APOBEC3A

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Protein-coding gene in the species Homo sapiens

title: "APOBEC3A" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["ec-3.5.4"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "general/ec-3-5-4" source: "https://en.wikipedia.org/wiki/APOBEC3A" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, also known as APOBEC3A, or A3A is a gene of the APOBEC3 family found in primates, including humans, and some other mammals. It is a single-domain DNA cytidine deaminase with antiviral effects. While other members of the family such as APOBEC3G are believed to act by editing ssDNA by removing an amino group from cytosine in DNA, introducing a cytosine to uracil change which can ultimately lead to a cytosine to thymine mutation, one study suggests that APOBEC3A can inhibit parvoviruses by another mechanism. The cellular function of APOBEC3A is likely to be the destruction of foreign DNA through extensive deamination of cytosine.

This gene is a member of the polynucleotide cytosine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. The APOBEC3 family of DNA editing enzymes are thought to be part of the innate immune system by restricting retroviruses, mobile genetic elements like retrotransposons and endogenous retroviruses. In addition, APOBEC3A is an important restrictive factor for HIV-1 and other retroviruses such as murine leukemia virus,

Structure

The basic structure APOBEC3A consists of a 5 stranded central β-sheet surrounded by 6 α-helices and a single catalytically active zinc finger domain. Similar to all APOBEC3 catalytic domains, the domain is a HAEx28Cx2-4C zinc binding motif. In such motifs, histidine residues (or cysteine residues in RNA cytidine deaminases) coordinate the zinc ion while a glutamic acid stabilizes the transition state and the proton shuttle. The zinc ion, in this case, is specifically coordinated by residues H70, C101 and C106.

A3A-ssDNA structure

Single stranded DNA, abbreviated ssDNA, is the substrate that is catalyzed in the C→U deamination reaction of APOBEC3A.

Activity

A3A has the highest catalytic activity among the APOBEC3 protein family.

mRNA editing activity

A3A was first found to induce an alternative form of the mRNA editing, GA, in Wilms' Tumor-1 (WT1) mRNA in cord blood mononuclear cells, particularly in the genomic polymorphic sites, apparently reflecting an amination process rather than a de-amination one. This was soon followed by a study showing A3A induce canonical widespread CU mRNA editing in human monocytes and macrophages.

Effect of pH on APOBEC3A

APOBEC3A functions best at an acidic pH, with maximal catalytic activity at pH 5.5. Another protein of the APOBEC family very similar to A3A, APOBEC3B, showed little activity at pH 4.5 and 4.0 and a similar assumption can be made of A3A activity at these lower pH levels.

A3A affinity for ssDNA is also pH dependent and closely correlated to the deamination activity of APOBEC3A. The enzyme has the highest affinity for ssDNA at pH 5.5 demonstrating that A3A's maximal catalytic activity and highest affinity for ssDNA occur at a similar pH.

Mechanism of Action

A3A has become an increasingly widely studied A3 because of its high catalytic activity compared to its family members and its relatively unknown mechanisms compared to more popular APOBEC3's such as APOBEC3G.

Context dependent binding to ssDNA

The binding of APOBEC3A to its substrate ssDNA is highly dependent on its surrounding nucleotides. The specificity for binding to its target deoxycytidine increases more than ten-fold when the target deoxycytidine is surrounded by deoxythymidine nucleotides.

References

References

  1. "Entrez Gene: APOBEC3A apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A".
  2. (May 2009). "Deaminase-independent inhibition of parvoviruses by the APOBEC3A cytidine deaminase". PLOS Pathogens.
  3. (February 2010). "APOBEC3 proteins mediate the clearance of foreign DNA from human cells". Nature Structural & Molecular Biology.
  4. (March 2021). "Foamy Viruses, Bet, and APOBEC3 Restriction". Viruses.
  5. (April 2021). "Degradation-Independent Inhibition of APOBEC3G by the HIV-1 Vif Protein". Viruses.
  6. (April 2017). "Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity". Nature Communications.
  7. (2013). "NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity". Nature Communications.
  8. (February 2020). "Deamination hotspots among APOBEC3 family members are defined by both target site sequence context and ssDNA secondary structure". Nucleic Acids Research.
  9. (May 2015). "The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization". Structure.
  10. (October 2012). "Methylcytosine and normal cytosine deamination by the foreign DNA restriction enzyme APOBEC3A". The Journal of Biological Chemistry.
  11. (2015-03-25). "APOBEC3A is implicated in a novel class of G-to-A mRNA editing in WT1 transcripts". PLOS ONE.
  12. (April 2015). "APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages". Nature Communications.
  13. (October 2013). "A biochemical analysis linking APOBEC3A to disparate HIV-1 restriction and skin cancer". The Journal of Biological Chemistry.
  14. (June 2017). "Family-Wide Comparative Analysis of Cytidine and Methylcytidine Deamination by Eleven Human APOBEC Proteins". Journal of Molecular Biology.
  15. (May 2018). "Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions". Scientific Reports.

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