Molecular Target Synopsis
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Drugs and Clinical Candidates
Ligand Efficiency Plot
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Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

A (P07636) - Overview - Molecular Target Synopsis


A, DDE-recombinase A
Enzyme Classification 3.1.22.-
UniProt P07636

Also Known as TNPA_BPMU, A

Responsible for viral genome integration into the host chromosome. During integration of the incoming virus, DDE-recombinase A cleaves both viral DNA ends and the resulting 3'-OH perform a nucleophilic attack of the host DNA. The 5' flanking DNA attached to the ends of the viral genome (flaps) are resected by the DDE-recombinase A endonuclease activity, with the help of host chaperone ClpX. The gaps created in the host chromosome by the viral genome insertion are repaired by the host primary machinery for double-strand break repair., Responsible for replication of the viral genome by replicative transposition. During replicative transposition, DDE-recombinase A is part of the transpososome complex. DDE-recombinase A cleaves the viral DNA and the resulting 3'-OH performs a nucleophilic attack of the host DNA. The 5' flanking DNA is not resected and an intermediary structure is formed. This structure is resolved by target-primed replication leading to two copies of the viral genome (the original one and the copied one). Host ClpX and translation initiation factor IF2 play an essential transpososome-remodeling role by releasing the block between transposition and DNA replication. Successive rounds of replicative transposition can lead up to 100 copies of the viral genome., Promotes replication and thereby lytic development by competing with repressor c (Repc) for binding to the internal activation sequence (IAS) in the enhancer/operator region. The outcome of this competition determines if the virus enters latency or starts replication. Homotetramer. Part of the transpososome complex composed of a DDE-recombinase A tetramer synapsing the ends of the viral genome and the enhancer element. Interacts with target DNA activator B; this interaction brings DDE-recombinase A to the transposition target site. Interacts with host ClpX; this interaction remodels the transpososome for replication and is required for the flaps endonuclease activity of DDE-recombinase A. Binds (via N-terminus) three distinct recognition sites in the AttR and AttL regions of the viral genome ends: R1, R2, and R3 on the right end and L1, L2, and L3 on the left, not all of which are essential for transposition. The active transpososome is formed by three DDE-recombinase A subunits tightly bound to R1, R2, L1 plus a fourth subunit tightly bound in the complex but weakly bound to the L2 recognition site. Only two subunits out of the four involved are responsible for catalysis. Each subunit performs the cleavage and joining reactions for one DNA end and acts in trans, ensuring the reaction is only initiated when both viral genome ends are paired.

Inspect Structure
See all 3D Structures for A

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform

Sub-cellular localization

UniProt: A is active in the following subcellular-locations: host cytoplasm.
GO terms: A is active in the following subcellular-locations: host, host cell cytoplasm.

GO terms

Gene Copy Number Variation

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

3D Structures

For A there are:
9 structures (11 chains) solved
0 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis