NFKBIA
NF-kappa-B inhibitor alpha
Also known as: IkappaBalpha, IKBA, IKBA_HUMAN, MAD-3, NFKBI
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P25963
- Gene
- NFKBIA
- Ensembl
- ENSG00000100906
- Chromosome
- 14
- Canonical length
- 317 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Cytosol
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
317 residues, UniProt reviewed canonical sequence.
>P25963|NFKBIA
1 MFQAAERPQE WAMEGPRDGL KKERLLDDRH DSGLDSMKDE EYEQMVKELQ EIRLEPQEVP
61 RGSEPWKQQL TEDGDSFLHL AIIHEEKALT MEVIRQVKGD LAFLNFQNNL QQTPLHLAVI
121 TNQPEIAEAL LGAGCDPELR DFRGNTPLHL ACEQGCLASV GVLTQSCTTP HLHSILKATN
181 YNGHTCLHLA SIHGYLGIVE LLVSLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG
241 ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEFTE
301 DELPYDDCVF GGQRLTLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against NFKBIA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.38
- Highest tissue expression
- 961 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 961 nTPM
- lung: 357 nTPM
- urinary bladder: 330 nTPM
- adipose tissue: 270 nTPM
- skin: 253 nTPM
- spleen: 219 nTPM
Single-cell type
- neutrophils: 7,959 nCPM
- epididymal basal cells: 3,421 nCPM
- basal keratinocytes: 2,778 nCPM
- monocytes: 2,714 nCPM
- mast cells: 2,589 nCPM
- suprabasal keratinocytes: 2,318 nCPM
Immune cell
- neutrophil: 749 nTPM
- total PBMC: 370 nTPM
- classical monocyte: 347 nTPM
- myeloid DC: 332 nTPM
- naive B-cell: 261 nTPM
- basophil: 257 nTPM
Brain region
- medulla oblongata: 79 nTPM
- cerebral cortex: 74 nTPM
- thalamus: 66 nTPM
- white matter: 58 nTPM
- choroid plexus: 57 nTPM
- pons: 54 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about NFKBIA.
Disease | AllUniProt
Conditions NFKBIA is implicated in, by any mechanism.
- Ectodermal dysplasia and immunodeficiency 2 (EDAID2) MIM:612132
Disease | GeneticClinVar
11 pathogenic / likely-pathogenic of 390 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Ectodermal dysplasia and immunodeficiency 2
Disease | ImmuneIEDB
Conditions an epitope on NFKBIA was assayed in.
- skin melanoma T cell
- type 1 diabetes mellitus T cell
- renal cell carcinoma T cell
- breast cancer T cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.19
- gnomAD pLI
- 0.99
- gnomAD missense Z
- 0.71
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- B cell receptor signaling pathway
- canonical NF-kappaB signal transduction
- cellular response to cold
- interleukin-1-mediated signaling pathway
- lipopolysaccharide-mediated signaling pathway
- negative regulation of canonical NF-kappaB signal transduction
- negative regulation of cholesterol transport
- negative regulation of cytokine production involved in inflammatory response
- negative regulation of lipid storage
- negative regulation of macrophage derived foam cell differentiation
- negative regulation of myeloid cell differentiation
- negative regulation of NF-kappaB transcription factor activity
- negative regulation of Notch signaling pathway
- negative regulation of protein import into nucleus
- negative regulation of transcription by RNA polymerase II
- non-canonical NF-kappaB signal transduction
- Notch signaling pathway
- nucleotide-binding oligomerization domain containing 1 signaling pathway
- nucleotide-binding oligomerization domain containing 2 signaling pathway
- positive regulation of inflammatory response
- positive regulation of transcription by RNA polymerase II
- positive regulation of transcription initiation by RNA polymerase II
- protein import into nucleus
- regulation of cell population proliferation
- response to exogenous dsRNA
- response to muramyl dipeptide
- response to muscle stretch
- toll-like receptor 4 signaling pathway
- tumor necrosis factor-mediated signaling pathway
Molecular functions
- enzyme binding
- identical protein binding
- molecular sequestering activity
- NF-kappaB binding
- nuclear localization sequence binding
- protein sequestering activity
- transcription regulator inhibitor activity
- ubiquitin protein ligase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of NFKBIA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads NFKBIA as an antibody target. Whether an autoantibody or antibody against NFKBIA could matter depends on whether native NFKBIA is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NFKBIA is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label NFKBIA as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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