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Q9Z1E3

- IKBA_MOUSE

UniProt

Q9Z1E3 - IKBA_MOUSE

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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

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

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
Complete GO annotation...

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
Complete GO annotation...

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

        10         20         30         40         50
MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE EYEQMVKELR
60 70 80 90 100
EIRLQPQEAP LAAEPWKQQL TEDGDSFLHL AIIHEEKPLT MEVIGQVKGD
110 120 130 140 150
LAFLNFQNNL QQTPLHLAVI TNQPGIAEAL LKAGCDPELR DFRGNTPLHL
160 170 180 190 200
ACEQGCLASV AVLTQTCTPQ HLHSVLQATN YNGHTCLHLA SIHGYLAIVE
210 220 230 240 250
HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG ADVNRVTYQG
260 270 280 290 300
YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEDEL
310
PYDDCVFGGQ RLTL
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

« Hide 'large scale' publications
  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 29, 2014
This is version 122 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