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Q9Z1E3 (IKBA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NF-kappa-B inhibitor alpha
Alternative name(s):
I-kappa-B-alpha
Short name=IkB-alpha
Short name=IkappaBalpha
Gene names
Name:Nfkbia
Synonyms:Ikba
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length314 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6

Subunit structure

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. Ref.4 Ref.5 Ref.6

Subcellular location

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

Tissue specificity

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

Post-translational modification

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. Ref.4 Ref.5 Ref.6

Sumoylated; sumoylation requires the presence of the nuclear import signal 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.

Sequence similarities

Belongs to the NF-kappa-B inhibitor family.

Contains 5 ANK repeats.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   DomainANK repeat
Repeat
   PTMHydroxylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcytoplasmic sequestering of NF-kappaB

Inferred from electronic annotation. Source: Ensembl

lipopolysaccharide-mediated signaling pathway

Inferred from direct assay PubMed 12872135PubMed 18261938. Source: MGI

negative regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of Notch signaling pathway

Inferred from mutant phenotype PubMed 15845452. Source: MGI

negative regulation of lipid storage

Inferred from electronic annotation. Source: Ensembl

negative regulation of macrophage derived foam cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of myeloid cell differentiation

Inferred from mutant phenotype PubMed 15845452. Source: MGI

nucleotide-binding oligomerization domain containing 1 signaling pathway

Inferred from direct assay PubMed 18261938. Source: MGI

nucleotide-binding oligomerization domain containing 2 signaling pathway

Inferred from direct assay PubMed 18261938. Source: MGI

positive regulation of cellular protein metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cholesterol efflux

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 18505784. Source: MGI

protein import into nucleus, translocation

Inferred from direct assay PubMed 11799106. Source: MGI

regulation of cell proliferation

Inferred from direct assay PubMed 11799106. Source: MGI

regulation of gene expression

Inferred from mutant phenotype PubMed 21737317. Source: MGI

response to exogenous dsRNA

Inferred from direct assay PubMed 12872135. Source: MGI

response to lipopolysaccharide

Inferred from direct assay PubMed 12872135. Source: MGI

response to muramyl dipeptide

Inferred from direct assay PubMed 15692051. Source: MGI

toll-like receptor 4 signaling pathway

Inferred from direct assay PubMed 18261938. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11799106PubMed 21874024. Source: MGI

cytosol

Inferred from direct assay PubMed 11799106. Source: MGI

nucleus

Inferred from direct assay PubMed 11799106. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionnuclear localization sequence binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 11896578. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 314314NF-kappa-B inhibitor alpha
PRO_0000067000

Regions

Repeat73 – 10331ANK 1
Repeat110 – 13930ANK 2
Repeat143 – 17230ANK 3
Repeat182 – 21130ANK 4
Repeat216 – 24530ANK 5
Motif30 – 367Destruction motif
Motif45 – 5410Nuclear export signal By similarity
Motif110 – 12011Nuclear import signal By similarity

Amino acid modifications

Modified residue321Phosphoserine; by IKKB Ref.4 Ref.5 Ref.6
Modified residue361Phosphoserine; by IKKA, IKKB, IKKE and TBK1 By similarity
Modified residue421Phosphotyrosine By similarity
Modified residue2101(3S)-3-hydroxyasparagine; by HIF1AN By similarity
Modified residue2441(3S)-3-hydroxyasparagine; by HIF1AN By similarity
Modified residue2831Phosphoserine; by CK2 By similarity
Modified residue2881Phosphoserine; by CK2 By similarity
Modified residue2911Phosphothreonine; by CK2 By similarity
Modified residue2931Phosphoserine; by CK2 By similarity
Modified residue2961Phosphothreonine By similarity
Cross-link21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.5
Cross-link22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.5

Experimental info

Sequence conflict1321K → R in BAE30547. Ref.1
Sequence conflict1921I → T in AAD10341. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9Z1E3 [UniParc].

Last modified October 25, 2004. Version 2.
Checksum: E1783F8E1BA93813

FASTA31435,071
        10         20         30         40         50         60 
MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE EYEQMVKELR EIRLQPQEAP 

        70         80         90        100        110        120 
LAAEPWKQQL TEDGDSFLHL AIIHEEKPLT MEVIGQVKGD LAFLNFQNNL QQTPLHLAVI 

       130        140        150        160        170        180 
TNQPGIAEAL LKAGCDPELR DFRGNTPLHL ACEQGCLASV AVLTQTCTPQ HLHSVLQATN 

       190        200        210        220        230        240 
YNGHTCLHLA SIHGYLAIVE HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG 

       250        260        270        280        290        300 
ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEDEL 

       310 
PYDDCVFGGQ RLTL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK151115 mRNA. Translation: BAE30124.1.
AK151608 mRNA. Translation: BAE30547.1.
BC046754 mRNA. Translation: AAH46754.1.
U57524 Genomic DNA. Translation: AAD10341.1.
CCDSCCDS25918.1.
RefSeqNP_035037.2. NM_010907.2.
UniGeneMm.170515.

3D structure databases

ProteinModelPortalQ9Z1E3.
SMRQ9Z1E3. Positions 70-281.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201753. 12 interactions.
DIPDIP-36160N.
IntActQ9Z1E3. 5 interactions.
MINTMINT-1523813.

Chemistry

ChEMBLCHEMBL1926493.

PTM databases

PhosphoSiteQ9Z1E3.

Proteomic databases

MaxQBQ9Z1E3.
PaxDbQ9Z1E3.
PRIDEQ9Z1E3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000021413; ENSMUSP00000021413; ENSMUSG00000021025.
GeneID18035.
KEGGmmu:18035.
UCSCuc007nor.2. mouse.

Organism-specific databases

CTD4792.
MGIMGI:104741. Nfkbia.

Phylogenomic databases

eggNOGCOG0666.
GeneTreeENSGT00550000074527.
HOGENOMHOG000059576.
HOVERGENHBG018875.
InParanoidQ9Z1E3.
KOK04734.
OMASIHGYLA.
OrthoDBEOG7W154S.
PhylomeDBQ9Z1E3.
TreeFamTF320166.

Gene expression databases

BgeeQ9Z1E3.
GenevestigatorQ9Z1E3.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamPF12796. Ank_2. 2 hits.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio293129.
PROQ9Z1E3.
SOURCESearch...

Entry information

Entry nameIKBA_MOUSE
AccessionPrimary (citable) accession number: Q9Z1E3
Secondary accession number(s): Q3U9W9, Q3UB40, Q80ZX5
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: October 25, 2004
Last modified: July 9, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot