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 11-NOV-2015, entry version 174. DE RecName: Full=DNA-directed RNA polymerase II subunit RPB1; DE Short=RNA polymerase II subunit B1; DE EC=2.7.7.6; 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; GN Name=POLR2A; Synonyms=POLR2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA 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 RT the 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, IDENTIFICATION IN THE RNA POLYMERASE II CORE-COMPLEX, AND RP 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 RT that conditionally express epitope-tagged subunits of the multiprotein RT complexes."; RL J. Biol. Chem. 273:34444-34453(1998). RN [7] 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 RT elements."; RL Nucleic Acids Res. 26:3542-3549(1998). RN [8] 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 RT HIV-1 transcription."; RL EMBO J. 18:3688-3701(1999). RN [9] RP INTERACTION WITH HTATSF1. RX PubMed=10454543; 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 [10] 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 [11] 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 RT the nuclear proteome link transcription to DNA/chromatin modification RT and RNA processing."; RL Mol. Cell. Proteomics 1:598-610(2002). RN [12] 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 RT coactivators CBP and p300."; RL Oncogene 22:151-156(2003). RN [13] 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 RT from human T cells using immobilized metal affinity chromatography and RT tandem mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [14] 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 RT in pre-mRNA splicing and induces apoptosis of human hepatocellular RT carcinoma cells."; RL J. Biol. Chem. 279:11639-11648(2004). RN [15] 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., RA Levine S.S., Lee J.C., Hayes D.N., Shanmugam K.S., Bhattacharjee A., RA Biondi C.A., Kay G.F., Hayward N.K., Hess J.L., Meyerson M.; RT "Menin associates with a trithorax family histone methyltransferase RT complex and with the hoxc8 locus."; RL Mol. Cell 13:587-597(2004). RN [16] 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 [17] 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 RT lysine 36 specific methyltransferase."; RL J. Biol. Chem. 280:35261-35271(2005). RN [18] 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 RT and its interaction with the hyperphosphorylated C-terminal domain of RT Rpb1."; RL Proc. Natl. Acad. Sci. U.S.A. 102:17636-17641(2005). RN [19] 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 RT phosphorylation analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [20] 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., RA Hollingsworth M.A., Batra S.K.; RT "The human homologue of the RNA polymerase II-associated factor 1 RT (hPaf1), localized on the 19q13 amplicon, is associated with RT tumorigenesis."; RL Oncogene 25:3247-3257(2006). RN [21] 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 [22] 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 RT polymerase II and shows methyltransferase activity."; RL Biochem. Biophys. Res. Commun. 372:719-724(2008). RN [23] 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 [24] RP FUNCTION AS RNA-DIRECTED RNA POLYMERASE. 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 [25] 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 RT of transcribed human genes."; RL Mol. Cell. Biol. 28:609-618(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1849; TYR-1874; RP SER-1896; TYR-1909; SER-1913; SER-1920; TYR-1923; SER-1927 AND RP SER-1934, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [28] 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 [29] 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., RA Eick D., Ansari A.Z.; RT "TFIIH kinase places bivalent marks on the carboxy-terminal domain of RT RNA polymerase II."; RL Mol. Cell 34:387-393(2009). RN [30] 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- RT terminal domain Ser7 residues, promoter-proximal pausing, and RT termination by RNA polymerase II."; RL Mol. Cell. Biol. 29:5455-5464(2009). RN [31] 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 [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1843; THR-1854; RP SER-1878; SER-1882; SER-1899; SER-1913; SER-1917; SER-1920; SER-1927; RP SER-1931 AND SER-1934, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP 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 [33] RP INTERACTION WITH RECQL5, AND FUNCTION. 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 RT helicase."; RL Mol. Cell. Biol. 30:2460-2472(2010). RN [34] 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [35] 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., RA Buerckstuemmer T., 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 [36] 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 [37] 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 [38] 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., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [39] 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- RT specific methylation."; RL Science 332:99-103(2011). RN [40] 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 RT to snRNA genes."; RL Mol. Cell 45:111-122(2012). RN [41] RP UBIQUITINATION. RX PubMed=22466610; DOI=10.1038/ng.2229; RA Nakazawa Y., Sasaki K., Mitsutake N., Matsuse M., Shimada M., RA Nardo T., Takahashi Y., Ohyama K., Ito K., Mishima H., Nomura M., RA Kinoshita A., Ono S., Takenaka K., Masuyama R., Kudo T., Slor H., RA Utani A., Tateishi S., Yamashita S., Stefanini M., Lehmann A.R., RA Yoshiura K.I., Ogi T.; RT "Mutations in UVSSA cause UV-sensitive syndrome and impair RNA RT polymerase IIo processing in transcription-coupled nucleotide-excision RT repair."; RL Nat. Genet. 44:586-592(2012). RN [42] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN ICP22. 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., RA 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 [43] 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 RT DNA damage response."; RL Mol. Cell. Biol. 33:406-417(2013). RN [44] 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 RT specificity of the R2TP cochaperone complex."; RL Cell Rep. 7:19-26(2014). RN [45] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1874; SER-1906; TYR-1909 RP AND TYR-1923, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [46] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1796-1803 IN COMPLEX WITH RP CTDSP1, 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., RA Gill G.N., Dixon J.E., Noel J.P.; RT "Determinants for dephosphorylation of the RNA polymerase II C- RT terminal domain by Scp1."; RL Mol. Cell 24:759-770(2006). RN [47] RP STRUCTURE BY ELECTRON MICROSCOPY IN COMPLEX WITH RECQL5, INTERACTION RP WITH RECQL5 AND TCEA1, SUBUNIT, AND FUNCTION. 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 RT polymerase II by the DNA helicase RECQL5."; RL Nat. Struct. Mol. Biol. 20:892-899(2013). CC -!- FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription CC of DNA into RNA using the four ribonucleoside triphosphates as CC substrates. Largest and catalytic component of RNA polymerase II CC which synthesizes mRNA precursors and many functional non-coding CC RNAs. Forms the polymerase active center together with the second CC largest subunit. Pol II is the central component of the basal RNA CC polymerase II transcription machinery. It is composed of mobile CC elements that move relative to each other. RPB1 is part of the CC core element with the central large cleft, the clamp element that CC moves to open and close the cleft and the jaws that are thought to CC grab the incoming DNA template. At the start of transcription, a CC single-stranded DNA template strand of the promoter is positioned CC within the central active site cleft of Pol II. A bridging helix CC emanates from RPB1 and crosses the cleft near the catalytic site CC and is thought to promote translocation of Pol II by acting as a CC ratchet that moves the RNA-DNA hybrid through the active site by CC switching from straight to bent conformations at each step of CC nucleotide addition. During transcription elongation, Pol II moves CC on the template as the transcript elongates. Elongation is CC influenced by the phosphorylation status of the C-terminal domain CC (CTD) of Pol II largest subunit (RPB1), which serves as a platform CC for assembly of factors that regulate transcription initiation, CC elongation, termination and mRNA processing. Acts as an RNA- CC dependent RNA polymerase when associated with small delta antigen CC of Hepatitis delta virus, acting both as a replicate and CC transcriptase for the viral RNA circular genome. CC {ECO:0000269|PubMed:18032511, ECO:0000269|PubMed:20231364, CC ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:9852112}. CC -!- CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate CC + RNA(n+1). CC -!- SUBUNIT: Interacts with SETX (PubMed:23149945). The large PER CC complex involved in the repression of transcriptional termination CC is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A CC (active). When phosphorylated at 'Ser-2', interacts with SUPT6H CC (via SH2 domain). Interacts with SCAF8. Interacts with MYO1C. CC Interacts with WWP2 (By similarity). Component of the RNA CC polymerase II (Pol II) complex consisting of 12 subunits. The CC phosphorylated C-terminal domain interacts with FNBP3 and SYNCRIP. CC Interacts with SAFB/SAFB1. Interacts with CCNL1. Interacts with CC CCNL2 and SFRS19. Component of a complex which is at least CC composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 CC and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. Interacts CC with PAF1. Interacts (via C-terminus) with CMTR1 and CTDSP1. CC Interacts via the phosphorylated C-terminal domain with WDR82 and CC with SETD1A and SETD1B only in the presence of WDR82. Interacts CC with ATF7IP. When phosphorylated at 'Ser-5', interacts with MEN1; CC the unphosphorylated form, or phosphorylated at 'Ser-2' does not CC interact. Interacts with DDX5. Interacts with RECQL5 and TCEA1; CC binding of RECQL5 prevents TCEA1 binding. Interacts (via the C- CC 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. Interacts with herpes simplex virus 1 protein ICP22; CC this interaction causes loss of CTD 'Ser-2' phosphorylation from CC pol II engaged in transcription (PubMed:23029222). Interacts CC (phosphorylated) with PIH1D1 (PubMed:24656813). CC {ECO:0000250|UniProtKB:P08775, ECO:0000269|PubMed:10393184, CC ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:12376575, CC ECO:0000269|PubMed:12381297, ECO:0000269|PubMed:12527917, CC ECO:0000269|PubMed:14684736, ECO:0000269|PubMed:14992727, 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:23029222, ECO:0000269|PubMed:23149945, CC ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:24656813, CC ECO:0000269|PubMed:9671816, ECO:0000269|PubMed:9852112}. CC -!- INTERACTION: CC Q6P1J9:CDC73; NbExp=5; IntAct=EBI-295301, EBI-930143; CC P17844:DDX5; NbExp=3; IntAct=EBI-295301, EBI-351962; CC Q8N7H5:PAF1; NbExp=5; IntAct=EBI-295301, EBI-2607770; CC Q9NQG5:RPRD1B; NbExp=5; IntAct=EBI-295301, EBI-747925; CC Q96H20:SNF8; NbExp=2; IntAct=EBI-295301, EBI-747719; CC O00267:SUPT5H; NbExp=3; IntAct=EBI-295301, EBI-710464; CC Q9HCS7:XAB2; NbExp=2; IntAct=EBI-295301, EBI-295232; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9852112}. 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 Note=No experimental confirmation available.; CC -!- DOMAIN: The C-terminal domain (CTD) serves as a platform for CC assembly of factors that regulate transcription initiation, CC elongation, termination and mRNA processing. CC {ECO:0000303|PubMed:22137580}. CC -!- PTM: The tandem 7 residues repeats in the C-terminal domain (CTD) CC can be highly phosphorylated. The phosphorylation activates Pol CC II. Phosphorylation occurs mainly at residues 'Ser-2' and 'Ser-5' CC of the heptapeptide repeat and is mediated, at least, by CDK7 and CC 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 CC repeat, which is required for efficient transcription of snRNA CC genes and processing of the transcripts. The phosphorylation state CC is believed to result from the balanced action of site-specific CC CTD kinases and phosphatases, and a 'CTD code' that specifies the CC position of Pol II within the transcription cycle has been CC proposed. Dephosphorylated by the protein phosphatase CTDSP1. CC -!- PTM: Ubiquitinated by WWP2 leading to proteasomal degradation (By CC similarity). Following UV treatment, the elongating form of RNA CC polymerase II (RNA pol IIo) is ubiquitinated UV damage sites CC without leading to degradation: ubiquitination is facilitated by CC KIAA1530/UVSSA and promotes RNA pol IIo backtracking to allow CC access to the nucleotide excision repair machinery. {ECO:0000250, CC ECO:0000269|PubMed:22466610}. CC -!- PTM: Methylated at Arg-1810 by CARM1. Methylation occurs only when CC the CTD is hypophosphorylated, and phosphorylation at Ser-1805 and CC Ser-1808 prevent methylation (in vitro). It is assumed that CC methylation occurs prior to phosphorylation and transcription CC initiation. CTD methylation may facilitate the expression of CC select RNAs. {ECO:0000269|PubMed:21454787}. CC -!- MISCELLANEOUS: The binding of ribonucleoside triphosphate to the CC RNA polymerase II transcribing complex probably involves a two- CC step mechanism. The initial binding seems to occur at the entry CC (E) site and involves a magnesium ion temporarily coordinated by CC three conserved aspartate residues of the two largest RNA Pol II CC subunits. The ribonucleoside triphosphate is transferred by a CC rotation to the nucleotide addition (A) site for pairing with the CC template DNA. The catalytic A site involves three conserved CC aspartate residues of the RNA Pol II largest subunit which CC permanently coordinate a second magnesium ion. 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 UniGene; Hs.270017; -. 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 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 ProteinModelPortal; P24928; -. DR SMR; P24928; 16-896, 1072-1475. DR BioGrid; 111426; 239. DR DIP; DIP-29011N; -. DR IntAct; P24928; 42. DR MINT; MINT-156582; -. DR STRING; 9606.ENSP00000314949; -. DR BindingDB; P24928; -. DR ChEMBL; CHEMBL1641353; -. DR PhosphoSite; P24928; -. DR BioMuta; POLR2A; -. DR DMDM; 281185484; -. DR MaxQB; P24928; -. DR PaxDb; P24928; -. DR PRIDE; P24928; -. DR Ensembl; ENST00000572844; ENSP00000461879; ENSG00000181222. [P24928-2] DR GeneID; 5430; -. DR KEGG; hsa:5430; -. DR UCSC; uc002ghe.3; human. DR UCSC; uc002ghf.4; human. [P24928-1] DR CTD; 5430; -. DR GeneCards; POLR2A; -. DR H-InvDB; HIX0173727; -. DR HGNC; HGNC:9187; POLR2A. DR HPA; CAB012226; -. DR HPA; CAB016388; -. DR HPA; CAB022311; -. DR HPA; CAB055172; -. DR HPA; HPA021563; -. DR HPA; HPA053012; -. DR MIM; 180660; gene+phenotype. DR neXtProt; NX_P24928; -. DR PharmGKB; PA33507; -. DR eggNOG; KOG0260; Eukaryota. DR eggNOG; COG0086; LUCA. DR GeneTree; ENSGT00730000110946; -. DR HOGENOM; HOG000222975; -. DR HOVERGEN; HBG004339; -. DR InParanoid; P24928; -. DR KO; K03006; -. DR OrthoDB; EOG7K0ZB8; -. DR PhylomeDB; P24928; -. DR TreeFam; TF103036; -. DR Reactome; R-HSA-110302; Formation of transcription-coupled NER (TC-NER) repair complex. DR Reactome; R-HSA-110304; Dual incision reaction in TC-NER. 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. 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-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation. DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells. DR Reactome; R-HSA-5578749; Transcriptional regulation by small RNAs. DR Reactome; R-HSA-5601884; PIWI-interacting RNA (piRNA) biogenesis. DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events. 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-73937; Transcription-coupled NER (TC-NER). 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 ChiTaRS; POLR2A; human. DR EvolutionaryTrace; P24928; -. DR GeneWiki; POLR2A; -. DR GenomeRNAi; 5430; -. DR NextBio; 21009; -. DR PRO; PR:P24928; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; P24928; -. DR CleanEx; HS_POLR2A; -. DR ExpressionAtlas; P24928; baseline and differential. DR Genevisible; P24928; HS. DR GO; GO:0005665; C:DNA-directed RNA polymerase II, core complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0003899; F:DNA-directed RNA polymerase activity; NAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0003968; F:RNA-directed RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. DR GO; GO:0006370; P:7-methylguanosine mRNA capping; TAS:Reactome. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome. DR GO; GO:0006289; P:nucleotide-excision repair; TAS:Reactome. DR GO; GO:0034587; P:piRNA metabolic process; TAS:Reactome. DR GO; GO:0033120; P:positive regulation of RNA splicing; IDA:UniProtKB. DR GO; GO:0050434; P:positive regulation of viral transcription; TAS:Reactome. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0008380; P:RNA splicing; TAS:Reactome. DR GO; GO:0035019; P:somatic stem cell population maintenance; TAS:Reactome. DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. 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; 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 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; 41. DR SMART; SM00663; RPOLA_N; 1. DR PROSITE; PS00115; RNA_POL_II_REPEAT; 42. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW DNA-binding; DNA-directed RNA polymerase; Magnesium; Metal-binding; KW Methylation; Nucleotidyltransferase; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; RNA-directed RNA polymerase; KW Transcription; Transferase; Ubl conjugation; Zinc. FT CHAIN 1 1970 DNA-directed RNA polymerase II subunit FT RPB1. FT /FTId=PRO_0000073940. FT REPEAT 1593 1599 1. FT REPEAT 1600 1606 2; approximate. FT REPEAT 1608 1614 3. FT REPEAT 1615 1621 4. FT REPEAT 1622 1628 5. FT REPEAT 1629 1635 6. FT REPEAT 1636 1642 7. FT REPEAT 1643 1649 8. FT REPEAT 1650 1656 9. FT REPEAT 1657 1663 10. FT REPEAT 1664 1670 11. FT REPEAT 1671 1677 12. FT REPEAT 1678 1684 13. FT REPEAT 1685 1691 14. FT REPEAT 1692 1698 15. FT REPEAT 1699 1705 16. FT REPEAT 1706 1712 17. FT REPEAT 1713 1719 18. FT REPEAT 1720 1726 19. FT REPEAT 1727 1733 20. FT REPEAT 1734 1740 21. FT REPEAT 1741 1747 22. FT REPEAT 1748 1754 23. FT REPEAT 1755 1761 24. FT REPEAT 1762 1768 25. FT REPEAT 1769 1775 26. FT REPEAT 1776 1782 27. FT REPEAT 1783 1789 28. FT REPEAT 1790 1796 29. FT REPEAT 1797 1803 30. FT REPEAT 1804 1810 31. FT REPEAT 1811 1817 32. FT REPEAT 1818 1824 33. FT REPEAT 1825 1831 34. FT REPEAT 1832 1838 35. FT REPEAT 1839 1845 36. FT REPEAT 1846 1852 37. FT REPEAT 1853 1859 38. FT REPEAT 1860 1866 39. FT REPEAT 1867 1873 40. FT REPEAT 1874 1880 41. FT REPEAT 1881 1887 42. FT REPEAT 1888 1894 43. FT REPEAT 1895 1901 44. FT REPEAT 1902 1908 45. FT REPEAT 1909 1915 46. FT REPEAT 1916 1922 47. FT REPEAT 1923 1929 48. FT REPEAT 1930 1936 49. FT REPEAT 1940 1946 50. FT REPEAT 1947 1953 51; approximate. FT REPEAT 1954 1960 52; approximate. FT REGION 833 845 Bridging helix. FT REGION 1593 1960 C-terminal domain (CTD); 52 X 7 AA FT approximate tandem repeats of Y-[ST]-P- FT [STQ]-[ST]-P-[SRTEVKGN]. FT METAL 71 71 Zinc 1. {ECO:0000250}. FT METAL 74 74 Zinc 1. {ECO:0000250}. FT METAL 81 81 Zinc 1. {ECO:0000250}. FT METAL 84 84 Zinc 1. {ECO:0000250}. FT METAL 111 111 Zinc 2. {ECO:0000250}. FT METAL 114 114 Zinc 2. {ECO:0000250}. FT METAL 154 154 Zinc 2. {ECO:0000250}. FT METAL 184 184 Zinc 2. {ECO:0000250}. FT METAL 495 495 Magnesium 1; catalytic. {ECO:0000250}. FT METAL 495 495 Magnesium 2; shared with RPB2. FT {ECO:0000250}. FT METAL 497 497 Magnesium 1; catalytic. {ECO:0000250}. FT METAL 497 497 Magnesium 2; shared with RPB2. FT {ECO:0000250}. FT METAL 499 499 Magnesium 1; catalytic. {ECO:0000250}. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:19413330}. FT MOD_RES 1810 1810 Omega-N-methylated arginine; by CARM1. FT {ECO:0000269|PubMed:21454787}. FT MOD_RES 1843 1843 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 1847 1847 Phosphoserine. FT {ECO:0000250|UniProtKB:P08775}. FT MOD_RES 1849 1849 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 1854 1854 Phosphothreonine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 1857 1857 Phosphoserine. FT {ECO:0000250|UniProtKB:P08775}. FT MOD_RES 1874 1874 Phosphotyrosine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 1878 1878 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 1882 1882 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 1894 1894 Phosphothreonine. FT {ECO:0000250|UniProtKB:P08775}. FT MOD_RES 1896 1896 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 1899 1899 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 1906 1906 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 1909 1909 Phosphotyrosine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 1912 1912 Phosphothreonine. FT {ECO:0000250|UniProtKB:P08775}. FT MOD_RES 1913 1913 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 1917 1917 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 1920 1920 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 1923 1923 Phosphotyrosine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 1926 1926 Phosphothreonine. FT {ECO:0000250|UniProtKB:P08775}. FT MOD_RES 1927 1927 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 1931 1931 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 1934 1934 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT VAR_SEQ 558 566 GEVMNLLMF -> VCGPNGNLA (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_056184. FT VAR_SEQ 567 1970 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_056185. FT VARIANT 292 292 R -> C (in dbSNP:rs2229198). FT /FTId=VAR_051872. FT MUTAGEN 1810 1810 R->A: Misexpression of a variety of small FT nuclear RNAs and small nucleolar RNAs. FT {ECO:0000269|PubMed:21454787}. FT CONFLICT 1067 1067 W -> L (in Ref. 2; CAA52862). FT {ECO:0000305}. FT CONFLICT 1449 1449 D -> Y (in Ref. 2; CAA52862). FT {ECO:0000305}. FT CONFLICT 1835 1835 A -> T (in Ref. 1; CAA45125 and 2; FT CAA52862). {ECO:0000305}. 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 //