lmmol · Proteins

DNA-directed RNA polymerase II subunit RPB1

UniProt P24928 Organism Homo sapiens Gene POLR2, POLR2A EC 2.7.7.6, 3.1.13.-, 2.7.7.48

Also known as: POLR2, POLR2A

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). 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).

Classification

Family (Pfam)
PF04997 RNA_pol_Rpb1_1, PF00623 RNA_pol_Rpb1_2, PF04983 RNA_pol_Rpb1_3, PF05000 RNA_pol_Rpb1_4, PF04998 RNA_pol_Rpb1_5, PF04992 RNA_pol_Rpb1_6, PF04990 RNA_pol_Rpb1_7, PF05001 RNA_pol_Rpb1_R
InterPro
DNA-dir_RpoC_beta_prime, RNA_pol_asu, RNA_pol_II_repeat_euk, RNA_pol_N, RNA_pol_Rpb1_1, RNA_pol_Rpb1_3, RNA_pol_Rpb1_3_sf, RNA_pol_Rpb1_4, RNA_pol_Rpb1_5, RNA_pol_Rpb1_6, RNA_pol_Rpb1_7, RNA_pol_Rpb1_7_sf, RNA_pol_Rpb1_clamp_domain, Rpb1_funnel_sf
Functional cluster
Central Metabolic Enzymes (KARI/Glycolysis)

Experimental structures · PDB · 53

A predicted model is available from AlphaFold.

Gene Ontology · 24

Disease associations

Drugs targeting this protein · 1

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 79 cited papers

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