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Protein

NF-kappa-B inhibitor alpha

Gene

Nfkbia

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

GO - Molecular functioni

  • heat shock protein binding Source: RGD
  • NF-kappaB binding Source: RGD
  • nuclear localization sequence binding Source: Ensembl
  • protein complex binding Source: RGD

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-RNO-1169091. Activation of NF-kappaB in B cells.
R-RNO-1810476. RIP-mediated NFkB activation via ZBP1.
R-RNO-202424. Downstream TCR signaling.
R-RNO-209560. NF-kB is activated and signals survival.
R-RNO-2871837. FCERI mediated NF-kB activation.
R-RNO-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-RNO-5607764. CLEC7A (Dectin-1) signaling.
R-RNO-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
RL/IF-1
Gene namesi
Name:Nfkbia
Synonyms:Ikba
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi3171. 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

  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • I-kappaB/NF-kappaB complex Source: RGD
  • nucleus Source: RGD
  • plasma membrane Source: Ensembl
  • protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670021 – 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 SUMO); alternateBy similarity
Cross-linki21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Sequence analysisBy similarity
Modified residuei32Phosphoserine; by IKKA and IKKBBy similarity1
Modified residuei36Phosphoserine; by IKKA, IKKB, IKKE and TBK1By similarity1
Modified residuei42Phosphotyrosine; by Tyr-kinasesBy 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

PaxDbiQ63746.
PRIDEiQ63746.

PTM databases

iPTMnetiQ63746.
PhosphoSitePlusiQ63746.

Expressioni

Inductioni

During liver regeneration.1 Publication

Gene expression databases

BgeeiENSRNOG00000007390.
GenevisibleiQ63746. RN.

Interactioni

Subunit structurei

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 (By similarity). Interacts with PRMT2. 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).By similarity

GO - Molecular functioni

  • heat shock protein binding Source: RGD
  • NF-kappaB binding Source: RGD
  • protein complex binding Source: RGD

Protein-protein interaction databases

BioGridi247526. 2 interactors.
DIPiDIP-59941N.
STRINGi10116.ENSRNOP00000009894.

Structurei

3D structure databases

ProteinModelPortaliQ63746.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi30 – 36Destruction motifBy similarity7
Motifi45 – 54Nuclear export signalBy similarity10
Motifi110 – 120Nuclear import signalBy similarityAdd BLAST11

Sequence similaritiesi

Belongs to the NF-kappa-B inhibitor family.Curated
Contains 4 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00550000074527.
HOGENOMiHOG000059576.
HOVERGENiHBG018875.
InParanoidiQ63746.
KOiK04734.
OMAiHNCLHLA.
OrthoDBiEOG091G0CSV.
PhylomeDBiQ63746.
TreeFamiTF320166.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
[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.

Q63746-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFQPAGHGQD WAMEGPRDGL KKERLVDDRH DSGLDSMKDE DYEQMVKELR
60 70 80 90 100
EIRLQPQEAP LAAEPWKQQL TEDGDSFLHL AIIHEEKTLT MEVIGQVKGD
110 120 130 140 150
LAFLNFQNNL QQTPLHLAVI TNQPGIAEAL LKAGCDPELR DFRGNTPLHL
160 170 180 190 200
ACEQGCLASV AVLTQTCTPQ HLHSVLQATN YNGHTCLHLA SIHGYLGIVE
210 220 230 240 250
HLVTLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG ADVNRVTYQG
260 270 280 290 300
YSPYQLTWGR PSTRIQQQLG QLTLENLQTL PESEDEESYD TESEFTEDEL
310
PYDDCVFGGQ RLTL
Length:314
Mass (Da):35,017
Last modified:November 1, 1996 - v1
Checksum:iCC4C9D0F6CDDA950
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63594 mRNA. Translation: CAA45138.1.
CH473947 Genomic DNA. Translation: EDM03428.1.
BC166886 mRNA. Translation: AAI66886.1.
PIRiA44437.
RefSeqiNP_001099190.2. NM_001105720.2.
UniGeneiRn.12550.

Genome annotation databases

EnsembliENSRNOT00000009894; ENSRNOP00000009894; ENSRNOG00000007390.
GeneIDi25493.
KEGGirno:25493.
UCSCiRGD:3171. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63594 mRNA. Translation: CAA45138.1.
CH473947 Genomic DNA. Translation: EDM03428.1.
BC166886 mRNA. Translation: AAI66886.1.
PIRiA44437.
RefSeqiNP_001099190.2. NM_001105720.2.
UniGeneiRn.12550.

3D structure databases

ProteinModelPortaliQ63746.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247526. 2 interactors.
DIPiDIP-59941N.
STRINGi10116.ENSRNOP00000009894.

PTM databases

iPTMnetiQ63746.
PhosphoSitePlusiQ63746.

Proteomic databases

PaxDbiQ63746.
PRIDEiQ63746.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000009894; ENSRNOP00000009894; ENSRNOG00000007390.
GeneIDi25493.
KEGGirno:25493.
UCSCiRGD:3171. rat.

Organism-specific databases

CTDi4792.
RGDi3171. Nfkbia.

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00550000074527.
HOGENOMiHOG000059576.
HOVERGENiHBG018875.
InParanoidiQ63746.
KOiK04734.
OMAiHNCLHLA.
OrthoDBiEOG091G0CSV.
PhylomeDBiQ63746.
TreeFamiTF320166.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ63746.

Gene expression databases

BgeeiENSRNOG00000007390.
GenevisibleiQ63746. RN.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
[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]
ProtoNetiSearch...

Entry informationi

Entry nameiIKBA_RAT
AccessioniPrimary (citable) accession number: Q63746
Secondary accession number(s): B2RYS5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 134 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.