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Q9Z1E3

- IKBA_MOUSE

UniProt

Q9Z1E3 - IKBA_MOUSE

Protein

NF-kappa-B inhibitor alpha

Gene

Nfkbia

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 2 (25 Oct 2004)
      Previous versions | rss
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    Functioni

    Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.2 Publications

    GO - Molecular functioni

    1. nuclear localization sequence binding Source: Ensembl
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. cytoplasmic sequestering of NF-kappaB Source: Ensembl
    2. lipopolysaccharide-mediated signaling pathway Source: MGI
    3. negative regulation of lipid storage Source: Ensembl
    4. negative regulation of macrophage derived foam cell differentiation Source: Ensembl
    5. negative regulation of myeloid cell differentiation Source: MGI
    6. negative regulation of NF-kappaB transcription factor activity Source: Ensembl
    7. negative regulation of Notch signaling pathway Source: MGI
    8. nucleotide-binding oligomerization domain containing 1 signaling pathway Source: MGI
    9. nucleotide-binding oligomerization domain containing 2 signaling pathway Source: MGI
    10. positive regulation of cellular protein metabolic process Source: Ensembl
    11. positive regulation of cholesterol efflux Source: Ensembl
    12. positive regulation of transcription, DNA-templated Source: MGI
    13. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    14. protein import into nucleus, translocation Source: MGI
    15. regulation of cell proliferation Source: MGI
    16. regulation of gene expression Source: MGI
    17. response to exogenous dsRNA Source: MGI
    18. response to lipopolysaccharide Source: MGI
    19. response to muramyl dipeptide Source: MGI
    20. toll-like receptor 4 signaling pathway Source: MGI

    Enzyme and pathway databases

    ReactomeiREACT_199121. Activation of NF-kappaB in B cells.
    REACT_202898. TRAF6 mediated NF-kB activation.
    REACT_205561. FCERI mediated NF-kB activation.
    REACT_218887. NF-kB is activated and signals survival.
    REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_222971. RIP-mediated NFkB activation via ZBP1.
    REACT_225145. Downstream TCR signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NF-kappa-B inhibitor alpha
    Alternative name(s):
    I-kappa-B-alpha
    Short name:
    IkB-alpha
    Short name:
    IkappaBalpha
    Gene namesi
    Name:Nfkbia
    Synonyms:Ikba
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:104741. Nfkbia.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytosol Source: MGI
    3. nucleus Source: MGI
    4. plasma membrane Source: Ensembl
    5. protein complex Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 314314NF-kappa-B inhibitor alphaPRO_0000067000Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki21 – 21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki22 – 22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei32 – 321Phosphoserine; by IKKB3 Publications
    Modified residuei36 – 361Phosphoserine; by IKKA, IKKB, IKKE and TBK1By similarity
    Modified residuei42 – 421PhosphotyrosineBy similarity
    Modified residuei210 – 2101(3S)-3-hydroxyasparagine; by HIF1ANBy similarity
    Modified residuei244 – 2441(3S)-3-hydroxyasparagine; by HIF1ANBy similarity
    Modified residuei283 – 2831Phosphoserine; by CK2By similarity
    Modified residuei288 – 2881Phosphoserine; by CK2By similarity
    Modified residuei291 – 2911Phosphothreonine; by CK2By similarity
    Modified residuei293 – 2931Phosphoserine; by CK2By similarity
    Modified residuei296 – 2961PhosphothreonineBy similarity

    Post-translational modificationi

    Phosphorylated; disables inhibition of NF-kappa-B DNA-binding activity. Phosphorylation at positions 32 and 36 is prerequisite to recognition by UBE2D3 leading to polyubiquitination and subsequent degradation By similarity.By similarity
    Sumoylated; sumoylation requires the presence of the nuclear import signal. Sumoylation blocks ubiquitination and proteasome-mediated degradation of the protein thereby increasing the protein stability By similarity.By similarity
    Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3. Ubiquitin chain elongation is then performed by CDC34 in cooperation with the SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. The resulting polyubiquitination leads to protein degradation. Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36 By similarity.By similarity

    Keywords - PTMi

    Hydroxylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9Z1E3.
    PaxDbiQ9Z1E3.
    PRIDEiQ9Z1E3.

    PTM databases

    PhosphoSiteiQ9Z1E3.

    Expressioni

    Tissue specificityi

    Highly expressed in lymph node, thymus followed by liver, brain, muscle, kidney, gastrointestinal and reproductive tract.

    Gene expression databases

    BgeeiQ9Z1E3.
    GenevestigatoriQ9Z1E3.

    Interactioni

    Subunit structurei

    Interacts with PRMT2 By similarity. Interacts with RELA; the interaction requires the nuclear import signal. Interacts with NKIRAS1 and NKIRAS2. Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Interacts with HBV protein X. Interacts with RWDD3; the interaction enhances sumoylation. Interacts (when phosphorylated at the 2 serine residues in the destruction motif D-S-G-X(2,3,4)-S) with BTRC. Associates with the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC; the association is mediated via interaction with BTRC. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with RELA; RELA interacts directly with NFKBIA. Interacts with PRKACA in platelets; this interaction is disrupted by thrombin and collagen. Interacts with HIF1AN By similarity. Interacts with MEFV By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Hdac3O888952EBI-644427,EBI-302263
    RelaQ042077EBI-644427,EBI-644400
    RelbQ048634EBI-644427,EBI-1209145

    Protein-protein interaction databases

    BioGridi201753. 12 interactions.
    DIPiDIP-36160N.
    IntActiQ9Z1E3. 5 interactions.
    MINTiMINT-1523813.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Z1E3.
    SMRiQ9Z1E3. Positions 70-281.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati73 – 10331ANK 1Add
    BLAST
    Repeati110 – 13930ANK 2Add
    BLAST
    Repeati143 – 17230ANK 3Add
    BLAST
    Repeati182 – 21130ANK 4Add
    BLAST
    Repeati216 – 24530ANK 5Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi30 – 367Destruction motif
    Motifi45 – 5410Nuclear export signalBy similarity
    Motifi110 – 12011Nuclear import signalBy similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the NF-kappa-B inhibitor family.Curated
    Contains 5 ANK repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    ANK repeat, Repeat

    Phylogenomic databases

    eggNOGiCOG0666.
    GeneTreeiENSGT00550000074527.
    HOGENOMiHOG000059576.
    HOVERGENiHBG018875.
    InParanoidiQ9Z1E3.
    KOiK04734.
    OMAiSIHGYLA.
    OrthoDBiEOG7W154S.
    PhylomeDBiQ9Z1E3.
    TreeFamiTF320166.

    Family and domain databases

    Gene3Di1.25.40.20. 1 hit.
    InterProiIPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    [Graphical view]
    PfamiPF12796. Ank_2. 2 hits.
    [Graphical view]
    PRINTSiPR01415. ANKYRIN.
    SMARTiSM00248. ANK. 5 hits.
    [Graphical view]
    SUPFAMiSSF48403. SSF48403. 1 hit.
    PROSITEiPS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 3 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Z1E3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE EYEQMVKELR    50
    EIRLQPQEAP LAAEPWKQQL TEDGDSFLHL AIIHEEKPLT MEVIGQVKGD 100
    LAFLNFQNNL QQTPLHLAVI TNQPGIAEAL LKAGCDPELR DFRGNTPLHL 150
    ACEQGCLASV AVLTQTCTPQ HLHSVLQATN YNGHTCLHLA SIHGYLAIVE 200
    HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG ADVNRVTYQG 250
    YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEDEL 300
    PYDDCVFGGQ RLTL 314
    Length:314
    Mass (Da):35,071
    Last modified:October 25, 2004 - v2
    Checksum:iE1783F8E1BA93813
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti132 – 1321K → R in BAE30547. (PubMed:16141072)Curated
    Sequence conflicti192 – 1921I → T in AAD10341. (PubMed:10199915)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK151115 mRNA. Translation: BAE30124.1.
    AK151608 mRNA. Translation: BAE30547.1.
    BC046754 mRNA. Translation: AAH46754.1.
    U57524 Genomic DNA. Translation: AAD10341.1.
    CCDSiCCDS25918.1.
    RefSeqiNP_035037.2. NM_010907.2.
    UniGeneiMm.170515.

    Genome annotation databases

    EnsembliENSMUST00000021413; ENSMUSP00000021413; ENSMUSG00000021025.
    GeneIDi18035.
    KEGGimmu:18035.
    UCSCiuc007nor.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK151115 mRNA. Translation: BAE30124.1 .
    AK151608 mRNA. Translation: BAE30547.1 .
    BC046754 mRNA. Translation: AAH46754.1 .
    U57524 Genomic DNA. Translation: AAD10341.1 .
    CCDSi CCDS25918.1.
    RefSeqi NP_035037.2. NM_010907.2.
    UniGenei Mm.170515.

    3D structure databases

    ProteinModelPortali Q9Z1E3.
    SMRi Q9Z1E3. Positions 70-281.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201753. 12 interactions.
    DIPi DIP-36160N.
    IntActi Q9Z1E3. 5 interactions.
    MINTi MINT-1523813.

    Chemistry

    ChEMBLi CHEMBL1926493.

    PTM databases

    PhosphoSitei Q9Z1E3.

    Proteomic databases

    MaxQBi Q9Z1E3.
    PaxDbi Q9Z1E3.
    PRIDEi Q9Z1E3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000021413 ; ENSMUSP00000021413 ; ENSMUSG00000021025 .
    GeneIDi 18035.
    KEGGi mmu:18035.
    UCSCi uc007nor.2. mouse.

    Organism-specific databases

    CTDi 4792.
    MGIi MGI:104741. Nfkbia.

    Phylogenomic databases

    eggNOGi COG0666.
    GeneTreei ENSGT00550000074527.
    HOGENOMi HOG000059576.
    HOVERGENi HBG018875.
    InParanoidi Q9Z1E3.
    KOi K04734.
    OMAi SIHGYLA.
    OrthoDBi EOG7W154S.
    PhylomeDBi Q9Z1E3.
    TreeFami TF320166.

    Enzyme and pathway databases

    Reactomei REACT_199121. Activation of NF-kappaB in B cells.
    REACT_202898. TRAF6 mediated NF-kB activation.
    REACT_205561. FCERI mediated NF-kB activation.
    REACT_218887. NF-kB is activated and signals survival.
    REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_222971. RIP-mediated NFkB activation via ZBP1.
    REACT_225145. Downstream TCR signaling.

    Miscellaneous databases

    NextBioi 293129.
    PROi Q9Z1E3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9Z1E3.
    Genevestigatori Q9Z1E3.

    Family and domain databases

    Gene3Di 1.25.40.20. 1 hit.
    InterProi IPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    [Graphical view ]
    Pfami PF12796. Ank_2. 2 hits.
    [Graphical view ]
    PRINTSi PR01415. ANKYRIN.
    SMARTi SM00248. ANK. 5 hits.
    [Graphical view ]
    SUPFAMi SSF48403. SSF48403. 1 hit.
    PROSITEi PS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 3 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Bone marrow.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6.
      Tissue: Brain.
    3. "Structural analysis, expression, and chromosomal localization of the mouse ikba gene."
      Rupec R.A., Poujol D., Grosgeorge J., Carle G.F., Livolsi A., Peyron J.-F., Schmid R.M., Baeuerle P.A., Messer G.
      Immunogenetics 49:395-403(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-314.
      Strain: 129/Sv.
      Tissue: Liver.
    4. "Identification of the receptor component of the IkappaBalpha-ubiquitin ligase."
      Yaron A., Hatzubai A., Davis M., Lavon I., Amit S., Manning A.M., Andersen J.S., Mann M., Mercurio F., Ben-Neriah Y.
      Nature 396:590-594(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BTRC, PHOSPHORYLATION AT SER-32 AND SER-36, UBIQUITINATION.
    5. "Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP."
      Spencer E., Jiang J., Chen Z.J.
      Genes Dev. 13:284-294(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND RELA, PHOSPHORYLATION AT SER-32 AND SER-36, UBIQUITINATION AT LYS-21 AND LYS-22.
    6. "Ubiquitin-dependent degradation of IkappaBalpha is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1."
      Hatakeyama S., Kitagawa M., Nakayama K., Shirane M., Matsumoto M., Hattori K., Higashi H., Nakano H., Okumura K., Onoe K., Good R.A., Nakayama K.
      Proc. Natl. Acad. Sci. U.S.A. 96:3859-3863(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND CUL1, PHOSPHORYLATION AT SER-32 AND SER-36, UBIQUITINATION.

    Entry informationi

    Entry nameiIKBA_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z1E3
    Secondary accession number(s): Q3U9W9, Q3UB40, Q80ZX5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 20, 2001
    Last sequence update: October 25, 2004
    Last modified: October 1, 2014
    This is version 121 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3