NEMO_RAT
ID NEMO_RAT Reviewed; 412 AA.
AC Q6TMG5;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=NF-kappa-B essential modulator;
DE Short=NEMO;
DE AltName: Full=IkB kinase-associated protein 1;
DE Short=IKKAP1;
DE AltName: Full=Inhibitor of nuclear factor kappa-B kinase subunit gamma;
DE Short=I-kappa-B kinase subunit gamma;
DE Short=IKK-gamma;
DE Short=IKKG;
DE Short=IkB kinase subunit gamma;
DE AltName: Full=NF-kappa-B essential modifier;
GN Name=Ikbkg; Synonyms=Nemo;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344;
RX PubMed=12968033; DOI=10.1074/jbc.m302549200;
RA Saito N., Courtois G., Chiba A., Yamamoto N., Nitta T., Hironaka N.,
RA Rowe M., Yamamoto N., Yamaoka S.;
RT "Two carboxyl-terminal activation regions of Epstein-Barr virus latent
RT membrane protein 1 activate NF-kappaB through distinct signaling pathways
RT in fibroblast cell lines.";
RL J. Biol. Chem. 278:46565-46575(2003).
CC -!- FUNCTION: Regulatory subunit of the IKK core complex which
CC phosphorylates inhibitors of NF-kappa-B thus leading to the
CC dissociation of the inhibitor/NF-kappa-B complex and ultimately the
CC degradation of the inhibitor. Its binding to scaffolding polyubiquitin
CC plays a key role in IKK activation by multiple signaling receptor
CC pathways. Can recognize and bind both 'Lys-63'-linked and linear
CC polyubiquitin upon cell stimulation, with a much highr affinity for
CC linear polyubiquitin. Could be implicated in NF-kappa-B-mediated
CC protection from cytokine toxicity. Essential for viral activation of
CC IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response;
CC this function requires 'Lys-27'-linked polyubiquitination.
CC {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Component of the I-kappa-B-kinase
CC (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four
CC alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG
CC subunits. The IKK core complex seems to associate with regulatory or
CC adapter proteins to form a IKK-signalosome holo-complex (By
CC similarity). The IKK complex associates with TERF2IP/RAP1, leading to
CC promote IKK-mediated phosphorylation of RELA/p65 (By similarity). Part
CC of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and
CC CREBBP. Interacts with COPS3, CYLD, NALP2, TRPC4AP and PIDD1. Interacts
CC with ATM; the complex is exported from the nucleus. Interacts with
CC TRAF6. Interacts with IKBKE. Interacts with TANK; the interaction is
CC enhanced by IKBKE and TBK1. Part of a ternary complex consisting of
CC TANK, IKBKB and IKBKG. Interacts with ZFAND5. Interacts with RIPK2.
CC Interacts with TNIP1 and TNFAIP3; TNIP1 facilitates the TNFAIP3-
CC mediated de-ubiquitination of IKBKG. Interacts with TNFAIP3; the
CC interaction is induced by TNF stimulation and by polyubiquitin. Binds
CC (via UBAN region) polyubiquitin; binds both 'Lys-63'-linked and linear
CC polyubiquitin, with higher affinity for linear ubiquitin. Interacts
CC with NLRP10. Interacts with TANK; this interaction increases in
CC response to DNA damage. Interacts with USP10; this interaction
CC increases in response to DNA damage. Interacts with ZC3H12A; this
CC interaction increases in response to DNA damage. Interacts with IFIT5;
CC the interaction synergizes the recruitment of IKK to MAP3K7 and
CC enhances IKK phosphorylation. Interacts with TRIM29; this interaction
CC induces IKBKG/NEMO ubiquitination and proteolytic degradation.
CC Interacts with TRIM13; this interaction leads to IKBKG/NEMO
CC ubiquitination. Interacts with ARFIP2 (By similarity). Interacts with
CC RIPK1 (By similarity). Interacts with (ubiquitinated) BCL10;
CC interaction with polyubiquitinated BCL10 via both 'Lys-63'-linked and
CC linear ubiquitin is required for TCR-induced NF-kappa-B activation (By
CC similarity). Interacts with MARCHF2; during the late stages of
CC macrophage viral and bacterial infection; the interaction leads to
CC ubiquitination and degradation of IKBKG/NEMO (By similarity).
CC {ECO:0000250|UniProtKB:O88522, ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y6K9}. Nucleus
CC {ECO:0000250|UniProtKB:Q9Y6K9}. Note=Sumoylated NEMO accumulates in the
CC nucleus in response to genotoxic stress.
CC {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- DOMAIN: The leucine-zipper domain and the CCHC NOA-type zinc-fingers
CC constitute the UBAN region and are essential for polyubiquitin binding
CC and for the activation of IRF3. {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Phosphorylation at Ser-68 attenuates aminoterminal
CC homodimerization. {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Polyubiquitinated on Lys-278 through 'Lys-63'; the ubiquitination
CC is mediated by NOD2 and RIPK2 and probably plays a role in signaling by
CC facilitating interactions with ubiquitin domain-containing proteins and
CC activates the NF-kappa-B pathway. Polyubiquitinated on Lys-392 through
CC 'Lys-63'; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and
CC probably plays a role in signaling by facilitating interactions with
CC ubiquitin domain-containing proteins and activates the NF-kappa-B
CC pathway. Monoubiquitinated on Lys-270 and Lys-302; promotes nuclear
CC export. Polyubiquitinated through 'Lys-27' by TRIM23; involved in
CC antiviral innate and inflammatory responses. Linear polyubiquitinated
CC on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-
CC 295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is
CC mediated by the LUBAC complex and plays a key role in NF-kappa-B
CC activation. Deubiquitinated by USP10 in a TANK-dependent and
CC -independent manner, leading to the negative regulation of NF-kappa-B
CC signaling upon DNA damage (By similarity). Ubiquitinated at Lys-319 by
CC MARCHF2 following bacterial and viral infection which leads to its
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification
CC results in phosphorylation of Ser-85 by ATM leading to a replacement of
CC the sumoylation by mono-ubiquitination on these residues.
CC {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Neddylated by TRIM40, resulting in stabilization of NFKBIA and
CC down-regulation of NF-kappa-B activity. {ECO:0000250|UniProtKB:Q9Y6K9}.
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; AY392762; AAQ94056.1; -; mRNA.
DR RefSeq; NP_954534.1; NM_199103.1.
DR RefSeq; XP_006229646.1; XM_006229584.3.
DR RefSeq; XP_006229647.1; XM_006229585.3.
DR AlphaFoldDB; Q6TMG5; -.
DR BMRB; Q6TMG5; -.
DR SMR; Q6TMG5; -.
DR BioGRID; 259339; 1.
DR CORUM; Q6TMG5; -.
DR STRING; 10116.ENSRNOP00000053114; -.
DR ChEMBL; CHEMBL4524001; -.
DR PhosphoSitePlus; Q6TMG5; -.
DR PaxDb; Q6TMG5; -.
DR PRIDE; Q6TMG5; -.
DR GeneID; 309295; -.
DR KEGG; rno:309295; -.
DR CTD; 8517; -.
DR RGD; 735223; Ikbkg.
DR VEuPathDB; HostDB:ENSRNOG00000060936; -.
DR eggNOG; ENOG502R4ZD; Eukaryota.
DR HOGENOM; CLU_034097_0_0_1; -.
DR InParanoid; Q6TMG5; -.
DR OMA; QHRCIEH; -.
DR OrthoDB; 745047at2759; -.
DR PhylomeDB; Q6TMG5; -.
DR Reactome; R-RNO-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-RNO-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-RNO-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-RNO-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-RNO-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-RNO-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-RNO-4755510; SUMOylation of immune response proteins.
DR Reactome; R-RNO-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-RNO-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-5689896; Ovarian tumor domain proteases.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR Reactome; R-RNO-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-RNO-937039; IRAK1 recruits IKK complex.
DR Reactome; R-RNO-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR PRO; PR:Q6TMG5; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000060936; Expressed in skeletal muscle tissue and 18 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0008385; C:IkappaB kinase complex; IDA:RGD.
DR GO; GO:0072686; C:mitotic spindle; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0000922; C:spindle pole; ISO:RGD.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:1990450; F:linear polyubiquitin binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; IPI:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:1990459; F:transferrin receptor binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; ISO:RGD.
DR GO; GO:0043276; P:anoikis; ISO:RGD.
DR GO; GO:0001782; P:B cell homeostasis; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0051650; P:establishment of vesicle localization; ISO:RGD.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR InterPro; IPR032419; CC2-LZ_dom.
DR InterPro; IPR021063; NEMO_N.
DR InterPro; IPR034735; NEMO_ZF.
DR Pfam; PF16516; CC2-LZ; 1.
DR Pfam; PF11577; NEMO; 1.
DR PROSITE; PS51801; ZF_CCHC_NOA; 1.
PE 2: Evidence at transcript level;
KW Coiled coil; Cytoplasm; Disulfide bond; DNA damage; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..412
FT /note="NF-kappa-B essential modulator"
FT /id="PRO_0000269197"
FT ZN_FING 382..412
FT /note="CCHC NOA-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT REGION 1..197
FT /note="Required for interaction with and ubiquitination by
FT MARCHF2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 44..111
FT /note="Interaction with CHUK/IKBKB"
FT /evidence="ECO:0000250"
FT REGION 150..250
FT /note="Interaction with TANK"
FT /evidence="ECO:0000250"
FT REGION 242..343
FT /note="Ubiquitin-binding (UBAN)"
FT REGION 246..358
FT /note="Self-association"
FT /evidence="ECO:0000250"
FT REGION 249..412
FT /note="Required for interaction with TNFAIP3"
FT /evidence="ECO:0000250"
FT REGION 315..336
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255"
FT REGION 375..412
FT /note="Interaction with CYLD"
FT /evidence="ECO:0000250"
FT COILED 49..343
FT /evidence="ECO:0000255"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 393
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 410
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT MOD_RES 31
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 43
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 85
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 369
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT DISULFID 54
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 340
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CROSSLNK 111
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 139
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 143
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 226
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 246
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 276
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 278
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 285
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 295
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 314
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 319
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 392
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
SQ SEQUENCE 412 AA; 48066 MW; 6D5D96B08A4CCEC2 CRC64;
MSRHLWKNQL SEMVQPSGGP AEDQDMLGEE SSLGKPAMLH LPSEQGTPET LQRCLEENQE
LRDAIRQSNQ MLRERCEELL HFQVSQREEK EFLMCKFQEA RKLVERLSLE KLDLRRQREQ
ALEDLEHLKK CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKERQTL EGRIRAVSEQ
VRQLESEREV LQQQHSVQVD QLRMQNQSVE AALRMERQAA SEEKRKLAQL QAAYHQLFQD
YDSHIKSSKG MQLEDLRQQL QQAEEALVAK QELIDKLKEE AEQHKIVMET VPVLKAQADI
YKADFQAERH AREKLVERKE LLQEQLEQLQ REFNKLKVGC HESARIEDMR KRHVETSQPP
LLPAPAHHSF HLALSNQRRS PPEEPPDFCC PKCQYQAPDM DTLQIHVMEC IE
