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DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV), herpes simplex virus 1 (HHV-1) and Epstein-Barr virus (EBV) and may inhibit the mobility of LTR and non-LTR retrotransposons. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.
基因功能參考文獻:
Data suggest that heat shock proteins, in particular Hsp90, stimulate APOBEC3-mediated DNA deamination activity toward hepatitis B viral DNA, suggesting a potential physiological role in mutagenesis/carcinogenesis and viral innate immunity; Hsp90 stimulates deamination activity of APOBEC3G, APOBEC3B, and APOBEC3C during co-expression in human liver HepG2 cells. PMID: 28637869
our results suggest that APOBEC3C is in fact involved in protecting hosts from lentiviruses. PMID: 27732658
Antiviral functions of APOBEC3C against HIV-1 and APOBEC3C binding capacity PMID: 28315663
These results suggest that functional potential of APOBEC3B and APOBEC3C involved in cancer mutagenesis is associated with estrogen receptor status. PMID: 26682542
High APOBEC3C is associated with the pathogenesis of primary effusion lymphoma. PMID: 25650088
Expression of APOBEC3A or 3C in 293FT cells reduced the infectivity of HPV16 pseudovirions. The reduced infectivity of virions assembled in the presence of APOBEC3A, but not 3C, was attributed to decreased copy number of the encapsidated reporter plasmid. PMID: 25576866
APOBEC3 deaminases upregulated by IFN-beta induce E2 hypermutation of HPV16 in cervical keratinocytes. PMID: 24227842
The mechanism of APOBEC3C (A3C)-mediated LINE-1 inhibition was found to be deaminase independent, required an intact dimerization site and the RNA-binding pocket mutation R122A abolished L1 restriction by A3C. PMID: 24101588
This study confirmed the association of the APOBEC3 deletion with breast cancer risk among women of European ancestry. PMID: 23715497
Decreases in APOBAC3A and APOBAC3C in the cortex of psychotic patients support the hypothesis that an epigenetic misregulation of gene expression may be operative in the pathogenesis of psychotic disorders. PMID: 22948384
a high-resolution crystal structure of APOBEC3C with the HIV-1 viral infectivity factor (Vif)-interaction interface. PMID: 23001005
Findings suggest that APOBEC3-mediated editing of HIV-1 could be modulated by host and virus genetic characteristics in the context of pediatric infection. PMID: 22145963
The result suggest that Core-A3C may be a candidate as a novel antiviral agent against human HBV infection. PMID: 21746770
The authors identified a single cysteine at position 320 (C320) that disrupts A3DE activity. PMID: 21430060
Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism. PMID: 21368204
The basic biology of the interactions between human APOBEC3 proteins and HIV-1 Vif, is reviewed. PMID: 20096141
different APOBEC3 family members function to neutralize specific lentiviruses PMID: 15466872
APOBEC3 proteins may help prevent the zoonotic infection of humans by simple retroviruses and provide a mechanism for how simple retroviruses can avoid inhibition by APOBEC3 family members. PMID: 15956565
evidence for a role of host-encoded APOBEC3 proteins in the regulation of L1 retrotransposition PMID: 16735504
reviews the current knowledge on the mechanism of APOBEC3-dependent retrovirus restriction and discuss whether this innate host-defense system actively contributes to HIV genetic variation PMID: 17078485
Differences in promiscuity of monocytes, macrophages, and DCs can be defined, at least partly, by disparities in APOBEC expression, with implications for enhancing cellular defenses against HIV-1. PMID: 17371941
The catalytic domain of APOBEC3 proteins may be important for proper folding and target factors such as RNA or protein interaction in addition to cytidine deamination. PMID: 17582006
These findings demonstrate that HBV is highly vulnerable to the editing activity of an endogenous human deaminase and suggest that A3C could contribute to innate anti-HBV host responses. PMID: 17625792
APOBEC3 suppresses HBV replication in hepatocytes by inhibiting hnRNP K-mediated transcription and expression of HBV genes as well as HBV core DNA synthesis. PMID: 17672864
study demonstrate that APOBEC3C is necessary and sufficient for G-to-A mutations in some HIV-1 strains PMID: 17967058
Stress causes APOBEC3A, APOBEC3B, APOBEC3C, and APOBEC3F to colocalize efficiently with Vif(IIIB) and mRNA-PABP1 complexes in stress granules PMID: 17977970
Study compared the antiviral activities of human and murine Apobec3 (A3), and found that, HIV is able to resist human A3G but is sensitive to murine A3, whereas murine leukemia virus is relatively resistant to murine A3 but sensitive to human A3G. PMID: 18032489
Partially active Vif alleles resulting in incomplete neutralization of cytoplasmic APOBEC3 molecules are directly responsible for the generation of a highly diverse, yet G-to-A biased, proviral reservoir PMID: 18391217
Cul5-E3 ubiquitin ligase appears to be a common pathway hijacked by HIV-1 and SIV Vif to defeat APOBEC3 proteins. PMID: 18419775
These results indicate that APOBEC3G, APOBEC3C and APOBEC3H have the ability to edit HBV DNA and that each protein is likely to contribute to various degrees to the generation of modified genomes in human liver cells. PMID: 18420796
Human APOBEC3 proteins inhibit porcine endogenous retrovirus replication, which may reduce risk for infection of human cells as a consequence of pig-to-human xenotransplantation. PMID: 18555089
IAPE and HERV-K elements are restricted at the entry, amplification and integration into their target genomes by the host APOBEC3 proteins. PMID: 18702815
Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins. PMID: 19088851
Major cellular components of human BRB could be primary cultured in vitro and different expression of APOBEC3 in human blood-retinal barrier was examined. PMID: 19369234
APOBEC3 roles in limiting viruse pathogenicity by partially restricting infection PMID: 19390611
The structure of APOBEC3C (A3C), a single-domain A3 with strong antilentiviral activity, was modeled. PMID: 19581596
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亞細胞定位:
Nucleus. Cytoplasm.
蛋白家族:
Cytidine and deoxycytidylate deaminase family
組織特異性:
Expressed in spleen, testes, peripherical blood lymphocytes, heart, thymus, prostate and ovary.