IRAK2_MOUSE
ID IRAK2_MOUSE Reviewed; 622 AA.
AC Q8CFA1; Q3U3K2; Q3U7F5; Q3UFX2; Q5U404; Q6YBR8; Q6YBR9; Q6YBS0; Q6YBS1;
AC Q8C5M0; Q8CC82; Q8CEA0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Interleukin-1 receptor-associated kinase-like 2;
DE Short=IRAK-2;
DE Short=mu-IRAK-2;
GN Name=Irak2;
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).
RC STRAIN=BALB/cJ;
RX PubMed=12220507; DOI=10.1016/s0006-291x(02)02130-7;
RA Rosati O., Martin M.U.;
RT "Identification and characterization of murine IRAK-2.";
RL Biochem. Biophys. Res. Commun. 297:52-58(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC STRAIN=C57BL/6J;
RX PubMed=15082713; DOI=10.1074/jbc.m403068200;
RA Hardy M.P., O'Neill L.A.;
RT "The murine IRAK2 gene encodes four alternatively spliced isoforms, two of
RT which are inhibitory.";
RL J. Biol. Chem. 279:27699-27708(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Bone marrow, Cecum, Medulla oblongata, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Trophoblast stem cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Binds to the IL-1 type I receptor following IL-1 engagement,
CC triggering intracellular signaling cascades leading to transcriptional
CC up-regulation and mRNA stabilization. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with MYD88. IL-1 stimulation leads to the formation
CC of a signaling complex which dissociates from the IL-1 receptor
CC following the binding of PELI1 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=IRAK-2a;
CC IsoId=Q8CFA1-1; Sequence=Displayed;
CC Name=2; Synonyms=IRAK-2b;
CC IsoId=Q8CFA1-2; Sequence=VSP_023027;
CC Name=3; Synonyms=IRAK-2d;
CC IsoId=Q8CFA1-3; Sequence=VSP_023026, VSP_023028;
CC Name=4; Synonyms=IRAK-2c;
CC IsoId=Q8CFA1-4; Sequence=VSP_023025;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with a higher expression
CC observed in brain, spleen and liver. Isoform 1 and isoform 2 are
CC considered agonist and isoform 3 and isoform 4 are considered
CC antagonist.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. Pelle subfamily. {ECO:0000305}.
CC -!- CAUTION: Asn-333 is present instead of the conserved Asp which is
CC expected to be an active site residue. {ECO:0000305}.
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DR EMBL; AJ440756; CAD29447.2; -; mRNA.
DR EMBL; AY162378; AAO24761.1; -; mRNA.
DR EMBL; AY162379; AAO24762.1; -; mRNA.
DR EMBL; AY162380; AAO24763.1; -; mRNA.
DR EMBL; AY162381; AAO24764.1; -; mRNA.
DR EMBL; AK028733; BAC26088.1; -; mRNA.
DR EMBL; AK033707; BAC28438.1; -; mRNA.
DR EMBL; AK078062; BAC37114.1; -; mRNA.
DR EMBL; AK148248; BAE28437.1; -; mRNA.
DR EMBL; AK150056; BAE29271.1; -; mRNA.
DR EMBL; AK151428; BAE30392.1; -; mRNA.
DR EMBL; AK152682; BAE31414.1; -; mRNA.
DR EMBL; AK154715; BAE32783.1; -; mRNA.
DR EMBL; BC085324; AAH85324.1; -; mRNA.
DR CCDS; CCDS20430.1; -. [Q8CFA1-1]
DR CCDS; CCDS51873.1; -. [Q8CFA1-2]
DR RefSeq; NP_001107025.1; NM_001113553.1. [Q8CFA1-2]
DR RefSeq; NP_751893.3; NM_172161.4. [Q8CFA1-1]
DR RefSeq; XP_006505388.1; XM_006505325.3. [Q8CFA1-4]
DR AlphaFoldDB; Q8CFA1; -.
DR SMR; Q8CFA1; -.
DR BioGRID; 224495; 17.
DR DIP; DIP-49685N; -.
DR IntAct; Q8CFA1; 4.
DR MINT; Q8CFA1; -.
DR STRING; 10090.ENSMUSP00000055073; -.
DR iPTMnet; Q8CFA1; -.
DR PhosphoSitePlus; Q8CFA1; -.
DR EPD; Q8CFA1; -.
DR MaxQB; Q8CFA1; -.
DR PaxDb; Q8CFA1; -.
DR PRIDE; Q8CFA1; -.
DR ProteomicsDB; 269328; -. [Q8CFA1-1]
DR ProteomicsDB; 269329; -. [Q8CFA1-2]
DR ProteomicsDB; 269330; -. [Q8CFA1-3]
DR ProteomicsDB; 269331; -. [Q8CFA1-4]
DR Antibodypedia; 4605; 717 antibodies from 42 providers.
DR DNASU; 108960; -.
DR Ensembl; ENSMUST00000059286; ENSMUSP00000055073; ENSMUSG00000060477. [Q8CFA1-1]
DR Ensembl; ENSMUST00000089022; ENSMUSP00000086416; ENSMUSG00000060477. [Q8CFA1-2]
DR Ensembl; ENSMUST00000089023; ENSMUSP00000086417; ENSMUSG00000060477. [Q8CFA1-3]
DR GeneID; 108960; -.
DR KEGG; mmu:108960; -.
DR UCSC; uc009dhc.3; mouse. [Q8CFA1-1]
DR UCSC; uc009dhe.3; mouse. [Q8CFA1-2]
DR UCSC; uc012eqf.2; mouse. [Q8CFA1-3]
DR CTD; 3656; -.
DR MGI; MGI:2429603; Irak2.
DR VEuPathDB; HostDB:ENSMUSG00000060477; -.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00940000159835; -.
DR HOGENOM; CLU_000288_173_0_1; -.
DR InParanoid; Q8CFA1; -.
DR OMA; ALSEWDW; -.
DR OrthoDB; 684563at2759; -.
DR PhylomeDB; Q8CFA1; -.
DR TreeFam; TF328924; -.
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-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-937042; IRAK2 mediated activation of TAK1 complex.
DR Reactome; R-MMU-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
DR Reactome; R-MMU-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR BioGRID-ORCS; 108960; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Irak2; mouse.
DR PRO; PR:Q8CFA1; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8CFA1; protein.
DR Bgee; ENSMUSG00000060477; Expressed in granulocyte and 59 other tissues.
DR ExpressionAtlas; Q8CFA1; baseline and differential.
DR Genevisible; Q8CFA1; MM.
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: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; ISO:MGI.
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:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 CDD; cd08795; Death_IRAK2; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR042151; Death_IRAK2.
DR InterPro; IPR033611; IRAK2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR PANTHER; PTHR24419:SF2; PTHR24419:SF2; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF00069; Pkinase; 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 Alternative splicing; ATP-binding; Nucleotide-binding; Reference proteome.
FT CHAIN 1..622
FT /note="Interleukin-1 receptor-associated kinase-like 2"
FT /id="PRO_0000277560"
FT DOMAIN 13..94
FT /note="Death"
FT DOMAIN 208..473
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 511..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 553..591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..591
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 214..222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 235
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 335..338
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..143
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15082713,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_023025"
FT VAR_SEQ 32..93
FT /note="ASYVITDLTQLRKIKSMERVQGVSITRELLWWWSMRQATVQQLVDLLCHLEL
FT YRAAQIVLSW -> G (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15082713"
FT /id="VSP_023026"
FT VAR_SEQ 94..141
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15082713,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_023027"
FT VAR_SEQ 490..499
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15082713"
FT /id="VSP_023028"
FT CONFLICT 129
FT /note="V -> A (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 142..151
FT /note="PIMAGAQRQR -> ALLPSFLLLF (in Ref. 3; BAC28438)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="R -> V (in Ref. 3; BAC37114)"
FT /evidence="ECO:0000305"
FT CONFLICT 188..190
FT /note="GLP -> SLH (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 267
FT /note="V -> I (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="F -> V (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="Q -> R (in Ref. 3; BAC37114)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="L -> F (in Ref. 4; AAH85324)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="C -> G (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 448
FT /note="V -> E (in Ref. 2; AAO24761/AAO24762/AAO24763/
FT AAO24764)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="K -> R (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="W -> G (in Ref. 4; AAH85324)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="S -> G (in Ref. 3; BAC26088)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="F -> S (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 585
FT /note="N -> D (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
FT CONFLICT 599
FT /note="K -> E (in Ref. 3; BAE28437)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 622 AA; 69047 MW; AD4692A0B6BFE733 CRC64;
MACYIYQLPS WVLDDLCRNI DTLSEWDWMQ FASYVITDLT QLRKIKSMER VQGVSITREL
LWWWSMRQAT VQQLVDLLCH LELYRAAQIV LSWKPVPEST SPLPAFPEAV KPGAVATSRR
NLKDEQEKVR PVKPRSLLDT GPIMAGAQRQ RPCEMDAPCS LKTDAPDSPQ SKYCSTSTSA
PKQERLLGLP GDRLFWSEAD VVQATEDFDQ SHRISEGTFA DIYQGQRNGV AFAFKKLREV
AGSSPGSMDR FLQAEMQLCL RCCHANVLPL LGFCTGRQFH SLIYPYMANG SLHDRLWAQG
NSDMLPWPQR ASICSGLLLA VEHLHSLDII HSNVKSANVL LDQHLNPKLA HPVAHPHPDN
KKTKYTVMRT HLFQASAAYL PEHFIRVGQL TKQVDIFSCG IVLAEVLTGI PAMDKDRSPV
YLKDLLLSEI PNSTSSVCSR KTSMGKAVVK EICQRHVEKR AGLLPEACEE AWATAVSVCL
RRRNASVEEA RVSLAGVEEQ LRGQLSLPWS RVSEATGSSS NTPEETDDVD NSSLSVPSLV
MMASCPGAAS SPLFTGHGAA QPSTSGRQEA DSSSEACTGP QTPQNATETS WKIEINEAKR
RLMENIVLYK EERLDSSELF GP
