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

GEN1 (Q17RS7) - Overview - Molecular Target Synopsis

Protein


GEN1, Flap endonuclease GEN homolog 1
Enzyme Classification 3.1.-.-
UniProt Q17RS7

Also Known as GEN_HUMAN, GEN1

Endonuclease which resolves Holliday junctions (HJs) by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated. Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation (PubMed:19020614, PubMed:26682650). Cleaves HJs by a nick and counter-nick mechanism involving dual coordinated incisions that lead to the formation of ligatable nicked duplex products. Cleavage of the first strand is rate limiting, while second strand cleavage is rapid. Largely monomeric, dimerizes on the HJ and the first nick occurs upon dimerization at the junction (PubMed:26578604). Efficiently cleaves both single and double HJs contained within large recombination intermediates. Exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA (PubMed:28049850). Has also endonuclease activity on 5'-flap and replication fork (RF) DNA substrates (PubMed:26578604). Largely monomeric, dimerizes on the Holliday junction and the first nick occurs upon dimerization at the junction.

5T9J
CRYSTAL STRUCTURE OF HUMAN GEN1 IN COMPLEX WITH HOLLIDAY JUNCTION DNA IN THE UPPER INTERFACE
RCSB/PDB
Inspect Structure
See all 3D Structures for GEN1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: GEN1 is active in the following subcellular-locations: nucleus.
GO terms: GEN1 is active in the following subcellular-locations: centrosome, nucleoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project GEN1 has gain in 4 cell-lines, loss in 0 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: K_562, SF_268, RXF_393

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-LY-10, NCI-H1155, EB2

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: K562, SK-N-SH, MCF-7

(see details)

3D Structures


For GEN1 there are:
1 structures (2 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


GEN1 has been screened with compounds ( bioactivities). (see details)