ABC3H_FELCA
ID ABC3H_FELCA Reviewed; 193 AA.
AC A9QA56;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=DNA dC->dU-editing enzyme APOBEC-3H {ECO:0000305};
DE Short=APOBEC3H {ECO:0000305};
DE EC=3.5.4.38 {ECO:0000269|PubMed:26491161};
DE AltName: Full=Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H {ECO:0000305};
DE Short=A3H {ECO:0000305};
DE AltName: Full=Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3Z3 {ECO:0000303|PubMed:26491161};
DE Short=A3Z3 {ECO:0000303|PubMed:26491161};
GN Name=APOBEC3H {ECO:0000312|EMBL:ABW83274.1};
GN Synonyms=APOBEC3Z3 {ECO:0000303|PubMed:26491161};
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685 {ECO:0000312|EMBL:ABW83274.1};
RN [1] {ECO:0000312|EMBL:ABW06962.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=18315870; DOI=10.1186/gb-2008-9-3-r48;
RA Munk C., Beck T., Zielonka J., Hotz-Wagenblatt A., Chareza S.,
RA Battenberg M., Thielebein J., Cichutek K., Bravo I.G., O'Brien S.J.,
RA Lochelt M., Yuhki N.;
RT "Functions, structure, and read-through alternative splicing of feline
RT APOBEC3 genes.";
RL Genome Biol. 9:RESEARCH48.1-RESEARCH48.2(2008).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, VARIANTS SER-65; ILE-65; GLN-68; THR-94 AND
RP ILE-96, AND MUTAGENESIS OF GLU-56 AND ALA-65.
RX PubMed=26491161; DOI=10.1128/jvi.02612-15;
RA Yoshikawa R., Izumi T., Yamada E., Nakano Y., Misawa N., Ren F.,
RA Carpenter M.A., Ikeda T., Muenk C., Harris R.S., Miyazawa T., Koyanagi Y.,
RA Sato K.;
RT "A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to
RT Feline Immunodeficiency Virus Infection.";
RL J. Virol. 90:474-485(2016).
CC -!- FUNCTION: DNA deaminase (cytidine deaminase) which acts as an inhibitor
CC of retrovirus replication and retrotransposon mobility via deaminase-
CC dependent and -independent mechanisms. Selectively targets single-
CC stranded DNA and does not deaminate double-stranded DNA or single- or
CC double-stranded RNA (By similarity). Exhibits single-stranded DNA
CC deaminase activity (in vitro) (PubMed:26491161). Incorporates into the
CC released virions of the virion infectivity factor (vif)-deficient
CC feline immunodeficiency virus (FIV) and suppresses FIV infectivity,
CC probably in a deaminase-dependent manner (in vitro) (PubMed:26491161).
CC Induces G-to-A hypermutations in vif-deficient FIV (in vitro)
CC (PubMed:26491161). The APOBEC3H/APOBEC3Z3 haplotype 5 exhibits
CC antiviral activity against vif-proficient FIV, strains Petaluma, C36
CC and Shizuoka (in vitro) (PubMed:26491161). Does not exhibit inhibitory
CC activity against feline leukemia virus (FeLV), feline endogenous
CC retrovirus (RD-114 virus) or a long interspersed nuclear element-1
CC (LINE-1) retrotransposon (in vitro) (PubMed:26491161).
CC {ECO:0000250|UniProtKB:P60705, ECO:0000269|PubMed:26491161}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in single-stranded DNA + H(+) + H2O = a 2'-
CC deoxyuridine in single-stranded DNA + NH4(+); Xref=Rhea:RHEA:50948,
CC Rhea:RHEA-COMP:12846, Rhea:RHEA-COMP:12847, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:85452,
CC ChEBI:CHEBI:133902; EC=3.5.4.38;
CC Evidence={ECO:0000269|PubMed:26491161};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9GZX7};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q19Q52}.
CC -!- TISSUE SPECIFICITY: Expressed in peripheral blood mononuclear cells.
CC {ECO:0000269|PubMed:18315870}.
CC -!- POLYMORPHISM: There are at least 7 different APOBEC3H/APOBEC3Z3
CC haplotypes in the feline population. The displayed haplotype 1 is
CC degraded in a feline immunodeficiency virus (FIV) virion infectivity
CC factor (vif)-dependent manner and is inefficient to block vif-
CC proficient FIV replication. Haplotype 5 is resistant to vif-mediated
CC degradation and is able to suppress vif-proficient FIV infectivity.
CC {ECO:0000269|PubMed:26491161}.
CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EU011792; ABW06962.1; -; mRNA.
DR EMBL; EU109281; ABW83274.1; -; Genomic_DNA.
DR AlphaFoldDB; A9QA56; -.
DR SMR; A9QA56; -.
DR HOGENOM; CLU_047918_0_0_1; -.
DR Proteomes; UP000011712; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR002125; CMP_dCMP_dom.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR SUPFAM; SSF53927; SSF53927; 1.
DR PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 1.
DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..193
FT /note="DNA dC->dU-editing enzyme APOBEC-3H"
FT /id="PRO_0000450385"
FT DOMAIN 24..126
FT /note="CMP/dCMP-type deaminase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT ACT_SITE 56
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT BINDING 54
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT BINDING 85
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT BINDING 88
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT VARIANT 65
FT /note="A -> I (in allele A3Z3; haplotype 5; confers
FT resistance to FIV vif-mediated degradation)"
FT /evidence="ECO:0000269|PubMed:26491161"
FT VARIANT 65
FT /note="A -> S (in allele A3Z3; haplotype 2; 3; 4 and 7)"
FT /evidence="ECO:0000269|PubMed:26491161"
FT VARIANT 68
FT /note="R -> Q (in allele A3Z3; haplotype 3 and 7)"
FT /evidence="ECO:0000269|PubMed:26491161"
FT VARIANT 94
FT /note="A -> T (in allele A3Z3; haplotype 3)"
FT /evidence="ECO:0000269|PubMed:26491161"
FT VARIANT 96
FT /note="V -> I (in allele A3Z3; haplotype 4 and 6)"
FT /evidence="ECO:0000269|PubMed:26491161"
FT MUTAGEN 56
FT /note="E->A: Probable loss of catalytic activity. Fails to
FT suppress FIV infectivity."
FT /evidence="ECO:0000269|PubMed:26491161"
FT MUTAGEN 65
FT /note="A->F,L,Y: Confers resistance to FIV vif-mediated
FT degradation."
FT /evidence="ECO:0000269|PubMed:26491161"
SQ SEQUENCE 193 AA; 23297 MW; 111B883DF54D2A7E CRC64;
MNPLQEVIFC RQFGNQHRVP KPYYRRKTYL CYQLKLPEGT LIHKDCLRNK KKRHAEMCFI
DKIKALTRDT SQRFEIICYI TWSPCPFCAE ELVAFVKDNP HLSLRIFASR LYVHWRWKYQ
QGLRHLHASG IPVAVMSLPE FEDCWRNFVD HQDRSFQPWP NLDQYSKSIK RRLGKILTPL
NDLRNDFRNL KLE
