IKBKG; AMCBX1; FIP-3; FIP3; Fip3p; IKK-gamma; IP; IP1; IP2; IPD2; NEMO; Ikkgamma Protein; Ikkg Protein

For Research Use Only. Not for use in diagnostic procedures.

Chromosome: X; NC_000023.10 (153769419..153796804). Location: Xq28

Sf9 insect cells

50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol.

Store product at -70 degree C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles.

Small volumes of IKK gamma recombinant protein vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.

Recombinant full-length human IKK gamma was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag.

Scientific Background: IKKgamma is a serine/threonine protein kinase that phosphorylates the I-kappa-B protein which is an inhibitor of the transcription factor NF-kappa-B complex. Phosphorylation of I-kappa-B protein triggers the degradation of the inhibitor via the ubiquitination pathway, thereby activating NF-kappa-B complex. IKKgamma forms dimers and trimers and interacts preferentially with IKKbeta but not IKKalpha (1). IKKgamma associates with activated ATM after the induction of DNA double-strand breaks (2). ATM phosphorylates serine-85 of IKKgamma to promote its ubiquitin-dependent nuclear export.

Cellular Proteins; Signaling Proteins - Cellular Proteins

Western Blot (WB)

~73 kDa

inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma

NF-kappa-B essential modulator; IKKG; IKKAP1; incontinentia pigmenti; IkB kinase gamma subunit; ikB kinase subunit gamma; NFkappaB essential modulator; NF-kappa-B essential modifier; I-kappa-B kinase subunit gamma; ikB kinase-associated protein 1; inhibitor of nuclear factor kappa-B kinase subunit gamma

NF-kappa-B essential modulator

FIP3; NEMO; NEMO; IKKAP1; I-kappa-B kinase subunit gamma; IKK-gamma; IKKG??[Similar Products]

NEMO_HUMAN

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. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene highly similar to this locus is located in an adjacent region of the X chromosome. [provided by RefSeq, Aug 2011]

Function: 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. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity

By similarity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination. Ref.27 Ref.39 Ref.43

Subunit structure: Homodimer; disulfide-linked. Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Interacts with COPS3, CYLD, NALP2, TRPC4AP and LRDD. Interacts with ATM; the complex is exported from the nucleus. Interacts with TRAF6. Interacts with HTLV-1 Tax oncoprotein; the interaction activates IKBKG. Interacts with TANK; the interaction is enhanced by IKBKE and TBK1. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with ZFAND5. Interacts with RIPK2. Interacts with TNIP1 and TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination of IKBKG

By similarity. Interacts with TNFAIP3; the interaction is induced by TNF stimulation and by polyubiquitin. Binds polyubiquitin; the interaction is mediated by two domains; reports about the binding to 'Lys-63'-linked and/or linear polyubiquitin, respective binding affinities and stoichiometry are conflicting. Interacts with Shigella flexneri ipah9.8; the interaction promotes TNIP1-dependent 'Lys-27'-linked polyubiquitination of IKBKG which perturbs NF-kappa-B activation during bacterial infection. Interacts with NLRP10. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.22 Ref.24 Ref.25 Ref.28 Ref.31 Ref.33 Ref.34 Ref.35 Ref.42 Ref.48 Ref.52 Ref.54 Ref.65

Subcellular location: Cytoplasm. Nucleus. Note: Sumoylated NEMO accumulates in the nucleus in response to genotoxic stress. Ref.19

Tissue specificity: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Domain: The leucine-zipper domain and the C2HC-type zinc-finger are essential for polyubiquitin binding and for the activation of IRF3. Ref.39 Ref.53

Post-translational modification: 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. 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.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. Ref.19Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity.

Involvement in disease: Ectodermal dysplasia, anhidrotic, with immunodeficiency X-linked (EDAID) [MIM:300291]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.29 Ref.47 Ref.55 Ref.56 Ref.58 Ref.59 Ref.60 Ref.62Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis and lymphedema (OLEDAID) [MIM:300301]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by the association of anhidrotic ectodermal dysplasia with severe immunodeficiency, osteopetrosis and lymphedema.Note: The disease is caused by mutations affecting the gene represented in this entry.Immunodeficiency, NEMO-related, without anhidrotic ectodermal dysplasia (NEMOID) [MIM:300584]: Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased susceptibility to infections. Patients suffer from multiple episodes of infectious diseases.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.62 Ref.63X-linked familial atypical micobacteriosis 1 (AMCBX1) [MIM:300636]: X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.55 Ref.64Recurrent isolated invasive pneumococcal disease 2 (IPD2) [MIM:300640]: Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.66Incontinentia pigmenti (IP) [MIM:308300]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.38 Ref.42 Ref.55 Ref.57 Ref.61 Ref.65 Ref.66

Sequence similarities: Contains 1 C2HC-type zinc finger.

1. Rothwarf, D. M. et al: IKK-gamma is an essential regulatory subunit of the I-kappa-B kinase complex. Nature 395: 297-300, 1998.
2. Wu, Z-H. et al: Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science 311: 1141-1146, 2006.

All of MyBioSource's Products are for scientific laboratory research purposes and are not for diagnostic, therapeutics, prophylactic or in vivo use. Through your purchase, you expressly represent and warrant to MyBioSource that you will properly test and use any Products purchased from MyBioSource in accordance with industry standards. MyBioSource and its authorized distributors reserve the right to refuse to process any order where we reasonably believe that the intended use will fall outside of our acceptable guidelines.

While every efforts were made to ensure the accuracy of the information provided in this datasheet, MyBioSource will not be liable for any omissions or errors contained herein. MyBioSource reserves the right to make changes to this datasheet at any time without prior notice.

It is the responsibility of the customer to report product performance issues to MyBioSource within 30 days of receipt of the product. Please visit our Terms & Conditions page for more information.