ID   IKBL_ASFP4              Reviewed;         238 AA.
AC   P0C966;
DT   05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 1.
DT   03-AUG-2022, entry version 45.
DE   RecName: Full=IkB-like protein;
DE   AltName: Full=Ankyrin repeat domain-containing protein A238L;
DE   AltName: Full=p28;
GN   Name=A238L; OrderedLocusNames=Pret-051;
OS   African swine fever virus (isolate Tick/South Africa/Pretoriuskop Pr4/1996)
OS   (ASFV).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Asfuvirales; Asfarviridae; Asfivirus.
OX   NCBI_TaxID=561443;
OH   NCBI_TaxID=6937; Ornithodoros (relapsing fever ticks).
OH   NCBI_TaxID=85517; Phacochoerus aethiopicus (Warthog).
OH   NCBI_TaxID=41426; Phacochoerus africanus (Warthog).
OH   NCBI_TaxID=273792; Potamochoerus larvatus (Bushpig).
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Kutish G.F., Rock D.L.;
RT   "African swine fever virus genomes.";
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: IkB-like protein that inhibits the binding of NF-kappa-B to
CC       DNA, thereby downregulating pro-inflammatory cytokine production (By
CC       similarity). Forms a heterodimer with the NF-kappa-B subunit RELA/p65
CC       and prevents the activation of the NF-kappa-B transcription factor (By
CC       similarity). Inhibits calcineurin function, which is required for the
CC       induction of nuclear factor of activated T cells (NFAT)-dependent
CC       immune response genes. Prevents the binding of substrates to
CC       calcineurin without affecting the phosphatase activity (By similarity).
CC       Does not contain the serine residues that are phosphorylated by host
CC       IkB kinase and thus is not degraded following stimulation of the NFkB
CC       pathway (By similarity). {ECO:0000250|UniProtKB:O36972,
CC       ECO:0000250|UniProtKB:Q76U48}.
CC   -!- SUBUNIT: Interacts with host PPIA. Interacts with host
CC       PPP3CA/Calcineurin (By similarity). Interacts with host RELA/p65;
CC       interaction of the 32 kDa form with host RELA results in the formation
CC       of a stable complex with NF-kappa-B (By similarity). Interacts with
CC       host PPP3R1 (By similarity). Interacts with host EP300; this
CC       interaction inhibits the association of host EP300 with host RELA, JUN
CC       and NFATC2 (By similarity). {ECO:0000250|UniProtKB:O36972,
CC       ECO:0000250|UniProtKB:Q76U48}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:Q76U48}. Host
CC       cytoplasm {ECO:0000250|UniProtKB:Q76U48}. Note=Binding to host
CC       PPP3CA/Calcineurin may mask the second nuclear localization signal
CC       thereby contributing to the cytoplasmic retention of A238L.
CC       {ECO:0000250|UniProtKB:Q76U48}.
CC   -!- INDUCTION: Expressed in the early phase of the viral replicative cycle.
CC       {ECO:0000305}.
CC   -!- DOMAIN: The C-terminal region contains the docking motifs PxIxITxC and
CC       FLCV, which are required and sufficient for binding to host
CC       calcineurin. {ECO:0000250|UniProtKB:O36972}.
CC   -!- PTM: The protein exists in a 28 kDa and a 32 kDa form, probably due to
CC       post-translational modifications which are neither phosphorylation, nor
CC       sumoylation. {ECO:0000250|UniProtKB:Q76U48}.
CC   -!- SIMILARITY: Belongs to the asfivirus A238L family. {ECO:0000305}.
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DR   EMBL; AY261363; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   SMR; P0C966; -.
DR   Proteomes; UP000000859; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR   Gene3D; 1.25.40.20; -; 1.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   SMART; SM00248; ANK; 4.
DR   SUPFAM; SSF48403; SSF48403; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 1.
PE   3: Inferred from homology;
KW   ANK repeat; Early protein; Host cytoplasm; Host nucleus;
KW   Host-virus interaction; Inhibition of host NF-kappa-B by virus; Repeat;
KW   Ubl conjugation.
FT   CHAIN           1..238
FT                   /note="IkB-like protein"
FT                   /id="PRO_0000372837"
FT   REPEAT          48..80
FT                   /note="ANK 1"
FT   REPEAT          87..118
FT                   /note="ANK 2"
FT   REPEAT          124..153
FT                   /note="ANK 3"
FT   REPEAT          158..187
FT                   /note="ANK 4"
FT   MOTIF           80..86
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q76U48"
FT   MOTIF           202..213
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q76U48"
FT   MOTIF           205..212
FT                   /note="PxIxITxC motif; Interaction with host PPP3CA"
FT                   /evidence="ECO:0000250|UniProtKB:O36972"
FT   MOTIF           227..230
FT                   /note="FLCV motif"
FT                   /evidence="ECO:0000250|UniProtKB:O36972"
SQ   SEQUENCE   238 AA;  28207 MW;  A5AA497AD1A38F65 CRC64;
     MEHMFPENQI ENLFVGWIKK HIRNGDLTLF EEFFKTDPWI VNRCDKNGSS VFMWICIYGR
     IDFLKFLFKQ ESYPGEIINH HRRDNDGNSA LHYLAEKKNH LILEEVLGYF GKNGTRICLP
     NFNGMTPVMK AAMRGRTLNM LSLIKFGADP TQKDYHRGFT AWDWAVFTGN MELVKSLNHD
     YQKPLYMHFP LYKLDVFHRW FKKKPKIIIT GCKNNVYEKL PEQNPNFLCV KKLNKYGK