Aprataxin (APTX) Antibody – Rabbit Polyclonal

This gene encodes a member of the histidine triad (HIT) superfamily. The encoded protein may play a role in single-stranded DNA repair through its nucleotide-binding activity and its diadenosine polyphosphate hydrolase activity. Mutations in this gene have been associated with ataxia-ocular apraxia. Alternatively spliced transcript variants have been identified for this gene.[provided by RefSeq, Aug 2010]

Function: DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH2) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity. Ref.12 Ref.14 Ref.16 Ref.17 Ref.18

Subunit structure: Interacts with single-strand break repair proteins XRCC1, XRCC4, ADPRT and p53/TP53. Interacts with NCL. Interacts (via FHA-like domain) with MDC1 (phosphorylated). Ref.12 Ref.13 Ref.14 Ref.15 Ref.20

Subcellular location: Nucleus › nucleoplasm. Nucleus › nucleolus. Note: Upon genotoxic stress, colocalizes with XRCC1 at sites of DNA damage. Colocalizes with MDC1 at sites of DNA double-strand breaks. Interaction with NCL is required for nucleolar localization. Ref.1 Ref.12 Ref.13 Ref.14 Ref.15 Ref.20Isoform 12: Cytoplasm Ref.1 Ref.12 Ref.13 Ref.14 Ref.15 Ref.20.

Tissue specificity: Widely expressed. In brain, it is expressed in the posterior cortex, cerebellum, hippocampus and olfactory bulb. Isoform 1 is highly expressed in the cerebral cortex and cerebellum, compared to isoform 2. Ref.10 Ref.11 Ref.12

Domain: The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide

By similarity.The FHA-like domain mediates interaction with NCL; XRCC1 and XRCC4.The HIT domain is required for enzymatic activity.The C2H2-type zinc finger mediates DNA-binding.

Involvement in disease: Ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]: An autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25

Sequence similarities: Contains 1 C2H2-type zinc finger.Contains 1 FHA-like domain.Contains 1 HIT domain.

Biophysicochemical propertiesKinetic parameters:KM=18 µM for AppppAKM=837.5 µM for AMP-NH2