POLR2A
entrez
5430
canonical
uniprot
P24928
canonical
ensembl
ENSG00000284832
resolver
ensp
ENSP00000494840
resolver
enst
ENST00000643490
resolver
genesymbol
POLR2A
resolver
genesymbol_syn
POLR2
resolver
hgnc
HGNC:9187
resolver
uniprot
A0AAG2TJB2
resolver
uniprot
A6NN93
resolver
uniprot
B9EH88
resolver
uniprot
Q6NX41
resolver
uniprot_entry
RPB1_HUMAN
resolver
uniprot_sec
A0AAG2TJB2
resolver
uniprot_sec
A6NN93
resolver
uniprot_sec
B9EH88
resolver
uniprot_sec
Q6NX41
resolver
activity_regulation
ACTIVITY REGULATION: Pol II enzymatic activities are inhibited by alpha-amanitin. 3'->5' exonuclease activity is stimulated by TCEA1/TFIIS, whereas pyrophosphorolysis is enhanced by TFIIF. {ECO:0000269|PubMed:8381534}.
uniprot
proteins
amino_acid_sequence
MHGGGPPSGDSACPLRTIKRVQFGVLSPDELKRMSVTEGGIKYPETTEGGRPKLGGLMDPRQGVIERTGRCQTCAGNMTECPGHFGHIELAKPVFHVGFLVKTMKVLRCVCFFCSKLLVDSNNPKIKDILAKSKGQPKKRLTHVYDLCKGKNICEGGEEMDNKFGVEQPEGDEDLTKEKGHGGCGRYQPRIRRSGLELYAEWKHVNEDSQEKKILLSPERVHEIFKRISDEECFVLGMEPRYARPEWMIVTVLPVPPLSVRPAVVMQGSARNQDDLTHKLADIVKINNQLRRNEQNGAAAHVIAEDVKLLQFHVATMVDNELPGLPRAMQKSGRPLKSLKQRLKGKEGRVRGNLMGKRVDFSARTVITPDPNLSIDQVGVPRSIAANMTFAEIVTPFNIDRLQELVRRGNSQYPGAKYIIRDNGDRIDLRFHPKPSDLHLQTGYKVERHMCDGDIVIFNRQPTLHKMSMMGHRVRILPWSTFRLNLSVTTPYNADFDGDEMNLHLPQSLETRAEIQELAMVPRMIVTPQSNRPVMGIVQDTLTAVRKFTKRDVFLERGEVMNLLMFLSTWDGKVPQPAILKPRPLWTGKQIFSLIIPGHINCIRTHSTHPDDEDSGPYKHISPGDTKVVVENGELIMGILCKKSLGTSAGSLVHISYLEMGHDITRLFYSNIQTVINNWLLIEGHTIGIGDSIADSKTYQDIQNTIKKAKQDVIEVIEKAHNNELEPTPGNTLRQTFENQVNRILNDARDKTGSSAQKSLSEYNNFKSMVVSGAKGSKINISQVIAVVGQQNVEGKRIPFGFKHRTLPHFIKDDYGPESRGFVENSYLAGLTPTEFFFHAMGGREGLIDTAVKTAETGYIQRRLIKSMESVMVKYDATVRNSINQVVQLRYGEDGLAGESVEFQNLATLKPSNKAFEKKFRFDYTNERALRRTLQEDLVKDVLSNAHIQNELEREFERMREDREVLRVIFPTGDSKVVLPCNLLRMIWNAQKIFHINPRLPSDLHPIKVVEGVKELSKKLVIVNGDDPLSRQAQENATLLFNIHLRSTLCSRRMAEEFRLSGEAFDWLLGEIESKFNQAIAHPGEMVGALAAQSLGEPATQMTLNTFHYAGVSAKNVTLGVPRLKELINISKKPKTPSLTVFLLGQSARDAERAKDILCRLEHTTLRKVTANTAIYYDPNPQSTVVAEDQEWVNVYYEMPDFDVARISPWLLRVELDRKHMTDRKLTMEQIAEKINAGFGDDLNCIFNDDNAEKLVLRIRIMNSDENKMQEEEEVVDKMDDDVFLRCIESNMLTDMTLQGIEQISKVYMHLPQTDNKKKIIITEDGEFKALQEWILETDGVSLMRVLSEKDVDPVRTTSNDIVEIFTVLGIEAVRKALERELYHVISFDGSYVNYRHLALLCDTMTCRGHLMAITRHGVNRQDTGPLMKCSFEETVDVLMEAAAHGESDPMKGVSENIMLGQLAPAGTGCFDLLLDAEKCKYGMEIPTNIPGLGAAGPTGMFFGSAPSPMGGISPAMTPWNQGATPAYGAWSPSVGSGMTPGAAGFSPSAASDASGFSPGYSPAWSPTPGSPGSPGPSSPYIPSPGGAMSPSYSPTSPAYEPRSPGGYTPQSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPSYSPTSPNYSPTSPNYTPTSPSYSPTSPSYSPTSPNYTPTSPNYSPTSPSYSPTSPSYSPTSPSYSPSSPRYTPQSPTYTPSSPSYSPSSPSYSPTSPKYTPTSPSYSPSSPEYTPTSPKYSPTSPKYSPTSPKYSPTSPTYSPTTPKYSPTSPTYSPTSPVYTPTSPKYSPTSPTYSPTSPKYSPTSPTYSPTSPKGSTYSPTSPGYSPTSPTYSLTSPAISPDDSDEEN
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (NEDHIB) [MIM:618603]: An autosomal dominant neurodevelopmental disorder characterized by profound infantile-onset hypotonia, developmental delay with poor speech, delayed walking, and impaired intellectual development. Additional variable features include feeding difficulties, dysmorphic features, and visual defects. {ECO:0000269|PubMed:31353023}. Note=The disease is caused by variants affecting the gene represented in this entry.
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) (PubMed:23748380, PubMed:27193682, PubMed:30190596, PubMed:9852112). 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:23748380, PubMed:27193682, PubMed:28108474, PubMed:30190596, PubMed:9852112). 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) (PubMed:30190596, PubMed:8381534, PubMed:9852112). 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:8381534). 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:26124092). {ECO:0000250|UniProtKB:G3MZY8, ECO:0000250|UniProtKB:P08775, ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:28108474, ECO:0000269|PubMed:30190596, ECO:0000269|PubMed:8381534, ECO:0000269|PubMed:9852112}.; 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:0000269|PubMed:23395899}.; FUNCTION: (Microbial infection) Acts as an RNA-dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus, acting both as a replicase and transcriptase for the viral RNA circular genome. {ECO:0000269|PubMed:18032511}.
uniprot
proteins
mass_dalton
217206
uniprot
proteins
mutagenesis
MUTAGEN 812..1970; /note="Missing: Decreases cell viability."; /evidence="ECO:0000269|PubMed:31353023"; MUTAGEN 1268; /note="K->R: Impairs ubiquitination, interaction with the TFIIH complex, and its degradation during transcription stress. Does not affect ubiquitination by the BCR(ARMC5) complex."; /evidence="ECO:0000269|PubMed:32142649, ECO:0000269|PubMed:32142654, ECO:0000269|PubMed:39667934"; MUTAGEN 1810; /note="R->A: Misexpression of a variety of small nuclear RNAs and small nucleolar RNAs. Loss of interaction with TDRD3 and SMN1/SMN2."; /evidence="ECO:0000269|PubMed:21454787, ECO:0000269|PubMed:26700805"; 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 1859; /note="K->R: 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:24207025"; MUTAGEN 1866; /note="K->R: 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:24207025"; MUTAGEN 1873; /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-1887; R-1908; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:24207025"; MUTAGEN 1887; /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-1908; R-1922 and R-1936."; /evidence="ECO:0000269|PubMed:24207025"; MUTAGEN 1908; /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-1922 and R-1936."; /evidence="ECO:0000269|PubMed:24207025"; MUTAGEN 1922; /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-1936."; /evidence="ECO:0000269|PubMed:24207025"; 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
uniprot
proteins
post_translational_modification
PTM: The tandem heptapeptide repeats in the C-terminal domain (CTD) can be highly phosphorylated (PubMed:17234882, PubMed:19450536, PubMed:19667075, PubMed:19136461, PubMed:26566685, PubMed:28076779, PubMed:32142654, PubMed:33243860, PubMed:34004147, PubMed:40858114). The phosphorylation activates Pol II (PubMed:33243860). Phosphorylation occurs mainly at residues 'Ser-2' and 'Ser-5' of the heptapeptide repeat and is mediated, at least, by CDK7 and CDK9 (PubMed:19450536, PubMed:19667075, PubMed:19136461, PubMed:21127351). POLR2A associated with DNA is specifically phosphorylated at 'Ser-5' of the CTD by CDK7, promoting transcription initiation by triggering dissociation from DNA (PubMed:19136461, PubMed:26257281, PubMed:28768201). Phosphorylated at 'Ser-2' of the CTD by CDK11 (CDK11A or CDK11B), regulating promoter-proximal pause-release (PubMed:40858114). Phosphorylated at 'Ser-2', 'Ser-5' and 'Ser-7' of the CTD by CDK9 (P-TEFb complex), promoting transcription elongation (PubMed:19667075, PubMed:21127351). 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 (PubMed:22137580). 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 (PubMed:19450536, PubMed:19667075, PubMed:19136461, PubMed:33243860, PubMed:34004147). 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 (PubMed:33243860, PubMed:34004147, PubMed:37080207). In response to replication stress, dephosphorylated at 'Ser-5' of the CTD by the PNUTS-PP1 complex, promoting RNA polymerase II degradation (PubMed:33264625). Dephosphorylated by the protein phosphatase CTDSP1 (PubMed:17157258). Dephosphorylated at 'Ser-2' following UV irradiation. {ECO:0000269|PubMed:17157258, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536, ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:22137580, ECO:0000269|PubMed:26257281, ECO:0000269|PubMed:26566685, ECO:0000269|PubMed:28076779, ECO:0000269|PubMed:28768201, ECO:0000269|PubMed:32142654, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:33264625, ECO:0000269|PubMed:34004147, ECO:0000269|PubMed:37080207, ECO:0000269|PubMed:40858114}.; 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. Regulates initiation or early elongation steps of transcription, especially for inducible genes. {ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:26566685, ECO:0000269|PubMed:26687004}.; 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:P08775, ECO:0000269|PubMed:26566685, ECO:0000269|PubMed:26687004, ECO:0000269|PubMed:26700805}.; 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 (PubMed:22466610, PubMed:32142649, PubMed:32142654, PubMed:34526721, PubMed:35633597). 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 (PubMed:35633597). 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 (PubMed:35687106, PubMed:39504960, PubMed:39667934). Ubiquitination by the BCR(ARMC5) complex takes place at residues distinct from Lys-1268 (PubMed:39667934). Ubiquitinated by WWP2 leading to proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P08775, ECO:0000269|PubMed:22466610, ECO:0000269|PubMed:32142649, ECO:0000269|PubMed:32142654, ECO:0000269|PubMed:34526721, ECO:0000269|PubMed:35633597, ECO:0000269|PubMed:35687106, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934}.
uniprot
proteins
protein_family
RNA polymerase beta' chain family
uniprot
proteins
pubmed
10393184
uniprot
proteins
pubmed
10454543
uniprot
proteins
pubmed
12376575
uniprot
proteins
pubmed
12381297
uniprot
proteins
pubmed
12527917
uniprot
proteins
pubmed
14684736
uniprot
proteins
pubmed
14992727
uniprot
proteins
pubmed
15144186
uniprot
proteins
pubmed
1542581
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15563843
uniprot
proteins
pubmed
15992770
uniprot
proteins
pubmed
16118227
uniprot
proteins
pubmed
16314571
uniprot
proteins
pubmed
16491129
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17157258
uniprot
proteins
pubmed
17234882
uniprot
proteins
pubmed
17998332
uniprot
proteins
pubmed
18032511
uniprot
proteins
pubmed
18533109
uniprot
proteins
pubmed
18550522
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19106100
uniprot
proteins
pubmed
19136461
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19450536
uniprot
proteins
pubmed
19667075
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20231364
uniprot
proteins
pubmed
21127351
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21454787
uniprot
proteins
pubmed
21536736
uniprot
proteins
pubmed
22137580
uniprot
proteins
pubmed
22466610
uniprot
proteins
pubmed
23029222
uniprot
proteins
pubmed
23149945
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23395899
uniprot
proteins
pubmed
23652018
uniprot
proteins
pubmed
23748380
uniprot
proteins
pubmed
24207025
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24656813
uniprot
proteins
pubmed
26124092
uniprot
proteins
pubmed
26257281
uniprot
proteins
pubmed
26566685
uniprot
proteins
pubmed
26655721
uniprot
proteins
pubmed
26687004
uniprot
proteins
pubmed
26700805
uniprot
proteins
pubmed
27193682
uniprot
proteins
pubmed
28076779
uniprot
proteins
pubmed
28108474
uniprot
proteins
pubmed
28768201
uniprot
proteins
pubmed
30190596
uniprot
proteins
pubmed
30538201
uniprot
proteins
pubmed
31353023
uniprot
proteins
pubmed
32142649
uniprot
proteins
pubmed
32142654
uniprot
proteins
pubmed
33243860
uniprot
proteins
pubmed
33264625
uniprot
proteins
pubmed
34004147
uniprot
proteins
pubmed
34237909
uniprot
proteins
pubmed
34526721
uniprot
proteins
pubmed
35633597
uniprot
proteins
pubmed
35687106
uniprot
proteins
pubmed
36869814
uniprot
proteins
pubmed
37080207
uniprot
proteins
pubmed
39504960
uniprot
proteins
pubmed
39667934
uniprot
proteins
pubmed
40858114
uniprot
proteins
pubmed
7622068
uniprot
proteins
pubmed
8381534
uniprot
proteins
pubmed
9671816
uniprot
proteins
pubmed
9852112
uniprot
proteins
sequence_length
1970
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26566685, ECO:0000269|PubMed:28076779, ECO:0000269|PubMed:9852112}. Cytoplasm {ECO:0000269|PubMed:26566685}. Chromosome {ECO:0000269|PubMed:28076779}. Note=Hypophosphorylated form is mainly found in the cytoplasm, while the hyperphosphorylated and active form is nuclear (PubMed:26566685). Co-localizes with kinase SRPK2 and helicase DDX23 at chromatin loci where unscheduled R-loops form (PubMed:28076779). {ECO:0000269|PubMed:26566685, ECO:0000269|PubMed:28076779}.
uniprot
proteins