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P25963 (IKBA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·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
Major histocompatibility complex enhancer-binding protein MAD3
Gene names
Name:NFKBIA
Synonyms:IKBA, MAD3, NFKBI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length317 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.11

Subunit structure

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 PRMT2. Interacts with PRKACA in platelets; this interaction is disrupted by thrombin and collagen. Interacts with HIF1AN. Interacts with MEFV. Ref.10 Ref.19 Ref.22 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29

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. Ref.16 Ref.23 Ref.24 Ref.26

Induction

Induced in adherent monocytes.

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. Ref.12 Ref.13 Ref.15 Ref.18 Ref.20 Ref.21

Sumoylated; sumoylation requires the presence of the nuclear import signal. Ref.24 Ref.28

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.

Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation.

Involvement in disease

Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency autosomal dominant (ADEDAID) [MIM:612132]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. This form of ectodermal dysplasia is associated with decreased production of pro-inflammatory cytokines and certain interferons, rendering patients susceptible to infection.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.34 Ref.35

Sequence similarities

Belongs to the NF-kappa-B inhibitor family.

Contains 5 ANK repeats.

Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentCytoplasm
Nucleus
   DiseaseDisease mutation
Ectodermal dysplasia
   DomainANK repeat
Repeat
   PTMHydroxylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement PubMed 10747850. Source: ProtInc

cellular response to cold

Non-traceable author statement PubMed 16750872. Source: BHF-UCL

cytoplasmic sequestering of NF-kappaB

Inferred from mutant phenotype PubMed 16938301. Source: BHF-UCL

cytoplasmic sequestering of transcription factor

Inferred from direct assay Ref.10. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA binding

Non-traceable author statement PubMed 3140380. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay PubMed 11931770. Source: MGI

negative regulation of Notch signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Traceable author statement. Source: Reactome

negative regulation of lipid storage

Inferred from mutant phenotype PubMed 16938301. Source: BHF-UCL

negative regulation of macrophage derived foam cell differentiation

Inferred from mutant phenotype PubMed 16938301. Source: BHF-UCL

negative regulation of myeloid cell differentiation

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing 1 signaling pathway

Inferred from electronic annotation. Source: Ensembl

nucleotide-binding oligomerization domain containing 2 signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Traceable author statement. Source: Reactome

positive regulation of cellular protein metabolic process

Inferred from mutant phenotype PubMed 16938301. Source: BHF-UCL

positive regulation of cholesterol efflux

Inferred from mutant phenotype PubMed 16938301. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19245366. Source: UniProtKB

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

regulation of NF-kappaB import into nucleus

Non-traceable author statement PubMed 3140380. Source: UniProtKB

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

response to muramyl dipeptide

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentI-kappaB/NF-kappaB complex

Traceable author statement PubMed 16938301. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 3140380. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.26PubMed 7679069. Source: UniProtKB

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_functionNF-kappaB binding

Inferred from physical interaction PubMed 7739562. Source: UniProtKB

enzyme binding

Inferred from physical interaction Ref.26. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 16951195. Source: IntAct

nuclear localization sequence binding

Inferred from physical interaction Ref.10. Source: UniProtKB

transcription factor binding

Traceable author statement PubMed 10928981. Source: ProtInc

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 9859996. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 317317NF-kappa-B inhibitor alpha
PRO_0000066999

Regions

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

Amino acid modifications

Modified residue321Phosphoserine; by IKKA and IKKE Ref.18 Ref.20
Modified residue361Phosphoserine; by IKKA, IKKB, IKKE and TBK1 Ref.18 Ref.20
Modified residue421Phosphotyrosine; by Tyr-kinases Ref.12
Modified residue2101(3S)-3-hydroxyasparagine; by HIF1AN; partial Ref.27
Modified residue2441(3S)-3-hydroxyasparagine; by HIF1AN; partial Ref.27
Modified residue2831Phosphoserine; by CK2 Ref.13 Ref.15
Modified residue2881Phosphoserine; by CK2 Ref.13
Modified residue2911Phosphothreonine; by CK2 Ref.13 Ref.15
Modified residue2931Phosphoserine; by CK2 Ref.13
Modified residue2991Phosphothreonine; by CK2 Ref.15
Cross-link21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO or ubiquitin) Ref.11 Ref.24 Ref.30
Cross-link22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11 Ref.30

Natural variations

Natural variant321S → I in ADEDAID. Ref.34
Corresponds to variant rs28933100 [ dbSNP | Ensembl ].
VAR_034871

Experimental info

Mutagenesis211K → R: Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-22. Ref.11 Ref.14 Ref.24 Ref.28
Mutagenesis221K → R: Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-21. Ref.11 Ref.14 Ref.24 Ref.28
Mutagenesis311D → A: Loss of phosphorylation; when associated with A-35. Ref.14
Mutagenesis321S → A: Loss of phosphorylation, ubiquitination and degradation; when associated with A-36. Ref.14 Ref.18
Mutagenesis321S → T: Decrease in phosphorylation and degradation; when associated with T-36. Ref.14 Ref.18
Mutagenesis351D → A: Loss in phosphorylation; when associated with A-31. Ref.14
Mutagenesis351D → G: No change neither in phosphorylation, nor on degradation. Ref.14
Mutagenesis361S → A: Loss of phosphorylation, ubiquitination, and degradation; when associated with A-32. Ref.14 Ref.18
Mutagenesis361S → T: Decrease in phosphorylation and degradation; when associated with T-32. Ref.14 Ref.18
Mutagenesis381K → R: No change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-47. Ref.11
Mutagenesis421Y → F: No phosphorylation. Ref.12
Mutagenesis45 – 528MVKELQEI → AAKEAQEA: No nuclear export. Ref.23
Mutagenesis471K → R: Little change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-38. Ref.11
Mutagenesis115 – 1206LHLAVI → AHAAVA: Greatly reduced nuclear localization. Great reduction in its ability to inhibit DNA binding of RELA. Ref.16
Mutagenesis2101N → A: Almost abolished ability to inhibit NF-kappa-B DNA-binding activity; when associated with A-244. Ref.27
Mutagenesis2341S → A: No inducible ubiquitination nor protein degradation. Ref.14
Mutagenesis2441N → A: Almost abolished ability to inhibit NF-kappa-B DNA-binding activity; when associated with A-210. Ref.27
Mutagenesis2621S → A: No inducible ubiquitination nor protein degradation. Ref.14
Mutagenesis2631T → A: No inducible ubiquitination nor protein degradation. Ref.14

Secondary structure

......................................... 317
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P25963 [UniParc].

Last modified May 1, 1992. Version 1.
Checksum: 088B313226786395

FASTA31735,609
        10         20         30         40         50         60 
MFQAAERPQE WAMEGPRDGL KKERLLDDRH DSGLDSMKDE EYEQMVKELQ EIRLEPQEVP 

        70         80         90        100        110        120 
RGSEPWKQQL TEDGDSFLHL AIIHEEKALT MEVIRQVKGD LAFLNFQNNL QQTPLHLAVI 

       130        140        150        160        170        180 
TNQPEIAEAL LGAGCDPELR DFRGNTPLHL ACEQGCLASV GVLTQSCTTP HLHSILKATN 

       190        200        210        220        230        240 
YNGHTCLHLA SIHGYLGIVE LLVSLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG 

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

       310 
DELPYDDCVF GGQRLTL 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity."
Haskill S., Beg A.A., Tompkins S.M., Morris J.S., Yurochko A.D., Sampson-Johannes A., Mondal K., Ralph P., Baldwin A.S. Jr.
Cell 65:1281-1289(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Monocyte.
[2]"Clonal deleterious mutations in the IkappaB alpha gene in the malignant cells in Hodgkin's lymphoma."
Jungnickel B., Staratschek-Jox A., Braeuninger A., Spieker T., Wolf J., Diehl V., Hansmann M.-L., Rajewsky K., Kueppers R.
J. Exp. Med. 191:395-402(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Lymph node.
[3]"Homo sapiens IkBa mRNA."
Liu B., Huang A.
Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]SeattleSNPs variation discovery resource
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cerebellum.
[7]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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].
Tissue: Brain and Kidney.
[10]"I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding."
Ganchi P.A., Sun S.C., Greene W.C., Ballard D.W.
Mol. Biol. Cell 3:1339-1352(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RELA.
[11]"Signal-induced degradation of IkappaB alpha requires site-specific ubiquitination."
Scherer D.C., Brockman J.A., Chen Z., Maniatis T., Ballard D.W.
Proc. Natl. Acad. Sci. U.S.A. 92:11259-11263(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-21 AND LYS-22, FUNCTION, MUTAGENESIS OF LYS-21; LYS-22; LYS-38 AND LYS-47.
[12]"Tyrosine phosphorylation of IkappaB-alpha activates NF-kappaB without proteolytic degradation of IkappaB-alpha."
Imbert V., Rupec R.A., Livolsi A., Pahl H.L., Traenckner E.B.-M., Mueller-Dieckmann C., Farahifar D., Rossi B., Auberger P., Baeuerle P.A., Peyron J.-F.
Cell 86:787-798(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-42, MUTAGENESIS OF TYR-42.
[13]"Casein kinase II phosphorylates I kappa B alpha at S-283, S-289, S-293, and T-291 and is required for its degradation."
McElhinny J.A., Trushin S.A., Bren G.D., Chester N., Paya C.V.
Mol. Cell. Biol. 16:899-906(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-283; SER-288; SER-293 AND THR-291.
[14]"Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation."
DiDonato J.A., Mercurio F., Rosette C., Wu-Li J., Suyang H., Ghosh S., Karin M.
Mol. Cell. Biol. 16:1295-1304(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-21; LYS-22; ASP-31; SER-32; ASP-35; SER-36; SER-234; SER-262 AND THR-263.
[15]"Phosphorylation of IkappaBalpha in the C-terminal PEST domain by casein kinase II affects intrinsic protein stability."
Lin R., Beauparlant P., Makris C., Meloche S., Hiscott J.
Mol. Cell. Biol. 16:1401-1409(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-291; SER-283 AND THR-299.
[16]"Nuclear localization of IkappaB alpha is mediated by the second ankyrin repeat: the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear import sequences."
Sachdev S., Hoffmann A., Hannink M.
Mol. Cell. Biol. 18:2524-2534(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, MUTAGENESIS OF 115-LEU--ILE-120.
[17]"A complex containing betaTrCP recruits Cdc34 to catalyse ubiquitination of IkappaBalpha."
Vuillard L., Nicholson J., Hay R.T.
FEBS Lett. 455:311-314(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY THE SCF(FBXW11) COMPLEX.
[18]"Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha."
Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C., Yamanaka K., Pagano M., Iwai K., Ciechanover A.
J. Biol. Chem. 274:14823-14830(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-32 AND SER-36, MUTAGENESIS OF SER-32 AND SER-36, UBIQUITINATION BY UBE2D2 AND UBE2D3.
[19]"Direct association and nuclear import of the hepatitis B virus X protein with the NF-kappaB inhibitor IkappaBalpha."
Weil R., Sirma H., Giannini C., Kremsdorf D., Bessia C., Dargemont C., Brechot C., Israel A.
Mol. Cell. Biol. 19:6345-6354(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HBV PROTEIN X.
[20]"IKK epsilon is part of a novel PMA-inducible IkappaB kinase complex."
Peters R.T., Liao S.-M., Maniatis T.
Mol. Cell 5:513-522(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-32 AND SER-36.
[21]"NAK is an IkappaB kinase-activating kinase."
Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S., Nakayama K., Kaneko Y., Nimura Y., Motoyama N., Ikeda K., Karin M., Nakanishi M.
Nature 404:778-782(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY TBK1.
[22]"A subclass of Ras proteins that regulate the degradation of IkappaB."
Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W., Ghosh S.
Science 287:869-873(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NKIRAS1 AND NKIRAS2.
[23]"A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes."
Huang T.T., Kudo N., Yoshida M., Miyamoto S.
Proc. Natl. Acad. Sci. U.S.A. 97:1014-1019(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF 45-MET--ILE-52.
[24]"SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting."
Rodriguez M.S., Dargemont C., Hay R.T.
J. Biol. Chem. 276:12654-12659(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-21, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-21 AND LYS-22.
[25]"Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex."
Gambaryan S., Kobsar A., Rukoyatkina N., Herterich S., Geiger J., Smolenski A., Lohmann S.M., Walter U.
J. Biol. Chem. 285:18352-18363(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKACA.
[26]"Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis."
Ganesh L., Yoshimoto T., Moorthy N.C., Akahata W., Boehm M., Nabel E.G., Nabel G.J.
Mol. Cell. Biol. 26:3864-3874(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRMT2, SUBCELLULAR LOCATION.
[27]"Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)."
Cockman M.E., Lancaster D.E., Stolze I.P., Hewitson K.S., McDonough M.A., Coleman M.L., Coles C.H., Yu X., Hay R.T., Ley S.C., Pugh C.W., Oldham N.J., Masson N., Schofield C.J., Ratcliffe P.J.
Proc. Natl. Acad. Sci. U.S.A. 103:14767-14772(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIF1AN, HYDROXYLATION AT ASN-210 AND ASN-244, MUTAGENESIS OF ASN-210 AND ASN-244.
[28]"RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia."
Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M., Silberstein S., Stalla G.K., Holsboer F., Arzt E.
Cell 131:309-323(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RWDD3, SUMOYLATION, MUTAGENESIS OF LYS-21 AND LSY-22.
[29]"The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment."
Chae J.J., Wood G., Richard K., Jaffe H., Colburn N.T., Masters S.L., Gumucio D.L., Shoham N.G., Kastner D.L.
Blood 112:1794-1803(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEFV.
[30]"Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for polyubiquitination on a SCF substrate."
Wu K., Kovacev J., Pan Z.Q.
Mol. Cell 37:784-796(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-21 AND LYS-22.
[31]"The cysteine protease domain of porcine reproductive and respiratory syndrome virus nonstructural protein 2 possesses deubiquitinating and interferon antagonism functions."
Sun Z., Chen Z., Lawson S.R., Fang Y.
J. Virol. 84:7832-7846(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DEUBIQUITINATION BY PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS NSP2 PROTEIN.
[32]"Structure of an IkappaBalpha/NF-kappaB complex."
Jacobs M.D., Harrison S.C.
Cell 95:749-758(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 70-282.
[33]"The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation."
Huxford T., Huang D.B., Malek S., Ghosh G.
Cell 95:759-770(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 73-302.
[34]"A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency."
Courtois G., Smahi A., Reichenbach J., Doffinger R., Cancrini C., Bonnet M., Puel A., Chable-Bessia C., Yamaoka S., Feinberg J., Dupuis-Girod S., Bodemer C., Livadiotti S., Novelli F., Rossi P., Fischer A., Israel A., Munnich A., Le Deist F., Casanova J.L.
J. Clin. Invest. 112:1108-1115(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ADEDAID ILE-32.
[35]"A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency."
Lopez-Granados E., Keenan J.E., Kinney M.C., Leo H., Jain N., Ma C.A., Quinones R., Gelfand E.W., Jain A.
Hum. Mutat. 29:861-868(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ADEDAID.
+Additional computationally mapped references.

Web resources

NFKBIAbase

NFKBIA mutation db

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M69043 mRNA. Translation: AAA16489.1.
AJ249294 expand/collapse EMBL AC list , AJ249295, AJ249283, AJ249284, AJ249285, AJ249286 Genomic DNA. Translation: CAB65556.2.
AY033600 mRNA. Translation: AAK51149.1.
BT007091 mRNA. Translation: AAP35754.1.
AY496422 Genomic DNA. Translation: AAR29599.1.
AK313421 mRNA. Translation: BAG36213.1.
AL133163 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW65875.1.
BC002601 mRNA. Translation: AAH02601.1.
BC004983 mRNA. Translation: AAH04983.1.
PIRA39935.
RefSeqNP_065390.1. NM_020529.2.
UniGeneHs.81328.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IKNX-ray2.30D67-302[»]
1NFIX-ray2.70E/F70-282[»]
DisProtDP00468.
ProteinModelPortalP25963.
SMRP25963. Positions 4-314.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110859. 102 interactions.
DIPDIP-139N.
IntActP25963. 45 interactions.
MINTMINT-120458.
STRING9606.ENSP00000216797.

Chemistry

BindingDBP25963.
ChEMBLCHEMBL2898.

PTM databases

PhosphoSiteP25963.

Polymorphism databases

DMDM126682.

Proteomic databases

PaxDbP25963.
PeptideAtlasP25963.
PRIDEP25963.

Protocols and materials databases

DNASU4792.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216797; ENSP00000216797; ENSG00000100906.
GeneID4792.
KEGGhsa:4792.
UCSCuc001wtf.4. human.

Organism-specific databases

CTD4792.
GeneCardsGC14M035870.
HGNCHGNC:7797. NFKBIA.
HPACAB003815.
HPA029207.
MIM164008. gene.
612132. phenotype.
neXtProtNX_P25963.
Orphanet251579. Giant cell glioblastoma.
251576. Gliosarcoma.
98813. Hypohidrotic ectodermal dysplasia with immunodeficiency.
PharmGKBPA31601.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000059576.
HOVERGENHBG018875.
InParanoidP25963.
KOK04734.
OMASIHGYLA.
OrthoDBEOG7W154S.
PhylomeDBP25963.
TreeFamTF320166.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SABIO-RKP25963.
SignaLinkP25963.

Gene expression databases

ArrayExpressP25963.
BgeeP25963.
CleanExHS_NFKBIA.
GenevestigatorP25963.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamPF00023. Ank. 4 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

ChiTaRSNFKBIA. human.
EvolutionaryTraceP25963.
GeneWikiI%CE%BAB%CE%B1.
GenomeRNAi4792.
NextBio18466.
PMAP-CutDBP25963.
PROP25963.
SOURCESearch...

Entry information

Entry nameIKBA_HUMAN
AccessionPrimary (citable) accession number: P25963
Secondary accession number(s): B2R8L6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: April 16, 2014
This is version 162 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM