IKBA_PIG
ID IKBA_PIG Reviewed; 314 AA.
AC Q08353; F2Q9A9;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=NF-kappa-B inhibitor alpha;
DE AltName: Full=ECI-6;
DE AltName: Full=I-kappa-B-alpha;
DE Short=IkB-alpha;
DE Short=IkappaBalpha;
GN Name=NFKBIA; Synonyms=IKBA;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Aorta;
RX PubMed=8334993;
RA De Martin R., Vanhove B., Cheng Q., Hofer E., Csizmadia V., Winkler H.,
RA Bach F.H.;
RT "Cytokine-inducible expression in endothelial cells of an IkappaB alpha-
RT like gene is regulated by NF-kappaB.";
RL EMBO J. 12:2773-2779(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7835710; DOI=10.1016/0378-1119(94)00726-9;
RA De Martin R., Holzmueller H., Hofer E., Bach F.H.;
RT "Intron-exon structure of the porcine IkappaB alpha-encoding gene.";
RL Gene 152:253-255(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-314.
RC TISSUE=Blood;
RX PubMed=21450812; DOI=10.1128/jvi.00331-11;
RA Palgrave C.J., Gilmour L., Lowden C.S., Lillico S.G., Mellencamp M.A.,
RA Whitelaw C.B.;
RT "Species-specific variation in RELA underlies differences in NF-kappaB
RT activity: a potential role in African swine fever pathogenesis.";
RL J. Virol. 85:6008-6014(2011).
CC -!- FUNCTION: Inhibits the activity of dimeric NF-kappa-B/REL complexes by
CC trapping REL dimers in the cytoplasm through masking of their nuclear
CC localization signals. On cellular stimulation by immune and pro-
CC inflammatory responses, becomes phosphorylated promoting ubiquitination
CC and degradation, enabling the dimeric RELA to translocate to the
CC nucleus and activate transcription.
CC -!- SUBUNIT: Interacts with RELA; the interaction requires the nuclear
CC import signal. Interacts with NKIRAS1 and NKIRAS2. Part of a 70-90 kDa
CC complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and
CC MAP3K14. Interacts with RWDD3; the interaction enhances sumoylation.
CC Interacts (when phosphorylated at the 2 serine residues in the
CC destruction motif D-S-G-X(2,3,4)-S) with BTRC. Associates with the
CC SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC; the association is
CC mediated via interaction with BTRC. Part of a SCF(BTRC)-like complex
CC lacking CUL1, which is associated with RELA; RELA interacts directly
CC with NFKBIA. Interacts with PRMT2. Interacts with PRKACA in platelets;
CC this interaction is disrupted by thrombin and collagen. Interacts with
CC HIF1AN. Interacts with MEFV. Interacts with DDRGK1; positively
CC regulates NFKBIA phosphorylation and degradation (By similarity).
CC {ECO:0000250|UniProtKB:P25963}.
CC -!- INTERACTION:
CC Q08353; PRO_0000038062 [P21530]; Xeno; NbExp=4; IntAct=EBI-12558699, EBI-12558622;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between the
CC nucleus and the cytoplasm by a nuclear localization signal (NLS) and a
CC CRM1-dependent nuclear export. {ECO:0000250}.
CC -!- PTM: Phosphorylated; disables inhibition of NF-kappa-B DNA-binding
CC activity. Phosphorylation at positions 32 and 36 is prerequisite to
CC recognition by UBE2D3 leading to polyubiquitination and subsequent
CC degradation (By similarity). {ECO:0000250}.
CC -!- PTM: Sumoylated; sumoylation requires the presence of the nuclear
CC import signal. Sumoylation blocks ubiquitination and proteasome-
CC mediated degradation of the protein thereby increasing the protein
CC stability (By similarity). {ECO:0000250}.
CC -!- PTM: Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3. Ubiquitin
CC chain elongation is then performed by CDC34 in cooperation with the
CC SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the
CC UBE2D3-primed NFKBIA-linked ubiquitin. The resulting polyubiquitination
CC leads to protein degradation. Also ubiquitinated by SCF(BTRC) following
CC stimulus-dependent phosphorylation at Ser-32 and Ser-36 (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family. {ECO:0000305}.
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DR EMBL; Z21968; CAA79979.1; -; Genomic_DNA.
DR EMBL; Z35483; CAA84619.1; -; Genomic_DNA.
DR EMBL; FN421467; CAZ65750.1; -; mRNA.
DR PIR; S35314; S35314.
DR RefSeq; NP_001005150.1; NM_001005150.1.
DR AlphaFoldDB; Q08353; -.
DR SMR; Q08353; -.
DR IntAct; Q08353; 1.
DR STRING; 9823.ENSSSCP00000002133; -.
DR PaxDb; Q08353; -.
DR PRIDE; Q08353; -.
DR Ensembl; ENSSSCT00000002184; ENSSSCP00000002133; ENSSSCG00000001952.
DR Ensembl; ENSSSCT00015039015; ENSSSCP00015015516; ENSSSCG00015029389.
DR Ensembl; ENSSSCT00025092560; ENSSSCP00025040620; ENSSSCG00025067390.
DR Ensembl; ENSSSCT00030082138; ENSSSCP00030037706; ENSSSCG00030058851.
DR Ensembl; ENSSSCT00035099812; ENSSSCP00035042295; ENSSSCG00035073638.
DR Ensembl; ENSSSCT00040055590; ENSSSCP00040023108; ENSSSCG00040041514.
DR Ensembl; ENSSSCT00045017158; ENSSSCP00045011831; ENSSSCG00045010107.
DR Ensembl; ENSSSCT00050008579; ENSSSCP00050003687; ENSSSCG00050006268.
DR Ensembl; ENSSSCT00055058871; ENSSSCP00055047145; ENSSSCG00055029632.
DR Ensembl; ENSSSCT00060088999; ENSSSCP00060038508; ENSSSCG00060065186.
DR Ensembl; ENSSSCT00065081421; ENSSSCP00065035456; ENSSSCG00065059454.
DR Ensembl; ENSSSCT00070014299; ENSSSCP00070011804; ENSSSCG00070007418.
DR Ensembl; ENSSSCT00070014305; ENSSSCP00070011807; ENSSSCG00070007418.
DR GeneID; 406188; -.
DR KEGG; ssc:406188; -.
DR CTD; 4792; -.
DR VGNC; VGNC:90721; NFKBIA.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000162733; -.
DR InParanoid; Q08353; -.
DR OMA; EIRIQPQ; -.
DR OrthoDB; 1341288at2759; -.
DR TreeFam; TF320166; -.
DR Reactome; R-SSC-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-SSC-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-SSC-202424; Downstream TCR signaling.
DR Reactome; R-SSC-209560; NF-kB is activated and signals survival.
DR Reactome; R-SSC-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-SSC-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-SSC-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-SSC-5689880; Ub-specific processing proteases.
DR Reactome; R-SSC-9020702; Interleukin-1 signaling.
DR Reactome; R-SSC-933542; TRAF6 mediated NF-kB activation.
DR Proteomes; UP000008227; Chromosome 7.
DR Proteomes; UP000314985; Chromosome 7.
DR Bgee; ENSSSCG00000001952; Expressed in endocardial endothelium and 45 other tissues.
DR Genevisible; Q08353; SS.
DR GO; GO:0005737; C:cytoplasm; ISS:AgBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:AgBase.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0051059; F:NF-kappaB binding; ISS:AgBase.
DR GO; GO:0008139; F:nuclear localization sequence binding; ISS:AgBase.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:AgBase.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0007253; P:cytoplasmic sequestering of NF-kappaB; IBA:GO_Central.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; ISS:AgBase.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:AgBase.
DR GO; GO:0010888; P:negative regulation of lipid storage; IEA:Ensembl.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; IEA:Ensembl.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISS:AgBase.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:AgBase.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IEA:Ensembl.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IEA:Ensembl.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:AgBase.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISS:AgBase.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:AgBase.
DR GO; GO:0032495; P:response to muramyl dipeptide; IEA:Ensembl.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 1: Evidence at protein level;
KW ANK repeat; Cytoplasm; Hydroxylation; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..314
FT /note="NF-kappa-B inhibitor alpha"
FT /id="PRO_0000067001"
FT REPEAT 110..139
FT /note="ANK 1"
FT REPEAT 143..172
FT /note="ANK 2"
FT REPEAT 182..211
FT /note="ANK 3"
FT REPEAT 216..245
FT /note="ANK 4"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 30..36
FT /note="Destruction motif"
FT /evidence="ECO:0000250"
FT MOTIF 45..54
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 110..120
FT /note="Nuclear import signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 15..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 32
FT /note="Phosphoserine; by IKKA and IKKB"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOD_RES 36
FT /note="Phosphoserine; by IKKA, IKKB, IKKE and TBK1"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOD_RES 42
FT /note="Phosphotyrosine; by Tyr-kinases"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOD_RES 210
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250"
FT MOD_RES 244
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250"
FT MOD_RES 283
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOD_RES 288
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOD_RES 291
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOD_RES 293
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOD_RES 296
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT CROSSLNK 21
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 21
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1E3"
FT CROSSLNK 22
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P25963, ECO:0000255"
SQ SEQUENCE 314 AA; 35230 MW; 629BEDB824562E95 CRC64;
MFQPAEPGQE WAMEGPRDAL KKERLLDDRH DSGLDSMKDE EYEQMVKELR EIRLEPQEAP
RGAEPWKQQL TEDGDSFLHL AIIHEEKALT MEVVRQVKGD LAFLNFQNNL QQTPLHLAVI
TNQPEIAEAL LEAGCDPELR DFRGNTPLHL ACEQGCLASV GVLTQPRGTQ HLHSILQATN
YNGHTCLHLA SIHGYLGIVE LLVSLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG
ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEDEL
PYDDCVLGGQ RLTL
