IKBA_MOUSE
ID IKBA_MOUSE Reviewed; 314 AA.
AC Q9Z1E3; Q3U9W9; Q3UB40; Q80ZX5;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 2.
DT 03-AUG-2022, 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;
GN Name=Nfkbia; Synonyms=Ikba;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-314.
RC STRAIN=129/Sv; TISSUE=Liver;
RX PubMed=10199915; DOI=10.1007/s002510050512;
RA Rupec R.A., Poujol D., Grosgeorge J., Carle G.F., Livolsi A., Peyron J.-F.,
RA Schmid R.M., Baeuerle P.A., Messer G.;
RT "Structural analysis, expression, and chromosomal localization of the mouse
RT ikba gene.";
RL Immunogenetics 49:395-403(1999).
RN [4]
RP INTERACTION WITH BTRC, PHOSPHORYLATION AT SER-32 AND SER-36, AND
RP UBIQUITINATION.
RX PubMed=9859996; DOI=10.1038/25159;
RA Yaron A., Hatzubai A., Davis M., Lavon I., Amit S., Manning A.M.,
RA Andersen J.S., Mann M., Mercurio F., Ben-Neriah Y.;
RT "Identification of the receptor component of the IkappaBalpha-ubiquitin
RT ligase.";
RL Nature 396:590-594(1998).
RN [5]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND RELA,
RP PHOSPHORYLATION AT SER-32 AND SER-36, AND UBIQUITINATION AT LYS-21 AND
RP LYS-22.
RX PubMed=9990853; DOI=10.1101/gad.13.3.284;
RA Spencer E., Jiang J., Chen Z.J.;
RT "Signal-induced ubiquitination of IkappaBalpha by the F-box protein
RT Slimb/beta-TrCP.";
RL Genes Dev. 13:284-294(1999).
RN [6]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND CUL1,
RP PHOSPHORYLATION AT SER-32 AND SER-36, AND UBIQUITINATION.
RX PubMed=10097128; DOI=10.1073/pnas.96.7.3859;
RA Hatakeyama S., Kitagawa M., Nakayama K., Shirane M., Matsumoto M.,
RA Hattori K., Higashi H., Nakano H., Okumura K., Onoe K., Good R.A.,
RA Nakayama K.;
RT "Ubiquitin-dependent degradation of IkappaBalpha is mediated by a ubiquitin
RT ligase Skp1/Cul 1/F-box protein FWD1.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3859-3863(1999).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. {ECO:0000269|PubMed:10097128,
CC ECO:0000269|PubMed:9990853}.
CC -!- SUBUNIT: Interacts with PRMT2 (By similarity). Interacts with RELA; the
CC interaction requires the nuclear import signal. Interacts with NKIRAS1
CC and NKIRAS2 (By similarity). Part of a 70-90 kDa complex at least
CC consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14 (By
CC similarity). Interacts with RWDD3; the interaction enhances sumoylation
CC (By similarity). Interacts (when phosphorylated at the 2 serine
CC residues in the destruction motif D-S-G-X(2,3,4)-S) with BTRC.
CC Associates with the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC;
CC the association is mediated via interaction with BTRC
CC (PubMed:10097128). Part of a SCF(BTRC)-like complex lacking CUL1, which
CC is associated with RELA; RELA interacts directly with NFKBIA
CC (PubMed:9990853). Interacts with PRKACA in platelets; this interaction
CC is disrupted by thrombin and collagen (By similarity). Interacts with
CC HIF1AN (By similarity). Interacts with MEFV (By similarity). Interacts
CC with DDRGK1; positively regulates NFKBIA phosphorylation and
CC degradation (By similarity). {ECO:0000250|UniProtKB:P25963,
CC ECO:0000269|PubMed:10097128, ECO:0000269|PubMed:9859996,
CC ECO:0000269|PubMed:9990853}.
CC -!- INTERACTION:
CC Q9Z1E3; O88895: Hdac3; NbExp=2; IntAct=EBI-644427, EBI-302263;
CC Q9Z1E3; Q04207: Rela; NbExp=9; IntAct=EBI-644427, EBI-644400;
CC Q9Z1E3; Q04863: Relb; NbExp=4; IntAct=EBI-644427, EBI-1209145;
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 -!- TISSUE SPECIFICITY: Highly expressed in lymph node, thymus followed by
CC liver, brain, muscle, kidney, gastrointestinal and reproductive tract.
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; AK151115; BAE30124.1; -; mRNA.
DR EMBL; AK151608; BAE30547.1; -; mRNA.
DR EMBL; BC046754; AAH46754.1; -; mRNA.
DR EMBL; U57524; AAD10341.1; -; Genomic_DNA.
DR CCDS; CCDS25918.1; -.
DR RefSeq; NP_035037.2; NM_010907.2.
DR AlphaFoldDB; Q9Z1E3; -.
DR SMR; Q9Z1E3; -.
DR BioGRID; 201753; 12.
DR CORUM; Q9Z1E3; -.
DR DIP; DIP-36160N; -.
DR IntAct; Q9Z1E3; 9.
DR MINT; Q9Z1E3; -.
DR STRING; 10090.ENSMUSP00000021413; -.
DR ChEMBL; CHEMBL1926493; -.
DR iPTMnet; Q9Z1E3; -.
DR PhosphoSitePlus; Q9Z1E3; -.
DR EPD; Q9Z1E3; -.
DR MaxQB; Q9Z1E3; -.
DR PaxDb; Q9Z1E3; -.
DR PeptideAtlas; Q9Z1E3; -.
DR PRIDE; Q9Z1E3; -.
DR ProteomicsDB; 267306; -.
DR Antibodypedia; 3541; 1894 antibodies from 49 providers.
DR DNASU; 18035; -.
DR Ensembl; ENSMUST00000021413; ENSMUSP00000021413; ENSMUSG00000021025.
DR GeneID; 18035; -.
DR KEGG; mmu:18035; -.
DR UCSC; uc007nor.2; mouse.
DR CTD; 4792; -.
DR MGI; MGI:104741; Nfkbia.
DR VEuPathDB; HostDB:ENSMUSG00000021025; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000162733; -.
DR HOGENOM; CLU_000134_6_3_1; -.
DR InParanoid; Q9Z1E3; -.
DR OMA; FPNYNGH; -.
DR OrthoDB; 1341288at2759; -.
DR PhylomeDB; Q9Z1E3; -.
DR TreeFam; TF320166; -.
DR Reactome; R-MMU-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-MMU-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-209560; NF-kB is activated and signals survival.
DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-MMU-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-MMU-4755510; SUMOylation of immune response proteins.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-933542; TRAF6 mediated NF-kB activation.
DR BioGRID-ORCS; 18035; 6 hits in 75 CRISPR screens.
DR ChiTaRS; Nfkbia; mouse.
DR PRO; PR:Q9Z1E3; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9Z1E3; protein.
DR Bgee; ENSMUSG00000021025; Expressed in peripheral lymph node and 270 other tissues.
DR Genevisible; Q9Z1E3; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI.
DR GO; GO:0008139; F:nuclear localization sequence binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:MGI.
DR GO; GO:0007253; P:cytoplasmic sequestering of NF-kappaB; ISO:MGI.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; ISO:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0010888; P:negative regulation of lipid storage; ISO:MGI.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; ISO:MGI.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IMP:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:MGI.
DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IDA:MGI.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:MGI.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:MGI.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0006606; P:protein import into nucleus; IDA:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0043330; P:response to exogenous dsRNA; IDA:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0032495; P:response to muramyl dipeptide; IDA:MGI.
DR GO; GO:0035994; P:response to muscle stretch; IDA:MGI.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
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_0000067000"
FT REPEAT 73..103
FT /note="ANK 1"
FT REPEAT 110..139
FT /note="ANK 2"
FT REPEAT 143..172
FT /note="ANK 3"
FT REPEAT 182..211
FT /note="ANK 4"
FT REPEAT 216..245
FT /note="ANK 5"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 30..36
FT /note="Destruction motif"
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..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 32
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000269|PubMed:10097128,
FT ECO:0000269|PubMed:9859996, ECO:0000269|PubMed:9990853"
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"
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 ubiquitin)"
FT /evidence="ECO:0000269|PubMed:9990853"
FT CROSSLNK 22
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:9990853"
FT CONFLICT 132
FT /note="K -> R (in Ref. 1; BAE30547)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="I -> T (in Ref. 3; AAD10341)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 35071 MW; E1783F8E1BA93813 CRC64;
MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE EYEQMVKELR EIRLQPQEAP
LAAEPWKQQL TEDGDSFLHL AIIHEEKPLT MEVIGQVKGD LAFLNFQNNL QQTPLHLAVI
TNQPGIAEAL LKAGCDPELR DFRGNTPLHL ACEQGCLASV AVLTQTCTPQ HLHSVLQATN
YNGHTCLHLA SIHGYLAIVE HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG
ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEDEL
PYDDCVFGGQ RLTL
