NFKBIA (NFKB inhibitor alpha)

Gene

• Entrez ID: 4792
• Gene name: NFKB inhibitor alpha
• Gene symbol: NFKBIA
• Synonyms: EDAID2, IKBA, MAD-3, NFKBI
• Chromosome: 14
• Chromosome location: 14q13.2
• Summary: This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease. [provided by RefSeq, Aug 2011]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28933100	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs121913664	C>T	Pathogenic	Stop gained, coding sequence variant
rs121913665	C>A	Pathogenic	Stop gained, coding sequence variant
rs142195196	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs886041411	G>A	Pathogenic	Coding sequence variant, stop gained
rs1555342918	C>T	Pathogenic	Stop gained, coding sequence variant
rs1566591073	A>C,T	Pathogenic	Coding sequence variant, missense variant
rs1566591076	G>T	Pathogenic	Coding sequence variant, missense variant
rs1566591082	G>A,C	Pathogenic	Synonymous variant, coding sequence variant, missense variant
rs1566591086	T>C	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006695	hsa-miR-30e-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	22156201
MIRT017719	hsa-miR-335-5p	Microarray	18185580
MIRT030500	hsa-miR-24-3p	Microarray	19748357
MIRT052129	hsa-let-7b-5p	CLASH	23622248
MIRT437422	hsa-miR-196a-5p	Luciferase reporter assay, qRT-PCR, Western blot	24504166
MIRT438759	hsa-miR-126-3p	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	23285182
MIRT733118	hsa-miR-891a-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	26446987
MIRT733709	hsa-miR-93-5p	Microarray, qRT-PCR	28057018
MIRT734780	hsa-miR-942-5p	Luciferase reporter assay, Microarray, Western blot	27440900
MIRT735421	hsa-miR-381-3p	Luciferase reporter assay, qRT-PCR, Western blot	27312547

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Activation	12885753
NFKB1	Repression	11744993
NFKB1	Unknown	10454561;15499023;17876798
PPARA	Activation	14976045
PPARA	Unknown	11981037
RELA	Activation	12885753
RELA	Repression	11744993
RELA	Unknown	15499023;17876798

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	9452483, 9520446, 9865693, 10498867, 10733566, 12482991, 12486103, 12730857, 14685242, 14743216, 15601829, 15799966, 16126728, 16195219, 16286467, 16319058, 16365431, 16683270, 16951195, 17003112, 17301240, 17318178, 17612295, 18045535, 18539148, 18632959, 18922877, 19008357, 191969
GO:0005634	Component	Nucleus	IDA	7679069, 16648481
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	3140380
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0006606	Process	Protein import into nucleus	IEA
GO:0006915	Process	Apoptotic process	TAS	10747850
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	IDA	25038658
GO:0007253	Process	Cytoplasmic sequestering of NF-kappaB	IMP	16938301
GO:0008134	Function	Transcription factor binding	TAS	10928981
GO:0008139	Function	Nuclear localization sequence binding	IPI	1493333
GO:0010745	Process	Negative regulation of macrophage derived foam cell differentiation	IMP	16938301
GO:0010875	Process	Positive regulation of cholesterol efflux	IMP	16938301
GO:0010888	Process	Negative regulation of lipid storage	IMP	16938301
GO:0016032	Process	Viral process	IEA
GO:0016579	Process	Protein deubiquitination	TAS
GO:0019899	Function	Enzyme binding	IPI	16648481
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	9859996
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IEA
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IDA	11931770
GO:0032270	Process	Positive regulation of cellular protein metabolic process	IMP	16938301
GO:0032495	Process	Response to muramyl dipeptide	IEA
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IDA	25038658
GO:0033256	Component	I-kappaB/NF-kappaB complex	TAS	16938301
GO:0034142	Process	Toll-like receptor 4 signaling pathway	IEA
GO:0035994	Process	Response to muscle stretch	IEA
GO:0042127	Process	Regulation of cell population proliferation	IEA
GO:0042802	Function	Identical protein binding	IPI	16951195
GO:0042994	Process	Cytoplasmic sequestering of transcription factor	IDA	1493333
GO:0043066	Process	Negative regulation of apoptotic process	TAS
GO:0043330	Process	Response to exogenous dsRNA	IEA
GO:0043392	Process	Negative regulation of DNA binding	NAS	3140380
GO:0045638	Process	Negative regulation of myeloid cell differentiation	IEA
GO:0045746	Process	Negative regulation of Notch signaling pathway	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	19245366, 23729669
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	16938301
GO:0050729	Process	Positive regulation of inflammatory response	IDA	25038658
GO:0051059	Function	NF-kappaB binding	IDA	11931770
GO:0051059	Function	NF-kappaB binding	IPI	7739562
GO:0070417	Process	Cellular response to cold	NAS	16750872
GO:0070427	Process	Nucleotide-binding oligomerization domain containing 1 signaling pathway	IEA
GO:0070431	Process	Nucleotide-binding oligomerization domain containing 2 signaling pathway	IEA
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:1901222	Process	Regulation of NIK/NF-kappaB signaling	NAS	3140380

Other IDs

• MIM: 164008
• HGNC: 7797
• e!Ensembl: ENSG00000100906

Protein

• UniProt ID: P25963
• Protein name: NF-kappa-B inhibitor alpha (I-kappa-B-alpha) (IkB-alpha) (IkappaBalpha) (Major histocompatibility complex enhancer-binding protein MAD3)
• Protein 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.
• PDB: 1IKN, 1NFI, 6TTU, 6Y1J
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00023	Ank	111 → 142	Ankyrin repeat	Repeat
  PF00023	Ank	143 → 175	Ankyrin repeat	Repeat
  PF00023	Ank	182 → 213	Ankyrin repeat	Repeat
  PF00023	Ank	216 → 248	Ankyrin repeat	Repeat

• Sequence:

  MFQAAERPQEWAMEGPRDGLKKERLLDDRHDSGLDSMKDEEYEQMVKELQEIRLEPQEVP
  RGSEPWKQQLTEDGDSFLHLAIIHEEKALTMEVIRQVKGDLAFLNFQNNLQQTPLHLAVI
  TNQPEIAEALLGAGCDPELRDFRGNTPLHLACEQGCLASVGVLTQSCTTPHLHSILKATN
  YNGHTCLHLASIHGYLGIVELLVSLGADVNAQEPCNGRTALHLAVDLQNPDLVSLLLKCG
  ADVNRVTYQGYSPYQLTWGRPSTRIQQQLGQLTLENLQMLPESEDEESYDTESEFTEFTE
  DELPYDDCVFGGQRLTL

• Sequence length: 317