IKBA_RAT
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 03-AUG-2022, entry version 169.
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 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 (By similarity). {ECO:0000250}.
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 (By similarity).
CC Interacts with HIF1AN (By similarity). Interacts with MEFV (By
CC similarity). Interacts with DDRGK1; positively regulates NFKBIA
CC phosphorylation and degradation (By similarity).
CC {ECO:0000250|UniProtKB:P25963}.
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 -!- INDUCTION: During liver regeneration. {ECO:0000269|PubMed:1588976}.
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; 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 iPTMnet; Q63746; -.
DR PhosphoSitePlus; Q63746; -.
DR PaxDb; Q63746; -.
DR Ensembl; ENSRNOT00000009894; ENSRNOP00000009894; ENSRNOG00000007390.
DR GeneID; 25493; -.
DR KEGG; rno:25493; -.
DR UCSC; RGD:3171; rat.
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 OMA; EIRIQPQ; -.
DR OrthoDB; 1341288at2759; -.
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 tissues.
DR Genevisible; Q63746; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0033256; C:I-kappaB/NF-kappaB complex; IC:RGD.
DR GO; GO:0005634; C:nucleus; IDA: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:0051059; F:NF-kappaB binding; IPI:RGD.
DR GO; GO:0008139; F:nuclear localization sequence binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; 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:0007253; P:cytoplasmic sequestering of NF-kappaB; IMP:RGD.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; ISO:RGD.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; 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: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:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0045746; P:negative regulation of 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:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; 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; -; 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 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"
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 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"
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; 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
