Polr2a
entrez
20020
canonical
uniprot
P08775
canonical
ensembl
ENSMUSG00000005198
resolver
ensp
ENSMUSP00000050771
resolver
enst
ENSMUST00000058470
resolver
genesymbol
Polr2a
resolver
genesymbol_syn
Rpii215
resolver
genesymbol_syn
Rpo2-1
resolver
uniprot
Q5F298
resolver
uniprot_entry
RPB1_MOUSE
resolver
uniprot_sec
Q5F298
resolver
amino_acid_sequence
MHGGGPPSGDSACPLRTIKRVQFGVLSPDELKRMSVTEGGIKYPETTEGGRPKLGGLMDPRQGVIERTGRCQTCAGNMTECPGHFGHIELAKPVFHVGFLVKTMKVLRCVCFFCSKLLVDSNNPKIKDILAKSKGQPKKRLTHVYDLCKGKNICEGGEEMDNKFGVEQPEGDEDLTKEKGHGGCGRYQPRIRRSGLELYAEWKHVNEDSQEKKILLSPERVHEIFKRISDEECFVLGMEPRYARPEWMIVTVLPVPPLSVRPAVVMQGSARNQDDLTHKLADIVKINNQLRRNEQNGAAAHVIAEDVKLLQFHVATMVDNELPGLPRAMQKSGRPLKSLKQRLKGKEGRVRGNLMGKRVDFSARTVITPDPNLSIDQVGVPRSIAANMTFAEIVTPFNIDRLQELVRRGNSQYPGAKYIIRDNGDRIDLRFHPKPSDLHLQTGYKVERHMCDGDIVIFNRQPTLHKMSMMGHRVRILPWSTFRLNLSVTTPYNADFDGDEMNLHLPQSLETRAEIQELAMVPRMIVTPQSNRPVMGIVQDTLTAVRKFTKRDVFLERGEVMNLLMFLSTWDGKVPQPAILKPRPLWTGKQIFSLIIPGHINCIRTHSTHPDDEDSGPYKHISPGDTKVVVENGELIMGILCKKSLGTSAGSLVHISYLEMGHDITRLFYSNIQTVINNWLLIEGHTIGIGDSIADSKTYQDIQNTIKKAKQDVIEVIEKAHNNELEPTPGNTLRQTFENQVNRILNDARDKTGSSAQKSLSEYNNFKSMVVSGAKGSKINISQVIAVVGQQNVEGKRIPFGFKHRTLPHFIKDDYGPESRGFVENSYLAGLTPTEFFFHAMGGREGLIDTAVKTAETGYIQRRLIKSMESVMVKYDATVRNSINQVVQLRYGEDGLAGESVEFQNLATLKPSNKAFEKKFRFDYTNERALRRTLQEDLVKDVLSNAHIQNELEREFERMREDREVLRVIFPTGDSKVVLPCNLLRMIWNAQKIFHINPRLPSDLHPIKVVEGVKELSKKLVIVNGDDPLSRQAQENATLLFNIHLRSTLCSRRMAEEFRLSGEAFDWLLGEIESKFNQAIAHPGEMVGALAAQSLGEPATQMTLNTFHYAGVSAKNVTLGVPRLKELINISKKPKTPSLTVFLLGQSARDAERAKDILCRLEHTTLRKVTANTAIYYDPNPQSTVVAEDQEWVNVYYEMPDFDVARISPWLLRVELDRKHMTDRKLTMEQIAEKINAGFGDDLNCIFNDDNAEKLVLRIRIMNSDENKMQEEEEVVDKMDDDVFLRCIESNMLTDMTLQGIEQISKVYMHLPQTDNKKKIIITEDGEFKALQEWILETDGVSLMRVLSEKDVDPVRTTSNDIVEIFTVLGIEAVRKALERELYHVISFDGSYVNYRHLALLCDTMTCRGHLMAITRHGVNRQDTGPLMKCSFEETVDVLMEAAAHGESDPMKGVSENIMLGQLAPAGTGCFDLLLDAEKCKYGMEIPTNIPGLGAAGPTGMFFGSAPSPMGGISPAMTPWNQGATPAYGAWSPSVGSGMTPGAAGFSPSAASDASGFSPGYSPAWSPTPGSPGSPGPSSPYIPSPGGAMSPSYSPTSPAYEPRSPGGYTPQSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPNYTPTSPSYSPTSPSYSPTSPNYTPTSPNYSPTSPSYSPTSPSYSPTSPSYSPSSPRYTPQSPTYTPSSPSYSPSSPSYSPTSPKYTPTSPSYSPSSPEYTPASPKYSPTSPKYSPTSPKYSPTSPTYSPTTPKYSPTSPTYSPTSPVYTPTSPKYSPTSPTYSPTSPKYSPTSPTYSPTSPKGSTYSPTSPGYSPTSPTYSLTSPAISPDDSDEEN
uniprot
proteins
ec_number
2.7.7.48
uniprot
proteins
ec_number
2.7.7.6
uniprot
proteins
ec_number
3.1.13.-
uniprot
proteins
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 (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:18252004, PubMed:24207025). 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 Mg(2+)-coordinating DxDGD motif, and POLR2B/RPB2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg(2+) 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 (By similarity). 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). 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) (PubMed:24207025, PubMed:26687004). {ECO:0000250|UniProtKB:G3MZY8, ECO:0000250|UniProtKB:P24928, ECO:0000269|PubMed:18252004, ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26687004}.; FUNCTION: 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. {ECO:0000250|UniProtKB:P24928}.
uniprot
proteins
mass_dalton
217176
uniprot
proteins
mutagenesis
MUTAGEN 1268; /note="K->R: Mice appear phenotypically normal. Simultaneous knockout of Xpa leads to growth retardation, skeletal abnormalities, cataracts, progressive motor neuron degeneration and death at 5-6 months."; /evidence="ECO:0000269|PubMed:32142649"; MUTAGEN 1838; /note="K->R: Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R-1859; R-1866; R-1873; R-1887; R-1908; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:24207025"; MUTAGEN 1838; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1859; S-1866; S-1873; S-1887; S-1908; S-1922 and S-1936."; /evidence="ECO:0000269|PubMed:26687004"; MUTAGEN 1859; /note="K->R: Loss of ubiquitination, no effect on interaction with WWP2; when associated with R-1866; R-1873; R-1887; R-1908 and R-1922. Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R-1838; R-1866; R-1873; R-1887; R-1908; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:17526739, ECO:0000269|PubMed:24207025"; MUTAGEN 1859; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1838; S-1866; S-1873; S-1887; S-1908; S-1922 and S-1936. Highly decreases methylation and dimethylation; when associated with S-1866; S-1873; S-1887; S-1908; S-1922 and S-1936. Decreases methylation but no effect on dimethylation; when associated with S-1866; S-1887; S-1908 and S-1936."; /evidence="ECO:0000269|PubMed:26687004"; MUTAGEN 1866; /note="K->R: Loss of ubiquitination, no effect on interaction with WWP2; when associated with R-1859; R-1873; R-1887; R-1908 and R-1922. Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R-1859; R-1859; R-1873; R-1887; R-1908; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:17526739, ECO:0000269|PubMed:24207025"; MUTAGEN 1866; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1838; S-1859; S-1873; S-1887; S-1908; S-1922 and S-1936. Highly decreases methylation and dimethylation; when associated with S-1859; S-1873; S-1887; S-1908; S-1922 and S-1936. Decreases methylation but no effect on dimethylation; when associated with S-1859; S-1887; S-1908 and S-1936."; /evidence="ECO:0000269|PubMed:26687004"; MUTAGEN 1873; /note="K->R: Loss of ubiquitination, no effect on interaction with WWP2; when associated with R-1859; R-1866; R-1887; R-1908 and R-1922. Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R-1838; R-1859; R-1866; R-1887; R-1908; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:17526739, ECO:0000269|PubMed:24207025"; MUTAGEN 1873; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1838; S-1859; S-1866; S-1887; S-1908; S-1922 and S-1936. Highly decreases methylation and dimethylation; when associated with S-1859; S-1866; S-1887; S-1908 and S-1936."; /evidence="ECO:0000269|PubMed:26687004"; MUTAGEN 1887; /note="K->R: Loss of ubiquitination, no effect on interaction with WWP2; when associated with R-1859; R-1866; R-1873; R-1908 and R-1922. Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R-1838; R-1859; R-1866; R-1873; R-1908; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:17526739, ECO:0000269|PubMed:24207025"; MUTAGEN 1887; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1838; S-1859; S-1866; S-1873; S-1908; S-1922 and S-1936. Highly decreases methylation and dimethylation; when associated with S-1859; S-1866; S-1873; S-1908; S-1922 and S-1936. Decreases methylation but no effect on dimethylation; when associated with S-1859; S-1866; S-1908 and S-1936."; /evidence="ECO:0000269|PubMed:26687004"; MUTAGEN 1908; /note="K->R: Loss of ubiquitination, no effect on interaction with WWP2; when associated with R-1859; R-1866; R-1873; R-1887 and R-1922. Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R.1838; R-1859; R-1866; R-1873; R-1887; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:17526739, ECO:0000269|PubMed:24207025"; MUTAGEN 1908; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1838; S-1859; S-1866; S-1873; S-1887; S-1922 and S-1936. Highly decreases methylation and dimethylation; when associated with S-1859; S-1866; S-1873; S-1887; S-1922 and S-1936. Decreases methylation but no effect on dimethylation; when associated with S-1859; S-1866; S-1887 and S-1936."; /evidence="ECO:0000269|PubMed:26687004"; MUTAGEN 1922; /note="K->R: Loss of ubiquitination, no effect on interaction with WWP2; when associated with R-1859; R-1866; R-1873; R-1887 and R-1908. Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R-1838; R-1859; R-1866; R-1873; R-1887; R-1908 and R-1936."; /evidence="ECO:0000269|PubMed:17526739, ECO:0000269|PubMed:24207025"; MUTAGEN 1922; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1838; S-1859; S-1866; S-1873; S-1887; S-1908 and S-1936. Highly decreases methylation and dimethylation; when associated with S-1859; S-1866; S-1873; S-1887; S-1908 and S-1936."; /evidence="ECO:0000269|PubMed:26687004"; MUTAGEN 1936; /note="K->R: Loss of acetylation and loss of regulation of growth-factor-induced gene expression; when associated with R-1838; R-1859; R-1866; R-1873; R-1887; R-1908 and R-1922."; /evidence="ECO:0000269|PubMed:24207025"; MUTAGEN 1936; /note="K->S: Loss of methylation and dimethylation but no effect on phosphorylation; when associated with S-1838; S-1859; S-1866; S-1873; S-1887; S-1908 and S-1922. Highly decreases methylation and dimethylation; when associated with S-1859; S-1866; S-1873; S-1887; S-1908 and S-1922. Decreases methylation but no effect on dimethylation; when associated with S-1859; S-1866 and S-1887."; /evidence="ECO:0000269|PubMed:26687004
uniprot
proteins
post_translational_modification
PTM: 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. POLR2A associated with DNA is specifically phosphorylated at 'Ser-5' of the CTD by CDK7, promoting transcription initiation by triggering dissociation from DNA. Phosphorylated at 'Ser-2' of the CTD by CDK11, regulating promoter-proximal pause-release. Phosphorylated at 'Ser-2', 'Ser-5' and 'Ser-7' of the CTD by CDK9 (P-TEFb complex), promoting transcription elongation. 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 INTAC complex when transcripts are unfavorably configured for transcriptional elongation, leading to premature transcription termination: dephosphorylation is mediated by the PPP2CA component of the INTAC complex. In response to replication stress, dephosphorylated at 'Ser-5' of the CTD by the PNUTS-PP1 complex, promoting RNA polymerase II degradation. Dephosphorylated by the protein phosphatase CTDSP1. Dephosphorylated at 'Ser-2' following UV irradiation. {ECO:0000250|UniProtKB:P24928}.; PTM: 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. It may regulate initiation or early elongation steps of transcription, especially for inducible genes. {ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26687004}.; PTM: Following transcription stress, the elongating form of RNA polymerase II (RNA pol IIo) is ubiquitinated by the DCX(ERCC8) complex (also named CSA complex) 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 (By similarity). 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). Ubiquitinated by the BCR(ARMC5) complex when transcripts are unfavorably configured for transcriptional elongation: the BCR(ARMC5) complex specifically catalyzes ubiquitination of POLR2A phosphorylated at 'Ser-5' of the C-terminal domain (CTD), leading to POLR2A degradation (By similarity). Ubiquitination by the BCR(ARMC5) complex takes place at residues distinct from Lys-1268 (By similarity). Ubiquitinated by WWP2 leading to proteasomal degradation (PubMed:17526739). {ECO:0000250|UniProtKB:P24928, ECO:0000269|PubMed:17526739}.; PTM: 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 trimethylation at 'Lys-7' of non-consensus heptapeptide repeats are exclusively associated with phosphorylated CTD. {ECO:0000250|UniProtKB:P24928, ECO:0000269|PubMed:26687004}.
uniprot
proteins
protein_family
RNA polymerase beta' chain family
uniprot
proteins
pubmed
11030652
uniprot
proteins
pubmed
1542581
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17526739
uniprot
proteins
pubmed
18252004
uniprot
proteins
pubmed
19141475
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22767893
uniprot
proteins
pubmed
24207025
uniprot
proteins
pubmed
26687004
uniprot
proteins
pubmed
2999785
uniprot
proteins
pubmed
3038894
uniprot
proteins
pubmed
32142649
uniprot
proteins
pubmed
8692929
uniprot
proteins
sequence_length
1970
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26687004}. Cytoplasm {ECO:0000250|UniProtKB:P24928}. Chromosome {ECO:0000250|UniProtKB:P24928}. 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. {ECO:0000250|UniProtKB:P24928}.
uniprot
proteins