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FUNCTION DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:16571802, PubMed:16920826, PubMed:18779051, PubMed:18827027, PubMed:20062055, PubMed:22915799, PubMed:29290613). The A3H-var/haplotype 2 exhibits antiviral activity against vif-deficient HIV-1 (PubMed:18299330, PubMed:21835787, PubMed:23097438, PubMed:29290613). 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 (PubMed:18299330). 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 (PubMed:18299330). Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA (PubMed:20062055). Exhibits antiviral activity also against T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons (PubMed:20062055, PubMed:22457529).CATALYTIC ACTIVITY a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)COFACTOR APOBEC3H activity is regulated by RNA (PubMed:29290613). While RNA-binding inhibits the DNA deaminase activity, double-stranded RNA is required for HIV-1 restriction by promoting APOBEC3H homodimerization and packaging into retroviral nucleocapsids (PubMed:29290613).ACTIVITY REGULATION (Microbial infection) Antiviral activity is inhibited to some extent by the HIV-1 virion infectivity factor (VIF), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.SUBUNIT Homodimer (PubMed:29290613). Interacts with AGO1, AGO2 and AGO3 (PubMed:22915799).SUBCELLULAR LOCATION Haplotype 1 is distributed in both the nucleus and cytoplasm, whereas haplotype 2 is predominantly cytoplasmic.ALTERNATIVE PRODUCTS Expressed in lymphoid organs. Also detected in non-lymphoid tissues including lung, testis, ovary, fetal liver and skin.PTM (Microbial infection) Following infection by some HIV-1 strains, such as isolate BRU/LAI, can be ubiquitinated by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, leading to its degradation (PubMed:37640699). Ubiquitination by the ECS complex is however less efficent compared to APOBEC3G or APOBEC3G (PubMed:37640699).POLYMORPHISM There are at least 4 different haplotypes in the human population (PubMed:18779051, PubMed:18945781). The allele A3H-var/haplotype 2 encodes a more stable protein which is able to block HIV-1 replication (PubMed:18779051, PubMed:18945781). The displayed allele (haplotype 1) is unstable and inefficient to block HIV-1 replication (PubMed:18779051, PubMed:18945781).MISCELLANEOUS APOBEC3H from old world monkeys has retained its antiviral activity, while it is lost in other primates.MISCELLANEOUS It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.SIMILARITY Belongs to the cytidine and deoxycytidylate deaminase family.
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