation of POLR2A associated with DNA promotes CC transcription initiation by triggering dissociation from DNA. CC Phosphorylation also takes place at 'Ser-7' of the heptapeptide repeat, CC which is required for efficient transcription of snRNA genes and CC processing of the transcripts. The phosphorylation state is believed to CC result from the balanced action of site-specific CTD kinases and CC phosphatases, and a 'CTD code' that specifies the position of Pol II CC within the transcription cycle has been proposed. Dephosphorylated by CC the protein phosphatase CTDSP1. Dephosphorylated at 'Ser-2' following CC UV irradiation. {ECO:0000269|PubMed:17157258, CC ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:19136461, CC ECO:0000269|PubMed:19450536, ECO:0000269|PubMed:19667075, CC ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:22137580, CC ECO:0000269|PubMed:26566685, ECO:0000269|PubMed:28076779, CC ECO:0000269|PubMed:32142654}. CC -!- PTM: Among tandem heptapeptide repeats of the C-terminal domain (CTD) CC some do not match the Y-S-P-T-S-P-S consensus, the seventh serine CC residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non- CC consensus heptapeptide repeats can be alternatively acetylated, CC methylated and dimethylated. EP300 is one of the enzyme able to CC acetylate 'Lys-7'. Acetylation at 'Lys-7' of non-consensus heptapeptide CC repeats is associated with 'Ser-2' phosphorylation and active CC transcription. Regulates initiation or early elongation steps of CC transcription specially for inducible genes. CC {ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26566685, CC ECO:0000269|PubMed:26687004}. CC -!- PTM: Methylated at Arg-1810 prior to transcription initiation when the CC CTD is hypophosphorylated, phosphorylation at Ser-1805 and Ser-1808 CC preventing this methylation. Symmetrically or asymmetrically CC dimethylated at Arg-1810 by PRMT5 and CARM1 respectively. Symmetric or CC asymmetric dimethylation modulates interactions with CTD-binding CC proteins like SMN1/SMN2 and TDRD3. SMN1/SMN2 interacts preferentially CC with the symmetrically dimethylated form while TDRD3 interacts with the CC asymmetric form. Through the recruitment of SMN1/SMN2, symmetric CC dimethylation is required for resolving RNA-DNA hybrids created by RNA CC polymerase II, that form R-loop in transcription terminal regions, an CC important step in proper transcription termination. CTD dimethylation CC may also facilitate the expression of select RNAs. Among tandem CC heptapeptide repeats of the C-terminal domain (CTD) some do not match CC the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being CC replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide CC repeats can be alternatively acetylated, methylated, dimethylated and CC trimethylated. Methylation occurs in the earliest transcription stages CC and precedes or is concomitant to 'Ser-5' and 'Ser-7' phosphorylation. CC Dimethylation and trimehtylation at 'Lys-7' of non-consensus CC heptapeptide repeats are exclusively associated with phosphorylated CC CTD. {ECO:0000250|UniProtKB:P08775, ECO:0000269|PubMed:26566685, CC ECO:0000269|PubMed:26687004, ECO:0000269|PubMed:26700805}. CC -!- PTM: Ubiquitinated by WWP2 leading to proteasomal degradation (By CC similarity). Following transcription stress, the elongating form of RNA CC polymerase II (RNA pol IIo) is ubiquitinated by NEDD4 on Lys-1268 at CC DNA damage sites without leading to degradation: ubiquitination CC promotes RNA pol IIo backtracking to allow access by the transcription- CC coupled nucleotide excision repair (TC-NER) machinery (PubMed:32142649, CC PubMed:32142654, PubMed:22466610, PubMed:35633597). At stalled RNA pol CC II where TC-NER has failed, RBX1-mediated polybiquitination at Lys-1268 CC may lead to proteasome-mediated degradation in a UBAP2- and UBAP2L- CC dependent manner; presumably to halt global transcription and enable CC 'last resort' DNA repair pathways (PubMed:35633597). CC {ECO:0000250|UniProtKB:P08775, ECO:0000269|PubMed:22466610, CC ECO:0000269|PubMed:32142649, ECO:0000269|PubMed:32142654, CC ECO:0000269|PubMed:35633597}. CC -!- DISEASE: Neurodevelopmental disorder with hypotonia and variable CC intellectual and behavioral abnormalities (NEDHIB) [MIM:618603]: An CC autosomal dominant neurodevelopmental disorder characterized by CC profound infantile-onset hypotonia, developmental delay with poor CC speech, delayed walking, and impaired intellectual development. CC Additional variable features include feeding difficulties, dysmorphic CC features, and visual defects. {ECO:0000269|PubMed:31353023}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the RNA polymerase beta' chain family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X63564; CAA45125.1; -; mRNA. DR EMBL; X74874; CAA52862.1; -; Genomic_DNA. DR EMBL; X74873; CAA52862.1; JOINED; Genomic_DNA. DR EMBL; X74872; CAA52862.1; JOINED; Genomic_DNA. DR EMBL; X74871; CAA52862.1; JOINED; Genomic_DNA. DR EMBL; X74870; CAA52862.1; JOINED; Genomic_DNA. DR EMBL; AC113189; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90181.1; -; Genomic_DNA. DR EMBL; BC067295; AAH67295.1; -; mRNA. DR EMBL; BC137231; AAI37232.1; -; mRNA. DR PIR; I38186; I38186. DR PIR; S21054; S21054. DR RefSeq; NP_000928.1; NM_000937.4. DR PDB; 2GHQ; X-ray; 2.05 A; C/D=1795-1803. DR PDB; 2GHT; X-ray; 1.80 A; C/D=1796-1803. DR PDB; 2LTO; NMR; -; B=1804-1816. DR PDB; 3D9K; X-ray; 2.20 A; Y/Z=1790-1803. DR PDB; 3D9L; X-ray; 2.20 A; Y/Z=1790-1803. DR PDB; 3D9M; X-ray; 1.75 A; Y/Z=1790-1803. DR PDB; 3D9N; X-ray; 1.60 A; Y/Z=1790-1803. DR PDB; 3D9O; X-ray; 2.00 A; Z=1790-1803. DR PDB; 3D9P; X-ray; 2.10 A; Y/Z=1790-1803. DR PDB; 4JXT; X-ray; 1.90 A; B=1787-1805. DR PDB; 5IY6; EM; 7.20 A; A=1-1970. DR PDB; 5IY7; EM; 8.60 A; A=1-1970. DR PDB; 5IY8; EM; 7.90 A; A=1-1970. DR PDB; 5IY9; EM; 6.30 A; A=1-1970. DR PDB; 5IYA; EM; 5.40 A; A=1-1970. DR PDB; 5IYB; EM; 3.90 A; A=1-1970. DR PDB; 5IYC; EM; 3.90 A; A=1-1970. DR PDB; 5IYD; EM; 3.90 A; A=1-1970. DR PDB; 5M3H; X-ray; 2.50 A; X/Y=1713-1740. DR PDB; 5M3J; X-ray; 3.50 A; X=1713-1740. DR PDB; 6DRD; EM; 3.90 A; A=1-1970. DR PDB; 6F5P; X-ray; 4.14 A; G=1713-1740. DR PDB; 6G0R; X-ray; 1.25 A; C=772-782. DR PDB; 6IC8; X-ray; 1.93 A; C/D=1790-1803. DR PDB; 6IC9; X-ray; 1.75 A; C/D=1790-1803. DR PDB; 6O9L; EM; 7.20 A; A=1-1970. DR PDB; 6Q5Y; X-ray; 2.85 A; E/F=1790-1803. DR PDB; 6XKB; X-ray; 1.60 A; F/G/I/J/K=1786-1805. DR PDB; 6XRE; EM; 4.60 A; A=1-1970. DR PDB; 7EGB; EM; 3.30 A; o=1-1970. DR PDB; 7EGC; EM; 3.90 A; o=1-1970. DR PDB; 7LBM; EM; 4.80 A; A=1-1970. DR PDB; 7YCX; EM; 4.18 A; 1=1-1970. DR PDB; 7Z1K; X-ray; 1.55 A; B=1788-1803. DR PDB; 7Z42; X-ray; 2.42 A; G/I/X/Y=1713-1740. DR PDBsum; 2GHQ; -. DR PDBsum; 2GHT; -. DR PDBsum; 2LTO; -. DR PDBsum; 3D9K; -. DR PDBsum; 3D9L; -. DR PDBsum; 3D9M; -. DR PDBsum; 3D9N; -. DR PDBsum; 3D9O; -. DR PDBsum; 3D9P; -. DR PDBsum; 4JXT; -. DR PDBsum; 5IY6; -. DR PDBsum; 5IY7; -. DR PDBsum; 5IY8; -. DR PDBsum; 5IY9; -. DR PDBsum; 5IYA; -. DR PDBsum; 5IYB; -. DR PDBsum; 5IYC; -. DR PDBsum; 5IYD; -. DR PDBsum; 5M3H; -. DR PDBsum; 5M3J; -. DR PDBsum; 6DRD; -. DR PDBsum; 6F5P; -. DR PDBsum; 6G0R; -. DR PDBsum; 6IC8; -. DR PDBsum; 6IC9; -. DR PDBsum; 6O9L; -. DR PDBsum; 6Q5Y; -. DR PDBsum; 6XKB; -. DR PDBsum; 6XRE; -. DR PDBsum; 7EGB; -. DR PDBsum; 7EGC; -. DR PDBsum; 7LBM; -. DR PDBsum; 7YCX; -. DR PDBsum; 7Z1K; -. DR PDBsum; 7Z42; -. DR AlphaFoldDB; P24928; -. DR EMDB; EMD-22294; -. DR EMDB; EMD-23255; -. DR EMDB; EMD-31111; -. DR EMDB; EMD-31112; -. DR EMDB; EMD-33741; -. DR EMDB; EMD-6340; -. DR EMDB; EMD-6400; -. DR EMDB; EMD-7997; -. DR EMDB; EMD-8132; -. DR EMDB; EMD-8133; -. DR EMDB; EMD-8134; -. DR EMDB; EMD-8135; -. DR EMDB; EMD-8136; -. DR EMDB; EMD-8137; -. DR EMDB; EMD-8138; -. DR SMR; P24928; -. DR BioGRID; 111426; 486. DR ComplexPortal; CPX-2387; DNA-directed RNA polymerase II complex, Pol II(G) variant. DR ComplexPortal; CPX-7481; DNA-directed RNA polymerase II complex. DR CORUM; P24928; -. DR DIP; DIP-29011N; -. DR IntAct; P24928; 146. DR MINT; P24928; -. DR STRING; 9606.ENSP00000461879; -. DR BindingDB; P24928; -. DR ChEMBL; CHEMBL1641353; -. DR GlyCosmos; P24928; 3 sites, 1 glycan. DR GlyGen; P24928; 9 sites, 1 O-linked glycan (9 sites). DR iPTMnet; P24928; -. DR MetOSite; P24928; -. DR PhosphoSitePlus; P24928; -. DR SwissPalm; P24928; -. DR BioMuta; POLR2A; -. DR DMDM; 281185484; -. DR EPD; P24928; -. DR jPOST; P24928; -. DR MassIVE; P24928; -. DR MaxQB; P24928; -. DR PaxDb; 9606-ENSP00000480158; -. DR PeptideAtlas; P24928; -. DR ProteomicsDB; 54240; -. [P24928-1] DR ProteomicsDB; 66745; -. DR Pumba; P24928; -. DR ABCD; P24928; 7 sequenced antibodies. DR DNASU; 5430; -. DR GeneID; 5430; -. DR KEGG; hsa:5430; -. DR UCSC; uc002ghe.4; human. [P24928-1] DR AGR; HGNC:9187; -. DR CTD; 5430; -. DR DisGeNET; 5430; -. DR GeneCards; POLR2A; -. DR HGNC; HGNC:9187; POLR2A. DR MalaCards; POLR2A; -. DR MIM; 180660; gene+phenotype. DR MIM; 618603; phenotype. DR neXtProt; NX_P24928; -. DR PharmGKB; PA33507; -. DR eggNOG; KOG0260; Eukaryota. DR HOGENOM; CLU_000487_3_1_1; -. DR InParanoid; P24928; -. DR OrthoDB; 169836at2759; -. DR PhylomeDB; P24928; -. DR TreeFam; TF103036; -. DR PathwayCommons; P24928; -. DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex. DR Reactome; R-HSA-113418; Formation of the Early Elongation Complex. DR Reactome; R-HSA-167152; Formation of HIV elongation complex in the absence of HIV Tat. DR Reactome; R-HSA-167158; Formation of the HIV-1 Early Elongation Complex. DR Reactome; R-HSA-167160; RNA Pol II CTD phosphorylation and interaction with CE during HIV infection. DR Reactome; R-HSA-167161; HIV Transcription Initiation. DR Reactome; R-HSA-167162; RNA Polymerase II HIV Promoter Escape. DR Reactome; R-HSA-167172; Transcription of the HIV genome. DR Reactome; R-HSA-167200; Formation of HIV-1 elongation complex containing HIV-1 Tat. DR Reactome; R-HSA-167238; Pausing and recovery of Tat-mediated HIV elongation. DR Reactome; R-HSA-167242; Abortive elongation of HIV-1 transcript in the absence of Tat. DR Reactome; R-HSA-167243; Tat-mediated HIV elongation arrest and recovery. DR Reactome; R-HSA-167246; Tat-mediated elongation of the HIV-1 transcript. DR Reactome; R-HSA-167287; HIV elongation arrest and recovery. DR Reactome; R-HSA-167290; Pausing and recovery of HIV elongation. DR Reactome; R-HSA-168325; Viral Messenger RNA Synthesis. DR Reactome; R-HSA-203927; MicroRNA (miRNA) biogenesis. DR Reactome; R-HSA-5578749; Transcriptional regulation by small RNAs. DR Reactome; R-HSA-5601884; PIWI-interacting RNA (piRNA) biogenesis. DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis. DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events. DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex. DR Reactome; R-HSA-6781827; Transcription-Coupled Nucleotide Excision Repair (TC-NER). DR Reactome; R-HSA-6782135; Dual incision in TC-NER. DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER. DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR Reactome; R-HSA-6803529; FGFR2 alternative splicing. DR Reactome; R-HSA-6807505; RNA polymerase II transcribes snRNA genes. DR Reactome; R-HSA-72086; mRNA Capping. DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway. DR Reactome; R-HSA-72165; mRNA Splicing - Minor Pathway. DR Reactome; R-HSA-72203; Processing of Capped Intron-Containing Pre-mRNA. DR Reactome; R-HSA-73776; RNA Polymerase II Promoter Escape. DR Reactome; R-HSA-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening. DR Reactome; R-HSA-75953; RNA Polymerase II Transcription Initiation. DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation. DR Reactome; R-HSA-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance. DR Reactome; R-HSA-77075; RNA Pol II CTD phosphorylation and interaction with CE. DR Reactome; R-HSA-8851708; Signaling by FGFR2 IIIa TM. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR Reactome; R-HSA-9670095; Inhibition of DNA recombination at telomere. DR SignaLink; P24928; -. DR SIGNOR; P24928; -. DR BioGRID-ORCS; 5430; 833 hits in 1169 CRISPR screens. DR ChiTaRS; POLR2A; human. DR EvolutionaryTrace; P24928; -. DR GeneWiki; POLR2A; -. DR GenomeRNAi; 5430; -. DR Pharos; P24928; Tbio. DR PRO; PR:P24928; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P24928; Protein. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005665; C:RNA polymerase II, core complex; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003899; F:DNA-directed 5'-3' RNA polymerase activity; TAS:ProtInc. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050436; F:microfibril binding; IDA:DisProt. DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0001055; F:RNA polymerase II activity; TAS:UniProt. DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. DR GO; GO:0006353; P:DNA-templated transcription termination; IMP:UniProtKB. DR GO; GO:0033120; P:positive regulation of RNA splicing; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; NAS:UniProtKB. DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:UniProtKB. DR CDD; cd02584; RNAP_II_Rpb1_C; 1. DR CDD; cd02733; RNAP_II_RPB1_N; 1. DR DisProt; DP01284; -. DR Gene3D; 1.10.132.30; -; 1. DR Gene3D; 1.10.150.390; -; 1. DR Gene3D; 2.40.40.20; -; 1. DR Gene3D; 3.30.1360.140; -; 1. DR Gene3D; 6.10.250.2940; -; 1. DR Gene3D; 6.20.50.80; -; 1. DR Gene3D; 3.30.1490.180; RNA polymerase ii; 1. DR Gene3D; 4.10.860.120; RNA polymerase II, clamp domain; 2. DR Gene3D; 1.10.274.100; RNA polymerase Rpb1, domain 3; 1. DR IDEAL; IID00126; -. DR InterPro; IPR045867; DNA-dir_RpoC_beta_prime. DR InterPro; IPR000722; RNA_pol_asu. DR InterPro; IPR000684; RNA_pol_II_repeat_euk. DR InterPro; IPR006592; RNA_pol_N. DR InterPro; IPR007080; RNA_pol_Rpb1_1. DR InterPro; IPR007066; RNA_pol_Rpb1_3. DR InterPro; IPR042102; RNA_pol_Rpb1_3_sf. DR InterPro; IPR007083; RNA_pol_Rpb1_4. DR InterPro; IPR007081; RNA_pol_Rpb1_5. DR InterPro; IPR007075; RNA_pol_Rpb1_6. DR InterPro; IPR007073; RNA_pol_Rpb1_7. DR InterPro; IPR038593; RNA_pol_Rpb1_7_sf. DR InterPro; IPR044893; RNA_pol_Rpb1_clamp_domain. DR InterPro; IPR038120; Rpb1_funnel_sf. DR PANTHER; PTHR19376; DNA-DIRECTED RNA POLYMERASE; 1. DR PANTHER; PTHR19376:SF37; DNA-DIRECTED RNA POLYMERASE II SUBUNIT RPB1; 1. DR Pfam; PF04997; RNA_pol_Rpb1_1; 1. DR Pfam; PF00623; RNA_pol_Rpb1_2; 1. DR Pfam; PF04983; RNA_pol_Rpb1_3; 1. DR Pfam; PF05000; RNA_pol_Rpb1_4; 1. DR Pfam; PF04998; RNA_pol_Rpb1_5; 1. DR Pfam; PF04992; RNA_pol_Rpb1_6; 1. DR Pfam; PF04990; RNA_pol_Rpb1_7; 1. DR Pfam; PF05001; RNA_pol_Rpb1_R; 36. DR PRINTS; PR01217; PRICHEXTENSN. DR SMART; SM00663; RPOLA_N; 1. DR SUPFAM; SSF64484; beta and beta-prime subunits of DNA dependent RNA-polymerase; 1. DR PROSITE; PS00115; RNA_POL_II_REPEAT; 42. DR Genevisible; P24928; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chromosome; Cytoplasm; KW Disease variant; DNA-binding; DNA-directed RNA polymerase; KW Host-virus interaction; Hydrolase; Intellectual disability; KW Isopeptide bond; Magnesium; Metal-binding; Methylation; KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; RNA-directed RNA polymerase; Transcription; Transferase; KW Ubl conjugation; Zinc. FT CHAIN 1..1970 FT /note="DNA-directed RNA polymerase II subunit RPB1" FT /id="PRO_0000073940" FT REPEAT 1593..1599 FT /note="1" FT /evidence="ECO:0000255" FT REPEAT 1600..1606 FT /note="2; approximate" FT /evidence="ECO:0000255" FT REPEAT 1608..1614 FT /note="3" FT /evidence="ECO:0000255" FT REPEAT 1615..1621 FT /note="4" FT /evidence="ECO:0000255" FT REPEAT 1622..1628 FT /note="5" FT /evidence="ECO:0000255" FT REPEAT 1629..1635 FT /note="6" FT /evidence="ECO:0000255" FT REPEAT 1636..1642 FT /note="7" FT /evidence="ECO:0000255" FT REPEAT 1643..1649 FT /note="8" FT /evidence="ECO:0000255" FT REPEAT 1650..1656 FT /note="9" FT /evidence="ECO:0000255" FT REPEAT 1657..1663 FT /note="10" FT /evidence="ECO:0000255" FT REPEAT 1664..1670 FT /note="11" FT /evidence="ECO:0000255" FT REPEAT 1671..1677 FT /note="12" FT /evidence="ECO:0000255" FT REPEAT 1678..1684 FT /note="13" FT /evidence="ECO:0000255" FT REPEAT 1685..1691 FT /note="14" FT /evidence="ECO:0000255" FT REPEAT 1692..1698 FT /note="15" FT /evidence="ECO:0000255" FT REPEAT 1699..1705 FT /note="16" FT /evidence="ECO:0000255" FT REPEAT 1706..1712 FT /note="17" FT /evidence="ECO:0000255" FT REPEAT 1713..1719 FT /note="18" FT /evidence="ECO:0000255" FT REPEAT 1720..1726 FT /note="19" FT /evidence="ECO:0000255" FT REPEAT 1727..1733 FT /note="20" FT /evidence="ECO:0000255" FT REPEAT 1734..1740 FT /note="21" FT /evidence="ECO:0000255" FT REPEAT 1741..1747 FT /note="22" FT /evidence="ECO:0000255" FT REPEAT 1748..1754 FT /note="23" FT /evidence="ECO:0000255" FT REPEAT 1755..1761 FT /note="24" FT /evidence="ECO:0000255" FT REPEAT 1762..1768 FT /note="25" FT /evidence="ECO:0000255" FT REPEAT 1769..1775 FT /note="26" FT /evidence="ECO:0000255" FT REPEAT 1776..1782 FT /note="27" FT /evidence="ECO:0000255" FT REPEAT 1783..1789 FT /note="28" FT /evidence="ECO:0000255" FT REPEAT 1790..1796 FT /note="29" FT /evidence="ECO:0000255" FT REPEAT 1797..1803 FT /note="30" FT /evidence="ECO:0000255" FT REPEAT 1804..1810 FT /note="31" FT /evidence="ECO:0000255" FT REPEAT 1811..1817 FT /note="32" FT /evidence="ECO:0000255" FT REPEAT 1818..1824 FT /note="33" FT /evidence="ECO:0000255" FT REPEAT 1825..1831 FT /note="34" FT /evidence="ECO:0000255" FT REPEAT 1832..1838 FT /note="35" FT /evidence="ECO:0000255" FT REPEAT 1839..1845 FT /note="36" FT /evidence="ECO:0000255" FT REPEAT 1846..1852 FT /note="37" FT /evidence="ECO:0000255" FT REPEAT 1853..1859 FT /note="38" FT /evidence="ECO:0000255" FT REPEAT 1860..1866 FT /note="39" FT /evidence="ECO:0000255" FT REPEAT 1867..1873 FT /note="40" FT /evidence="ECO:0000255" FT REPEAT 1874..1880 FT /note="41" FT /evidence="ECO:0000255" FT REPEAT 1881..1887 FT /note="42" FT /evidence="ECO:0000255" FT REPEAT 1888..1894 FT /note="43" FT /evidence="ECO:0000255" FT REPEAT 1895..1901 FT /note="44" FT /evidence="ECO:0000255" FT REPEAT 1902..1908 FT /note="45" FT /evidence="ECO:0000255" FT REPEAT 1909..1915 FT /note="46" FT /evidence="ECO:0000255" FT REPEAT 1916..1922 FT /note="47" FT /evidence="ECO:0000255" FT REPEAT 1923..1929 FT /note="48" FT /evidence="ECO:0000255" FT REPEAT 1930..1936 FT /note="49" FT /evidence="ECO:0000255" FT REPEAT 1940..1946 FT /note="50" FT /evidence="ECO:0000255" FT REPEAT 1947..1953 FT /note="51; approximate" FT /evidence="ECO:0000255" FT REPEAT 1954..1960 FT /note="52; approximate" FT /evidence="ECO:0000255" FT REGION 832..873 FT /note="Bridging helix" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT REGION 1083..1124 FT /note="Trigger loop" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT REGION 1546..1970 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1593..1960 FT /note="C-terminal domain (CTD); 52 X 7 AA approximate FT tandem repeats of Y-[ST]-P-[STQ]-[ST]-P-[SRTEVKGN]" FT COMPBIAS 1565..1584 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1607..1963 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 67 FT /ligand="RNA" FT /ligand_id="ChEBI:CHEBI:33697" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 71 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 74 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 81 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 84 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 111 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 114 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 154 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 184 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 346 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 358 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 460 FT /ligand="RNA" FT /ligand_id="ChEBI:CHEBI:33697" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 493 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 495 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 495 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /ligand_note="ligand shared with POLR2B/RPB2" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 497 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 497 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /ligand_note="ligand shared with POLR2B/RPB2" FT /evidence="ECO:0000250|UniProtKB:P04050" FT BINDING 499 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:27193682, FT ECO:0007744|PDB:5IY6" FT BINDING 499 FT /ligand="RNA" FT /ligand_id="ChEBI:CHEBI:33697" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 1416 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 1421 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="nontemplate strand" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 27 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 217 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1603 FT /note="Omega-N-methylated arginine; by CARM1; in vitro" FT /evidence="ECO:0000269|PubMed:26700805" FT MOD_RES 1810 FT /note="Asymmetric dimethylarginine; alternate; by CARM1" FT /evidence="ECO:0000269|PubMed:21454787, FT ECO:0000269|PubMed:26700805" FT MOD_RES 1810 FT /note="Symmetric dimethylarginine; alternate; by PRMT5" FT /evidence="ECO:0000269|PubMed:26700805" FT MOD_RES 1838 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1838 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1840 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1843 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1845 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1847 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1849 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:18669648" FT MOD_RES 1850 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1854 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1857 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1859 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1859 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1860 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1861 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1863 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1864 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1866 FT /note="N6,N6,N6-trimethyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1866 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1866 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1866 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1867 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1868 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1870 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1873 FT /note="N6,N6,N6-trimethyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1873 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1873 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1874 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:24275569" FT MOD_RES 1875 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1877 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1878 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 1881 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1882 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 1885 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1887 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1887 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1887 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1894 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1896 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1899 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1906 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1908 FT /note="N6,N6-dimethyllysine" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1909 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1912 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1913 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1915 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1916 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1917 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692" FT MOD_RES 1919 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1920 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1922 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1922 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000305|PubMed:26566685" FT MOD_RES 1922 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000305|PubMed:26566685" FT MOD_RES 1923 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1926 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1927 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1929 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1930 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1931 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26566685, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692" FT MOD_RES 1933 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26566685" FT MOD_RES 1934 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 1936 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08775" FT MOD_RES 1936 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000305|PubMed:26566685" FT MOD_RES 1936 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000305|PubMed:26566685" FT CROSSLNK 1268 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); by NEDD4" FT /evidence="ECO:0000269|PubMed:32142649, FT ECO:0000305|PubMed:32142654" FT VAR_SEQ 558..566 FT /note="GEVMNLLMF -> VCGPNGNLA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056184" FT VAR_SEQ 567..1970 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056185" FT VARIANT 292 FT /note="R -> C (in dbSNP:rs2229198)" FT /id="VAR_051872" FT VARIANT 371 FT /note="P -> L (in NEDHIB; uncertain significance; mild)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082988" FT VARIANT 457 FT /note="I -> T (in NEDHIB; uncertain significance; severe; FT no effect on cell viability)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082989" FT VARIANT 531 FT /note="N -> S (in NEDHIB; uncertain significance; no effect FT on cell viability)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082990" FT VARIANT 669 FT /note="Missing (in NEDHIB; moderate)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082991" FT VARIANT 700..1970 FT /note="Missing (in NEDHIB; mild)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082992" FT VARIANT 735..1970 FT /note="Missing (in NEDHIB; mild)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082993" FT VARIANT 736 FT /note="T -> M (in NEDHIB; profound; decreased cell FT viability)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082994" FT VARIANT 755 FT /note="Missing (in NEDHIB; uncertain significance; mild; FT decreased cell viability)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082995" FT VARIANT 769 FT /note="M -> T (in NEDHIB; uncertain significance; severe)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082996" FT VARIANT 848 FT /note="I -> T (in NEDHIB; uncertain significance; FT moderate)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082997" FT VARIANT 1109 FT /note="Y -> H (in NEDHIB; uncertain significance; FT moderate)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082998" FT VARIANT 1124 FT /note="L -> P (in NEDHIB; mild; decreased cell viability)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_082999" FT VARIANT 1125 FT /note="Missing (in NEDHIB; uncertain significance; mild)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_083000" FT VARIANT 1251 FT /note="N -> S (in NEDHIB; uncertain significance; severe; FT no effect on cell viability)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_083001" FT VARIANT 1603 FT /note="R -> H (in NEDHIB; uncertain significance; moderate; FT no effect on cell viability)" FT /evidence="ECO:0000269|PubMed:31353023" FT /id="VAR_083002" FT MUTAGEN 812..1970 FT /note="Missing: Decreases cell viability." FT /evidence="ECO:0000269|PubMed:31353023" FT MUTAGEN 1268 FT /note="K->R: Impairs ubiquitination, interaction with the FT TFIIH complex, and its degradation during transcription FT stress." FT /evidence="ECO:0000269|PubMed:32142649, FT ECO:0000269|PubMed:32142654" FT MUTAGEN 1810 FT /note="R->A: Misexpression of a variety of small nuclear FT RNAs and small nucleolar RNAs. Loss of interaction with FT TDRD3 and SMN1/SMN2." FT /evidence="ECO:0000269|PubMed:21454787, FT ECO:0000269|PubMed:26700805" FT MUTAGEN 1838 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R-1859; R-1866; R-1873; R-1887; R-1908; R-1922 and R-1936." FT /evidence="ECO:0000269|PubMed:24207025" FT MUTAGEN 1859 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R-1838; R-1866; R-1873; R-1887; R-1908; R-1922 and R-1936." FT /evidence="ECO:0000269|PubMed:24207025" FT MUTAGEN 1866 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R-1859; R-1859; R-1873; R-1887; R-1908; R-1922 and R-1936." FT /evidence="ECO:0000269|PubMed:24207025" FT MUTAGEN 1873 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R-1838; R-1859; R-1866; R-1887; R-1908; R-1922 and R-1936." FT /evidence="ECO:0000269|PubMed:24207025" FT MUTAGEN 1887 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R-1838; R-1859; R-1866; R-1873; R-1908; R-1922 and R-1936." FT /evidence="ECO:0000269|PubMed:24207025" FT MUTAGEN 1908 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R.1838; R-1859; R-1866; R-1873; R-1887; R-1922 and R-1936." FT /evidence="ECO:0000269|PubMed:24207025" FT MUTAGEN 1922 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R-1838; R-1859; R-1866; R-1873; R-1887; R-1908 and R-1936." FT /evidence="ECO:0000269|PubMed:24207025" FT MUTAGEN 1936 FT /note="K->R: Loss of acetylation and loss of regulation of FT growth-factor-induced gene expression; when associated with FT R-1838; R-1859; R-1866; R-1873; R-1887; R-1908 and R-1922." FT /evidence="ECO:0000269|PubMed:24207025" FT CONFLICT 1067 FT /note="W -> L (in Ref. 2; CAA52862)" FT /evidence="ECO:0000305" FT CONFLICT 1449 FT /note="D -> Y (in Ref. 2; CAA52862)" FT /evidence="ECO:0000305" FT CONFLICT 1835 FT /note="A -> T (in Ref. 1; CAA45125 and 2; CAA52862)" FT /evidence="ECO:0000305" FT HELIX 1718..1720 FT /evidence="ECO:0007829|PDB:7Z42" FT STRAND 1722..1724 FT /evidence="ECO:0007829|PDB:5M3H" SQ SEQUENCE 1970 AA; 217176 MW; 28D6FD25693A6472 CRC64; MHGGGPPSGD SACPLRTIKR VQFGVLSPDE LKRMSVTEGG IKYPETTEGG RPKLGGLMDP RQGVIERTGR CQTCAGNMTE CPGHFGHIEL AKPVFHVGFL VKTMKVLRCV CFFCSKLLVD SNNPKIKDIL AKSKGQPKKR LTHVYDLCKG KNICEGGEEM DNKFGVEQPE GDEDLTKEKG HGGCGRYQPR IRRSGLELYA EWKHVNEDSQ EKKILLSPER VHEIFKRISD EECFVLGMEP RYARPEWMIV TVLPVPPLSV RPAVVMQGSA RNQDDLTHKL ADIVKINNQL RRNEQNGAAA HVIAEDVKLL QFHVATMVDN ELPGLPRAMQ KSGRPLKSLK QRLKGKEGRV RGNLMGKRVD FSARTVITPD PNLSIDQVGV PRSIAANMTF AEIVTPFNID RLQELVRRGN SQYPGAKYII RDNGDRIDLR FHPKPSDLHL QTGYKVERHM CDGDIVIFNR QPTLHKMSMM GHRVRILPWS TFRLNLSVTT PYNADFDGDE MNLHLPQSLE TRAEIQELAM VPRMIVTPQS NRPVMGIVQD TLTAVRKFTK RDVFLERGEV MNLLMFLSTW DGKVPQPAIL KPRPLWTGKQ IFSLIIPGHI NCIRTHSTHP DDEDSGPYKH ISPGDTKVVV ENGELIMGIL CKKSLGTSAG SLVHISYLEM GHDITRLFYS NIQTVINNWL LIEGHTIGIG DSIADSKTYQ DIQNTIKKAK QDVIEVIEKA HNNELEPTPG NTLRQTFENQ VNRILNDARD KTGSSAQKSL SEYNNFKSMV VSGAKGSKIN ISQVIAVVGQ QNVEGKRIPF GFKHRTLPHF IKDDYGPESR GFVENSYLAG LTPTEFFFHA MGGREGLIDT AVKTAETGYI QRRLIKSMES VMVKYDATVR NSINQVVQLR YGEDGLAGES VEFQNLATLK PSNKAFEKKF RFDYTNERAL RRTLQEDLVK DVLSNAHIQN ELEREFERMR EDREVLRVIF PTGDSKVVLP CNLLRMIWNA QKIFHINPRL PSDLHPIKVV EGVKELSKKL VIVNGDDPLS RQAQENATLL FNIHLRSTLC SRRMAEEFRL SGEAFDWLLG EIESKFNQAI AHPGEMVGAL AAQSLGEPAT QMTLNTFHYA GVSAKNVTLG VPRLKELINI SKKPKTPSLT VFLLGQSARD AERAKDILCR LEHTTLRKVT ANTAIYYDPN PQSTVVAEDQ EWVNVYYEMP DFDVARISPW LLRVELDRKH MTDRKLTMEQ IAEKINAGFG DDLNCIFNDD NAEKLVLRIR IMNSDENKMQ EEEEVVDKMD DDVFLRCIES NMLTDMTLQG IEQISKVYMH LPQTDNKKKI IITEDGEFKA LQEWILETDG VSLMRVLSEK DVDPVRTTSN DIVEIFTVLG IEAVRKALER ELYHVISFDG SYVNYRHLAL LCDTMTCRGH LMAITRHGVN RQDTGPLMKC SFEETVDVLM EAAAHGESDP MKGVSENIML GQLAPAGTGC FDLLLDAEKC KYGMEIPTNI PGLGAAGPTG MFFGSAPSPM GGISPAMTPW NQGATPAYGA WSPSVGSGMT PGAAGFSPSA ASDASGFSPG YSPAWSPTPG SPGSPGPSSP YIPSPGGAMS PSYSPTSPAY EPRSPGGYTP QSPSYSPTSP SYSPTSPSYS PTSPNYSPTS PSYSPTSPSY SPTSPSYSPT SPSYSPTSPS YSPTSPSYSP TSPSYSPTSP SYSPTSPSYS PTSPSYSPTS PSYSPTSPSY SPTSPSYSPT SPSYSPTSPS YSPTSPNYSP TSPNYTPTSP SYSPTSPSYS PTSPNYTPTS PNYSPTSPSY SPTSPSYSPT SPSYSPSSPR YTPQSPTYTP SSPSYSPSSP SYSPASPKYT PTSPSYSPSS PEYTPTSPKY SPTSPKYSPT SPKYSPTSPT YSPTTPKYSP TSPTYSPTSP VYTPTSPKYS PTSPTYSPTS PKYSPTSPTY SPTSPKGSTY SPTSPGYSPT SPTYSLTSPA ISPDDSDEEN //