RPB1_HUMAN
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 03-AUG-2022, entry version 231.
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;
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 {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, 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 that
RT 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 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 HIV-
RT 1 transcription.";
RL EMBO J. 18:3688-3701(1999).
RN [9]
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 [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 the
RT nuclear proteome link transcription to DNA/chromatin modification and RNA
RT 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 coactivators
RT 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 from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 mechanisms--
RT interacting with RNA polymerase II and acting as a helicase.";
RL Mol. Cell. Biol. 30:2460-2472(2010).
RN [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
RP ACETYLATION BY EP300, AND FUNCTION.
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
RP INTERACTION WITH POLR2A, 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 [55]
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 [56]
RP STRUCTURE BY ELECTRON MICROSCOPY IN COMPLEX WITH RECQL5, INTERACTION WITH
RP 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 polymerase II
RT by the DNA helicase RECQL5.";
RL Nat. Struct. Mol. Biol. 20:892-899(2013).
RN [57]
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: DNA-dependent RNA polymerase catalyzes the transcription of
CC DNA into RNA using the four ribonucleoside triphosphates as substrates.
CC Largest and catalytic component of RNA polymerase II which synthesizes
CC mRNA precursors and many functional non-coding RNAs. Forms the
CC polymerase active center together with the second largest subunit. Pol
CC II is the central component of the basal RNA polymerase II
CC transcription machinery. It is composed of mobile elements that move
CC relative to each other. RPB1 is part of the core element with the
CC central large cleft, the clamp element that moves to open and close the
CC cleft and the jaws that are thought to grab the incoming DNA template.
CC At the start of transcription, a single-stranded DNA template strand of
CC the promoter is positioned within the central active site cleft of Pol
CC II. A bridging helix emanates from RPB1 and crosses the cleft near the
CC catalytic site and is thought to promote translocation of Pol II by
CC acting as a ratchet that moves the RNA-DNA hybrid through the active
CC site by switching from straight to bent conformations at each step of
CC nucleotide addition. During transcription elongation, Pol II moves on
CC the template as the transcript elongates. Elongation is influenced by
CC the phosphorylation status of the C-terminal domain (CTD) of Pol II
CC largest subunit (RPB1), which serves as a platform for assembly of
CC factors that regulate transcription initiation, elongation, termination
CC and mRNA processing. Regulation of gene expression levels depends on
CC the balance between methylation and acetylation levels of tha CTD-
CC lysines (By similarity). Initiation or early elongation steps of
CC transcription of growth-factors-induced immediate early genes are
CC regulated by the acetylation status of the CTD (PubMed:24207025).
CC Methylation and dimethylation have a repressive effect on target genes
CC expression (By similarity). {ECO:0000250|UniProtKB:P08775,
CC ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:23748380,
CC ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26124092,
CC ECO:0000269|PubMed:9852112}.
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 replicate 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;
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;
CC -!- SUBUNIT: Component of the RNA polymerase II (Pol II) complex consisting
CC of 12 subunits. Component of a complex which is at least composed of
CC HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA
CC polymerase II, SUPT5H, and NCL/nucleolin. The large PER complex
CC involved in the repression of transcriptional termination is composed
CC of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active).
CC Interacts (via the C-terminal domain (CTD)) with U2AF2; recruits PRPF19
CC and the Prp19 complex to the pre-mRNA and may couple transcription to
CC pre-mRNA splicing. Interacts (via the C-terminal domain (CTD)) with
CC SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes.
CC Interacts via the phosphorylated C-terminal domain with WDR82 and with
CC SETD1A and SETD1B only in the presence of WDR82. When phosphorylated at
CC 'Ser-5', interacts with MEN1; the unphosphorylated form, or
CC phosphorylated at 'Ser-2' does not interact. When phosphorylated at
CC 'Ser-2', interacts with SUPT6H (via SH2 domain). Interacts with RECQL5
CC and TCEA1; binding of RECQL5 prevents TCEA1 binding. The phosphorylated
CC C-terminal domain interacts with FNBP3 and SYNCRIP. Interacts with
CC ATF7IP. Interacts with DDX5. Interacts with WWP2. Interacts with SETX.
CC Interacts (phosphorylated) with PIH1D1. Interacts (via the C-terminal
CC domain (CTD)) with TDRD3. Interacts with PRMT5. Interacts with XRN2.
CC Interacts with SAFB/SAFB1. Interacts with CCNL1. Interacts with CCNL2,
CC MYO1C, PAF1 and SFRS19. Interacts (via C-terminus) with CMTR1, CTDSP1
CC and SCAF8. Interacts (via the C-terminal domain (CTD)) with CCNT2
CC (PubMed:15563843). Interacts with FUS. Interacts with MCM3AP isoform
CC GANP (PubMed:23652018). Interacts with kinase SRPK2; the interaction
CC occurs during the co-transcriptional formation of inappropriate R-loops
CC (PubMed:28076779). {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:28076779, ECO:0000269|PubMed:9671816,
CC ECO:0000269|PubMed:9852112}.
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 -!- 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. {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 -!- 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 UV treatment, the elongating form of RNA
CC polymerase II (RNA pol IIo) is ubiquitinated on UV damage sites without
CC leading to degradation: ubiquitination is facilitated by KIAA1530/UVSSA
CC and promotes RNA pol IIo backtracking to allow access to the nucleotide
CC excision repair machinery. {ECO:0000250|UniProtKB:P08775,
CC ECO:0000269|PubMed:22466610}.
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 -!- MISCELLANEOUS: The binding of ribonucleoside triphosphate to the RNA
CC polymerase II transcribing complex probably involves a two-step
CC mechanism. The initial binding seems to occur at the entry (E) site and
CC involves a magnesium ion temporarily coordinated by three conserved
CC aspartate residues of the two largest RNA Pol II subunits. The
CC ribonucleoside triphosphate is transferred by a rotation to the
CC nucleotide addition (A) site for pairing with the template DNA. The
CC catalytic A site involves three conserved aspartate residues of the RNA
CC Pol II largest subunit which permanently coordinate a second magnesium
CC ion.
CC -!- SIMILARITY: Belongs to the RNA polymerase beta' chain family.
CC {ECO:0000305}.
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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 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 AlphaFoldDB; P24928; -.
DR SMR; P24928; -.
DR BioGRID; 111426; 435.
DR CORUM; P24928; -.
DR DIP; DIP-29011N; -.
DR IntAct; P24928; 137.
DR MINT; P24928; -.
DR STRING; 9606.ENSP00000480158; -.
DR BindingDB; P24928; -.
DR ChEMBL; CHEMBL1641353; -.
DR GlyGen; P24928; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P24928; -.
DR MetOSite; P24928; -.
DR PhosphoSitePlus; P24928; -.
DR BioMuta; POLR2A; -.
DR DMDM; 281185484; -.
DR EPD; P24928; -.
DR jPOST; P24928; -.
DR MassIVE; P24928; -.
DR MaxQB; P24928; -.
DR PaxDb; P24928; -.
DR PeptideAtlas; P24928; -.
DR PRIDE; P24928; -.
DR ProteomicsDB; 54240; -. [P24928-1]
DR ProteomicsDB; 66745; -.
DR ABCD; P24928; 7 sequenced antibodies.
DR DNASU; 5430; -.
DR GeneID; 5430; -.
DR KEGG; hsa:5430; -.
DR UCSC; uc002ghe.4; human. [P24928-1]
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; 591636at2759; -.
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; 805 hits in 1094 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 Genevisible; P24928; HS.
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:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003968; F:RNA-directed 5'-3' 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 transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:UniProtKB.
DR DisProt; DP01284; -.
DR Gene3D; 1.10.132.30; -; 1.
DR Gene3D; 1.10.274.100; -; 1.
DR Gene3D; 3.30.1360.140; -; 1.
DR Gene3D; 4.10.860.120; -; 2.
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; PTHR19376; 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; 42.
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; Chromosome; Cytoplasm;
KW Disease variant; DNA-binding; DNA-directed RNA polymerase;
KW Host-virus interaction; Intellectual disability; Magnesium; Metal-binding;
KW Methylation; Nucleotidyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-directed RNA polymerase; Transcription;
KW Transferase; 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 REPEAT 1600..1606
FT /note="2; approximate"
FT REPEAT 1608..1614
FT /note="3"
FT REPEAT 1615..1621
FT /note="4"
FT REPEAT 1622..1628
FT /note="5"
FT REPEAT 1629..1635
FT /note="6"
FT REPEAT 1636..1642
FT /note="7"
FT REPEAT 1643..1649
FT /note="8"
FT REPEAT 1650..1656
FT /note="9"
FT REPEAT 1657..1663
FT /note="10"
FT REPEAT 1664..1670
FT /note="11"
FT REPEAT 1671..1677
FT /note="12"
FT REPEAT 1678..1684
FT /note="13"
FT REPEAT 1685..1691
FT /note="14"
FT REPEAT 1692..1698
FT /note="15"
FT REPEAT 1699..1705
FT /note="16"
FT REPEAT 1706..1712
FT /note="17"
FT REPEAT 1713..1719
FT /note="18"
FT REPEAT 1720..1726
FT /note="19"
FT REPEAT 1727..1733
FT /note="20"
FT REPEAT 1734..1740
FT /note="21"
FT REPEAT 1741..1747
FT /note="22"
FT REPEAT 1748..1754
FT /note="23"
FT REPEAT 1755..1761
FT /note="24"
FT REPEAT 1762..1768
FT /note="25"
FT REPEAT 1769..1775
FT /note="26"
FT REPEAT 1776..1782
FT /note="27"
FT REPEAT 1783..1789
FT /note="28"
FT REPEAT 1790..1796
FT /note="29"
FT REPEAT 1797..1803
FT /note="30"
FT REPEAT 1804..1810
FT /note="31"
FT REPEAT 1811..1817
FT /note="32"
FT REPEAT 1818..1824
FT /note="33"
FT REPEAT 1825..1831
FT /note="34"
FT REPEAT 1832..1838
FT /note="35"
FT REPEAT 1839..1845
FT /note="36"
FT REPEAT 1846..1852
FT /note="37"
FT REPEAT 1853..1859
FT /note="38"
FT REPEAT 1860..1866
FT /note="39"
FT REPEAT 1867..1873
FT /note="40"
FT REPEAT 1874..1880
FT /note="41"
FT REPEAT 1881..1887
FT /note="42"
FT REPEAT 1888..1894
FT /note="43"
FT REPEAT 1895..1901
FT /note="44"
FT REPEAT 1902..1908
FT /note="45"
FT REPEAT 1909..1915
FT /note="46"
FT REPEAT 1916..1922
FT /note="47"
FT REPEAT 1923..1929
FT /note="48"
FT REPEAT 1930..1936
FT /note="49"
FT REPEAT 1940..1946
FT /note="50"
FT REPEAT 1947..1953
FT /note="51; approximate"
FT REPEAT 1954..1960
FT /note="52; approximate"
FT REGION 833..845
FT /note="Bridging helix"
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 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 495
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 495
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="ligand shared with RPB2"
FT /evidence="ECO:0000250"
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"
FT BINDING 497
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="ligand shared with RPB2"
FT /evidence="ECO:0000250"
FT BINDING 499
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
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 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; mild; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31353023"
FT /id="VAR_082988"
FT VARIANT 457
FT /note="I -> T (in NEDHIB; severe; unknown pathological
FT significance; no effect on cell viability)"
FT /evidence="ECO:0000269|PubMed:31353023"
FT /id="VAR_082989"
FT VARIANT 531
FT /note="N -> S (in NEDHIB; unknown pathological
FT significance; no effect 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; mild; unknown pathological
FT significance; decreased cell viability)"
FT /evidence="ECO:0000269|PubMed:31353023"
FT /id="VAR_082995"
FT VARIANT 769
FT /note="M -> T (in NEDHIB; severe; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31353023"
FT /id="VAR_082996"
FT VARIANT 848
FT /note="I -> T (in NEDHIB; moderate; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31353023"
FT /id="VAR_082997"
FT VARIANT 1109
FT /note="Y -> H (in NEDHIB; moderate; unknown pathological
FT significance)"
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; mild; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31353023"
FT /id="VAR_083000"
FT VARIANT 1251
FT /note="N -> S (in NEDHIB; severe; unknown pathological
FT significance; no effect on cell viability)"
FT /evidence="ECO:0000269|PubMed:31353023"
FT /id="VAR_083001"
FT VARIANT 1603
FT /note="R -> H (in NEDHIB; moderate; unknown pathological
FT significance; 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 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 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
