Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
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Interaction Network
Gene Expression
Gene Copy Number Variation
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RPO21 (P04050) - Overview - Molecular Target Synopsis

Protein


RPO21, DNA-directed RNA polymerase II subunit RPB1
Enzyme Classification 2.7.7.6
UniProt P04050

Also Known as RPB1_YEAST, RPO21, RPB1, RPB220, SUA8

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. During a transcription cycle, Pol II, general transcription factors and the Mediator complex assemble as the preinitiation complex (PIC) at the promoter. 11-15 base pairs of DNA surrounding the transcription start site are melted and the single-stranded DNA template strand of the promoter is positioned deeply within the central active site cleft of Pol II to form the open complex. After synthesis of about 30 bases of RNA, Pol II releases its contacts with the core promoter and the rest of the transcription machinery (promoter clearance) and enters the stage of transcription elongation in which it moves on the template as the transcript elongates. Pol II appears to oscillate between inactive and active conformations at each step of nucleotide addition. 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. Pol II is composed of mobile elements that move relative to each other. The core element with the central large cleft comprises RPB3, RBP10, RPB11, RPB12 and regions of RPB1 and RPB2 forming the active center. The clamp element (portions of RPB1, RPB2 and RPB3) is connected to the core through a set of flexible switches and moves to open and close the cleft. 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. In elongating Pol II, the lid loop (RPB1) appears to act as a wedge to drive apart the DNA and RNA strands at the upstream end of the transcription bubble and guide the RNA strand toward the RNA exit groove located near the base of the largely unstructured CTD domain of RPB1. The rudder loop (RPB1) interacts with single-stranded DNA after separation from the RNA strand, likely preventing reassociation with the exiting RNA. The cleft is surrounded by jaws: an upper jaw formed by portions of RBP1, RPB2 and RPB9, and a lower jaw, formed by RPB5 and portions of RBP1. The jaws are thought to grab the incoming DNA template, mainly by RPB5 direct contacts to DNA. Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Interacts with ASK10, ESS1, RTT103 and SHE2.

6O6C
RNA POLYMERASE II ELONGATION COMPLEX ARRESTED AT A CPD LESION
RCSB/PDB
Inspect Structure
See all 3D Structures for RPO21

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1733P04050-1

Sub-cellular localization


UniProt: RPO21 is active in the following subcellular-locations: nucleus.
GO terms: RPO21 is active in the following subcellular-locations: cytoplasmic stress granule, mitochondrion, nucleus, RNA polymerase II.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RPO21 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures


For RPO21 there are:
142 structures (145 chains) solved
10 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RPO21 has been screened with compounds ( bioactivities). (see details)