IRAK1_MOUSE
ID IRAK1_MOUSE Reviewed; 710 AA.
AC Q62406; B1AUW4; Q6Y3Z5; Q6Y3Z6;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 3.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Interleukin-1 receptor-associated kinase 1;
DE Short=IRAK;
DE Short=IRAK-1;
DE EC=2.7.11.1;
DE AltName: Full=Pelle-like protein kinase;
DE Short=mPLK;
GN Name=Irak1; Synonyms=Il1rak;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kopp E.B., Ghosh S.;
RT "Cloning of mouse IRAK.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=10723722; DOI=10.1007/s003350010035;
RA Reichwald K., Thiesen J., Wiehe T., Weitzel J., Poustka W.A., Rosenthal A.,
RA Platzer M., Stratling W.H., Kioschis P.;
RT "Comparative sequence analysis of the MECP2-locus in human and mouse
RT reveals new transcribed regions.";
RL Mamm. Genome 11:182-190(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-710 (ISOFORM 1), FUNCTION, DEVELOPMENTAL
RP STAGE, TISSUE SPECIFICITY, AND AUTOPHOSPHORYLATION.
RC TISSUE=Embryo;
RX PubMed=8663605; DOI=10.1074/jbc.271.30.17609;
RA Trofimova M., Sprenkle A.B., Green M., Sturgill T.W., Goebl M.G.,
RA Harrington M.A.;
RT "Developmental and tissue-specific expression of mouse pelle-like protein
RT kinase.";
RL J. Biol. Chem. 271:17609-17612(1996).
RN [5]
RP INTERACTION WITH IRAK1BP1.
RX PubMed=11096118; DOI=10.1074/jbc.m010399200;
RA Vig E., Green M., Liu Y., Yu K.-Y., Kwon H.-J., Tian J., Goebl M.G.,
RA Harrington M.A.;
RT "SIMPL is a tumor necrosis factor-specific regulator of nuclear factor-
RT kappaB activity.";
RL J. Biol. Chem. 276:7859-7866(2001).
RN [6]
RP DIMERIZATION, AND MUTAGENESIS OF THR-66.
RX PubMed=12138165; DOI=10.1074/jbc.m205160200;
RA Ross K., Yang L., Dower S., Volpe F., Guesdon F.;
RT "Identification of threonine 66 as a functionally critical residue of the
RT interleukin-1 receptor-associated kinase.";
RL J. Biol. Chem. 277:37414-37421(2002).
RN [7]
RP INTERACTION WITH PELI2.
RX PubMed=12370331; DOI=10.4049/jimmunol.169.8.4075;
RA Yu K.-Y., Kwon H.-J., Norman D.A.M., Vig E., Goebl M.G., Harrington M.A.;
RT "Mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling.";
RL J. Immunol. 169:4075-4078(2002).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=15767370; DOI=10.1084/jem.20042372;
RA Uematsu S., Sato S., Yamamoto M., Hirotani T., Kato H., Takeshita F.,
RA Matsuda M., Coban C., Ishii K.J., Kawai T., Takeuchi O., Akira S.;
RT "Interleukin-1 receptor-associated kinase-1 plays an essential role for
RT Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha}
RT induction.";
RL J. Exp. Med. 201:915-923(2005).
RN [9]
RP IDENTIFICATION IN COMPLEX WITH IRAK4; MYD88; PELI1 AND TRAF6.
RX PubMed=16951688; DOI=10.1038/ni1383;
RA Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S.,
RA Kim I.H., Kim S.J., Park S.H.;
RT "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor
RT signaling through direct interaction with the adapter Pellino-1.";
RL Nat. Immunol. 7:1057-1065(2006).
RN [10]
RP INTERACTION WITH RSAD2, AND SUBCELLULAR LOCATION.
RX PubMed=21435586; DOI=10.1016/j.immuni.2011.03.010;
RA Saitoh T., Satoh T., Yamamoto N., Uematsu S., Takeuchi O., Kawai T.,
RA Akira S.;
RT "Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like
RT receptor 9-mediated type I interferon production in plasmacytoid dendritic
RT cells.";
RL Immunity 34:352-363(2011).
RN [11]
RP INTERACTION WITH ZC3H12A.
RX PubMed=22037600; DOI=10.1038/ni.2137;
RA Iwasaki H., Takeuchi O., Teraguchi S., Matsushita K., Uehata T.,
RA Kuniyoshi K., Satoh T., Saitoh T., Matsushita M., Standley D.M., Akira S.;
RT "The IkappaB kinase complex regulates the stability of cytokine-encoding
RT mRNA induced by TLR-IL-1R by controlling degradation of regnase-1.";
RL Nat. Immunol. 12:1167-1175(2011).
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. Association with MYD88 leads to IRAK1 phosphorylation by
CC IRAK4 and subsequent autophosphorylation and kinase activation.
CC Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and
CC PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then,
CC the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated
CC IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the
CC NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA
CC and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and
CC activation. Alternatively, phosphorylates TIRAP to promote its
CC ubiquitination and subsequent degradation. Phosphorylates the
CC interferon regulatory factor 7 (IRF7) to induce its activation and
CC translocation to the nucleus, resulting in transcriptional activation
CC of type I IFN genes, which drive the cell in an antiviral state. When
CC sumoylated, translocates to the nucleus and phosphorylates STAT3 (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:8663605}.
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;
CC -!- SUBUNIT: Homodimer (By similarity). Forms a complex with TRAF6, PELI1,
CC IRAK4 and MYD88 (PubMed:16951688). Direct binding of SMAD6 to PELI1
CC prevents complex formation and hence negatively regulates IL1R-TLR
CC signaling and eventually NF-kappa-B-mediated gene expression (By
CC similarity). The TRAF6-PELI1-IRAK4-MYD88 complex recruits MAP3K7/TAK1,
CC TAB1 and TAB2 to mediate NF-kappa-B activation (By similarity).
CC Interaction with MYD88 recruits IRAK1 to the stimulated receptor
CC complex (By similarity). Interacts with TOLLIP; this interaction occurs
CC in the cytosol prior to receptor activation (By similarity). Interacts
CC with IL1RL1 (By similarity). Interacts (when polyubiquitinated) with
CC IKBKG/NEMO (By similarity). Interacts with RSAD2/viperin
CC (PubMed:21435586). Interacts with IRAK1BP1 (PubMed:11096118). Interacts
CC with PELI2 (PubMed:12370331). Interacts with ZC3H12A; this interaction
CC increases the interaction between ZC3H12A and IKBKB/IKKB
CC (PubMed:22037600). Interacts with IRAK4 (By similarity). Interacts with
CC PELI3 (By similarity). Interacts with PELI1 and TRAF6 (By similarity).
CC Interacts with INAVA; the interaction takes place upon PRR stimulation
CC (By similarity). Interacts (via C-terminus) with NFATC4 (via N-
CC terminus) (By similarity). {ECO:0000250|UniProtKB:P51617,
CC ECO:0000269|PubMed:11096118, ECO:0000269|PubMed:12370331,
CC ECO:0000269|PubMed:16951688, ECO:0000269|PubMed:21435586,
CC ECO:0000269|PubMed:22037600}.
CC -!- INTERACTION:
CC Q62406; P22366: Myd88; NbExp=3; IntAct=EBI-448533, EBI-525108;
CC Q62406; Q8BST6: Peli2; NbExp=2; IntAct=EBI-448533, EBI-448554;
CC Q62406; Q793I8: Tifa; NbExp=2; IntAct=EBI-448533, EBI-524817;
CC Q62406; Q9QZ06: Tollip; NbExp=2; IntAct=EBI-448533, EBI-74272;
CC Q62406; P39429: Traf2; NbExp=2; IntAct=EBI-448533, EBI-520016;
CC Q62406-1; Q3THG9: Aarsd1; NbExp=4; IntAct=EBI-488313, EBI-646572;
CC Q62406-1; P37889-1: Fbln2; NbExp=10; IntAct=EBI-488313, EBI-645953;
CC Q62406-1; P70196: Traf6; NbExp=4; IntAct=EBI-488313, EBI-448028;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Lipid droplet {ECO:0000269|PubMed:21435586}. Note=Translocates to the
CC nucleus when sumoylated (By similarity). RSAD2/viperin recruits it to
CC the lipid droplet. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q62406-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q62406-2; Sequence=VSP_011852;
CC -!- TISSUE SPECIFICITY: Highly expressed in liver, followed by kidney and
CC skeletal muscle. {ECO:0000269|PubMed:8663605}.
CC -!- DEVELOPMENTAL STAGE: Expressed from 11 dpc to 18 dpc.
CC {ECO:0000269|PubMed:8663605}.
CC -!- DOMAIN: The ProST region is composed of many proline and serine
CC residues (more than 20 of each) and some threonines. This region is the
CC site of IRAK-1 hyperphosphorylation (By similarity). {ECO:0000250}.
CC -!- PTM: Following recruitment on the activated receptor complex,
CC phosphorylated on Thr-209, probably by IRAK4, resulting in a
CC conformational change of the kinase domain, allowing further
CC phosphorylations to take place. Thr-387 phosphorylation in the
CC activation loop is required to achieve full enzymatic activity (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Polyubiquitinated by TRAF6 after cell stimulation with IL-1-beta
CC by PELI1, PELI2 and PELI3. Polyubiquitination occurs with polyubiquitin
CC chains linked through 'Lys-63'. Ubiquitination promotes interaction
CC with NEMO/IKBKG. Also sumoylated; leading to nuclear translocation (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice show a loss in TLR7- and TLR9-mediated IFN-
CC alpha production in plasmacytoid dendritic cells demonstrating an
CC important role in innate immune response.
CC {ECO:0000269|PubMed:15767370}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. Pelle subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD13224.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF103876; AAD13224.1; ALT_INIT; mRNA.
DR EMBL; AY184363; AAO63013.1; -; mRNA.
DR EMBL; AY184364; AAO63014.1; -; mRNA.
DR EMBL; AL672002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U56773; AAC52694.2; -; mRNA.
DR CCDS; CCDS30219.2; -. [Q62406-1]
DR CCDS; CCDS53103.1; -. [Q62406-2]
DR RefSeq; NP_001171445.1; NM_001177974.1. [Q62406-1]
DR RefSeq; NP_001171447.1; NM_001177976.1. [Q62406-2]
DR RefSeq; NP_032389.2; NM_008363.2. [Q62406-1]
DR AlphaFoldDB; Q62406; -.
DR SMR; Q62406; -.
DR BioGRID; 200627; 25.
DR DIP; DIP-31491N; -.
DR ELM; Q62406; -.
DR IntAct; Q62406; 29.
DR MINT; Q62406; -.
DR STRING; 10090.ENSMUSP00000033769; -.
DR iPTMnet; Q62406; -.
DR PhosphoSitePlus; Q62406; -.
DR MaxQB; Q62406; -.
DR PRIDE; Q62406; -.
DR ProteomicsDB; 267149; -. [Q62406-1]
DR ProteomicsDB; 267150; -. [Q62406-2]
DR Antibodypedia; 3845; 1053 antibodies from 47 providers.
DR DNASU; 16179; -.
DR Ensembl; ENSMUST00000068286; ENSMUSP00000064448; ENSMUSG00000031392. [Q62406-1]
DR Ensembl; ENSMUST00000114352; ENSMUSP00000109992; ENSMUSG00000031392. [Q62406-1]
DR Ensembl; ENSMUST00000114360; ENSMUSP00000110000; ENSMUSG00000031392. [Q62406-2]
DR GeneID; 16179; -.
DR KEGG; mmu:16179; -.
DR UCSC; uc009tnn.2; mouse. [Q62406-1]
DR UCSC; uc012hkn.1; mouse. [Q62406-2]
DR CTD; 3654; -.
DR MGI; MGI:107420; Irak1.
DR VEuPathDB; HostDB:ENSMUSG00000031392; -.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00940000160502; -.
DR InParanoid; Q62406; -.
DR OMA; HFQTQAC; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-209543; p75NTR recruits signalling complexes.
DR Reactome; R-MMU-209560; NF-kB is activated and signals survival.
DR Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-937039; IRAK1 recruits IKK complex.
DR Reactome; R-MMU-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR BioGRID-ORCS; 16179; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Irak1; mouse.
DR PRO; PR:Q62406; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q62406; protein.
DR Bgee; ENSMUSG00000031392; Expressed in lacrimal gland and 256 other tissues.
DR ExpressionAtlas; Q62406; baseline and differential.
DR Genevisible; Q62406; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IPI:MGI.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; ISO:MGI.
DR GO; GO:0034605; P:cellular response to heat; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:MGI.
DR GO; GO:0045087; P:innate immune response; IEP:UniProtKB.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; ISO:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0090370; P:negative regulation of cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:BHF-UCL.
DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; ISO:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0001959; P:regulation of cytokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:0070555; P:response to interleukin-1; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0032494; P:response to peptidoglycan; IDA:MGI.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; IDA:MGI.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:MGI.
DR GO; GO:0060337; P:type I interferon signaling pathway; ISO:MGI.
DR CDD; cd08794; Death_IRAK1; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR035533; Death_IRAK1.
DR InterPro; IPR035536; IRAK1.
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 PANTHER; PTHR24419:SF1; PTHR24419:SF1; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47986; SSF47986; 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 Alternative splicing; ATP-binding; Cytoplasm; Immunity; Innate immunity;
KW Isopeptide bond; Kinase; Lipid droplet; Magnesium; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..710
FT /note="Interleukin-1 receptor-associated kinase 1"
FT /id="PRO_0000086031"
FT DOMAIN 27..106
FT /note="Death"
FT DOMAIN 212..521
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 107..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 110..211
FT /note="ProST region"
FT /evidence="ECO:0000250"
FT REGION 169..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 527..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 689..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 172..189
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 536..559
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..592
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..655
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 340
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 218..226
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 239
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 342..345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 358
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 66
FT /note="Phosphothreonine; by PKC/PRKCI"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT MOD_RES 131
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT MOD_RES 209
FT /note="Phosphothreonine; by IRAK4"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT MOD_RES 387
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT CROSSLNK 134
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT CROSSLNK 180
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P51617"
FT VAR_SEQ 691..710
FT /note="GLDLEPEKSQGPEESDEFQS -> DFVDIDAIGIEAFMSELFINHI (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:10723722"
FT /id="VSP_011852"
FT MUTAGEN 66
FT /note="T->A: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:12138165"
FT MUTAGEN 66
FT /note="T->E: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:12138165"
FT CONFLICT 702
FT /note="P -> L (in Ref. 2; AAO63013)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 710 AA; 77269 MW; 8A501F002CD3EBD2 CRC64;
MAGGPGPGEP VVPGAQHFLY EVPPWVMCRF YKVMDALEPA DWCQFAALIV RDQTELRLCE
RSEQRTASVL WPWINRNARV ADLVHILTHL QLLRARDIIT AWHPPAPVVP PSTAAPRPSS
ISAGSEAGDW SPRKLQSSAS TFLSPAFPGS QTHSESELLQ VPLPVSLGPP LPSSAPSSTK
SSPESPVSGL QRAHPSPFCW PFCEISQGTC NFSEELRIGE GGFGCVYRAV MRNTTYAVKR
LKEEADLEWT MVKQSFLTEV EQLSRFRHPN IVDFAGYCAE SGLYCLVYGF LPNGSLEDQL
HLQTQACSPL SWPQRLDILL GTARAIQFLH QDSPSLIHGD IKSSNVLLDE RLMPKLGDFG
LARFSRFAGA KASQSSTVAR TSTVRGTLAY LPEEYIKTGR LAVDTDTFSF GVVILETLAG
QRAVRTQGAK TKYLKDLIED EAEEAGVTLK STQPTLWVGV ATDAWAAPIA AQIYKKHLDS
RPGPCPPQLG LALAQLACCC MHRRAKKRPP MTQVYKRLEG LQAGPPWELE VAGHGSPSPQ
ENSYMSTTGS AQSGDEPWQP LVVTTRAPAQ AAQQLQRSPN QPVESDESVP GLSATLHSWH
LTPGSHPSPA SFREASCTQG GTTRESSVRS SPGFQPTTME GSPTGSSSLL SSEPPQIIIN
PARQKMVQKL ALYEEGVLDS LQLLSSGFFP GLDLEPEKSQ GPEESDEFQS
