UniProt functional annotation for Q6NTF7



	UniProt functional annotation for Q6NTF7

UniProt code: Q6NTF7.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase- dependent and -independent mechanisms. The A3H-var/haplotype 2 exhibits antiviral activity against vif-deficient HIV-1. 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 also against T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. {ECO:0000269|PubMed:16571802, ECO:0000269|PubMed:16920826, ECO:0000269|PubMed:18299330, ECO:0000269|PubMed:18779051, ECO:0000269|PubMed:18827027, ECO:0000269|PubMed:20062055, ECO:0000269|PubMed:21835787, ECO:0000269|PubMed:22457529, ECO:0000269|PubMed:22915799, ECO:0000269|PubMed:23097438}.

Catalytic activity: Reaction=a 2'-deoxycytidine in single-stranded DNA + H(+) + H2O = a 2'- deoxyuridine in single-stranded DNA + NH4(+); Xref=Rhea:RHEA:50948, Rhea:RHEA-COMP:12846, Rhea:RHEA-COMP:12847, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:85452, ChEBI:CHEBI:133902; EC=3.5.4.38;

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};

Activity regulation: Antiviral activity is neutralized 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. {ECO:0000269|PubMed:21835787}.

Subunit: Interacts with AGO1, AGO2 and AGO3. {ECO:0000269|PubMed:22915799}.

Subcellular location: Nucleus. Cytoplasm. Cytoplasm, P-body. Note=Haplotype 1 is distributed in both the nucleus and cytoplasm, whereas haplotype 2 is predominantly cytoplasmic.

Tissue specificity: Expressed in lymphoid organs. Also detected in non- lymphoid tissues including lung, testis, ovary, fetal liver and skin. {ECO:0000269|PubMed:16571802, ECO:0000269|PubMed:20308164}.

Polymorphism: There are at least 4 different haplotypes in the human population. The allele A3H-var/haplotype 2 encodes a more stable protein which is able to block HIV-1 replication. The displayed allele (haplotype 1) is unstable and inefficient to block HIV-1 replication.

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. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase- dependent and -independent mechanisms. The A3H-var/haplotype 2 exhibits antiviral activity against vif-deficient HIV-1. 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 also against T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. {ECO:0000269\|PubMed:16571802, ECO:0000269\|PubMed:16920826, ECO:0000269\|PubMed:18299330, ECO:0000269\|PubMed:18779051, ECO:0000269\|PubMed:18827027, ECO:0000269\|PubMed:20062055, ECO:0000269\|PubMed:21835787, ECO:0000269\|PubMed:22457529, ECO:0000269\|PubMed:22915799, ECO:0000269\|PubMed:23097438}.


Catalytic activity:		Reaction=a 2'-deoxycytidine in single-stranded DNA + H(+) + H2O = a 2'- deoxyuridine in single-stranded DNA + NH4(+); Xref=Rhea:RHEA:50948, Rhea:RHEA-COMP:12846, Rhea:RHEA-COMP:12847, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:85452, ChEBI:CHEBI:133902; EC=3.5.4.38;
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
Activity regulation:		Antiviral activity is neutralized 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. {ECO:0000269\|PubMed:21835787}.
Subunit:		Interacts with AGO1, AGO2 and AGO3. {ECO:0000269\|PubMed:22915799}.
Subcellular location:		Nucleus. Cytoplasm. Cytoplasm, P-body. Note=Haplotype 1 is distributed in both the nucleus and cytoplasm, whereas haplotype 2 is predominantly cytoplasmic.
Tissue specificity:		Expressed in lymphoid organs. Also detected in non- lymphoid tissues including lung, testis, ovary, fetal liver and skin. {ECO:0000269\|PubMed:16571802, ECO:0000269\|PubMed:20308164}.
Polymorphism:		There are at least 4 different haplotypes in the human population. The allele A3H-var/haplotype 2 encodes a more stable protein which is able to block HIV-1 replication. The displayed allele (haplotype 1) is unstable and inefficient to block HIV-1 replication.
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. {ECO:0000305}.