ID IKBA_RAT Reviewed; 314 AA.
AC Q63746; B2RYS5;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 178.
DE RecName: Full=NF-kappa-B inhibitor alpha;
DE AltName: Full=I-kappa-B-alpha;
DE Short=IkB-alpha;
DE Short=IkappaBalpha;
DE AltName: Full=RL/IF-1;
GN Name=Nfkbia; Synonyms=Ikba;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1741294; DOI=10.1093/nar/20.3.607;
RA Tewari M., Mohn K.L., Yue F.E., Taub R.A.;
RT "Sequence of rat RL/IF-1 encoding an IkappaB, and comparison with related
RT proteins containing Notch-like repeats.";
RL Nucleic Acids Res. 20:607-607(1992).
RN [2]
RP ERRATUM OF PUBMED:1741294.
RA Tewari M., Mohn K.L., Yue F.E., Taub R.A.;
RL Nucleic Acids Res. 20:2624-2624(1992).
RN [3]
RP ERRATUM OF PUBMED:1741294.
RA Tewari M., Mohn K.L., Yue F.E., Taub R.A.;
RL Nucleic Acids Res. 20:2931-2931(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INDUCTION.
RX PubMed=1588976; DOI=10.1128/mcb.12.6.2898-2908.1992;
RA Tewari M., Dobrzanski P., Mohn K.L., Cressman D.E., Hsu J.C., Bravo R.,
RA Taub R.;
RT "Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that
RT inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B
RT site-binding complex.";
RL Mol. Cell. Biol. 12:2898-2908(1992).
CC -!- FUNCTION: Inhibits the activity of dimeric NF-kappa-B/REL complexes by
CC trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by
CC masking their nuclear localization signals. On cellular stimulation by
CC immune and pro-inflammatory responses, becomes phosphorylated promoting
CC ubiquitination and degradation, enabling the dimeric RELA to
CC translocate to the nucleus and activate transcription.
CC {ECO:0000250|UniProtKB:P25963}.
CC -!- SUBUNIT: Interacts with RELA; the interaction requires the nuclear
CC import signal. Part of a 70-90 kDa complex at least consisting of CHUK,
CC IKBKB, NFKBIA, RELA, ELP1 and MAP3K14. Interacts with NKIRAS1 and
CC NKIRAS2. Interacts with RWDD3; the interaction enhances sumoylation.
CC Interacts with PRMT2. Interacts with PRKACA in platelets; this
CC interaction is disrupted by thrombin and collagen. Interacts with MEFV.
CC Interacts with DDRGK1; positively regulates NFKBIA phosphorylation and
CC degradation. {ECO:0000250|UniProtKB:P25963}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P25963}. Nucleus
CC {ECO:0000250|UniProtKB:P25963}. Note=Shuttles between the nucleus and
CC the cytoplasm by a nuclear localization signal (NLS) and a CRM1-
CC dependent nuclear export. {ECO:0000250|UniProtKB:P25963}.
CC -!- INDUCTION: During liver regeneration. {ECO:0000269|PubMed:1588976}.
CC -!- PTM: Phosphorylated at Ser-32 and Ser-36 by IKKA/CHUK and IKKB/IKBKB;
CC disables inhibition of NF-kappa-B DNA-binding activity. Phosphorylation
CC at positions 32 and 36 is prerequisite to recognition by the
CC SCF(FBXW11) and SCF(BTRC) complexes, leading to polyubiquitination and
CC subsequent degradation. {ECO:0000250|UniProtKB:P25963}.
CC -!- PTM: Polyubiquitinated at Lys-21 and/or Lys-22 following
CC phosphorylation at Ser-32 and Ser-36. Monoubiquitinated at Lys-21
CC and/or Lys-22 by UBE2D3. Ubiquitin chain elongation is then performed
CC by CDC34 in cooperation with the SCF(FBXW11) E3 ligase complex,
CC building ubiquitin chains from the UBE2D3-primed NFKBIA-linked
CC ubiquitin. The resulting polyubiquitination leads to protein
CC degradation. Also ubiquitinated by the SCF(BTRC) complex following
CC stimulus-dependent phosphorylation at Ser-32 and Ser-36.
CC Deubiquitinated by USP38, leading to NF-kappa-B inhibition (By
CC similarity). {ECO:0000250|UniProtKB:P25963}.
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. {ECO:0000250|UniProtKB:P25963}.
CC -!- PTM: Hydroxylated by HIF1AN. {ECO:0000250|UniProtKB:P25963}.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor 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; X63594; CAA45138.1; -; mRNA.
DR EMBL; CH473947; EDM03428.1; -; Genomic_DNA.
DR EMBL; BC166886; AAI66886.1; -; mRNA.
DR PIR; A44437; A44437.
DR RefSeq; NP_001099190.2; NM_001105720.2.
DR AlphaFoldDB; Q63746; -.
DR SMR; Q63746; -.
DR BioGRID; 247526; 3.
DR DIP; DIP-59941N; -.
DR IntAct; Q63746; 1.
DR STRING; 10116.ENSRNOP00000009894; -.
DR GlyGen; Q63746; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q63746; -.
DR PhosphoSitePlus; Q63746; -.
DR PaxDb; 10116-ENSRNOP00000009894; -.
DR Ensembl; ENSRNOT00000009894.7; ENSRNOP00000009894.5; ENSRNOG00000007390.7.
DR Ensembl; ENSRNOT00055023251; ENSRNOP00055018878; ENSRNOG00055013559.
DR Ensembl; ENSRNOT00060032368; ENSRNOP00060026378; ENSRNOG00060018781.
DR Ensembl; ENSRNOT00065007544; ENSRNOP00065005221; ENSRNOG00065005143.
DR GeneID; 25493; -.
DR KEGG; rno:25493; -.
DR UCSC; RGD:3171; rat.
DR AGR; RGD:3171; -.
DR CTD; 4792; -.
DR RGD; 3171; Nfkbia.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000163080; -.
DR HOGENOM; CLU_000134_6_3_1; -.
DR InParanoid; Q63746; -.
DR OrthoDB; 621606at2759; -.
DR PhylomeDB; Q63746; -.
DR TreeFam; TF320166; -.
DR Reactome; R-RNO-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-RNO-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-RNO-209560; NF-kB is activated and signals survival.
DR Reactome; R-RNO-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-RNO-4755510; SUMOylation of immune response proteins.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR Reactome; R-RNO-933542; TRAF6 mediated NF-kB activation.
DR PRO; PR:Q63746; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Proteomes; UP000234681; Chromosome 6.
DR Bgee; ENSRNOG00000007390; Expressed in lung and 20 other cell types or tissues.
DR Genevisible; Q63746; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0033256; C:I-kappaB/NF-kappaB complex; IC:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0031072; F:heat shock protein binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0140313; F:molecular sequestering activity; ISO:RGD.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:RGD.
DR GO; GO:0008139; F:nuclear localization sequence binding; ISO:RGD.
DR GO; GO:0140311; F:protein sequestering activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; ISO:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:RGD.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IEP:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; ISO:RGD.
DR GO; GO:0010888; P:negative regulation of lipid storage; ISO:RGD.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; ISO:RGD.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISO:RGD.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISO:RGD.
DR GO; GO:0038061; P:non-canonical NF-kappaB signal transduction; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; ISO:RGD.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; ISO:RGD.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; ISO:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0032495; P:response to muramyl dipeptide; ISO:RGD.
DR GO; GO:0035994; P:response to muscle stretch; ISO:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; ISO:RGD.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:RGD.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR PANTHER; PTHR46680; NF-KAPPA-B INHIBITOR ALPHA; 1.
DR PANTHER; PTHR46680:SF1; NF-KAPPA-B INHIBITOR ALPHA; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13857; Ank_5; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 2: Evidence at transcript 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_0000067002"
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..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 30..36
FT /note="Destruction motif"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOTIF 45..54
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT MOTIF 110..120
FT /note="Nuclear import signal"
FT /evidence="ECO:0000250|UniProtKB:P25963"
FT COMPBIAS 14..39
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|UniProtKB:P25963"
FT MOD_RES 244
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250|UniProtKB:P25963"
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|UniProtKB:Q9Z1E3"
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; 35017 MW; CC4C9D0F6CDDA950 CRC64;
MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE DYEQMVKELR EIRLQPQEAP
LAAEPWKQQL TEDGDSFLHL AIIHEEKTLT MEVIGQVKGD LAFLNFQNNL QQTPLHLAVI
TNQPGIAEAL LKAGCDPELR DFRGNTPLHL ACEQGCLASV AVLTQTCTPQ HLHSVLQATN
YNGHTCLHLA SIHGYLGIVE HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG
ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQTL PESEDEESYD TESEFTEDEL
PYDDCVFGGQ RLTL
//
