# APOBEC > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/APOBEC > Markdown URL: https://mediated.wiki/source/APOBEC.md > Source: https://en.wikipedia.org/wiki/APOBEC > Source revision: 1334721777 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) Enzyme involved in messenger RNA editing **Example of a member of the APOBEC family, APOBEC-2**. A cytidine deaminase from *Homo sapiens*.[1] Protein domain APOBEC-like N-terminal domain Identifiers Symbol APOBEC_N Pfam PF08210 InterPro IPR013158 Available protein structures: PDB IPR013158 PF08210 (ECOD; PDBsum) AlphaFold IPR013158 PF08210 Protein domain APOBEC-like C-terminal domain Identifiers Symbol APOBEC_C Pfam PF05240 InterPro IPR007904 Available protein structures: PDB IPR007904 PF05240 (ECOD; PDBsum) AlphaFold IPR007904 PF05240 **APOBEC** ("apolipoprotein B mRNA editing enzyme, catalytic polypeptide") is a family of evolutionarily conserved [cytidine deaminases](/source/Cytidine_deaminase). ## Function A mechanism of generating protein diversity is [mRNA](/source/Messenger_RNA) editing. The APOBEC family of proteins perform mRNA modifications by deaminating cytidine bases to uracil. The [N-terminal](/source/N-terminus) domain of APOBEC-like proteins is the catalytic domain, while the [C-terminal](/source/C-terminus) domain is a pseudocatalytic domain. More specifically, the catalytic domain is a zinc dependent cytidine deaminase domain and is essential for cytidine deamination. The positively charged zinc ion in the catalytic domain attracts to the partial-negative charge of RNA. In the case of APOBEC-1, the mRNA transcript of intestinal apolipoprotein B is altered. RNA editing by APOBEC-1 requires homodimerization and this complex interacts with RNA-binding proteins to form the [editosome](/source/Editosome).[2] The resulting structure interacts with the codon CAA at codon 2153 and deaminates it into UAA, producing a stop codon that results in mRNA that is translated into the intestinal apoB-48 [isoform](/source/Isoform).[3] For other APOBEC-modified transcripts such as in the site-specific deamination of a CGA to a UGA stop codon in neurofibromatosis type 1 (*[NF1](/source/Neurofibromin_1)*) mRNA, the resulting proteins are predicted to be truncated as well, although these transcripts are possibly degraded.[4] C-to-U modifications do not always result in the truncation of proteins. For example, in humans/mammals they help protect from viral infections.[5][6] APOBEC family proteins are widely expressed in cells of the human innate immune system.[7] ## Cancer These enzymes, when misregulated, are a major source of mutation in numerous cancer types.[5][6][8] When the expression of APOBEC family proteins is triggered, accidental mutations in somatic cells can lead to the development of oncogenes, cells which have the potential to develop into a tumor. APOBEC proteins are further expressed in attempt to regulate tumor formation. This makes APOBEC proteins a helpful marker for diagnosing malignant tumors.[9] ## Structure A 2013 review discussed the structural and biophysical aspects of APOBEC3 family enzymes.[10] Many of the APOBEC protein features are described in the widely studied [APOBEC3G](/source/APOBEC3G)'s page.[*[tone](https://en.wikipedia.org/wiki/Wikipedia:Writing_better_articles#Tone)*] ## Family members Human genes encoding members of the APOBEC protein family include: - [APOBEC1](/source/APOBEC1) - [APOBEC2](/source/APOBEC2) - [APOBEC3A](/source/APOBEC3A) - [APOBEC3B](/source/APOBEC3B) - [APOBEC3C](/source/APOBEC3C) - [APOBEC3D](/source/APOBEC3D) ("[APOBEC3E](/source/APOBEC3E)" now refers to this) - [APOBEC3F](/source/APOBEC3F) - [APOBEC3G](/source/APOBEC3G) - [APOBEC3H](/source/APOBEC3H) - [APOBEC4](/source/APOBEC4) - [Activation-induced (cytidine) deaminase](/source/Activation-induced_(cytidine)_deaminase) (AID) ## References 1. **[^](#cite_ref-Prochnow1_1-0)** [PDB](/source/Protein_Data_Bank): [2NYT](https://www.rcsb.org/structure/2NYT)​; Prochnow C, Bransteitter R, Klein MG, Goodman MF, Chen XS (January 2007). "The APOBEC-2 crystal structure and functional implications for the deaminase AID". *Nature*. **445** (7126): 447–451. [Bibcode](/source/Bibcode_(identifier)):[2007Natur.445..447P](https://ui.adsabs.harvard.edu/abs/2007Natur.445..447P). [doi](/source/Doi_(identifier)):[10.1038/nature05492](https://doi.org/10.1038%2Fnature05492). [PMID](/source/PMID_(identifier)) [17187054](https://pubmed.ncbi.nlm.nih.gov/17187054). [S2CID](/source/S2CID_(identifier)) [4394772](https://api.semanticscholar.org/CorpusID:4394772).; rendered using [PyMOL](http://pymol.sourceforge.net). 1. **[^](#cite_ref-pmid12683974_2-0)** Wedekind JE, Dance GS, Sowden MP, Smith HC (April 2003). "Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business". *Trends in Genetics*. **19** (4): 207–216. [doi](/source/Doi_(identifier)):[10.1016/S0168-9525(03)00054-4](https://doi.org/10.1016%2FS0168-9525%2803%2900054-4). [PMID](/source/PMID_(identifier)) [12683974](https://pubmed.ncbi.nlm.nih.gov/12683974). 1. **[^](#cite_ref-3)** McKusick VA, Hamosh A (19 December 2019) [Originally published 27 September 1994]. ["APOLIPOPROTEIN B mRNA-EDITING ENZYME, CATALYTIC POLYPEPTIDE 1; APOBEC1"](https://www.omim.org/entry/600130). *Online Mendelian Inheritance in Man*. Retrieved 23 December 2023. 1. **[^](#cite_ref-4)** Blanc V, Davidson NO (January 2003). ["C-to-U RNA editing: mechanisms leading to genetic diversity"](https://doi.org/10.1074%2Fjbc.r200024200). *The Journal of Biological Chemistry*. **278** (3): 1395–1398. [doi](/source/Doi_(identifier)):[10.1074/jbc.r200024200](https://doi.org/10.1074%2Fjbc.r200024200). [PMID](/source/PMID_(identifier)) [12446660](https://pubmed.ncbi.nlm.nih.gov/12446660). 1. ^ [***a***](#cite_ref-APOBEC3-2016_5-0) [***b***](#cite_ref-APOBEC3-2016_5-1) ["*Unexpected DNA-Binding Mechanism Suggests Ways to Block Enzyme Activity in Cancer*"](http://www.genengnews.com/gen-news-highlights/unexpected-dna-binding-mechanism-suggests-ways-to-block-enzyme-activity-in-cancer/81253584). Dec 2016. Based on ("Structural Basis for Targeted DNA Cytosine Deamination and Mutagenesis by APOBEC3A and APOBEC3B") online in Nature Structural and Molecular Biology. 1. ^ [***a***](#cite_ref-pmid34353635_6-0) [***b***](#cite_ref-pmid34353635_6-1) Cervantes-Gracia K, Gramalla-Schmitz A, Weischedel J, Chahwan R (November 2021). ["APOBECs orchestrate genomic and epigenomic editing across health and disease"](https://doi.org/10.1016%2Fj.tig.2021.07.003). *Trends in Genetics*. **37** (11): 1028–1043. [doi](/source/Doi_(identifier)):[10.1016/j.tig.2021.07.003](https://doi.org/10.1016%2Fj.tig.2021.07.003). [PMID](/source/PMID_(identifier)) [34353635](https://pubmed.ncbi.nlm.nih.gov/34353635). [S2CID](/source/S2CID_(identifier)) [236934922](https://api.semanticscholar.org/CorpusID:236934922). 1. **[^](#cite_ref-7)** Koito A, Ikeda T (2013). ["Intrinsic immunity against retrotransposons by APOBEC cytidine deaminases"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576619). *Frontiers in Microbiology*. **4**: 28. [doi](/source/Doi_(identifier)):[10.3389/fmicb.2013.00028](https://doi.org/10.3389%2Ffmicb.2013.00028). [PMC](/source/PMC_(identifier)) [3576619](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576619). [PMID](/source/PMID_(identifier)) [23431045](https://pubmed.ncbi.nlm.nih.gov/23431045). 1. **[^](#cite_ref-8)** Butler K, Banday AR (March 2023). ["APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044795). *Journal of Hematology & Oncology*. **16** (1) 31. [doi](/source/Doi_(identifier)):[10.1186/s13045-023-01425-5](https://doi.org/10.1186%2Fs13045-023-01425-5). [PMC](/source/PMC_(identifier)) [10044795](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044795). [PMID](/source/PMID_(identifier)) [36978147](https://pubmed.ncbi.nlm.nih.gov/36978147). 1. **[^](#cite_ref-9)** Okazaki IM, Kotani A, Honjo T (2007-01-01). "Role of AID in tumorigenesis". *AID for Immunoglobulin Diversity*. Advances in Immunology. Vol. 94. Academic Press. pp. 245–273. [doi](/source/Doi_(identifier)):[10.1016/s0065-2776(06)94008-5](https://doi.org/10.1016%2Fs0065-2776%2806%2994008-5). [ISBN](/source/ISBN_(identifier)) [9780123737069](https://en.wikipedia.org/wiki/Special:BookSources/9780123737069). [PMID](/source/PMID_(identifier)) [17560277](https://pubmed.ncbi.nlm.nih.gov/17560277). 1. **[^](#cite_ref-10)** Vasudevan AA, Smits SH, Höppner A, Häussinger D, Koenig BW, Münk C (November 2013). ["Structural features of antiviral DNA cytidine deaminases"](http://juser.fz-juelich.de/record/139785/files/FZJ-2013-05757.pdf) (PDF). *Biological Chemistry*. **394** (11): 1357–1370. [doi](/source/Doi_(identifier)):[10.1515/hsz-2013-0165](https://doi.org/10.1515%2Fhsz-2013-0165). [PMID](/source/PMID_(identifier)) [23787464](https://pubmed.ncbi.nlm.nih.gov/23787464). [S2CID](/source/S2CID_(identifier)) [4151961](https://api.semanticscholar.org/CorpusID:4151961). ## Bibliography - Gupta, A., Gazzo, A., Selenica, P. et al., *APOBEC3 mutagenesis drives therapy resistance in breast cancer*, *Nature Genetics* (April 1, 2025) [doi](/source/Doi_(identifier)):[10.1038/s41588-025-02187-1](https://doi.org/10.1038%2Fs41588-025-02187-1) This article incorporates text from the public domain [Pfam](/source/Pfam) and [InterPro](/source/InterPro): [IPR013158](https://www.ebi.ac.uk/interpro/entry/IPR013158) v t e Hydrolases: carbon-nitrogen non-peptide (EC 3.5) 3.5.1: Linear amides / Amidohydrolases Asparaginase Glutaminase Urease Biotinidase Aminoacylase ACY1 Aspartoacylase(ACY2) ACY3 Ceramidase Aspartylglucosaminidase Fatty acid amide hydrolase Histone deacetylase Sirtuin 3.5.2: Cyclic amides/ Amidohydrolases Barbiturase Beta-lactamase Dihydroorotase 3.5.3: Linear amidines/ Ureohydrolases Arginase Agmatinase Protein-arginine deiminase 3.5.4: Cyclic amidines/ Aminohydrolases Guanine deaminase Adenosine deaminase AMP deaminase Inosine monophosphate synthase DCMP deaminase GTP cyclohydrolase I Cytidine deaminase AICDA Activation-induced cytidine deaminase 3.5.5: Nitriles/ Aminohydrolases Nitrilase 3.5.99: Other Riboflavinase Thiaminase II v t e Enzymes Activity Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis Regulation Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator Classification EC number Enzyme superfamily Enzyme family List of enzymes Kinetics Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics Types EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list) [Portal](https://en.wikipedia.org/wiki/Wikipedia:Contents/Portals): - [Biology](https://en.wikipedia.org/wiki/Portal:Biology) --- Adapted from the Wikipedia article [APOBEC](https://en.wikipedia.org/wiki/APOBEC) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/APOBEC?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.