NFKBIA
entrez
4792
canonical
uniprot
P25963
canonical
ensembl
ENSG00000100906
resolver
ensp
ENSP00000216797
resolver
enst
ENST00000216797
resolver
genesymbol
NFKBIA
resolver
genesymbol_syn
IKBA
resolver
genesymbol_syn
MAD3
resolver
genesymbol_syn
NFKBI
resolver
hgnc
HGNC:7797
resolver
uniprot
B2R8L6
resolver
uniprot_entry
IKBA_HUMAN
resolver
uniprot_sec
B2R8L6
resolver
amino_acid_sequence
MFQAAERPQEWAMEGPRDGLKKERLLDDRHDSGLDSMKDEEYEQMVKELQEIRLEPQEVPRGSEPWKQQLTEDGDSFLHLAIIHEEKALTMEVIRQVKGDLAFLNFQNNLQQTPLHLAVITNQPEIAEALLGAGCDPELRDFRGNTPLHLACEQGCLASVGVLTQSCTTPHLHSILKATNYNGHTCLHLASIHGYLGIVELLVSLGADVNAQEPCNGRTALHLAVDLQNPDLVSLLLKCGADVNRVTYQGYSPYQLTWGRPSTRIQQQLGQLTLENLQMLPESEDEESYDTESEFTEFTEDELPYDDCVFGGQRLTL
uniprot
proteins
disease_involvement
DISEASE: Ectodermal dysplasia and immunodeficiency 2 (EDAID2) [MIM:612132]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. This form of ectodermal dysplasia is associated with decreased production of pro-inflammatory cytokines and certain interferons, rendering patients susceptible to infection. EDAID2 inheritance is autosomal dominant. {ECO:0000269|PubMed:14523047, ECO:0000269|PubMed:18412279}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:36651806, PubMed:7479976). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed:7479976, PubMed:7628694, PubMed:7796813, PubMed:7878466). {ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:36651806, ECO:0000269|PubMed:7479976, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813, ECO:0000269|PubMed:7878466}.
uniprot
proteins
mass_dalton
35609
uniprot
proteins
mutagenesis
MUTAGEN 21; /note="K->R: Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-22. Does not affect activation by FK506."; /evidence="ECO:0000269|PubMed:11124955, ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:7479976, ECO:0000269|PubMed:8657102"; MUTAGEN 22; /note="K->R: Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-21. Does not affect activation by FK506."; /evidence="ECO:0000269|PubMed:11124955, ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:7479976, ECO:0000269|PubMed:8657102"; MUTAGEN 31; /note="D->A: Loss of phosphorylation; when associated with A-35."; /evidence="ECO:0000269|PubMed:8657102"; MUTAGEN 32; /note="S->A: Loss of phosphorylation, ubiquitination and degradation; when associated with A-36. Abolished activation by FK506."; /evidence="ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10574930, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813, ECO:0000269|PubMed:7878466, ECO:0000269|PubMed:8631829, ECO:0000269|PubMed:8657102"; MUTAGEN 32; /note="S->E: Mimics phosphorylation; promoting ubiquitination and degradation; when associated with E-36."; /evidence="ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813"; MUTAGEN 32; /note="S->T: Decrease in phosphorylation and degradation; when associated with T-36."; /evidence="ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:8657102"; MUTAGEN 35; /note="D->A: Loss in phosphorylation; when associated with A-31."; /evidence="ECO:0000269|PubMed:8657102"; MUTAGEN 35; /note="D->G: No change neither in phosphorylation, nor on degradation."; /evidence="ECO:0000269|PubMed:8657102"; MUTAGEN 36; /note="S->A: Loss of phosphorylation, ubiquitination, and degradation; when associated with A-32. Does not affect activation by FK506."; /evidence="ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813, ECO:0000269|PubMed:7878466, ECO:0000269|PubMed:8631829, ECO:0000269|PubMed:8657102"; MUTAGEN 36; /note="S->E: Mimics phosphorylation; promoting ubiquitination and degradation; when associated with E-32."; /evidence="ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813"; MUTAGEN 36; /note="S->T: Decrease in phosphorylation and degradation; when associated with T-32."; /evidence="ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:8657102"; MUTAGEN 38; /note="K->R: No change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-47."; /evidence="ECO:0000269|PubMed:7479976"; MUTAGEN 42; /note="Y->F: No phosphorylation."; /evidence="ECO:0000269|PubMed:8797825"; MUTAGEN 45..52; /note="MVKELQEI->AAKEAQEA: No nuclear export."; /evidence="ECO:0000269|PubMed:10655476"; MUTAGEN 47; /note="K->R: Little change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-38."; /evidence="ECO:0000269|PubMed:7479976"; MUTAGEN 115..120; /note="LHLAVI->AHAAVA: Greatly reduced nuclear localization. Great reduction in its ability to inhibit DNA binding of RELA."; /evidence="ECO:0000269|PubMed:9566872"; MUTAGEN 210; /note="N->A: Almost abolished ability to inhibit NF-kappa-BDNA-binding activity; when associated with A-244."; /evidence="ECO:0000269|PubMed:17003112"; MUTAGEN 234; /note="S->A: No inducible ubiquitination nor protein degradation."; /evidence="ECO:0000269|PubMed:8657102"; MUTAGEN 244; /note="N->A: Almost abolished ability to inhibit NF-kappa-BDNA-binding activity; when associated with A-210."; /evidence="ECO:0000269|PubMed:17003112"; MUTAGEN 262; /note="S->A: No inducible ubiquitination nor protein degradation."; /evidence="ECO:0000269|PubMed:8657102"; MUTAGEN 263; /note="T->A: No inducible ubiquitination nor protein degradation."; /evidence="ECO:0000269|PubMed:8657102
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Ser-32 and Ser-36 by IKKA/CHUK, IKKB/IKBKB and IKKE/IKBKE; disables inhibition of NF-kappa-B DNA-binding activity (PubMed:10329681, PubMed:10882136, PubMed:7628694, PubMed:7796813, PubMed:7878466, PubMed:8631829, PubMed:9701247). Phosphorylation at positions 32 and 36 is prerequisite to recognition by the SCF(FBXW11) and SCF(BTRC) complexes, leading to polyubiquitination and subsequent degradation (PubMed:10329681, PubMed:7628694, PubMed:8631829, PubMed:9701247). Phosphorylated at Ser-32 in response to FK506 treatment: phosphorylation is independent of IKKA/CHUK and IKKB/IKBKB and promotes NFKBIA degradation, followed by NF-kappa-B activation (PubMed:10574930). Phosphorylated at Tyr-42: its effect is however unclear (PubMed:8797825, PubMed:8940099). According to a report, phosphorylation at Tyr-42 activates NF-kappa-B without triggering proteolytic degradation of NFKBIA (PubMed:8797825). According to another publication, phosphorylation at Tyr-42 inhibits NF-kappa-B activity by preventing phosphorylation at Ser-32 and Ser-36 and subsequent ubiquitination and degradation (PubMed:8940099). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10574930, ECO:0000269|PubMed:10882136, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813, ECO:0000269|PubMed:7878466, ECO:0000269|PubMed:8631829, ECO:0000269|PubMed:8797825, ECO:0000269|PubMed:8940099, ECO:0000269|PubMed:9701247}.; PTM: Polyubiquitinated at Lys-21 and/or Lys-22 following phosphorylation at Ser-32 and Ser-36 (PubMed:10329681, PubMed:20347421, PubMed:7479976, PubMed:8631829, PubMed:9701247). Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3 (PubMed:10329681, PubMed:20347421, PubMed:7479976). 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 (PubMed:10437795, PubMed:20347421). The resulting polyubiquitination leads to protein degradation (PubMed:20347421, PubMed:7479976, PubMed:7628694). Also ubiquitinated by the SCF(BTRC) complex following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (PubMed:10644755). Deubiquitinated by USP38, leading to NF-kappa-B inhibition (PubMed:36651806). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10437795, ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:36651806, ECO:0000269|PubMed:7479976, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:8631829, ECO:0000269|PubMed:9701247}.; PTM: 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. {ECO:0000269|PubMed:11124955, ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:20504922}.; PTM: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:17003112}.; PTM: (Microbial infection) Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation. {ECO:0000269|PubMed:20504922}.
uniprot
proteins
protein_family
NF-kappa-B inhibitor family
uniprot
proteins
pubmed
10329681
uniprot
proteins
pubmed
10437795
uniprot
proteins
pubmed
10454581
uniprot
proteins
pubmed
10574930
uniprot
proteins
pubmed
10637284
uniprot
proteins
pubmed
10644755
uniprot
proteins
pubmed
10655476
uniprot
proteins
pubmed
10657303
uniprot
proteins
pubmed
10783893
uniprot
proteins
pubmed
10882136
uniprot
proteins
pubmed
11124955
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
14523047
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
1493333
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16648481
uniprot
proteins
pubmed
17003112
uniprot
proteins
pubmed
17956732
uniprot
proteins
pubmed
1829648
uniprot
proteins
pubmed
18412279
uniprot
proteins
pubmed
18577712
uniprot
proteins
pubmed
20347421
uniprot
proteins
pubmed
20356841
uniprot
proteins
pubmed
20504922
uniprot
proteins
pubmed
23469069
uniprot
proteins
pubmed
23675531
uniprot
proteins
pubmed
36651806
uniprot
proteins
pubmed
37643469
uniprot
proteins
pubmed
7479976
uniprot
proteins
pubmed
7628694
uniprot
proteins
pubmed
7796813
uniprot
proteins
pubmed
7878466
uniprot
proteins
pubmed
8622692
uniprot
proteins
pubmed
8631829
uniprot
proteins
pubmed
8657102
uniprot
proteins
pubmed
8657113
uniprot
proteins
pubmed
8797825
uniprot
proteins
pubmed
8940099
uniprot
proteins
pubmed
9566872
uniprot
proteins
pubmed
9701247
uniprot
proteins
pubmed
9751059
uniprot
proteins
pubmed
9865693
uniprot
proteins
pubmed
9865694
uniprot
proteins
sequence_length
317
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10655476}. Nucleus {ECO:0000269|PubMed:10655476, ECO:0000269|PubMed:16648481, ECO:0000269|PubMed:9566872}. Note=Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export. {ECO:0000269|PubMed:10655476, ECO:0000269|PubMed:9566872}.
uniprot
proteins