ID NEMO_HUMAN STANDARD; PRT; 419 AA. AC Q9Y6K9; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 13-JUN-2006, entry version 62. DE NF-kappa-B essential modulator (NEMO) (NF-kappa-B essential modifier) DE (Inhibitor of nuclear factor kappa-B kinase gamma subunit) (IkB kinase DE gamma subunit) (I-kappa-B kinase gamma) (IKK-gamma) (IKKG) (IkB DE kinase-associated protein 1) (IKKAP1) (FIP-3). GN Name=IKBKG; Synonyms=FIP3, NEMO; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=99128359; PubMed=9927690; DOI=10.1073/pnas.96.3.1042; RA Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A., RA Wallach D., Horwitz M.S.; RT "Identification of a cell protein (FIP-3) as a modulator of NF-kappaB RT activity and as a target of an adenovirus inhibitor of tumor necrosis RT factor alpha-induced apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 96:1042-1047(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Mammary cancer; RX MEDLINE=99189402; PubMed=10087442; DOI=10.1159/000025378; RA Jin D.-Y., Jeang K.-T.; RT "Isolation of full-length cDNA and chromosomal localization of human RT NF-kappaB modulator NEMO to Xq28."; RL J. Biomed. Sci. 6:115-120(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Cervix carcinoma; RX MEDLINE=98421680; PubMed=9751060; DOI=10.1038/26261; RA Rothwarf D.M., Zandi E., Natoli G., Karin M.; RT "IKK-gamma is an essential regulatory subunit of the IkappaB kinase RT complex."; RL Nature 395:297-300(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT IP2 VAL-407. RX MEDLINE=20296353; PubMed=10839543; DOI=10.1038/35013114; RA Smahi A., Courtois G., Vabres P., Yamaoka S., Heuertz S., Munnich A., RA Israel A., Heiss N.S., Klauck S.M., Kioschis P., Wiemann S., RA Poustka A., Esposito T., Bardaro T., Gianfrancesco F., Ciccodicola A., RA D'Urso M., Woffendin H., Jakins T., Donnai D., Stewart H., RA Kenwrick S.J., Aradhya S., Yamagata T., Levy M., Lewis R.A., RA Nelson D.L.; RT "Genomic rearrangement in NEMO impairs NF-kappaB activation and is a RT cause of incontinentia pigmenti."; RL Nature 405:466-472(2000). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Astrocytoma; RX MEDLINE=20403900; PubMed=10944468; DOI=10.1006/bbrc.2000.3282; RA Ye Z., Connor J.R.; RT "cDNA cloning by amplification of circularized first strand cDNAs RT reveals non-IRE-regulated iron-responsive mRNAs."; RL Biochem. Biophys. Res. Commun. 275:223-227(2000). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, Placenta, and Skin; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 51-419, AND PROTEIN SEQUENCE OF 144-159. RC TISSUE=Cervix carcinoma; RX MEDLINE=99108125; PubMed=9891086; RA Mercurio F., Murray B.W., Shevchenko A., Bennett B.L., Young D.B., RA Li J.W., Pascual G., Motiwala A., Zhu H., Mann M., Manning A.M.; RT "IkappaB kinase (IKK)-associated protein 1, a common component of the RT heterogeneous IKK complex."; RL Mol. Cell. Biol. 19:1526-1538(1999). RN [9] RP FUNCTION. RX MEDLINE=99292691; PubMed=10364167; DOI=10.1074/jbc.274.25.17402; RA Jin D.-Y., Giordano V., Kibler K.V., Nakano H., Jeang K.-T.; RT "Role of adapter function in oncoprotein-mediated activation of NF- RT kappaB: human T-cell leukemia virus type I Tax interacts directly with RT IkappaB kinase gamma."; RL J. Biol. Chem. 274:17402-17405(1999). RN [10] RP INTERACTION WITH COPS3. RX PubMed=11418127; DOI=10.1016/S0014-5793(01)02535-2; RA Hong X., Xu L.-G., Li X., Zhai Z., Shu H.-B.; RT "CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced RT NF-kappaB activation."; RL FEBS Lett. 499:133-136(2001). RN [11] RP SUBUNIT OF THE IKK COMPLEX. RX MEDLINE=21264955; PubMed=11080499; DOI=10.1074/jbc.M008353200; RA Li X.-H., Fang X., Gaynor R.B.; RT "Role of ikkgamma/nemo in assembly of the IkappaB kinase complex."; RL J. Biol. Chem. 276:4494-4500(2001). RN [12] RP SUBUNIT OF A COMPLEX CONTAINING CREBBP; NCOA2; NCOA3; IKKA AND IKKB. RX MEDLINE=21968797; PubMed=11971985; RX DOI=10.1128/MCB.22.10.3549-3561.2002; RA Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., RA O'Malley B.W.; RT "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator RT activity by I kappa B kinase."; RL Mol. Cell. Biol. 22:3549-3561(2002). RN [13] RP INTERACTION WITH CYLD. RX PubMed=12917691; DOI=10.1038/nature01802; RA Kovalenko A., Chable-Bessia C., Cantarella G., Israeel A., Wallach D., RA Courtois G.; RT "The tumour suppressor CYLD negatively regulates NF-kappaB signalling RT by deubiquitination."; RL Nature 424:801-805(2003). RN [14] RP INTERACTION WITH NALP2. RX PubMed=15456791; DOI=10.1074/jbc.M406741200; RA Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., RA Reed J.C.; RT "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates RT NF-kappaB and caspase-1 activation in macrophages."; RL J. Biol. Chem. 279:51897-51907(2004). RN [15] RP VARIANTS EDA-ID ARG-417 AND PHE-417. RX MEDLINE=20530236; PubMed=11047757; DOI=10.1086/316914; RA Zonana J., Elder M.E., Schneider L.C., Orlow S.J., Moss C., Golabi M., RA Shapira S.K., Farndon P.A., Wara D.W., Emmal S.A., Ferguson B.M.; RT "A novel X-linked disorder of immune deficiency and hypohidrotic RT ectodermal dysplasia is allelic to incontinentia pigmenti and due to RT mutations in IKK-gamma (NEMO)."; RL Am. J. Hum. Genet. 67:1555-1562(2000). RN [16] RP VARIANTS IP2 LYS-57 AND VAL-407. RX PubMed=11590134; DOI=10.1093/hmg/10.19.2171; RA Aradhya S., Woffendin H., Jakins T., Bardaro T., Esposito T., RA Smahi A., Shaw C., Levy M., Munnich A., D'Urso M., Lewis R.A., RA Kenwrick S., Nelson D.L.; RT "A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) RT gene accounts for the vast majority of incontinentia pigmenti RT mutations."; RL Hum. Mol. Genet. 10:2171-2179(2001). RN [17] RP VARIANTS EDA-ID PRO-175; PRO-227; GLY-288; ASN-311; ARG-417 AND RP PHE-417. RX MEDLINE=21135089; PubMed=11242109; DOI=10.1038/85837; RA Doeffinger R., Smahi A., Bessia C., Geissmann F., Feinberg J., RA Durandy A., Bodemer C., Kenwrick S.J., Dupuis-Girod S., Blanche S., RA Wood P., Rabia S.H., Headon D.J., Overbeek P.A., Le Deist F., RA Holland S.M., Belani K., Kumararatne D.S., Fischer A., Shapiro R., RA Conley M.E., Reimund E., Kalhoff H., Abinun M., Munnich A., RA Israael A., Courtois G., Casanova J.-L.; RT "X-linked anhidrotic ectodermal dysplasia with immunodeficiency is RT caused by impaired NF-kappa B signaling."; RL Nat. Genet. 27:277-285(2001). RN [18] RP VARIANTS EDA-ID VAL-406 AND ARG-417. RX MEDLINE=21163376; PubMed=11224521; DOI=10.1038/85277; RA Jain A., Ma C.A., Liu S., Brown M., Cohen J., Strober W.; RT "Specific missense mutations in NEMO result in hyper-IgM syndrome with RT hypohydrotic ectodermal dysplasia."; RL Nat. Immunol. 2:223-228(2001). RN [19] RP VARIANTS EDA-ID ARG-153 AND ARG-417. RX PubMed=12045264; RA Orange J.S., Brodeur S.R., Jain A., Bonilla F.A., Schneider L.C., RA Kretschmer R., Nurko S., Rasmussen W.L., Koehler J.R., Gellis S.E., RA Ferguson B.M., Strominger J.L., Zonana J., Ramesh N., Ballas Z.K., RA Geha R.S.; RT "Deficient natural killer cell cytotoxicity in patients with IKK- RT gamma/NEMO mutations."; RL J. Clin. Invest. 109:1501-1509(2002). RN [20] RP VARIANTS IP2 LYS-57; LYS-90 DEL; ASN-113 AND TRP-123, AND RP CHARACTERIZATION OF VARIANTS IP2 LYS-57; LYS-90 DEL; ASN-113 AND RP TRP-123. RX PubMed=15229184; DOI=10.1093/hmg/ddh192; RA Fusco F., Bardaro T., Fimiani G., Mercadante V., Miano M.G., Falco G., RA Israeel A., Courtois G., D'Urso M., Ursini M.V.; RT "Molecular analysis of the genetic defect in a large cohort of IP RT patients and identification of novel NEMO mutations interfering with RT NF-kappaB activation."; RL Hum. Mol. Genet. 13:1763-1773(2004). RN [21] RP VARIANTS EDA-ID ARG-153; ARG-417 AND TYR-417. RX PubMed=15100680; DOI=10.1016/j.jaci.2004.01.762; RA Orange J.S., Jain A., Ballas Z.K., Schneider L.C., Geha R.S., RA Bonilla F.A.; RT "The presentation and natural history of immunodeficiency caused by RT nuclear factor kappaB essential modulator mutation."; RL J. Allergy Clin. Immunol. 113:725-733(2004). RN [22] RP INVOLVEMENT IN IMMUNODEFICIENCY WITHOUT ANHIDROTIC ECTODERMAL RP DYSPLASIA. RX PubMed=15356572; DOI=10.1016/j.jaci.2004.06.052; RA Orange J.S., Levy O., Brodeur S.R., Krzewski K., Roy R.M., RA Niemela J.E., Fleisher T.A., Bonilla F.A., Geha R.S.; RT "Human nuclear factor kappa B essential modulator mutation can result RT in immunodeficiency without ectodermal dysplasia."; RL J. Allergy Clin. Immunol. 114:650-656(2004). CC -!- FUNCTION: Regulatory subunit part of the IKK-signalosome complex CC activation. Also considered to be a mediator for TAX activation of CC NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection CC from cytokine toxicity. CC -!- SUBUNIT: Interacts preferentially with IKK-beta but also able to CC interact with IKK-alpha, IKAP, RIP and MAP3K14/NIK. Found in a CC complex composed of NCOA2, NCOA3, IKKA, IKKB and CREBBP. Interacts CC with COPS3, CYLD, NALP2 and TRPC4AP. Binds to T-cell leukemia CC virus type I TAX oncoprotein. CC -!- INTERACTION: CC O15111:CHUK; NbExp=3; IntAct=EBI-81279, EBI-81249; CC Q9UNS2:COPS3; NbExp=1; IntAct=EBI-81279, EBI-350590; CC O14920:IKBKB; NbExp=2; IntAct=EBI-81279, EBI-81266; CC Q9Y6Q9:NCOA3; NbExp=1; IntAct=EBI-81279, EBI-81196; CC P12931:SRC; NbExp=1; IntAct=EBI-81279, EBI-621482; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal CC muscle, kidney and pancreas. CC -!- DISEASE: Defects in IKBKG are the cause of anhidrotic ectodermal CC dysplasia with immunodeficiency (EDA-ID) [MIM:300291]; also known CC as hypohidrotic ectodermal dysplasia with immunodeficiency (HED- CC ID). EDA-ID is a X-linked recessive disorder characterized by CC absence of sweat glands, sparse scalp hair, rare conical teeth and CC immunological abnormalities resulting in severe infectious CC diseases. CC -!- DISEASE: Defects in IKBKG are the cause of anhidrotic ectodermal CC dysplasia with immunodeficiency, osteopetrosis and lymphedema (OL- CC EDA-ID) [MIM:300301]. CC -!- DISEASE: Defects in IKBKG are a cause of immunodeficiency without CC anhidrotic ectodermal dysplasia [MIM:300584]; also called isolated CC immunodeficiency or pure immunodeficiency. CC -!- DISEASE: Defects in IKBKG are the cause of familial incontinentia CC pigmenti type II (IP2) [MIM:308300]. IP2 is a X-linked dominant CC disease causing death in male fetuses. In heterozygous female, it CC is characterized by disturbance of skin pigmentation sometimes CC associated with a variety of malformations of the eye, nails, CC teeth, skeleton, heart, and central nervous system. The prominent CC skin signs occur in four classic cutaneous stages: perinatal CC inflammatory vesicles, verrucous patches, a distinctive pattern of CC hyperpigmentation and dermal scarring. CC -!- WEB RESOURCE: NAME=GeneReviews; CC URL="http://www.genetests.org/query?gene=IKBKG". CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF062089; AAD12183.1; -; mRNA. DR EMBL; AF091453; AAD38081.1; -; mRNA. DR EMBL; AF074382; AAC36330.1; -; mRNA. DR EMBL; AJ271718; CAB93146.1; -; Genomic_DNA. DR EMBL; AF261086; AAF99679.1; -; mRNA. DR EMBL; BT019621; AAV38427.1; -; mRNA. DR EMBL; BC000299; AAH00299.1; -; mRNA. DR EMBL; BC012114; AAH12114.1; -; mRNA. DR EMBL; BC050612; AAH50612.1; -; mRNA. DR UniGene; Hs.43505; -. DR IntAct; Q9Y6K9; -. DR Ensembl; ENSG00000073009; Homo sapiens. DR HGNC; HGNC:5961; IKBKG. DR MIM; 300248; gene. DR MIM; 300291; phenotype. DR MIM; 300301; phenotype. DR MIM; 300584; phenotype. DR MIM; 308300; phenotype. DR LinkHub; Q9Y6K9; -. DR RZPD-ProtExp; IOH3445; -. DR RZPD-ProtExp; K2036; -. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0004871; F:signal transducer activity; TAS. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; TAS. DR GO; GO:0006955; P:immune response; TAS. DR GO; GO:0006917; P:induction of apoptosis; TAS. DR InterPro; IPR009053; Prefoldin. KW Anhidrotic ectodermal dysplasia; Coiled coil; KW Direct protein sequencing; Disease mutation; Nuclear protein; KW Transcription; Transcription regulation. FT CHAIN 1 419 NF-kappa-B essential modulator. FT /FTId=PRO_0000096782. FT DOMAIN 322 343 Leucine-zipper (Potential). FT REGION 382 419 Interaction with CYLD. FT COILED 49 356 Potential. FT VARIANT 57 57 E -> K (in IP2; shows the same luciferase FT activity as the control). FT /FTId=VAR_026491. FT VARIANT 90 90 Missing (in IP2; only 46.3% of the FT activation obtained with the wild-type FT protein). FT /FTId=VAR_026492. FT VARIANT 113 113 D -> N (in IP2; shows the same luciferase FT activity as the control). FT /FTId=VAR_026493. FT VARIANT 123 123 R -> W (in IP2; shows the same luciferase FT activity as the control). FT /FTId=VAR_026494. FT VARIANT 153 153 L -> R (in EDA-ID). FT /FTId=VAR_026495. FT VARIANT 175 175 R -> P (in EDA-ID). FT /FTId=VAR_011320. FT VARIANT 227 227 L -> P (in EDA-ID). FT /FTId=VAR_011321. FT VARIANT 288 288 A -> G (in EDA-ID). FT /FTId=VAR_011322. FT VARIANT 311 311 D -> N (in EDA-ID). FT /FTId=VAR_011323. FT VARIANT 406 406 D -> V (in EDA-ID). FT /FTId=VAR_011324. FT VARIANT 407 407 M -> V (in IP2). FT /FTId=VAR_009182. FT VARIANT 417 417 C -> F (in EDA-ID). FT /FTId=VAR_011325. FT VARIANT 417 417 C -> R (in EDA-ID). FT /FTId=VAR_011326. FT VARIANT 417 417 C -> Y (in EDA-ID). FT /FTId=VAR_026496. FT CONFLICT 341 341 S -> R (in Ref. 1). FT CONFLICT 387 387 S -> R (in Ref. 1). SQ SEQUENCE 419 AA; 48198 MW; 322D1037881447FF CRC64; MNRHLWKSQL CEMVQPSGGP AADQDVLGEE SPLGKPAMLH LPSEQGAPET LQRCLEENQE LRDAIRQSNQ ILRERCEELL HFQASQREEK EFLMCKFQEA RKLVERLGLE KLDLKRQKEQ ALREVEHLKR CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKECQAL EGRARAASEQ ARQLESEREA LQQQHSVQVD QLRMQGQSVE AALRMERQAA SEEKRKLAQL QVAYHQLFQE YDNHIKSSVV GSERKRGMQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV LKAQADIYKA DFQAERQARE KLAEKKELLQ EQLEQLQREY SKLKASCQES ARIEDMRKRH VEVSQAPLPP APAYLSSPLA LPSQRRSPPE EPPDFCCPKC QYQAPDMDTL QIHVMECIE //