Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

RNASEL (Q05823) - Overview - Molecular Target Synopsis

Protein


RNASEL, 2-5A-dependent ribonuclease
Enzyme Classification 3.1.26.-
UniProt Q05823

Also Known as RN5A_HUMAN, RNASEL, RNS4

Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis (PubMed:26263979). Might play a central role in the regulation of mRNA turnover (PubMed:11585831). Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length. Monomer (inactive form) or homodimer. Interacts with ABCE1; this interaction inhibits the RNASEL.

4OAU
COMPLETE HUMAN RNASE L IN COMPLEX WITH BIOLOGICAL ACTIVATORS.
RCSB/PDB
Inspect Structure
See all 3D Structures for RNASEL

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
741ENSG00000135828ENST00000444138, ENST00000367559ENSP00000411147, ENSP00000356530Q05823-1
652ENSG00000135828ENST00000539397ENSP00000440844Q05823-2

Sub-cellular localization


UniProt: RNASEL is active in the following subcellular-locations: cytoplasm, mitochondrion.
GO terms: RNASEL is active in the following subcellular-locations: cytosol, mitochondrial matrix, nuclear matrix.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RNASEL has gain in 0 cell-lines, loss in 2 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_539, MALME_3M, M14

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: UMC-11, SKM-1, WSU-FSCCL

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, A549, HSMM

(see details)

RNA Interference


RNASEL was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HUO3N1, OS25HAL. (see details)

3D Structures


For RNASEL there are:
5 structures (10 chains) solved
4 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RNASEL has been screened with 108 compounds (177 bioactivities), 29 compounds have bioactivities that show binding affinity of <= 500nM (51 bioactivities). (see details)