IKBL_ASFB7
ID IKBL_ASFB7 Reviewed; 238 AA.
AC Q76U48;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 1.
DT 25-MAY-2022, entry version 51.
DE RecName: Full=IkB-like protein;
DE AltName: Full=Ankyrin repeat domain-containing protein A238L;
DE AltName: Full=p28;
GN Name=A238L;
OS African swine fever virus (strain Badajoz 1971 Vero-adapted) (Ba71V)
OS (ASFV).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Asfuvirales; Asfarviridae; Asfivirus.
OX NCBI_TaxID=10498;
OH NCBI_TaxID=6937; Ornithodoros (relapsing fever ticks).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11831707; DOI=10.1006/viro.1995.1149;
RA Yanez R.J., Rodriguez J.M., Nogal M.L., Yuste L., Enriquez C.,
RA Rodriguez J.F., Vinuela E.;
RT "Analysis of the complete nucleotide sequence of African swine fever
RT virus.";
RL Virology 208:249-278(1995).
RN [2]
RP FUNCTION, ABSENCE OF PHOSPHORYLATION, ABSENCE OF SUMOYLATION, AND
RP INTERACTION WITH HOST RELA.
RX PubMed=10934190; DOI=10.1074/jbc.m000320200;
RA Tait S.W., Reid E.B., Greaves D.R., Wileman T.E., Powell P.P.;
RT "Mechanism of inactivation of NF-kappa B by a viral homologue of I kappa b
RT alpha. Signal-induced release of i kappa b alpha results in binding of the
RT viral homologue to NF-kappa B.";
RL J. Biol. Chem. 275:34656-34664(2000).
RN [3]
RP INTERACTION WITH HOST EP300, AND SUBCELLULAR LOCATION.
RX PubMed=16365438; DOI=10.4049/jimmunol.176.1.451;
RA Granja A.G., Nogal M.L., Hurtado C., Del Aguila C., Carrascosa A.L.,
RA Salas M.L., Fresno M., Revilla Y.;
RT "The viral protein A238L inhibits TNF-alpha expression through a CBP/p300
RT transcriptional coactivators pathway.";
RL J. Immunol. 176:451-462(2006).
RN [4]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNALS, AND INTERACTION WITH
RP HOST PPP3CA.
RX PubMed=18261759; DOI=10.1016/j.virol.2008.01.005;
RA Abrams C.C., Chapman D.A., Silk R., Liverani E., Dixon L.K.;
RT "Domains involved in calcineurin phosphatase inhibition and nuclear
RT localisation in the African swine fever virus A238L protein.";
RL Virology 374:477-486(2008).
RN [5]
RP INDUCTION.
RX PubMed=32075923; DOI=10.1128/jvi.00119-20;
RA Cackett G., Matelska D., Sykora M., Portugal R., Malecki M., Baehler J.,
RA Dixon L., Werner F.;
RT "The African Swine Fever Virus Transcriptome.";
RL J. Virol. 94:0-0(2020).
CC -!- FUNCTION: I-kappa-B- (IkB)-like protein that inhibits the binding of
CC NF-kappa-B to DNA, thereby down-regulating pro-inflammatory cytokine
CC production (By similarity). Forms a heterodimer with the NF-kappa-B
CC subunit RELA/p65 and prevents the activation of the NF-kappa-B
CC transcription factor (PubMed:10934190). Also inhibits the host
CC calcineurin phosphatase activity, which is required for the induction
CC of nuclear factor of activated T cells(NFAT)-dependent immune response
CC genes (By similarity). Inhibits calcineurin function, which is required
CC for the induction of nuclear factor of activated T cells (NFAT)-
CC dependent immune response genes (By similarity). Prevents the binding
CC of substrates to calcineurin without affecting the phosphatase activity
CC (By similarity). Does not contain the serine residues that are
CC phosphorylated by host IkB kinase and thus is not degraded following
CC stimulation of the NFkB pathway (PubMed:10934190).
CC {ECO:0000250|UniProtKB:O36972, ECO:0000269|PubMed:10934190}.
CC -!- SUBUNIT: Interacts with host PPIA (By similarity). Interacts with host
CC PPP3CA/Calcineurin (PubMed:18261759). 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 (PubMed:10934190). 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 (PubMed:16365438). {ECO:0000250|UniProtKB:O36972,
CC ECO:0000269|PubMed:10934190, ECO:0000269|PubMed:16365438,
CC ECO:0000269|PubMed:18261759}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:16365438,
CC ECO:0000269|PubMed:18261759}. Host cytoplasm
CC {ECO:0000269|PubMed:18261759}. Note=Binding to host PPP3CA/Calcineurin
CC may mask the second nuclear localization signal thereby contributing to
CC the cytoplasmic retention of A238L. {ECO:0000269|PubMed:18261759}.
CC -!- INDUCTION: Expressed in the early phase of the viral replicative cycle.
CC {ECO:0000269|PubMed:32075923}.
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:0000269|PubMed:10934190}.
CC -!- SIMILARITY: Belongs to the asfivirus A238L family. {ECO:0000305}.
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DR EMBL; U18466; AAA65269.1; -; Genomic_DNA.
DR RefSeq; NP_042733.1; NC_001659.2.
DR SMR; Q76U48; -.
DR GeneID; 22220421; -.
DR KEGG; vg:22220421; -.
DR Proteomes; UP000000624; 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 1: Evidence at protein level;
KW ANK repeat; Early protein; Host cytoplasm; Host nucleus;
KW Host-virus interaction; Inhibition of host NF-kappa-B by virus;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..238
FT /note="IkB-like protein"
FT /id="PRO_0000444973"
FT REPEAT 48..77
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 86..115
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 123..152
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 157..187
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT MOTIF 80..86
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:18261759"
FT MOTIF 202..213
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:18261759"
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; 28191 MW; 2F58EF8375D7906B CRC64;
MEHMFPEREI ENLFVKWIKK HIRNGNLTLF EEFFKTDPWI VNRCDKNGSS VFMWICIYGR
IDFLKFLFEQ ESYPGEIINP HRRDKDGNSA LHYLAEKKNH LILEEVLGYF GKNGTKICLP
NFNGMTPVMK AAIRGRTSNV LSLIKFGADP TQKDYHRGFT AWDWAVFTGN MELVKSLNHD
YQKPLYMHFP LYKLDVFHRW FKKKPKIIIT GCKNNVYEKL PEQNPNFLCV KKLNKYGK
