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UniProtKB/Swiss-Prot entry P24928


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name RPB1_HUMAN
Primary accession number P24928
Secondary accession numbers None
Integrated into Swiss-Prot on March 1, 1992
Sequence was last modified on March 1, 1992 (Sequence version 1)
Annotations were last modified on    November 25, 2008 (Entry version 93)
Name and origin of the protein
Protein name DNA-directed RNA polymerase II subunit RPB1
Synonyms RNA polymerase II subunit B1
EC 2.7.7.6
DNA-directed RNA polymerase II subunit A
DNA-directed RNA polymerase III largest subunit
Gene name
Name: POLR2A
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1093/nar/20.4.910; PubMed=1542581 [NCBI, ExPASy, EBI, Israel, Japan]
Wintzerith M., Acker J., Vicaire S., Vigneron M., Kedinger C.;
"Complete sequence of the human RNA polymerase II largest subunit.";
Nucleic Acids Res. 20:910-910(1992).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1016/0378-1119(95)00081-G; PubMed=7622068 [NCBI, ExPASy, EBI, Israel, Japan]
Mita K., Tsuji H., Morimyo M., Takahashi E., Nenoi M., Ichimura S., Yamauchi M., Hongo E., Hayashi A.;
"The human gene encoding the largest subunit of RNA polymerase II.";
Gene 159:285-286(1995).
[3]
INTERACTION WITH SAFB.
DOI=10.1093/nar/26.15.3542; PubMed=9671816 [NCBI, ExPASy, EBI, Israel, Japan]
Nayler O., Straetling W., Bourquin J.-P., Stagljar I., Lindemann L., Jasper H., Hartmann A.M., Fackelmeyer F.O., Ullrich A., Stamm S.;
"SAF-B couples transcription and pre-mRNA splicing to SAR/MAR elements.";
Nucleic Acids Res. 26:3542-3549(1998).
[4]
IDENTIFICATION IN A COMPLEX WITH HTATSF1; CCNT1; NCL; SUPT5H AND CDK9.
DOI=10.1093/emboj/18.13.3688; PubMed=10393184 [NCBI, ExPASy, EBI, Israel, Japan]
Parada C.A., Roeder R.G.;
"A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription.";
EMBO J. 18:3688-3701(1999).
[5]
INTERACTION WITH HTATSF1.
PubMed=10454543 [NCBI, ExPASy, EBI, Israel, Japan]
Kim J.B., Yamaguchi Y., Wada T., Handa H., Sharp P.A.;
"Tat-SF1 protein associates with RAP30 and human SPT5 proteins.";
Mol. Cell. Biol. 19:5960-5968(1999).
[6]
INTERACTION WITH FNBP3.
DOI=10.1016/S0022-2836(02)00968-3; PubMed=12381297 [NCBI, ExPASy, EBI, Israel, Japan]
Allen M., Friedler A., Schon O., Bycroft M.;
"The structure of an FF domain from human HYPA/FBP11.";
J. Mol. Biol. 323:411-416(2002).
[7]
INTERACTION WITH SYNCRIP.
DOI=10.1074/mcp.M200029-MCP200; PubMed=12376575 [NCBI, ExPASy, EBI, Israel, Japan]
Carty S.M., Greenleaf A.L.;
"Hyperphosphorylated C-terminal repeat domain-associating proteins in the nuclear proteome link transcription to DNA/chromatin modification and RNA processing.";
Mol. Cell. Proteomics 1:598-610(2002).
[8]
INTERACTION WITH CCNL2.
DOI=10.1074/jbc.M312895200; PubMed=14684736 [NCBI, ExPASy, EBI, Israel, Japan]
Yang L., Li N., Wang C., Yu Y., Yuan L., Zhang M., Cao X.;
"Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells.";
J. Biol. Chem. 279:11639-11648(2004).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1896 AND SER-1934, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[10]
INTERACTION WITH SFRS19.
DOI=10.1016/j.bbrc.2005.06.053; PubMed=15992770 [NCBI, ExPASy, EBI, Israel, Japan]
Katsarou M.E., Papakyriakou A., Katsaros N., Scorilas A.;
"Expression of the C-terminal domain of novel human SR-A1 protein: interaction with the CTD domain of RNA polymerase II.";
Biochem. Biophys. Res. Commun. 334:61-68(2005).
[11]
INTERACTION WITH SETD2.
DOI=10.1074/jbc.M504012200; PubMed=16118227 [NCBI, ExPASy, EBI, Israel, Japan]
Sun X.-J., Wei J., Wu X.-Y., Hu M., Wang L., Wang H.-H., Zhang Q.-H., Chen S.-J., Huang Q.-H., Chen Z.;
"Identification and characterization of a novel human histone H3 lysine 36 specific methyltransferase.";
J. Biol. Chem. 280:35261-35271(2005).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-145, AND MASS SPECTROMETRY.
DOI=10.1038/nbt1046; PubMed=15592455 [NCBI, ExPASy, EBI, Israel, Japan]
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.;
"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
Nat. Biotechnol. 23:94-101(2005).
[13]
INTERACTION WITH SETD2.
DOI=10.1073/pnas.0506350102; PubMed=16314571 [NCBI, ExPASy, EBI, Israel, Japan]
Li M., Phatnani H.P., Guan Z., Sage H., Greenleaf A.L., Zhou P.;
"Solution structure of the Set2-Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1.";
Proc. Natl. Acad. Sci. U.S.A. 102:17636-17641(2005).
[14]
INTERACTION WITH PAF1 IN PAF1/RNA POLYMERASE II.
TISSUE=Fetal pancreas;
DOI=10.1038/sj.onc.1209353; PubMed=16491129 [NCBI, ExPASy, EBI, Israel, Japan]
Moniaux N., Nemos C., Schmied B.M., Chauhan S.C., Deb S., Morikane K., Choudhury A., Vanlith M., Sutherlin M., Sikela J.M., Hollingsworth M.A., Batra S.K.;
"The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis.";
Oncogene 25:3247-3257(2006).
[15]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-772 AND SER-777, AND MASS SPECTROMETRY.
DOI=10.2116/analsci.24.161; PubMed=18187866 [NCBI, ExPASy, EBI, Israel, Japan]
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Anal. Sci. 24:161-166(2008).
Comments
  • FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing.
  • CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
  • SUBUNIT: Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits (By similarity). The phosphorylated C-terminal domain interacts with FNBP3 and SYNCRIP. Interacts with SAFB/SAFB1. Interacts with CCNL1 (By similarity). Interacts with CCNL2 and SFRS19. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. Interacts with PAF1.
  • INTERACTION:
    Q86UL8:MAGI2; NbExp=1; IntAct=EBI-295301, EBI-311035;
    O00267:SUPT5H; NbExp=2; IntAct=EBI-295301, EBI-710464;
    Q9HCS7:XAB2; NbExp=1; IntAct=EBI-295301, EBI-295232;
  • SUBCELLULAR LOCATION: Nucleus.
  • PTM: The tandem 7 residues repeats in the C-terminal domain (CTD) can be highly phosphorylated. The phosphorylation activates Pol II. Phosphorylation occurs mainly at residues 'Ser-2' and 'Ser-5' of the heptapepdtide repeat. The phosphorylation state is believed to result from the balanced action of site-specific CTD kinases and phosphataes, and a "CTD code" that specifies the position of Pol II within the transcription cycle has been proposed.
  • MISCELLANEOUS: The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion temporarily coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits. The ribonucleoside triphosphate is transferred by a rotation to the nucelotide addition (A) site for pairing with the template DNA. The catalytic A site involves three conserved aspartate residues of the RNA Pol II largest subunit which permanently coordinate a second magnesium ion.
  • SIMILARITY: Belongs to the RNA polymerase beta' chain family.
  • SIMILARITY: Contains 1 C2H2-type zinc finger.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X63564; CAA45125.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X74874; CAA52862.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X74873; CAA52862.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X74872; CAA52862.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X74871; CAA52862.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X74870; CAA52862.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR I38186; I38186.
S21054; S21054.
RefSeq NP_000928.1; -.
UniGene Hs.270017
3D structure databases
PDB
2GHQ; X-ray; 2.05 A; D=1725-1733.[ExPASy / RCSB / EBI]
PDBsum 2GHQ; -.
ModBase P24928.
Protein-protein interaction databases
DIP DIP:29011N; -.
IntAct P24928; -.
PTM databases
PhosphoSite P24928; -.
Enzyme and pathway databases
Reactome REACT_1675; mRNA Processing.
REACT_1788; Transcription.
REACT_1892; Elongation arrest and recovery.
REACT_216; DNA Repair.
REACT_6143; Pausing and recovery of Tat-mediated HIV-1 elongation.
REACT_6167; Influenza Infection.
REACT_6185; HIV Infection.
REACT_6244; Pausing and recovery of HIV-1 elongation.
REACT_6259; HIV-1 elongation arrest and recovery.
REACT_6344; Tat-mediated HIV-1 elongation arrest and recovery.
REACT_71; Gene Expression.
REACT_769; Pausing and recovery of elongation.
Organism-specific databases
H-InvDB HIX0039202; -.
HGNC HGNC:9187; POLR2A.
GenAtlas POLR2A.
HPA CAB012226; -.
CAB016388; -.
MIM 180660; gene+phenotype. [NCBI / EBI]
PharmGKB PA33507; -.
GeneCards P24928.
Gene expression databases
ArrayExpress P24928; -.
CleanEx HS_POLR2A; -.
GermOnline ENSG00000181222; Homo sapiens.
Ontologies
GO
GO:0005665; Cellular component: DNA-directed RNA polymerase II, core complex (traceable author statement from ProtInc).
GO:0005730; Cellular component: nucleolus (inferred from direct assay from MGI).
GO:0003677; Molecular function: DNA binding (non-traceable author statement from UniProtKB).
GO:0003899; Molecular function: DNA-directed RNA polymerase activity (non-traceable author statement from UniProtKB).
GO:0000287; Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0031625; Molecular function: ubiquitin protein ligase binding (inferred from physical interaction from UniProtKB).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0000398; Biological process: nuclear mRNA splicing, via spliceosome (inferred from experiment from Reactome).
GO:0006355; Biological process: regulation of transcription, DNA-dependent (non-traceable author statement from UniProtKB).
GO:0006368; Biological process: RNA elongation from RNA polymerase II promoter (inferred from experiment from Reactome).
GO:0006367; Biological process: transcription initiation from RNA polymerase II promoter (inferred from experiment from Reactome).
QuickGo view.
Family and domain databases
InterPro IPR000722; RNA_pol_A.
IPR000684; RNA_pol_II_repeat_euk.
IPR006592; RNA_pol_N.
IPR007080; RNA_pol_Rpb1_1.
IPR007066; RNA_pol_Rpb1_3.
IPR007083; RNA_pol_Rpb1_4.
IPR007081; RNA_pol_Rpb1_5.
IPR007075; RNA_pol_Rpb1_6.
IPR007073; RNA_pol_Rpb1_7.
Graphical view of domain structure.
Gene3D G3DSA:2.40.40.30; RNA_pol_A; 1.
G3DSA:3.90.1120.10; RNA_pol_Rpb1_1; 1.
G3DSA:3.30.1360.90; RNA_pol_Rpb1_7; 1.
Pfam PF04997; RNA_pol_Rpb1_1; 1.
PF00623; RNA_pol_Rpb1_2; 1.
PF04983; RNA_pol_Rpb1_3; 1.
PF05000; RNA_pol_Rpb1_4; 1.
PF04998; RNA_pol_Rpb1_5; 1.
PF04992; RNA_pol_Rpb1_6; 1.
PF04990; RNA_pol_Rpb1_7; 1.
PF05001; RNA_pol_Rpb1_R; 26.
Pfam graphical view of domain structure.
SMART SM00663; RPOLA_N; 1.
SMART graphical view of domain structure.
PROSITE PS00115; RNA_POL_II_REPEAT; 43.
ProtoNet P24928.
Genome annotation databases
Ensembl ENSG00000181222; Homo sapiens. [Contig view]
GeneID 5430; -.
KEGG hsa:5430; -.
Phylogenomic databases
HOVERGEN P24928; -.
Other
LinkHub P24928; -.
NextBio 21009; -.
SOURCE POLR2A; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; DNA-binding; DNA-directed RNA polymerase; Magnesium; Metal-binding; Nucleotidyltransferase; Nucleus; Phosphoprotein; Repeat; Transcription; Transferase; Zinc; Zinc-finger.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
CHAIN   1   1970  1970     DNA-directed RNA polymerase II subunit RPB1. PRO_0000073940
REPEAT   1593   1599  7     1. 
REPEAT   1600   1606  7     2; approximate. 
REPEAT   1608   1614  7     3. 
REPEAT   1615   1621  7     4. 
REPEAT   1622   1628  7     5. 
REPEAT   1629   1635  7     6. 
REPEAT   1636   1642  7     7. 
REPEAT   1643   1649  7     8. 
REPEAT   1650   1656  7     9. 
REPEAT   1657   1663  7     10. 
REPEAT   1664   1670  7     11. 
REPEAT   1671   1677  7     12. 
REPEAT   1678   1684  7     13. 
REPEAT   1685   1691  7     14. 
REPEAT   1692   1698  7     15. 
REPEAT   1699   1705  7     16. 
REPEAT   1706   1712  7     17. 
REPEAT   1713   1719  7     18. 
REPEAT   1720   1726  7     19. 
REPEAT   1727   1733  7     20. 
REPEAT   1734   1740  7     21. 
REPEAT   1741   1747  7     22. 
REPEAT   1748   1754  7     23. 
REPEAT   1755   1761  7     24. 
REPEAT   1762   1768  7     25. 
REPEAT   1769   1775  7     26. 
REPEAT   1776   1782  7     27. 
REPEAT   1783   1789  7     28. 
REPEAT   1790   1796  7     29. 
REPEAT   1797   1803  7     30. 
REPEAT   1804   1810  7     31. 
REPEAT   1811   1817  7     32. 
REPEAT   1818   1824  7     33. 
REPEAT   1825   1831  7     34. 
REPEAT   1832   1838  7     35. 
REPEAT   1839   1845  7     36. 
REPEAT   1846   1852  7     37. 
REPEAT   1853   1859  7     38. 
REPEAT   1860   1866  7     39. 
REPEAT   1867   1873  7     40. 
REPEAT   1874   1880  7     41. 
REPEAT   1881   1887  7     42. 
REPEAT   1888   1894  7     43. 
REPEAT   1895   1901  7     44. 
REPEAT   1902   1908  7     45. 
REPEAT   1909   1915  7     46. 
REPEAT   1916   1922  7     47. 
REPEAT   1923   1929  7     48. 
REPEAT   1930   1936  7     49. 
REPEAT   1940   1946  7     50. 
REPEAT   1947   1953  7     51; approximate. 
REPEAT   1954   1960  7     52; approximate. 
ZN_FING   71     87  17     C2H2-type (By similarity). 
REGION   833    845  13     Bridging helix. 
REGION   1593   1960  368     52 X 7 AA approximate tandem repeats of Y-[ST]-P-[STQ]-[ST]-P-[SRTEVKGN]. 
METAL   71     71        Zinc 1 (By similarity). 
METAL   74     74        Zinc 1 (By similarity). 
METAL   81     81        Zinc 1 (By similarity). 
METAL   84     84        Zinc 1 (By similarity). 
METAL   111    111        Zinc 2 (By similarity). 
METAL   114    114        Zinc 2 (By similarity). 
METAL   154    154        Zinc 2 (By similarity). 
METAL   184    184        Zinc 2 (By similarity). 
METAL   495    495        Magnesium 1; catalytic (By similarity). 
METAL   495    495        Magnesium 2; shared with RPB2 (By similarity). 
METAL   497    497        Magnesium 1; catalytic (By similarity). 
METAL   497    497        Magnesium 2; shared with RPB2 (By similarity). 
METAL   499    499        Magnesium 1; catalytic (By similarity). 
MOD_RES   145    145        Phosphotyrosine. 
MOD_RES   772    772        Phosphoserine. 
MOD_RES   777    777        Phosphoserine. 
MOD_RES   1878   1878        Phosphoserine (By similarity). 
MOD_RES   1896   1896        Phosphoserine. 
MOD_RES   1923   1923        Phosphotyrosine (By similarity). 
MOD_RES   1927   1927        Phosphoserine (By similarity). 
MOD_RES   1933   1933        Phosphothreonine (By similarity). 
MOD_RES   1934   1934        Phosphoserine. 
CONFLICT   1067   1067        W -> L (in Ref. 2; CAA52862). 
CONFLICT   1449   1449        D -> Y (in Ref. 2; CAA52862). 
Sequence information
Length: 1970 AA [This is the length of the unprocessed precursor] Molecular weight: 217206 Da [This is the MW of the unprocessed precursor] CRC64: 6876FC25692A657E [This is a checksum on the sequence]
        10         20         30         40         50         60 
MHGGGPPSGD SACPLRTIKR VQFGVLSPDE LKRMSVTEGG IKYPETTEGG RPKLGGLMDP 

        70         80         90        100        110        120 
RQGVIERTGR CQTCAGNMTE CPGHFGHIEL AKPVFHVGFL VKTMKVLRCV CFFCSKLLVD 

       130        140        150        160        170        180 
SNNPKIKDIL AKSKGQPKKR LTHVYDLCKG KNICEGGEEM DNKFGVEQPE GDEDLTKEKG 

       190        200        210        220        230        240 
HGGCGRYQPR IRRSGLELYA EWKHVNEDSQ EKKILLSPER VHEIFKRISD EECFVLGMEP 

       250        260        270        280        290        300 
RYARPEWMIV TVLPVPPLSV RPAVVMQGSA RNQDDLTHKL ADIVKINNQL RRNEQNGAAA 

       310        320        330        340        350        360 
HVIAEDVKLL QFHVATMVDN ELPGLPRAMQ KSGRPLKSLK QRLKGKEGRV RGNLMGKRVD 

       370        380        390        400        410        420 
FSARTVITPD PNLSIDQVGV PRSIAANMTF AEIVTPFNID RLQELVRRGN SQYPGAKYII 

       430        440        450        460        470        480 
RDNGDRIDLR FHPKPSDLHL QTGYKVERHM CDGDIVIFNR QPTLHKMSMM GHRVRILPWS 

       490        500        510        520        530        540 
TFRLNLSVTT PYNADFDGDE MNLHLPQSLE TRAEIQELAM VPRMIVTPQS NRPVMGIVQD 

       550        560        570        580        590        600 
TLTAVRKFTK RDVFLERGEV