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Protein

NF-kappa-B inhibitor alpha

Gene

Nfkbia

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-MMU-1169091. Activation of NF-kappaB in B cells.
R-MMU-1810476. RIP-mediated NFkB activation via ZBP1.
R-MMU-202424. Downstream TCR signaling.
R-MMU-209560. NF-kB is activated and signals survival.
R-MMU-2871837. FCERI mediated NF-kB activation.
R-MMU-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-MMU-446652. Interleukin-1 family signaling.
R-MMU-5607764. CLEC7A (Dectin-1) signaling.
R-MMU-5689880. Ub-specific processing proteases.
R-MMU-933542. TRAF6 mediated NF-kB activation.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:104741. Nfkbia.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1926493.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670001 – 314NF-kappa-B inhibitor alphaAdd BLAST314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei32Phosphoserine; by IKKB3 Publications1
Modified residuei36Phosphoserine; by IKKA, IKKB, IKKE and TBK1By similarity1
Modified residuei42PhosphotyrosineBy similarity1
Modified residuei210(3S)-3-hydroxyasparagine; by HIF1ANBy similarity1
Modified residuei244(3S)-3-hydroxyasparagine; by HIF1ANBy similarity1
Modified residuei283Phosphoserine; by CK2By similarity1
Modified residuei288Phosphoserine; by CK2By similarity1
Modified residuei291Phosphothreonine; by CK2By similarity1
Modified residuei293Phosphoserine; by CK2By similarity1
Modified residuei296PhosphothreonineBy similarity1

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

EPDiQ9Z1E3.
MaxQBiQ9Z1E3.
PaxDbiQ9Z1E3.
PeptideAtlasiQ9Z1E3.
PRIDEiQ9Z1E3.

PTM databases

iPTMnetiQ9Z1E3.
PhosphoSitePlusiQ9Z1E3.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000021025.
GenevisibleiQ9Z1E3. MM.

Interactioni

Subunit structurei

Interacts with PRMT2 (By similarity). Interacts with RELA; the interaction requires the nuclear import signal. Interacts with NKIRAS1 and NKIRAS2 (By similarity). Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14 (By similarity). Interacts with RWDD3; the interaction enhances sumoylation (By similarity). 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 (PubMed:10097128). Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with RELA; RELA interacts directly with NFKBIA (PubMed:9990853). Interacts with PRKACA in platelets; this interaction is disrupted by thrombin and collagen (By similarity). Interacts with HIF1AN (By similarity). Interacts with MEFV (By similarity). Interacts with DDRGK1; positively regulates NFKBIA phosphorylation and degradation (By similarity).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201753. 12 interactors.
CORUMiQ9Z1E3.
DIPiDIP-36160N.
IntActiQ9Z1E3. 8 interactors.
MINTiMINT-1523813.
STRINGi10090.ENSMUSP00000021413.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1E3.
SMRiQ9Z1E3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati73 – 103ANK 1Add BLAST31
Repeati110 – 139ANK 2Add BLAST30
Repeati143 – 172ANK 3Add BLAST30
Repeati182 – 211ANK 4Add BLAST30
Repeati216 – 245ANK 5Add BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi30 – 36Destruction motif7
Motifi45 – 54Nuclear export signalBy similarity10
Motifi110 – 120Nuclear import signalBy similarityAdd BLAST11

Sequence similaritiesi

Belongs to the NF-kappa-B inhibitor family.Curated

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00550000074527.
HOGENOMiHOG000059576.
HOVERGENiHBG018875.
InParanoidiQ9Z1E3.
KOiK04734.
OMAiGHNCLHL.
OrthoDBiEOG091G0CSV.
PhylomeDBiQ9Z1E3.
TreeFamiTF320166.

Family and domain databases

CDDicd00204. ANK. 1 hit.
Gene3Di1.25.40.20. 1 hit.
InterProiView protein in InterPro
IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
PfamiView protein in Pfam
PF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PRINTSiPR01415. ANKYRIN.
SMARTiView protein in SMART
SM00248. ANK. 5 hits.
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiView protein in PROSITE
PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.

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)DescriptionActionsGraphical viewLength
Sequence conflicti132K → R in BAE30547 (PubMed:16141072).Curated1
Sequence conflicti192I → T in AAD10341 (PubMed:10199915).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Similar proteinsi

Entry informationi

Entry nameiIKBA_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1E3
Secondary accession number(s): Q3U9W9, Q3UB40, Q80ZX5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: October 25, 2004
Last modified: September 27, 2017
This is version 149 of the entry and version 2 of the sequence. See 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