IKKA_DANRE
ID IKKA_DANRE Reviewed; 758 AA.
AC Q4G3H4; Q7ZTU1;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit alpha;
DE Short=I kappa-B kinase alpha;
DE Short=IKK-A;
DE Short=IKK-alpha;
DE Short=IkBKA;
DE Short=IkappaB kinase;
DE EC=2.7.11.10;
DE AltName: Full=Conserved helix-loop-helix ubiquitous kinase;
DE AltName: Full=I-kappa-B kinase 1;
DE Short=IKK1;
DE AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase alpha;
DE Short=NFKBIKA;
GN Name=chuk; Synonyms=ikk1; ORFNames=zgc:56539;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND INTERACTION WITH
RP IKBKG.
RX PubMed=16051172; DOI=10.1016/j.cub.2005.06.023;
RA Correa R.G., Matsui T., Tergaonkar V., Rodriguez-Esteban C.,
RA Izpisua-Belmonte J.C., Verma I.M.;
RT "Zebrafish IkappaB kinase 1 negatively regulates NF-kappaB activity.";
RL Curr. Biol. 15:1291-1295(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=SJD;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: 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. Phosphorylates 'Ser-10' of histone H3 at
CC NF-kappa-B-regulated promoters during inflammatory responses triggered
CC by cytokines. {ECO:0000250|UniProtKB:O15111}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[I-kappa-B protein] = ADP + H(+) + O-phospho-L-
CC seryl-[I-kappa-B protein]; Xref=Rhea:RHEA:19073, Rhea:RHEA-
CC COMP:13698, Rhea:RHEA-COMP:13699, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.10;
CC -!- ACTIVITY REGULATION: Activated when phosphorylated and inactivated when
CC dephosphorylated. {ECO:0000250}.
CC -!- SUBUNIT: Directly interacts with ikbkg/nemo.
CC {ECO:0000269|PubMed:16051172}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Shuttles between the cytoplasm and the nucleus. {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Abundantly expressed from the blastula period
CC through early gastrulation. During early somitogenesis, transcripts are
CC dorsally localized at the level of the segmental plate and the
CC presumptive notochord. At the 18-somite stage, expression becomes
CC largely detectable throughout the somitic tissue At late embryonic
CC stages, expression is particularly evident in the tectum, cerebellum,
CC hindbrain region, and eyes. After hatching, transcripts can also be
CC detected in the myotomes and pectoral fins.
CC {ECO:0000269|PubMed:16051172}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. I-kappa-B kinase subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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; AY735397; AAW68010.1; -; mRNA.
DR EMBL; BC051614; AAH51614.1; -; mRNA.
DR RefSeq; NP_956611.1; NM_200317.1.
DR AlphaFoldDB; Q4G3H4; -.
DR SMR; Q4G3H4; -.
DR STRING; 7955.ENSDARP00000013115; -.
DR PaxDb; Q4G3H4; -.
DR GeneID; 393287; -.
DR KEGG; dre:393287; -.
DR CTD; 1147; -.
DR ZFIN; ZDB-GENE-040426-1069; chuk.
DR eggNOG; KOG4250; Eukaryota.
DR InParanoid; Q4G3H4; -.
DR OrthoDB; 1013139at2759; -.
DR PhylomeDB; Q4G3H4; -.
DR Reactome; R-DRE-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-DRE-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-DRE-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-DRE-202424; Downstream TCR signaling.
DR Reactome; R-DRE-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-DRE-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-DRE-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-DRE-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-DRE-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-DRE-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-DRE-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-DRE-9020702; Interleukin-1 signaling.
DR Reactome; R-DRE-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-DRE-937039; IRAK1 recruits IKK complex.
DR Reactome; R-DRE-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR PRO; PR:Q4G3H4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0008385; C:IkappaB kinase complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IMP:ZFIN.
DR GO; GO:0055113; P:epiboly involved in gastrulation with mouth forming second; IMP:ZFIN.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:ZFIN.
DR GO; GO:0007252; P:I-kappaB phosphorylation; IEA:GOC.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ZFIN.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:ZFIN.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0001757; P:somite specification; IMP:ZFIN.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IBA:GO_Central.
DR Gene3D; 1.20.1270.250; -; 1.
DR InterPro; IPR041185; IKBKB_SDD.
DR InterPro; IPR046375; IKBKB_SDD_sf.
DR InterPro; IPR022007; IKKbetaNEMObind.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF18397; IKBKB_SDD; 1.
DR Pfam; PF12179; IKKbetaNEMObind; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM01239; IKKbetaNEMObind; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..758
FT /note="Inhibitor of nuclear factor kappa-B kinase subunit
FT alpha"
FT /id="PRO_0000268827"
FT DOMAIN 15..301
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 456..477
FT /note="Leucine-zipper"
FT REGION 741..746
FT /note="NEMO-binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 145
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 21..29
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CONFLICT 61
FT /note="G -> E (in Ref. 1; AAW68010)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="S -> L (in Ref. 1; AAW68010)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="L -> P (in Ref. 1; AAW68010)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="L -> P (in Ref. 1; AAW68010)"
FT /evidence="ECO:0000305"
FT CONFLICT 756
FT /note="P -> A (in Ref. 1; AAW68010)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 758 AA; 87147 MW; 9E3355AEAE5EE7F7 CRC64;
MEKPPFRQNQ VCGSWVMKER LGTGGFGHVY LYQNQETSEK IAVKLCRLEL NSKNKDRWSR
GIQIMKKLKH LNVVTAKDVP EEMMHIALND LPLLAMEYCS KGDLRKLLSK PENCCGLKES
EVLSLLNDVG SGIQYLHENK IIHRDLKPEN IVLQEINGKL VHKIIDLGYA KDLDQGSLCT
SFVGTLQYLA PELFEGKSYT VTVDFWSFGT MIFECCCGFR PFLHNLQPVQ WTSKVRNKGP
KDIMAVEDMN GEVRFSTHLP YPNNLSRTLL EPLEGLLQLM LKWDPVQRGL GLNTDSKQPQ
CFVLLDQILS MKVVHILNMT TTQVHSFLLS PDEGLHSLQQ RIENETKIEL LNQDLLQETG
VMSDPRKPAA QCVLDGVRGW DSYIVYLFDK SLTKYMGPLT ARTLPESVNF IVRETKTQLP
LSTLKKVWGE AVSYICGLRE DYSRLFQGQR AAMLSLLRFN TNLTRYKNMM FSFSQQLKAK
LDFFKTSIQY DLEKYSDQMQ YGISSEKMLK AWHENEERAA AFAQVAEIGH LDEEIMALHS
EIVELQRSPY ARRQGDVMEQ LQEKAIELYK QLKAKCKMPD PQHGYSDSSE MVKVIVQTVQ
NQDRVLRDLY AHLSKILLSK QKIIDLFPKI ERTLECIKEA DTTVMQMQIK RQREFWHLLK
IACAQNTTRS SVSQSGEMPS SLSTWNQTQA QCSSRLPMSL QVPHEGDSVN HLLEENQRYL
TQLTSLLQET TEEKSESIMA QDWSWTKYES LVAKSPRL
