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NF-kappa-B essential modulator; NEMO; NF-kappa-B essential modifier; inhibitor of nuclear factor kappa-B kinase subunit gamma; IkB kinase subunit gamma; I-kappa-B kinase gamma; IKK-gamma; IKKG; IkB kinase-associated protein 1; IKKAP1;FIP-3 (IKBKG, FIP3, NEMO)

Function: -regulatory subunit of the IKK core complex - does not have kinase activity - 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 (putative) - phosphorylation at Ser-68 attenuates aminoterminal homodimerization - polyubiquitinated on Lys-285 through Lys-63; ubiquitination is mediated by NOD2 & RIPK2 - polyubiquitinated on Lys-399 through Lys-63; ubiquitination is mediated by BCL10, MALT1 & TRAF6 - ubiquitination probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins - ubiquitination activates the NF-kappa-B pathway - sumoylated on Lys-277 & Lys-309 by SUMO1; this results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues - mono-ubiquitinated on Lys-277 & Lys-309; promotes nuclear export - part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG & CREBBP - interacts with COPS3, CYLD, NALP2, TRPC4AP & 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 & TBK1 - part of a ternary complex consisting of TANK, IKBKB & IKBKG Structure: - homodimer; disulfide-linked - contains 1 C2HC-type Zn+2 finger Compartment: cytoplasm. nucleus Expression: - expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas Pathology: - defects in IKBKG are the cause of a) X-linked anhidrotic ectodermal dysplasia with immunodeficiency b) anhidrotic ectodermal dysplasia with immunodeficiency- osteopetrosis-lymphedema c) isolated immunodeficiency (without ectodermal dysplasia) d) X-linked susceptibility to mycobacterial disease type 1 e) recurrent isolated invasive pneumococcal disease type 2 f) incontinentia pigmenti

Related

ikbkg gene

General

C2H2 type zinc finger protein nuclear protein phosphoprotein

Properties

SIZE: entity length = 419 aa MW = 48 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S31} Ser phosphorylation site {S43} CHUK/IKBKB interaction {44-111} coiled coil {49-356} MOTIF: cysteine residue {C54} MODIFICATION: cysteine residue {C-INTERCHAIN} Ser phosphorylation site {S68} Ser phosphorylation site {S85} Self-association {246-365} MOTIF: leucine zipper SITE: 322-343 FOR-BINDING-VIA: leucine zipper cysteine residue {C347} MODIFICATION: cysteine residue {C-INTERCHAIN} Ser phosphorylation site {S376} Ser phosphorylation site {S377} CYLD interaction {382-419} MOTIF: Ser phosphorylation site {S387} Zn finger C2HC-type SITE: 396-417 EFFECTOR-BOUND: Zn+2

Database Correlations

OMIM correlations UniProt Q9Y6K9 Entrez Gene 8517 Kegg hsa:8517

References

  1. Rothwarf DM et al IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature 395:297-300, 1998 PMID: 9751060
  2. Yamaoka S et al Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Cell 93:1231-40, 1998 PMID: 9657155
  3. UniProt :accession Q9Y6K9
  4. IKBKGbase; Note: IKBKG mutation db http://bioinf.uta.fi/IKBKGbase/
  5. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=IKBKG

Component-of

IkB kinase complex