G3MZY8 · RPB1_BOVIN
- ProteinDNA-directed RNA polymerase II subunit RPB1
- GenePOLR2A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1970 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates (PubMed:16769904, PubMed:26789250).
Pol II-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol II pre-initiation complex (PIC) is recruited to DNA promoters, with focused-type promoters containing either the initiator (Inr) element, or the TATA-box found in cell-type specific genes and dispersed-type promoters that often contain hypomethylated CpG islands usually found in housekeeping genes. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Transcription termination involves the release of the RNA transcript and polymerase from the DNA (By similarity) (PubMed:16769904, PubMed:26789250).
Forms Pol II active center together with the second largest subunit POLR2B/RPB2. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR2A/RPB1 most likely contributing a Mg2+-coordinating DxDGD motif, and POLR2B/RPB2 participating in the coordination of a second Mg2+ ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg2+ ions direct a 5' nucleoside triphosphate to form a phosphodiester bond with the 3' hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. The reversible pyrophosphorolysis can occur at high pyrophosphate concentrations (PubMed:16769904, PubMed:26789250).
Can proofread the nascent RNA transcript by means of a 3' -> 5' exonuclease activity. If a ribonucleotide is mis-incorporated, backtracks along the template DNA and cleaves the phosphodiester bond releasing the mis-incorporated 5'-ribonucleotide (By similarity) (PubMed:9604937).
Through its unique C-terminal domain (CTD, 52 heptapeptide tandem repeats) serves as a platform for assembly of factors that regulate transcription initiation, elongation and termination. CTD phosphorylation on Ser-5 mediates Pol II promoter escape, whereas phosphorylation on Ser-2 is required for Pol II pause release during transcription elongation and further pre-mRNA processing. Additionally, the regulation of gene expression levels depends on the balance between methylation and acetylation levels of the CTD-lysines. Initiation or early elongation steps of transcription of growth-factor-induced immediate early genes are regulated by the acetylation status of the CTD. Methylation and dimethylation have a repressive effect on target genes expression. Cooperates with mRNA splicing machinery in co-transcriptional 5'-end capping and co-transcriptional splicing of pre-mRNA (By similarity).
Pol II-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol II pre-initiation complex (PIC) is recruited to DNA promoters, with focused-type promoters containing either the initiator (Inr) element, or the TATA-box found in cell-type specific genes and dispersed-type promoters that often contain hypomethylated CpG islands usually found in housekeeping genes. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Transcription termination involves the release of the RNA transcript and polymerase from the DNA (By similarity) (PubMed:16769904, PubMed:26789250).
Forms Pol II active center together with the second largest subunit POLR2B/RPB2. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR2A/RPB1 most likely contributing a Mg2+-coordinating DxDGD motif, and POLR2B/RPB2 participating in the coordination of a second Mg2+ ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg2+ ions direct a 5' nucleoside triphosphate to form a phosphodiester bond with the 3' hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. The reversible pyrophosphorolysis can occur at high pyrophosphate concentrations (PubMed:16769904, PubMed:26789250).
Can proofread the nascent RNA transcript by means of a 3' -> 5' exonuclease activity. If a ribonucleotide is mis-incorporated, backtracks along the template DNA and cleaves the phosphodiester bond releasing the mis-incorporated 5'-ribonucleotide (By similarity) (PubMed:9604937).
Through its unique C-terminal domain (CTD, 52 heptapeptide tandem repeats) serves as a platform for assembly of factors that regulate transcription initiation, elongation and termination. CTD phosphorylation on Ser-5 mediates Pol II promoter escape, whereas phosphorylation on Ser-2 is required for Pol II pause release during transcription elongation and further pre-mRNA processing. Additionally, the regulation of gene expression levels depends on the balance between methylation and acetylation levels of the CTD-lysines. Initiation or early elongation steps of transcription of growth-factor-induced immediate early genes are regulated by the acetylation status of the CTD. Methylation and dimethylation have a repressive effect on target genes expression. Cooperates with mRNA splicing machinery in co-transcriptional 5'-end capping and co-transcriptional splicing of pre-mRNA (By similarity).
RNA-dependent RNA polymerase that catalyzes the extension of a non-coding RNA (ncRNA) at the 3'-end using the four ribonucleoside triphosphates as substrates. An internal ncRNA sequence near the 3'-end serves as a template in a single-round Pol II-mediated RNA polymerization reaction. May decrease the stability of ncRNAs that repress Pol II-mediated gene transcription.
Catalytic activity
- a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)This reaction proceeds in the forward and the backward directions.
- a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)This reaction proceeds in the forward direction.
- a 3'-end ribonucleotidyl-ribonucleotide-RNA + H2O = a 3'-end ribonucleotide-RNA + a ribonucleoside 5'-phosphate + H+This reaction proceeds in the forward direction.
Cofactor
Note: Two Mg2+ ions are coordinated by both the catalytic residues and the nucleic acid substrate to enhance substrate recognition and catalytic efficiency.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 67 | RNA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 71 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 74 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 81 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 84 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 111 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 114 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 154 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 184 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 346 | DNA template strand (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 358 | DNA template strand (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 460 | RNA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 493 | Mg2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: N | ||||||
Binding site | 495 | Mg2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 495 | Mg2+ 2 (UniProtKB | ChEBI); ligand shared with POLR2B/RPB2 | ||||
Sequence: D | ||||||
Binding site | 497 | Mg2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 497 | Mg2+ 2 (UniProtKB | ChEBI); ligand shared with POLR2B/RPB2 | ||||
Sequence: D | ||||||
Binding site | 499 | Mg2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 499 | RNA (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1416 | DNA template strand (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1421 | DNA nontemplate strand (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | euchromatin | |
Cellular Component | RNA polymerase II, core complex | |
Molecular Function | core promoter sequence-specific DNA binding | |
Molecular Function | DNA-directed 5'-3' RNA polymerase activity | |
Molecular Function | DNA/RNA hybrid binding | |
Molecular Function | hydrolase activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | RNA-dependent RNA polymerase activity | |
Molecular Function | zinc ion binding | |
Biological Process | transcription by RNA polymerase II |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA-directed RNA polymerase II subunit RPB1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionG3MZY8
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Hypophosphorylated form is mainly found in the cytoplasm, while the hyperphosphorylated and active form is nuclear. Co-localizes with kinase SRPK2 and helicase DDX23 at chromatin loci where unscheduled R-loops form.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000459629 | 1-1970 | DNA-directed RNA polymerase II subunit RPB1 | |||
Sequence: MHGGGPPSGDSACPLRTIKRVQFGVLSPDELKRMSVTEGGIKYPETTEGGRPKLGGLMDPRQGVIERTGRCQTCAGNMTECPGHFGHIELAKPVFHVGFLVKTMKVLRCVCFFCSKLLVDSNNPKIKDILAKSKGQPKKRLTHVYDLCKGKNICEGGEEMDNKFGVEQPEGDEDLTKEKGHGGCGRYQPRIRRSGLELYAEWKHVNEDSQEKKILLSPERVHEIFKRISDEECFVLGMEPRYARPEWMIVTVLPVPPLSVRPAVVMQGSARNQDDLTHKLADIVKINNQLRRNEQNGAAAHVIAEDVKLLQFHVATMVDNELPGLPRAMQKSGRPLKSLKQRLKGKEGRVRGNLMGKRVDFSARTVITPDPNLSIDQVGVPRSIAANMTFAEIVTPFNIDRLQELVRRGNSQYPGAKYIIRDNGDRIDLRFHPKPSDLHLQTGYKVERHMCDGDIVIFNRQPTLHKMSMMGHRVRILPWSTFRLNLSVTTPYNADFDGDEMNLHLPQSLETRAEIQELAMVPRMIVTPQSNRPVMGIVQDTLTAVRKFTKRDVFLERGEVMNLLMFLSTWDGKVPQPAILKPRPLWTGKQIFSLIIPGHINCIRTHSTHPDDEDSGPYKHISPGDTKVVVENGELIMGILCKKSLGTSAGSLVHISYLEMGHDITRLFYSNIQTVINNWLLIEGHTIGIGDSIADSKTYQDIQNTIKKAKQDVIEVIEKAHNNELEPTPGNTLRQTFENQVNRILNDARDKTGSSAQKSLSEYNNFKSMVVSGAKGSKINISQVIAVVGQQNVEGKRIPFGFKHRTLPHFIKDDYGPESRGFVENSYLAGLTPTEFFFHAMGGREGLIDTAVKTAETGYIQRRLIKSMESVMVKYDATVRNSINQVVQLRYGEDGLAGESVEFQNLATLKPSNKAFEKKFRFDYTNERALRRTLQEDLVKDVLSNAHIQNELEREFERMREDREVLRVIFPTGDSKVVLPCNLLRMIWNAQKIFHINPRLPSDLHPIKVVEGVKELSKKLVIVNGDDPLSRQAQENATLLFNIHLRSTLCSRRMAEEFRLSGEAFDWLLGEIESKFNQAIAHPGEMVGALAAQSLGEPATQMTLNTFHYAGVSAKNVTLGVPRLKELINISKKPKTPSLTVFLLGQSARDAERAKDILCRLEHTTLRKVTANTAIYYDPNPQSTVVAEDQEWVNVYYEMPDFDVARISPWLLRVELDRKHMTDRKLTMEQIAEKINAGFGDDLNCIFNDDNAEKLVLRIRIMNSDENKMQEEEEVVDKMDDDVFLRCIESNMLTDMTLQGIEQISKVYMHLPQTDNKKKIIITEDGEFKALQEWILETDGVSLMRVLSEKDVDPVRTTSNDIVEIFTVLGIEAVRKALERELYHVISFDGSYVNYRHLALLCDTMTCRGHLMAITRHGVNRQDTGPLMKCSFEETVDVLMEAAAHGESDPMKGVSENIMLGQLAPAGTGCFDLLLDAEKCKYGMEIPTNIPGLGAAGPTGMFFGSAPSPMGGISPAMTPWNQGATPAYGAWSPSVGSGMTPGAAGFSPSAASDASGFSPGYSPAWSPTPGSPGSPGPSSPYIPSPGGAMSPSYSPTSPAYEPRSPGGYTPQSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPNYTPTSPSYSPTSPSYSPTSPNYTPTSPNYSPTSPSYSPTSPSYSPTSPSYSPSSPRYTPQSPTYTPSSPSYSPSSPSYSPTSPKYTPTSPSYSPSSPEYTPTSPKYSPTSPKYSPTSPKYSPTSPTYSPTTPKYSPTSPTYSPTSPVYTPTSPKYSPTSPTYSPTSPKYSPTSPTYSPTSPKGSTYSPTSPGYSPTSPTYSLTSPAISPDDSDDEN | ||||||
Modified residue | 27 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 217 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 1268 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); by NEDD4 | ||||
Sequence: K | ||||||
Modified residue | 1603 | Omega-N-methylated arginine | ||||
Sequence: R | ||||||
Modified residue | 1810 | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 1810 | Symmetric dimethylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 1838 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1838 | N6-methyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1840 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1843 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1845 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1847 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1849 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1850 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1854 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1857 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1859 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1859 | N6-methyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1860 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1861 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1863 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1864 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1866 | N6,N6,N6-trimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1866 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1866 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1866 | N6-methyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1867 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1868 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1870 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1873 | N6,N6,N6-trimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1873 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1873 | N6-methyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1874 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1875 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1877 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1878 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1881 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1882 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1885 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1887 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1887 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1887 | N6-methyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1894 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1896 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1899 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1906 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1908 | N6,N6-dimethyllysine | ||||
Sequence: K | ||||||
Modified residue | 1909 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1912 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1913 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1915 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1916 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1917 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1919 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1920 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1922 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1922 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1922 | N6-methyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1923 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1926 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1927 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1929 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1930 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 1931 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1933 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1934 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1936 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1936 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 1936 | N6-methyllysine; alternate | ||||
Sequence: K |
Post-translational modification
The tandem heptapeptide 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 heptapeptide repeat and is mediated, at least, by CDK7 and CDK9. CDK7 phosphorylation of POLR2A associated with DNA promotes transcription initiation by triggering dissociation from DNA. Phosphorylation also takes place at 'Ser-7' of the heptapeptide repeat, which is required for efficient transcription of snRNA genes and processing of the transcripts. The phosphorylation state is believed to result from the balanced action of site-specific CTD kinases and phosphatases, and a 'CTD code' that specifies the position of Pol II within the transcription cycle has been proposed. Dephosphorylated by the protein phosphatase CTDSP1. Dephosphorylated at 'Ser-2' following UV irradiation.
Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated and dimethylated. EP300 is one of the enzyme able to acetylate 'Lys-7'. Acetylation at 'Lys-7' of non-consensus heptapeptide repeats is associated with 'Ser-2' phosphorylation and active transcription. Regulates initiation or early elongation steps of transcription specially for inducible genes.
Methylated at Arg-1810 prior to transcription initiation when the CTD is hypophosphorylated, phosphorylation at Ser-1805 and Ser-1808 preventing this methylation. Symmetrically or asymmetrically dimethylated at Arg-1810 by PRMT5 and CARM1 respectively. Symmetric or asymmetric dimethylation modulates interactions with CTD-binding proteins like SMN1/SMN2 and TDRD3. SMN1/SMN2 interacts preferentially with the symmetrically dimethylated form while TDRD3 interacts with the asymmetric form. Through the recruitment of SMN1/SMN2, symmetric dimethylation is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. CTD dimethylation may also facilitate the expression of select RNAs. Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated, dimethylated and trimethylated. Methylation occurs in the earliest transcription stages and precedes or is concomitant to 'Ser-5' and 'Ser-7' phosphorylation. Dimethylation and trimehtylation at 'Lys-7' of non-consensus heptapeptide repeats are exclusively associated with phosphorylated CTD.
Ubiquitinated by WWP2 leading to proteasomal degradation (By similarity).
Following transcription stress, the elongating form of RNA polymerase II (RNA pol IIo) is ubiquitinated by NEDD4 on Lys-1268 at DNA damage sites without leading to degradation: ubiquitination promotes RNA pol IIo backtracking to allow access by the transcription-coupled nucleotide excision repair (TC-NER) machinery. At stalled RNA pol II where TC-NER has failed, RBX1-mediated polybiquitination at Lys-1268 may lead to proteasome-mediated degradation in a UBAP2- and UBAP2L-dependent manner; presumably to halt global transcription and enable 'last resort' DNA repair pathways (By similarity).
Following transcription stress, the elongating form of RNA polymerase II (RNA pol IIo) is ubiquitinated by NEDD4 on Lys-1268 at DNA damage sites without leading to degradation: ubiquitination promotes RNA pol IIo backtracking to allow access by the transcription-coupled nucleotide excision repair (TC-NER) machinery. At stalled RNA pol II where TC-NER has failed, RBX1-mediated polybiquitination at Lys-1268 may lead to proteasome-mediated degradation in a UBAP2- and UBAP2L-dependent manner; presumably to halt global transcription and enable 'last resort' DNA repair pathways (By similarity).
Keywords
- PTM
Proteomic databases
Expression
Gene expression databases
Interaction
Subunit
Component of the RNA polymerase II (Pol II) core complex consisting of 12 subunits: a ten-subunit catalytic core composed of POLR2A/RPB1, POLR2B/RPB2, POLR2C/RPB3, POLR2I/RPB9, POLR2J/RPB11, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5 and a mobile stalk composed of two subunits POLR2D/RPB4 and POLR2G/RPB7, protruding from the core and functioning primarily in transcription initiation. Part of Pol II(G) complex, in which Pol II core associates with an additional subunit POLR2M; unlike conventional Pol II, Pol II(G) functions as a transcriptional repressor. Part of Pol II pre-initiation complex (PIC), in which Pol II core assembles with Mediator, general transcription factors and other specific initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and TBP; this large multi-subunit PIC complex mediates DNA unwinding and targets Pol II core to the transcription start site where the first phosphodiester bond forms (PubMed:16769904, PubMed:26789250, PubMed:28892040).
Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, Pol II, SUPT5H, and NCL/nucleolin. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts (via the C-terminal domain (CTD)) with U2AF2; recruits PRPF19 and the Prp19 complex to the pre-mRNA and may couple transcription to pre-mRNA splicing. Interacts (via the C-terminal domain (CTD)) with SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes. Interacts via the phosphorylated C-terminal domain with WDR82 and with SETD1A and SETD1B only in the presence of WDR82. When phosphorylated at 'Ser-5', interacts with MEN1; the unphosphorylated form, or phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-5', interacts with ZMYND8; the form phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-2', interacts with SUPT6H (via SH2 domain). Interacts with RECQL5 and TCEA1; binding of RECQL5 prevents TCEA1 binding. The phosphorylated C-terminal domain interacts with FNBP3. The phosphorylated C-terminal domain interacts with SYNCRIP. Interacts with ATF7IP. Interacts with DDX5 (By similarity).
Interacts with WWP2 (By similarity).
Interacts with SETX. Interacts (phosphorylated) with PIH1D1. Interacts (via the C-terminal domain (CTD)) with TDRD3. Interacts with PRMT5. Interacts with XRN2. Interacts with SAFB/SAFB1. Interacts with CCNL1. Interacts with CCNL2 (By similarity).
Interacts with MYO1C (By similarity).
Interacts with PAF1. Interacts with SFRS19. Interacts (via C-terminus) with CMTR1. Interacts (via C-terminus) with CTDSP1. Interacts (via C-terminus) with SCAF8. Interacts (via the C-terminal domain (CTD)) with CCNT2. Interacts with FUS. Interacts with MCM3AP isoform GANP. Interacts with kinase SRPK2; the interaction occurs during the co-transcriptional formation of inappropriate R-loops. Interacts with SETD2. Interacts with UVSSA. Interacts with ERCC6. Interacts with the TFIIH complex (By similarity).
Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, Pol II, SUPT5H, and NCL/nucleolin. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts (via the C-terminal domain (CTD)) with U2AF2; recruits PRPF19 and the Prp19 complex to the pre-mRNA and may couple transcription to pre-mRNA splicing. Interacts (via the C-terminal domain (CTD)) with SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes. Interacts via the phosphorylated C-terminal domain with WDR82 and with SETD1A and SETD1B only in the presence of WDR82. When phosphorylated at 'Ser-5', interacts with MEN1; the unphosphorylated form, or phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-5', interacts with ZMYND8; the form phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-2', interacts with SUPT6H (via SH2 domain). Interacts with RECQL5 and TCEA1; binding of RECQL5 prevents TCEA1 binding. The phosphorylated C-terminal domain interacts with FNBP3. The phosphorylated C-terminal domain interacts with SYNCRIP. Interacts with ATF7IP. Interacts with DDX5 (By similarity).
Interacts with WWP2 (By similarity).
Interacts with SETX. Interacts (phosphorylated) with PIH1D1. Interacts (via the C-terminal domain (CTD)) with TDRD3. Interacts with PRMT5. Interacts with XRN2. Interacts with SAFB/SAFB1. Interacts with CCNL1. Interacts with CCNL2 (By similarity).
Interacts with MYO1C (By similarity).
Interacts with PAF1. Interacts with SFRS19. Interacts (via C-terminus) with CMTR1. Interacts (via C-terminus) with CTDSP1. Interacts (via C-terminus) with SCAF8. Interacts (via the C-terminal domain (CTD)) with CCNT2. Interacts with FUS. Interacts with MCM3AP isoform GANP. Interacts with kinase SRPK2; the interaction occurs during the co-transcriptional formation of inappropriate R-loops. Interacts with SETD2. Interacts with UVSSA. Interacts with ERCC6. Interacts with the TFIIH complex (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | G3MZY8 | POLR2B A5PJW8 | 6 | EBI-6551200, EBI-15586776 | |
BINARY | G3MZY8 | POLR2E Q2T9T3 | 8 | EBI-6551200, EBI-15586877 | |
XENO | G3MZY8 | SUPT5H O00267 | 2 | EBI-6551200, EBI-710464 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 832-873 | Bridging helix | ||||
Sequence: TPTEFFFHAMGGREGLIDTAVKTAETGYIQRRLIKSMESVMV | ||||||
Region | 1083-1124 | Trigger loop | ||||
Sequence: PGEMVGALAAQSLGEPATQMTLNTFHYAGVSAKNVTLGVPRL | ||||||
Region | 1546-1970 | Disordered | ||||
Sequence: FSPSAASDASGFSPGYSPAWSPTPGSPGSPGPSSPYIPSPGGAMSPSYSPTSPAYEPRSPGGYTPQSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPNYTPTSPSYSPTSPSYSPTSPNYTPTSPNYSPTSPSYSPTSPSYSPTSPSYSPSSPRYTPQSPTYTPSSPSYSPSSPSYSPTSPKYTPTSPSYSPSSPEYTPTSPKYSPTSPKYSPTSPKYSPTSPTYSPTTPKYSPTSPTYSPTSPVYTPTSPKYSPTSPTYSPTSPKYSPTSPTYSPTSPKGSTYSPTSPGYSPTSPTYSLTSPAISPDDSDDEN | ||||||
Compositional bias | 1565-1584 | Pro residues | ||||
Sequence: WSPTPGSPGSPGPSSPYIPS | ||||||
Repeat | 1593-1599 | 1 | ||||
Sequence: YSPTSPA | ||||||
Region | 1593-1960 | C-terminal domain (CTD); 52 X 7 AA approximate tandem repeats of Y-[ST]-P-[STQ]-[ST]-P-[SRTEVKGN] | ||||
Sequence: YSPTSPAYEPRSPGGYTPQSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPNYTPTSPSYSPTSPSYSPTSPNYTPTSPNYSPTSPSYSPTSPSYSPTSPSYSPSSPRYTPQSPTYTPSSPSYSPSSPSYSPTSPKYTPTSPSYSPSSPEYTPTSPKYSPTSPKYSPTSPKYSPTSPTYSPTTPKYSPTSPTYSPTSPVYTPTSPKYSPTSPTYSPTSPKYSPTSPTYSPTSPKGSTYSPTSPGYSPTSPTYSLTSPA | ||||||
Repeat | 1600-1606 | 2; approximate | ||||
Sequence: YEPRSPG | ||||||
Compositional bias | 1607-1963 | Polar residues | ||||
Sequence: GYTPQSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPNYTPTSPSYSPTSPSYSPTSPNYTPTSPNYSPTSPSYSPTSPSYSPTSPSYSPSSPRYTPQSPTYTPSSPSYSPSSPSYSPTSPKYTPTSPSYSPSSPEYTPTSPKYSPTSPKYSPTSPKYSPTSPTYSPTTPKYSPTSPTYSPTSPVYTPTSPKYSPTSPTYSPTSPKYSPTSPTYSPTSPKGSTYSPTSPGYSPTSPTYSLTSPAISP | ||||||
Repeat | 1608-1614 | 3 | ||||
Sequence: YTPQSPS | ||||||
Repeat | 1615-1621 | 4 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1622-1628 | 5 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1629-1635 | 6 | ||||
Sequence: YSPTSPN | ||||||
Repeat | 1636-1642 | 7 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1643-1649 | 8 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1650-1656 | 9 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1657-1663 | 10 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1664-1670 | 11 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1671-1677 | 12 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1678-1684 | 13 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1685-1691 | 14 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1692-1698 | 15 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1699-1705 | 16 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1706-1712 | 17 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1713-1719 | 18 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1720-1726 | 19 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1727-1733 | 20 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1734-1740 | 21 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1741-1747 | 22 | ||||
Sequence: YSPTSPN | ||||||
Repeat | 1748-1754 | 23 | ||||
Sequence: YSPTSPN | ||||||
Repeat | 1755-1761 | 24 | ||||
Sequence: YTPTSPS | ||||||
Repeat | 1762-1768 | 25 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1769-1775 | 26 | ||||
Sequence: YSPTSPN | ||||||
Repeat | 1776-1782 | 27 | ||||
Sequence: YTPTSPN | ||||||
Repeat | 1783-1789 | 28 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1790-1796 | 29 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1797-1803 | 30 | ||||
Sequence: YSPTSPS | ||||||
Repeat | 1804-1810 | 31 | ||||
Sequence: YSPSSPR | ||||||
Repeat | 1811-1817 | 32 | ||||
Sequence: YTPQSPT | ||||||
Repeat | 1818-1824 | 33 | ||||
Sequence: YTPSSPS | ||||||
Repeat | 1825-1831 | 34 | ||||
Sequence: YSPSSPS | ||||||
Repeat | 1832-1838 | 35 | ||||
Sequence: YSPTSPK | ||||||
Repeat | 1839-1845 | 36 | ||||
Sequence: YTPTSPS | ||||||
Repeat | 1846-1852 | 37 | ||||
Sequence: YSPSSPE | ||||||
Repeat | 1853-1859 | 38 | ||||
Sequence: YTPTSPK | ||||||
Repeat | 1860-1866 | 39 | ||||
Sequence: YSPTSPK | ||||||
Repeat | 1867-1873 | 40 | ||||
Sequence: YSPTSPK | ||||||
Repeat | 1874-1880 | 41 | ||||
Sequence: YSPTSPT | ||||||
Repeat | 1881-1887 | 42 | ||||
Sequence: YSPTTPK | ||||||
Repeat | 1888-1894 | 43 | ||||
Sequence: YSPTSPT | ||||||
Repeat | 1895-1901 | 44 | ||||
Sequence: YSPTSPV | ||||||
Repeat | 1902-1908 | 45 | ||||
Sequence: YTPTSPK | ||||||
Repeat | 1909-1915 | 46 | ||||
Sequence: YSPTSPT | ||||||
Repeat | 1916-1922 | 47 | ||||
Sequence: YSPTSPK | ||||||
Repeat | 1923-1929 | 48 | ||||
Sequence: YSPTSPT | ||||||
Repeat | 1930-1936 | 49 | ||||
Sequence: YSPTSPK | ||||||
Repeat | 1940-1946 | 50 | ||||
Sequence: YSPTSPG | ||||||
Repeat | 1947-1953 | 51; approximate | ||||
Sequence: YSPTSPT | ||||||
Repeat | 1954-1960 | 52; approximate | ||||
Sequence: YSLTSPA |
Domain
The C-terminal domain (CTD) serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing.
The trigger loop allows entry of NTPs into the active site, switching between an open and closed state with each NTP addition cycle.
The bridging helix crosses the cleft near the catalytic site and is thought to promote polymerase translocation by acting as a ratchet that moves the DNA-RNA hybrid through the active site.
Sequence similarities
Belongs to the RNA polymerase beta' chain family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,970
- Mass (Da)217,192
- Last updated2019-04-10 v2
- Checksum6876FD95692A657E
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1565-1584 | Pro residues | ||||
Sequence: WSPTPGSPGSPGPSSPYIPS | ||||||
Compositional bias | 1607-1963 | Polar residues | ||||
Sequence: GYTPQSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPNYTPTSPSYSPTSPSYSPTSPNYTPTSPNYSPTSPSYSPTSPSYSPTSPSYSPSSPRYTPQSPTYTPSSPSYSPSSPSYSPTSPKYTPTSPSYSPSSPEYTPTSPKYSPTSPKYSPTSPKYSPTSPTYSPTTPKYSPTSPTYSPTSPVYTPTSPKYSPTSPTYSPTSPKYSPTSPTYSPTSPKGSTYSPTSPGYSPTSPTYSLTSPAISP |
Keywords
- Technical term