NEMO_BOVIN
ID NEMO_BOVIN Reviewed; 419 AA.
AC Q95KU9; A2VDM3; Q5E9T0; Q5EA16;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 128.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBUNIT OF THE IKK COMPLEX.
RX PubMed=12459277; DOI=10.1016/s0378-1119(02)01011-9;
RA Rottenberg S., Schmuckli-Maurer J., Grimm S., Heussler V.T.,
RA Dobbelaere D.A.E.;
RT "Characterization of the bovine IkappaB kinases (IKK)alpha and IKKbeta, the
RT regulatory subunit NEMO and their substrate IkappaBalpha.";
RL Gene 299:293-300(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). Component of the
CC I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and
CC IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with
CC four gamma/IKBKG subunits (PubMed:12459277). The IKK core complex seems
CC to associate with regulatory or adapter proteins to form a IKK-
CC signalosome holo-complex (PubMed:12459277). The IKK complex associates
CC with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of
CC RELA/p65 (By similarity). Part of a complex composed of NCOA2, NCOA3,
CC CHUK/IKKA, IKBKB, IKBKG and CREBBP. Interacts with COPS3, CYLD, NALP2,
CC TRPC4AP and PIDD1. Interacts with ATM; the complex is exported from the
CC nucleus. Interacts with TRAF6. Interacts with IKBKE. Interacts with
CC TANK; the interaction is enhanced by IKBKE and TBK1. Part of a ternary
CC complex consisting of TANK, IKBKB and IKBKG. Interacts with ZFAND5.
CC Interacts with RIPK2. Interacts with TNIP1 and TNFAIP3; TNIP1
CC facilitates the TNFAIP3-mediated de-ubiquitination of IKBKG. Interacts
CC with TNFAIP3; the interaction is induced by TNF stimulation and by
CC polyubiquitin. Binds (via UBAN region) polyubiquitin; binds both 'Lys-
CC 63'-linked and linear polyubiquitin, with higher affinity for linear
CC ubiquitin. Interacts with NLRP10. Interacts with TANK; this interaction
CC increases in response to DNA damage. Interacts with USP10; this
CC interaction increases in response to DNA damage. Interacts with
CC ZC3H12A; this interaction increases in response to DNA damage.
CC Interacts with IFIT5; the interaction synergizes the recruitment of IKK
CC to MAP3K7 and enhances IKK phosphorylation. Interacts with TRIM29; this
CC interaction induces IKBKG/NEMO ubiquitination and proteolytic
CC degradation. Interacts with TRIM13; this interaction leads to
CC IKBKG/NEMO ubiquitination. Interacts with ARFIP2 (By similarity).
CC Interacts with RIPK1 (By similarity). Interacts with (ubiquitinated)
CC BCL10; interaction with polyubiquitinated BCL10 via both 'Lys-63'-
CC linked and linear ubiquitin is required for TCR-induced NF-kappa-B
CC activation (By similarity). Interacts with MARCHF2; during the late
CC stages of macrophage viral and bacterial infection; the interaction
CC leads to ubiquitination and degradation of IKBKG/NEMO (By similarity).
CC {ECO:0000250|UniProtKB:O88522, ECO:0000250|UniProtKB:Q9Y6K9,
CC ECO:0000269|PubMed:12459277}.
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-285 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-399 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-277 and Lys-309; 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-264, Lys-277, Lys-285, Lys-
CC 292, Lys-302, Lys-309 and Lys-326; the head-to-tail polyubiquitination
CC is 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-326 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-277 and Lys-309 with SUMO1.
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; AJ414557; CAC93688.1; -; mRNA.
DR EMBL; BT020840; AAX08857.1; -; mRNA.
DR EMBL; BT020753; AAX08770.1; -; mRNA.
DR EMBL; BT020767; AAX08784.1; -; mRNA.
DR EMBL; BT020872; AAX08889.1; -; mRNA.
DR EMBL; BC133306; AAI33307.1; -; mRNA.
DR RefSeq; NP_776779.1; NM_174354.3.
DR RefSeq; XP_005227784.1; XM_005227727.3.
DR RefSeq; XP_005227785.1; XM_005227728.3.
DR RefSeq; XP_005227786.1; XM_005227729.3.
DR RefSeq; XP_015316989.1; XM_015461503.1.
DR AlphaFoldDB; Q95KU9; -.
DR SMR; Q95KU9; -.
DR BioGRID; 159166; 4.
DR STRING; 9913.ENSBTAP00000008224; -.
DR PaxDb; Q95KU9; -.
DR PRIDE; Q95KU9; -.
DR Ensembl; ENSBTAT00000008224; ENSBTAP00000008224; ENSBTAG00000006268.
DR GeneID; 281855; -.
DR KEGG; bta:281855; -.
DR CTD; 8517; -.
DR VEuPathDB; HostDB:ENSBTAG00000006268; -.
DR VGNC; VGNC:30102; IKBKG.
DR eggNOG; ENOG502R4ZD; Eukaryota.
DR GeneTree; ENSGT00530000063808; -.
DR HOGENOM; CLU_034097_0_0_1; -.
DR InParanoid; Q95KU9; -.
DR OMA; QHRCIEH; -.
DR OrthoDB; 745047at2759; -.
DR TreeFam; TF326608; -.
DR Proteomes; UP000009136; Chromosome X.
DR Bgee; ENSBTAG00000006268; Expressed in choroid plexus and 106 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0008385; C:IkappaB kinase complex; IBA:GO_Central.
DR GO; GO:0072686; C:mitotic spindle; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000922; C:spindle pole; IEA:Ensembl.
DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl.
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:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:1990459; F:transferrin receptor binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0051650; P:establishment of vesicle localization; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
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; IEA:Ensembl.
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 1: Evidence at protein 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..419
FT /note="NF-kappa-B essential modulator"
FT /id="PRO_0000269196"
FT ZN_FING 389..419
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..257
FT /note="Interaction with TANK"
FT /evidence="ECO:0000250"
FT REGION 242..350
FT /note="Ubiquitin-binding (UBAN)"
FT REGION 246..365
FT /note="Self-association"
FT /evidence="ECO:0000250"
FT REGION 251..419
FT /note="Required for interaction with TNFAIP3"
FT /evidence="ECO:0000250"
FT REGION 322..343
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255"
FT REGION 356..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 382..419
FT /note="Interaction with CYLD"
FT /evidence="ECO:0000250"
FT COILED 49..353
FT /evidence="ECO:0000255"
FT BINDING 397
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 400
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 413
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 417
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 376
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT DISULFID 54
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 347
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 264
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 277
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 277
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 283
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 292
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 ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 309
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 309
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 321
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 325
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O88522"
FT CROSSLNK 326
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 399
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CONFLICT 211
FT /note="A -> T (in Ref. 2; AAX08770)"
FT /evidence="ECO:0000305"
FT CONFLICT 262..265
FT /note="DLKQ -> ISA (in Ref. 2; AAX08857)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 419 AA; 48570 MW; 95DBC093DC464F78 CRC64;
MSRPPWKSPL CEMVQPSGSP AGDQDMLGEE SSLGKPAMLH VPSEQGTPET FQRCLEENQE
LRDAIRQSNQ MLRERCEELQ HFQGNQREEK AFLMQKFQEA RDLVVRLSLE KRELRQQREQ
ALKEVERLKT CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKERQAL ESRARVASEK
ARQLESEREA LEQRHSVQVD QLVLQNESME AALRMERQAA SEEKRKLAQL QVAYHQLFQE
YDNHMKSSMV SSERNRGLQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV
LKAQADIYKA DFQAERQARE KLAEKKEFLQ EQLEQLQREY SRLKTSCQES ARIEDMRKRH
VEVSQPPLAP GPAHHSFHLN PSSQRRSPPD EPPKFCCPKC QYQAPDIDTL QIHVMECIE
