image:Apobec.J.Steinfeld.D.png, 300px, upExample of a member of the APOBEC family, APOBEC-2. A cytidine deaminase from ''Homo sapiens''.; ; rendered usin
PyMOL
APOBEC ("apolipoprotein B mRNA editing enzyme, catalytic polypeptide") is a family of evolutionarily conserved cytidine deaminases.

Function

A mechanism of generating protein diversity is

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

editing. The APOBEC family of proteins perform mRNA modifications by deaminating cytidine bases to uracil. The

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

domain of APOBEC-like proteins is the catalytic domain, while the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

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 RNA editing (also RNA modification) is a molecular process through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after it has been generated by RNA polymerase. It occurs in all living organisms ...

. 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 A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

. 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. C-to-U modifications do not always result in the truncation of proteins. For example, in humans/mammals they help protect from viral infections. APOBEC family proteins are widely expressed in cells of the human innate immune system.

Cancer

These enzymes, when misregulated, are a major source of mutation in numerous cancer types. 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.

Structure

A 2013 review discussed the structural and biophysical aspects of APOBEC3 family enzymes. Many of the APOBEC protein features are described in the widely studied APOBEC3G's page.

Family members

Human genes encoding members of the APOBEC protein family include: *

APOBEC1 Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 also known as C->U-editing enzyme APOBEC-1 is a protein that in humans is encoded by the ''APOBEC1'' gene. This gene encodes a member of the APOBEC, APOBEC protein family and the cyti ...

* APOBEC2 * APOBEC3A * APOBEC3B * APOBEC3C *

APOBEC3D Probable DNA dC->dU-editing enzyme APOBEC-3D is a protein that in humans is encoded by the ''APOBEC3D'' gene. This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a Genetic cluster, ...

(" APOBEC3E" now refers to this) * APOBEC3F * APOBEC3G * APOBEC3H * APOBEC4 * Activation-induced (cytidine) deaminase (AID)

References

Bibliography

*Gupta, A., Gazzo, A., Selenica, P. et al., ''APOBEC3 mutagenesis drives therapy resistance in breast cancer'', ''Nature Genetics'' (April 1, 2025) {{protein-stub EC 3.5.4