UniProt Accession

 IKBA_HUMAN; P25963; B2R8L6 

Genbank Protein ID

 M69043; AJ249294; AJ249295; AJ249283; AJ249284; AJ249285; AJ249286; AY033600; BT007091; AY496422; AK313421; AL133163; CH471078; BC002601; BC004983 

Genbank Nucleotide ID

 AAA16489.1; CAB65556.2; CAB65556.2; CAB65556.2; CAB65556.2; CAB65556.2; CAB65556.2; AAK51149.1; AAP35754.1; AAR29599.1; BAG36213.1; EAW65875.1; AAH02601.1; AAH04983.1 

Protein Name

 NF-kappa-B inhibitor alpha 

Protein Synonyms/Alias

 I-kappa-B-alpha; IkB-alpha; IkappaBalpha; Major histocompatibility complex enhancer-binding protein MAD3 

Gene Name

 NFKBIA 

Gene Synonyms/Alias

 IKBA; MAD3; NFKBI 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
21	EGPRDGLKKERLLDD	sumoylation	[1, 2]
22	GPRDGLKKERLLDDR	ubiquitination	[3]
238	DLVSLLLKCGADVNR	ubiquitination	[4]

Reference

 [1] SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation.
 Desterro JM, Rodriguez MS, Hay RT.
 Mol Cell. 1998 Aug;2(2):233-9. [PMID: 9734360]
 [2] At the crossroads of SUMO and NF-kappaB.
 Kracklauer MP, Schmidt C.
 Mol Cancer. 2003 Nov 5;2:39. [PMID: 14613580]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 

Functional Description

 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. 

Sequence Annotation

 REPEAT 73 103 ANK 1.
 REPEAT 110 139 ANK 2.
 REPEAT 143 172 ANK 3.
 REPEAT 182 211 ANK 4.
 REPEAT 216 245 ANK 5.
 MOTIF 30 36 Destruction motif.
 MOTIF 45 54 Nuclear export signal.
 MOTIF 110 120 Nuclear import signal.
 MOD_RES 32 32 Phosphoserine; by IKKA and IKKE.
 MOD_RES 36 36 Phosphoserine; by IKKA, IKKB, IKKE and
 MOD_RES 42 42 Phosphotyrosine; by Tyr-kinases.
 MOD_RES 210 210 (3S)-3-hydroxyasparagine; by HIF1AN;
 MOD_RES 244 244 (3S)-3-hydroxyasparagine; by HIF1AN;
 MOD_RES 283 283 Phosphoserine; by CK2.
 MOD_RES 288 288 Phosphoserine; by CK2.
 MOD_RES 291 291 Phosphothreonine; by CK2.
 MOD_RES 293 293 Phosphoserine; by CK2.
 MOD_RES 299 299 Phosphothreonine; by CK2.
 CROSSLNK 21 21 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 22 22 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; ANK repeat; Complete proteome; Cytoplasm; Disease mutation; Ectodermal dysplasia; Host-virus interaction; Hydroxylation; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 317 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0033256; C:I-kappaB/NF-kappaB complex; TAS:BHF-UCL.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0051059; F:NF-kappaB binding; IDA:MGI.
 GO:0008139; F:nuclear localization sequence binding; IPI:UniProtKB.
 GO:0006915; P:apoptotic process; TAS:ProtInc.
 GO:0070417; P:cellular response to cold; NAS:BHF-UCL.
 GO:0007253; P:cytoplasmic sequestering of NF-kappaB; IMP:BHF-UCL.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Compara.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; TAS:Reactome.
 GO:0043392; P:negative regulation of DNA binding; NAS:UniProtKB.
 GO:0010888; P:negative regulation of lipid storage; IMP:BHF-UCL.
 GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; IMP:BHF-UCL.
 GO:0045638; P:negative regulation of myeloid cell differentiation; IEA:Compara.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:MGI.
 GO:0045746; P:negative regulation of Notch signaling pathway; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IEA:Compara.
 GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IEA:Compara.
 GO:0032270; P:positive regulation of cellular protein metabolic process; IMP:BHF-UCL.
 GO:0010875; P:positive regulation of cholesterol efflux; IMP:BHF-UCL.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0000060; P:protein import into nucleus, translocation; IEA:Compara.
 GO:0042127; P:regulation of cell proliferation; IEA:Compara.
 GO:0043330; P:response to exogenous dsRNA; IEA:Compara.
 GO:0032495; P:response to muramyl dipeptide; IEA:Compara.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR002110; Ankyrin_rpt.
 IPR020683; Ankyrin_rpt-contain_dom. 

Pfam

 PF00023; Ank 

SMART

 SM00248; ANK 

PROSITE

 PS50297; ANK_REP_REGION
 PS50088; ANK_REPEAT 

PRINTS

 PR01415; ANKYRIN.