ID   ORF4_PCV2               Reviewed;          59 AA.
AC   O56125; Q782A8; Q9YJN0;
DT   07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   23-FEB-2022, entry version 55.
DE   RecName: Full=Anti-apoptotic ORF4 protein;
GN   Name=ORF4; Synonyms=ORF4 protein;
OS   Porcine circovirus 2 (PCV2).
OC   Viruses; Monodnaviria; Shotokuvirae; Cressdnaviricota; Arfiviricetes;
OC   Cirlivirales; Circoviridae; Circovirus.
OX   NCBI_TaxID=85708;
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Porcine circovirus Type II;
RX   PubMed=9747726; DOI=10.1099/0022-1317-79-9-2171;
RA   Meehan B.M., McNeilly F., Todd D., Kennedy S., Jewhurst V.A., Ellis J.A.,
RA   Hassard L.E., Clark E.G., Haines D.M., Allan G.M.;
RT   "Characterization of novel circovirus DNAs associated with wasting
RT   syndromes in pigs.";
RL   J. Gen. Virol. 79:2171-2179(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Pmws PCV;
RX   PubMed=9573301; DOI=10.1128/jvi.72.6.5262-5267.1998;
RA   Hamel A.L., Lin L.L., Nayar G.P.;
RT   "Nucleotide sequence of porcine circovirus associated with postweaning
RT   multisystemic wasting syndrome in pigs.";
RL   J. Virol. 72:5262-5267(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=FD;
RX   PubMed=23775757; DOI=10.1007/s11262-013-0933-z;
RA   Gao Z., Dong Q., Jiang Y., Opriessnig T., Wang J., Quan Y., Yang Z.;
RT   "Identification and characterization of two novel transcription units of
RT   porcine circovirus 2.";
RL   Virus Genes 47:268-275(2013).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=PCV2b;
RX   PubMed=29730308; DOI=10.1016/j.virusres.2018.04.019;
RA   Cruz T.F., Magro A.J., de Castro A.M., Pedraza-Ordonez F.J., Tsunemi M.H.,
RA   Perahia D., Araujo J.P. Jr.;
RT   "In vitro and in silico studies reveal capsid-mutant Porcine circovirus 2b
RT   with novel cytopathogenic and structural characteristics.";
RL   Virus Res. 251:22-33(2018).
RN   [5]
RP   REVIEW.
RX   PubMed=25011695; DOI=10.1007/s11262-014-1099-z;
RA   Lv Q.Z., Guo K.K., Zhang Y.M.;
RT   "Current understanding of genomic DNA of porcine circovirus type 2.";
RL   Virus Genes 49:1-10(2014).
RN   [6]
RP   FUNCTION.
RX   PubMed=24503223; DOI=10.1016/j.virusres.2014.01.024;
RA   Gao Z., Dong Q., Jiang Y., Opriessnig T., Wang J., Quan Y., Yang Z.;
RT   "ORF4-protein deficient PCV2 mutants enhance virus-induced apoptosis and
RT   show differential expression of mRNAs in vitro.";
RL   Virus Res. 183:56-62(2014).
RN   [7]
RP   INTERACTION WITH FTH1.
RX   PubMed=26333394; DOI=10.1007/s12038-015-9551-3;
RA   Lv Q., Guo K., Wang T., Zhang C., Zhang Y.;
RT   "Porcine circovirus type 2 ORF4 protein binds heavy chain ferritin.";
RL   J. Biosci. 40:477-485(2015).
RN   [8]
RP   FUNCTION, INTERACTION WITH HOST FTH1, AND SUBCELLULAR LOCATION.
RX   PubMed=27030984; DOI=10.1099/jgv.0.000472;
RA   Lv Q., Guo K., Zhang G., Zhang Y.;
RT   "The ORF4 protein of porcine circovirus type 2 antagonizes apoptosis by
RT   stabilizing the concentration of ferritin heavy chain through physical
RT   interaction.";
RL   J. Gen. Virol. 97:1636-1646(2016).
RN   [9]
RP   INTERACTION WITH HOST ANT3.
RX   PubMed=29491154; DOI=10.1128/jvi.00238-18;
RA   Lin C., Gu J., Wang H., Zhou J., Li J., Wang S., Jin Y., Liu C., Liu J.,
RA   Yang H., Jiang P., Zhou J.;
RT   "Caspase-Dependent Apoptosis Induction via Viral Protein ORF4 of Porcine
RT   Circovirus 2 Binding to Mitochondrial Adenine Nucleotide Translocase 3.";
RL   J. Virol. 92:0-0(2018).
CC   -!- FUNCTION: Antagonizes host cell apoptosis by interacting with host
CC       ferritin heavy chain. The ORF4 protein physically binds host FHC,
CC       resulting in the reduction of FHC protein levels in host cells.
CC       Reduction of FHC concentration further inhibits the accumulation of
CC       reactive oxygen in host cells, leading to reduced apoptosis.
CC       {ECO:0000269|PubMed:24503223, ECO:0000269|PubMed:26333394,
CC       ECO:0000269|PubMed:27030984}.
CC   -!- SUBUNIT: Interacts with host FTH1 (PubMed:26333394, PubMed:27030984).
CC       May interact with host ANT3 (PubMed:29491154).
CC       {ECO:0000269|PubMed:26333394, ECO:0000269|PubMed:27030984,
CC       ECO:0000269|PubMed:29491154}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:23775757}.
CC   -!- CAUTION: Other experiments suggest that it may enhance apoptosis
CC       instead of antagonizing it. {ECO:0000269|PubMed:29491154}.
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DR   EMBL; AF055391; AAC35301.1; -; Genomic_DNA.
DR   EMBL; AF055392; AAC35312.1; -; Genomic_DNA.
DR   EMBL; AF055393; AAC35323.1; -; Genomic_DNA.
DR   EMBL; AF055394; AAC35333.1; -; Genomic_DNA.
DR   EMBL; AF027217; AAC59465.1; -; Genomic_DNA.
DR   EMBL; AF201897; AAG41229.1; -; Genomic_DNA.
DR   EMBL; KC741192; AGO32666.1; -; Genomic_DNA.
DR   EMBL; KT336602; ANZ52566.1; -; Genomic_DNA.
DR   EMBL; KT336603; ANZ52570.1; -; Genomic_DNA.
DR   EMBL; MF150182; AWO14537.1; -; Genomic_DNA.
DR   EMBL; MF150183; AWO14541.1; -; Genomic_DNA.
DR   EMBL; MF150184; AWO14545.1; -; Genomic_DNA.
DR   EMBL; MF150185; AWO14549.1; -; Genomic_DNA.
DR   EMBL; MF150186; AWO14553.1; -; Genomic_DNA.
DR   EMBL; MF150187; AWO14557.1; -; Genomic_DNA.
DR   EMBL; MF150188; AWO14561.1; -; Genomic_DNA.
DR   EMBL; MF150189; AWO14565.1; -; Genomic_DNA.
DR   EMBL; MF150190; AWO14569.1; -; Genomic_DNA.
DR   EMBL; MF150191; AWO14573.1; -; Genomic_DNA.
DR   EMBL; AB072301; BAB69434.1; -; Genomic_DNA.
DR   EMBL; AB072303; BAB69443.1; -; Genomic_DNA.
DR   Proteomes; UP000115010; Genome.
DR   Proteomes; UP000124612; Genome.
DR   Proteomes; UP000130671; Genome.
DR   Proteomes; UP000150239; Genome.
DR   Proteomes; UP000161967; Genome.
DR   Proteomes; UP000164093; Genome.
DR   Proteomes; UP000174112; Genome.
DR   Proteomes; UP000179422; Genome.
DR   Proteomes; UP000180329; Genome.
DR   Proteomes; UP000180332; Genome.
DR   Proteomes; UP000286849; Genome.
DR   Proteomes; UP000287313; Genome.
DR   Proteomes; UP000287586; Genome.
DR   Proteomes; UP000287698; Genome.
DR   Proteomes; UP000288176; Genome.
DR   Proteomes; UP000288263; Genome.
DR   Proteomes; UP000288319; Genome.
DR   Proteomes; UP000288320; Genome.
DR   Proteomes; UP000288556; Genome.
DR   Proteomes; UP000288616; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR   InterPro; IPR009757; Circovirus2_Orf4.
DR   Pfam; PF07038; DUF1324; 1.
PE   1: Evidence at protein level;
KW   Host cytoplasm; Host-virus interaction;
KW   Modulation of host cell apoptosis by virus.
FT   CHAIN           1..59
FT                   /note="Anti-apoptotic ORF4 protein"
FT                   /id="PRO_0000445707"
SQ   SEQUENCE   59 AA;  6516 MW;  8FAC44F691BC41F4 CRC64;
     MTCTLVFQSR FCIFPLTFKS SASPRKFLTN VTGCCSATVT RLPLSNKVLT AVDRSLRCP