ID NEMO_HUMAN STANDARD; PRT; 419 AA. AC Q9Y6K9; DT 30-MAY-2000 (Rel. 39, Created) DT 30-MAY-2000 (Rel. 39, Last sequence update) DT 16-OCT-2001 (Rel. 40, Last annotation update) DE NF-kappaB essential modulator (NEMO) (NF-kappaB 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 IKBKG OR NEMO OR FIP3. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=99128359; PubMed=9927690; 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 SEQUENCE FROM N.A. RC TISSUE=Breast cancer; RX MEDLINE=99189402; PubMed=10087442; 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 SEQUENCE FROM N.A., AND PARTIAL SEQUENCE. RC TISSUE=Cervical carcinoma; RX MEDLINE=98421680; PubMed=9751060; 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 SEQUENCE FROM N.A., AND VARIANT IP2 VAL-407. RX MEDLINE=20296353; PubMed=10839543; 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 SEQUENCE FROM N.A. RC TISSUE=Astrocytoma; RX MEDLINE=20403900; PubMed=10944468; 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 SEQUENCE FROM N.A. RC TISSUE=Lung; RA Strausberg R.; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [7] RP SEQUENCE OF 51-419 FROM N.A., AND SEQUENCE OF 144-159. RC TISSUE=Cervical 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 [8] RP FUNCTION. RX MEDLINE=99292691; PubMed=10364167; RA Jin D.-Y., Giordano V., Kibler K.V., Nakano H., Jeang K.-T.; RT "Role of adapter function in oncoprotein-mediated activation of RT NF-kappaB: Human T-cell leukemia virus type I Tax interacts directly RT with IkappaB kinase gamma."; RL J. Biol. Chem. 274:17402-17405(1999). RN [9] RP IKK COMPLEX. RX MEDLINE=21264955; PubMed=11080499; 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 [10] RP VARIANTS EDA-ID ARG-417 AND PHE-417. RX MEDLINE=20530236; PubMed=11047757; 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 [11] RP VARIANTS EDA-ID PRO-175; PRO-227; GLY-288; ASN-311; ARG-417 & PHE-417. RX MEDLINE=21135089; PubMed=11242109; 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 [12] RP VARIANTS EDA-ID VAL-406 AND ARG-417. RX MEDLINE=21163376; PubMed=11224521; 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). 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, TAX, RIP AND MAP3K14/NIK. BINDS TO CC T-CELL LEUKEMIA VIRUS TYPE I TAX ONCOPROTEIN. CC -!- SUBCELLULAR LOCATION: Cytoplasmic and nuclear. 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), A X-LINKED RECESSIVE CC DISORDER CHARACTERIZED BY ABSENCE OF SWEAT GLANDS, SPARSE SCALP CC HAIR, RARE CONICAL TEETH AND IMMUNOLOGICAL ABNORMALITIES RESULTING CC IN SEVERE INFECTIOUS DISEASES. CC -!- DISEASE: DEFECTS IN IKBKG ARE THE CAUSE OF ANHIDROTIC ECTODERMAL CC DYSPLASIA WITH IMMUNODEFICIENCY, OSTEOPETROSIS AND LYMPHEDEMA (OL- CC EDA-ID). CC -!- DISEASE: DEFECTS IN IKBKG ARE THE CAUSE OF FAMILIAL INCONTINENTIA CC PIGMENTI TYPE II (IP2). IP2 IS A X-LINKED DOMINANT DISEASE CAUSING CC DEATH IN MALE FETUSES. IN HETEROZYGOUS FEMALE, IT IS CHARACTERIZED CC BY DISTURBANCE OF SKIN PIGMENTATION SOMETIMES ASSOCIATED WITH A CC VARIETY OF MALFORMATIONS OF THE EYE, NAILS, TEETH, SKELETON, CC HEART, AND CENTRAL NERVOUS SYSTEM. THE PROMINENT SKIN SIGNS OCCUR CC IN FOUR CLASSIC CUTANEOUS STAGES: PERINATAL INFLAMMATORY VESICLES, CC VERRUCOUS PATCHES, A DISTINCTIVE PATTERN OF HYPERPIGMENTATION AND CC DERMAL SCARRING. 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; -. DR EMBL; AF091453; AAD38081.1; -. DR EMBL; AF074382; AAC36330.1; -. DR EMBL; AJ271718; CAB93146.1; -. DR EMBL; AF261086; AAF99679.1; -. DR EMBL; BC000299; AAH00299.1; -. DR MIM; 300248; -. DR MIM; 300291; -. DR MIM; 300301; -. DR MIM; 308300; -. DR InterPro; IPR000822; Znf-C2H2. DR Pfam; PF00096; zf-C2H2; 1. KW Coiled coil; Transcription regulation; Nuclear protein; KW Disease mutation. FT DOMAIN 49 356 COILED COIL (POTENTIAL). FT DOMAIN 322 343 LEUCINE-ZIPPER (POTENTIAL). 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 CONFLICT 341 341 S -> R (IN REF. 1). FT CONFLICT 387 387 S -> R (IN REF. 1). SQ SEQUENCE 419 AA; 48197 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 //