IKBKG

This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. A pseudogene highly similar to this locus is located in an adjacent region of the X chromosome. [provided by RefSeq, Mar 2016]

Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Gamma

Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:9751060, PubMed:14695475, PubMed:20724660).

Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:21606507, PubMed:27777308, PubMed:19185524, PubMed:33567255).

Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin (PubMed:16547522, PubMed:18287044, PubMed:27777308, PubMed:19033441, PubMed:21606507, PubMed:19185524).

Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3 (PubMed:19854139).

Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (PubMed:20724660).

(Microbial infection) Also considered to be a mediator for HTLV-1 Tax oncoprotein activation of NF-kappa-B.

Anoikis Source: BHF-UCL
Apoptotic process Source: ProtInc
Cellular response to DNA damage stimulus Source: UniProtKB
Establishment of vesicle localization Source: UniProtKB
I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Immune response Source: ProtInc
Inflammatory response Source: UniProtKB
Innate immune response Source: UniProtKB
Negative regulation of neuron death Source: ParkinsonsUK-UCL
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of macroautophagy Source: BHF-UCL
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Positive regulation of T cell receptor signaling pathway Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Protein-containing complex assembly Source: UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signaling Source: GO_Central
Response to virus Source: UniProtKB
T cell receptor signaling pathway Source: UniProtKB

Nucleus; Cytoplasm. Sumoylated NEMO accumulates in the nucleus in response to genotoxic stress.

Ectodermal dysplasia and immunodeficiency 1 (EDAID1):
A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDAID1 is an X-linked recessive disorder characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, and may be fatal in childhood.
Immunodeficiency 33 (IMD33):
An X-linked recessive disorder characterized by variably impaired immunologic function and early-onset recurrent infections, usually due to pneumococcus, H. influenzae, and atypical mycobacteria. Features of hypohidrotic ectodermal dysplasia are generally not present, although some patients may have conical teeth or hypodontia.
Incontinentia pigmenti (IP):
A genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.

Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.
Polyubiquitinated on Lys-285 through 'Lys-63'; the ubiquitination is mediated by NOD2 and RIPK2 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway. Polyubiquitinated on Lys-399 through 'Lys-63'; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway. Monoubiquitinated on Lys-277 and Lys-309; promotes nuclear export. Polyubiquitinated through 'Lys-27' by TRIM23; involved in antiviral innate and inflammatory responses. Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-264, Lys-277, Lys-285, Lys-292, Lys-302, Lys-309 and Lys-326; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation. Deubiquitinated by USP10 in a TANK-dependent and -independent manner, leading to the negative regulation of NF-kappa-B signaling upon DNA damage (PubMed:25861989). Ubiquitinated at Lys-326 by MARCHF2 following bacterial and viral infection which leads to its degradation (PubMed:32935379).
Sumoylated on Lys-277 and Lys-309 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.
Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity.
(Microbial infection) Cleaved by hepatitis A virus (HAV) protease 3C allowing the virus to disrupt the host innate immune signaling.
(Microbial infection) Polyubiquitinated on Lys-309 and Lys-321 via 'Lys-27'-linked ubiquitin by Shigella flexneri E3 ubiquitin-protein ligase ipah9.8, leading to its degradation by the proteasome.
(Microbial infection) Polyubiquitination through 'Lys-63' is interrupted by interaction with SARS coronavirus-2/SARS-CoV-2 virus protein ORF9B which inhibits the NF-kappa-B pathway.