APOBEC
| APOBEC-like N-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | APOBEC_N | ||||||||
| Pfam | PF08210 | ||||||||
| InterPro | IPR013158 | ||||||||
| |||||||||
| APOBEC-like C-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | APOBEC_C | ||||||||
| Pfam | PF05240 | ||||||||
| InterPro | IPR007904 | ||||||||
| |||||||||
APOBEC ("apolipoprotein B mRNA editing enzyme, catalytic polypeptide") is a family of evolutionarily conserved cytidine deaminases.
Function
[edit | edit source]A mechanism of generating protein diversity is mRNA editing. The APOBEC family of proteins perform mRNA modifications by deaminating cytidine bases to uracil. The N-terminal domain of APOBEC-like proteins is the catalytic domain, while the C-terminal 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.[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.[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) 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
[edit | edit source]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
[edit | edit source]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's page.[tone]
Family members
[edit | edit source]Human genes encoding members of the APOBEC protein family include:
- APOBEC1
- APOBEC2
- APOBEC3A
- APOBEC3B
- APOBEC3C
- APOBEC3D ("APOBEC3E" now refers to this)
- APOBEC3F
- APOBEC3G
- APOBEC3H
- APOBEC4
- Activation-induced (cytidine) deaminase (AID)
References
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Bibliography
[edit | edit source]- Gupta, A., Gazzo, A., Selenica, P. et al., APOBEC3 mutagenesis drives therapy resistance in breast cancer, Nature Genetics (April 1, 2025) Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
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