IRAK4_BOVIN
ID IRAK4_BOVIN Reviewed; 461 AA.
AC Q1RMT8;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Interleukin-1 receptor-associated kinase 4;
DE Short=IRAK-4;
DE EC=2.7.11.1;
GN Name=IRAK4;
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 [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine-protein kinase that plays a critical role in
CC initiating innate immune response against foreign pathogens. Involved
CC in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly
CC recruited by MYD88 to the receptor-signaling complex upon TLR
CC activation to form the Myddosome together with IRAK2. Phosphorylates
CC initially IRAK1, thus stimulating the kinase activity and intensive
CC autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases
CC Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated
CC polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of
CC IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the
CC IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In
CC turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to
CC NF-kappa-B nuclear translocation and activation. Alternatively,
CC phosphorylates TIRAP to promote its ubiquitination and subsequent
CC degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation
CC after LPS stimulation suggesting a similar mechanism during microbial
CC infections (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- SUBUNIT: Associates with MYD88 and IRAK2 to form a ternary complex
CC called the Myddosome. Once phosphorylated, IRAK4 dissociates from the
CC receptor complex and then associates with the TNF receptor-associated
CC factor 6 (TRAF6), IRAK1, and PELI1; this intermediate complex is
CC required for subsequent NF-kappa-B activation. Direct binding of SMAD6
CC to PELI1 prevents complex formation and hence negatively regulates
CC IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression.
CC Interacts with IL1RL1. Interacts (when phosphorylated) with IRAK1. May
CC interact (when phosphorylated) with IRAK3.
CC {ECO:0000250|UniProtKB:Q9NWZ3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. Pelle subfamily. {ECO:0000305}.
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DR EMBL; BC114720; AAI14721.1; -; mRNA.
DR RefSeq; NP_001069466.1; NM_001075998.1.
DR RefSeq; XP_005206483.1; XM_005206426.3.
DR AlphaFoldDB; Q1RMT8; -.
DR SMR; Q1RMT8; -.
DR STRING; 9913.ENSBTAP00000028115; -.
DR PaxDb; Q1RMT8; -.
DR Ensembl; ENSBTAT00000028115; ENSBTAP00000028115; ENSBTAG00000021105.
DR GeneID; 533692; -.
DR KEGG; bta:533692; -.
DR CTD; 51135; -.
DR VEuPathDB; HostDB:ENSBTAG00000021105; -.
DR VGNC; VGNC:30268; IRAK4.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00940000158792; -.
DR HOGENOM; CLU_000288_21_15_1; -.
DR InParanoid; Q1RMT8; -.
DR OMA; WHQRCLI; -.
DR OrthoDB; 684563at2759; -.
DR TreeFam; TF351380; -.
DR Reactome; R-BTA-9020702; Interleukin-1 signaling.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000021105; Expressed in monocyte and 107 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IEA:Ensembl.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0002446; P:neutrophil mediated immunity; ISS:UniProtKB.
DR GO; GO:1990266; P:neutrophil migration; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR CDD; cd08793; Death_IRAK4; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR017428; IRAK4.
DR InterPro; IPR037970; IRAK4_Death.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF038189; IRAK4; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cytoplasm; Immunity; Innate immunity; Kinase;
KW Magnesium; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..461
FT /note="Interleukin-1 receptor-associated kinase 4"
FT /id="PRO_0000260158"
FT DOMAIN 20..104
FT /note="Death"
FT DOMAIN 187..455
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 312
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 193..201
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 314..317
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 330
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWZ3"
FT MOD_RES 34
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWZ3"
FT MOD_RES 343
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWZ3"
FT MOD_RES 346
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWZ3"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NWZ3"
SQ SEQUENCE 461 AA; 51575 MW; EF9DE6D50AD2D9CC CRC64;
MNKPITASTY VRCLSLGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ FHIRRFEALL
QIGKSPTCEL LFDWGTTNCT VGDLVDILVQ NEFFAPASLL LPDAVPKNVN TLPSKVTVVA
VQQKPKPLCG KDRTSVISDE NPEQNYVLPD SSSPENTSLE FSDTRFHSFS FFELKDVTNN
FDERPISVGG NKMGEGGFGV VYKGYVNNRT VAVKKLAAMV DISTEELKQQ FDQEIKVMAK
CQHENLVELL GFSSDGDDLC LVYVYMPNGS LLDRLSCLDG TPPLSWNMRC KIAQGAANGL
SYLHENHHIH RDIKSANILL DEDFTAKISD FGLARASEKF AQTVMTSRIV GTTAYMAPEA
LRGEITPKSD IYSFGVVLLE IITGLPAVDE HREPQLLLDI KEEIEDEEKT IEDYVDRKMN
DIDSTSIETM YSVASQCLHE KKNKRPDIKK VQQLLEEMTG S
