APOBEC4, a New Member of the AID/APOBEC Family of Polynucleotide (Deoxy)Cytidine Deaminases Predicted by Computational Analysis

Using iterative database searches, we identified a new subfamily of the AID/APOBEC family of RNA/DNA editing cytidine deaminases. The new subfamily, which is represented by readily identifiable orthologs in mammals, chicken, and frog, but not fishes, was designated APOBEC4. The zinc-coordinating motifs involved in catalysis and the secondary structure of the APOBEC4 deaminase domain are evolutionarily conserved, suggesting that APOBEC4 proteins are active polynucleotide (deoxy)cytidine deaminases. In reconstructed maximum likelihood phylogenetic trees, APOBEC4 forms distinct clade with a high statistical support. APOBEC4 and APOBEC1 are joined in a moderately supported cluster clearly separated from AID, APOBEC2 and APOBEC3 subfamilies. In mammals, APOBEC4 is expressed primarily in testis which suggests the possibility that it is an editing enzyme for mRNAs involved in spermatogenesis.

[1]  M. Malim,et al.  Cytidine deamination and resistance to retroviral infection: towards a structural understanding of the APOBEC proteins. , 2005, Virology.

[2]  M. Liddament,et al.  The Retroviral Hypermutation Specificity of APOBEC3F and APOBEC3G Is Governed by the C-terminal DNA Cytosine Deaminase Domain* , 2005, Journal of Biological Chemistry.

[3]  M. Goodman,et al.  Reward versus risk: DNA cytidine deaminases triggering immunity and disease. , 2005, Biochemistry.

[4]  M. Neuberger,et al.  Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases. , 2005, Molecular biology and evolution.

[5]  Jianzhi Zhang,et al.  Rapid evolution of primate antiviral enzyme APOBEC3G. , 2004, Human molecular genetics.

[6]  M. Emerman,et al.  Ancient Adaptive Evolution of the Primate Antiviral DNA-Editing Enzyme APOBEC3G , 2004, PLoS biology.

[7]  Sudhir Kumar,et al.  MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment , 2004, Briefings Bioinform..

[8]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[10]  O. Gascuel,et al.  A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. , 2003, Systematic biology.

[11]  A. Durandy Mini‐review Activation‐induced cytidine deaminase: a dual role in class‐switch recombination and somatic hypermutation , 2003, European journal of immunology.

[12]  Reuben S Harris,et al.  Immunity through DNA deamination. , 2003, Trends in biochemical sciences.

[13]  M. Malim,et al.  Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein , 2002, Nature.

[14]  D. Mukhopadhyay,et al.  ARCD-1, an apobec-1-related cytidine deaminase, exerts a dominant negative effect on C to U RNA editing. , 2001, American journal of physiology. Cell physiology.

[15]  I. Mian,et al.  Identification of the yeast cytidine deaminase CDD1 as an orphan C-->U RNA editase. , 2001, Nucleic acids research.

[16]  H Philippe,et al.  Opinion: long branch attraction and protist phylogeny. , 2000, Protist.

[17]  A. Fischer,et al.  Activation-Induced Cytidine Deaminase (AID) Deficiency Causes the Autosomal Recessive Form of the Hyper-IgM Syndrome (HIGM2) , 2000, Cell.

[18]  T. Honjo,et al.  Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme , 2000, Cell.

[19]  R. DeSalle,et al.  Adaptive Evolution of Genes and Genomes , 2000, Heredity.

[20]  D T Jones,et al.  Protein secondary structure prediction based on position-specific scoring matrices. , 1999, Journal of molecular biology.

[21]  L. Chan,et al.  APOBEC-2, a cardiac- and skeletal muscle-specific member of the cytidine deaminase supergene family. , 1999, Biochemical and biophysical research communications.

[22]  N. Navaratnam,et al.  Molecular modelling and the biosynthesis of apolipoprotein B containing lipoproteins. , 1998, Atherosclerosis.

[23]  C Carter,et al.  Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate recognition. , 1998, Journal of molecular biology.

[24]  J. Morrison,et al.  The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase. , 1993, The Journal of biological chemistry.

[25]  C. Burant,et al.  Molecular cloning of an apolipoprotein B messenger RNA editing protein. , 1993, Science.

[26]  N. Saitou,et al.  On the maximum likelihood method in molecular phylogenetics , 1991, Journal of Molecular Evolution.

[27]  P. Nygaard,et al.  Mutants Constitutive for Nucleoside‐Catabolizing Enzymes in Escherichia coli K 12 , 1972 .

[28]  R. Wolfenden,et al.  Cytidine deaminase from Escherichia coli. Purification, properties and inhibition by the potential transition state analog 3,4,5,6-tetrahydrouridine. , 1971, The Journal of biological chemistry.

[29]  笹田 亜麻子 APOBEC3G targets human T-cell leukemia virus type 1 , 2006 .

[30]  Gapped BLAST and PSI-BLAST: A new , 1997 .

[31]  J. Felsenstein Inferring phylogenies from protein sequences by parsimony, distance, and likelihood methods. , 1996, Methods in enzymology.

[32]  C. Carter The nucleoside deaminases for cytidine and adenosine: structure, transition state stabilization, mechanism, and evolution. , 1995, Biochimie.

[33]  P. Nygaard,et al.  Mutants constitutive for nucleoside-catabolizing enzymes in Escherichia coli K12. Isolation, charactrization and mapping. , 1972, European journal of biochemistry.