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Q8CFA1

- IRAK2_MOUSE

UniProt

Q8CFA1 - IRAK2_MOUSE

Protein

Interleukin-1 receptor-associated kinase-like 2

Gene

Irak2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 94 (01 Oct 2014)
      Sequence version 2 (01 Jun 2003)
      Previous versions | rss
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    Functioni

    Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei235 – 2351ATPPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi214 – 2229ATPPROSITE-ProRule annotation
    Nucleotide bindingi335 – 3384ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: BHF-UCL
    3. protein kinase activity Source: MGI

    GO - Biological processi

    1. interleukin-1-mediated signaling pathway Source: Ensembl
    2. lipopolysaccharide-mediated signaling pathway Source: MGI
    3. negative regulation of NF-kappaB transcription factor activity Source: Ensembl
    4. negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
    5. positive regulation of NF-kappaB transcription factor activity Source: MGI
    6. regulation of cytokine-mediated signaling pathway Source: Ensembl

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_198536. IRAK2 mediated activation of TAK1 complex.
    REACT_198690. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
    REACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
    REACT_211125. NOD1/2 Signaling Pathway.
    REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_224208. Interleukin-1 signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interleukin-1 receptor-associated kinase-like 2
    Short name:
    IRAK-2
    Short name:
    mu-IRAK-2
    Gene namesi
    Name:Irak2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 6

    Organism-specific databases

    MGIiMGI:2429603. Irak2.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 622622Interleukin-1 receptor-associated kinase-like 2PRO_0000277560Add
    BLAST

    Proteomic databases

    PRIDEiQ8CFA1.

    PTM databases

    PhosphoSiteiQ8CFA1.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed, with a higher expression observed in brain, spleen and liver. Isoform 1 and isoform 2 are considered agonist and isoform 3 and isoform 4 are considered antagonist.

    Gene expression databases

    BgeeiQ8CFA1.
    CleanExiMM_IRAK2.
    GenevestigatoriQ8CFA1.

    Interactioni

    Subunit structurei

    Interacts with MYD88. IL-1 stimulation leads to the formation of a signaling complex which dissociates from the IL-1 receptor following the binding of PELI1 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi224495. 2 interactions.
    DIPiDIP-49685N.
    IntActiQ8CFA1. 4 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CFA1.
    SMRiQ8CFA1. Positions 2-94, 195-498.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini13 – 9482DeathAdd
    BLAST
    Domaini208 – 473266Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The protein kinase domain is predicted to be catalytically inactive.

    Sequence similaritiesi

    Contains 1 death domain.Curated
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00530000063073.
    HOVERGENiHBG052145.
    InParanoidiQ8CFA1.
    KOiK04731.
    OMAiLSEWDWM.
    OrthoDBiEOG747PHP.
    PhylomeDBiQ8CFA1.
    TreeFamiTF328924.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    InterProiIPR011029. DEATH-like_dom.
    IPR000488. Death_domain.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    [Graphical view]
    PfamiPF00531. Death. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8CFA1-1) [UniParc]FASTAAdd to Basket

    Also known as: IRAK-2a

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MACYIYQLPS WVLDDLCRNI DTLSEWDWMQ FASYVITDLT QLRKIKSMER    50
    VQGVSITREL LWWWSMRQAT VQQLVDLLCH LELYRAAQIV LSWKPVPEST 100
    SPLPAFPEAV KPGAVATSRR NLKDEQEKVR PVKPRSLLDT GPIMAGAQRQ 150
    RPCEMDAPCS LKTDAPDSPQ SKYCSTSTSA PKQERLLGLP GDRLFWSEAD 200
    VVQATEDFDQ SHRISEGTFA DIYQGQRNGV AFAFKKLREV AGSSPGSMDR 250
    FLQAEMQLCL RCCHANVLPL LGFCTGRQFH SLIYPYMANG SLHDRLWAQG 300
    NSDMLPWPQR ASICSGLLLA VEHLHSLDII HSNVKSANVL LDQHLNPKLA 350
    HPVAHPHPDN KKTKYTVMRT HLFQASAAYL PEHFIRVGQL TKQVDIFSCG 400
    IVLAEVLTGI PAMDKDRSPV YLKDLLLSEI PNSTSSVCSR KTSMGKAVVK 450
    EICQRHVEKR AGLLPEACEE AWATAVSVCL RRRNASVEEA RVSLAGVEEQ 500
    LRGQLSLPWS RVSEATGSSS NTPEETDDVD NSSLSVPSLV MMASCPGAAS 550
    SPLFTGHGAA QPSTSGRQEA DSSSEACTGP QTPQNATETS WKIEINEAKR 600
    RLMENIVLYK EERLDSSELF GP 622
    Length:622
    Mass (Da):69,047
    Last modified:June 1, 2003 - v2
    Checksum:iAD4692A0B6BFE733
    GO
    Isoform 2 (identifier: Q8CFA1-2) [UniParc]FASTAAdd to Basket

    Also known as: IRAK-2b

    The sequence of this isoform differs from the canonical sequence as follows:
         94-141: Missing.

    Show »
    Length:574
    Mass (Da):63,870
    Checksum:iEFA629937D2F6335
    GO
    Isoform 3 (identifier: Q8CFA1-3) [UniParc]FASTAAdd to Basket

    Also known as: IRAK-2d

    The sequence of this isoform differs from the canonical sequence as follows:
         32-93: ASYVITDLTQLRKIKSMERVQGVSITRELLWWWSMRQATVQQLVDLLCHLELYRAAQIVLSW → G
         490-499: Missing.

    Show »
    Length:551
    Mass (Da):60,734
    Checksum:iE4030CE5C6EB366A
    GO
    Isoform 4 (identifier: Q8CFA1-4) [UniParc]FASTAAdd to Basket

    Also known as: IRAK-2c

    The sequence of this isoform differs from the canonical sequence as follows:
         1-143: Missing.

    Show »
    Length:479
    Mass (Da):52,463
    Checksum:iA029C4439FAC23D2
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti129 – 1291V → A in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti142 – 15110PIMAGAQRQR → ALLPSFLLLF in BAC28438. (PubMed:16141072)Curated
    Sequence conflicti151 – 1511R → V in BAC37114. (PubMed:16141072)Curated
    Sequence conflicti188 – 1903GLP → SLH in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti267 – 2671V → I in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti273 – 2731F → V in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti343 – 3431Q → R in BAC37114. (PubMed:16141072)Curated
    Sequence conflicti345 – 3451L → F in AAH85324. (PubMed:15489334)Curated
    Sequence conflicti438 – 4381C → G in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti448 – 4481V → E in AAO24761. (PubMed:15082713)Curated
    Sequence conflicti448 – 4481V → E in AAO24762. (PubMed:15082713)Curated
    Sequence conflicti448 – 4481V → E in AAO24763. (PubMed:15082713)Curated
    Sequence conflicti448 – 4481V → E in AAO24764. (PubMed:15082713)Curated
    Sequence conflicti459 – 4591K → R in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti509 – 5091W → G in AAH85324. (PubMed:15489334)Curated
    Sequence conflicti535 – 5351S → G in BAC26088. (PubMed:16141072)Curated
    Sequence conflicti554 – 5541F → S in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti585 – 5851N → D in BAE28437. (PubMed:16141072)Curated
    Sequence conflicti599 – 5991K → E in BAE28437. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 143143Missing in isoform 4. 2 PublicationsVSP_023025Add
    BLAST
    Alternative sequencei32 – 9362ASYVI…IVLSW → G in isoform 3. 1 PublicationVSP_023026Add
    BLAST
    Alternative sequencei94 – 14148Missing in isoform 2. 2 PublicationsVSP_023027Add
    BLAST
    Alternative sequencei490 – 49910Missing in isoform 3. 1 PublicationVSP_023028

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ440756 mRNA. Translation: CAD29447.2.
    AY162378 mRNA. Translation: AAO24761.1.
    AY162379 mRNA. Translation: AAO24762.1.
    AY162380 mRNA. Translation: AAO24763.1.
    AY162381 mRNA. Translation: AAO24764.1.
    AK028733 mRNA. Translation: BAC26088.1.
    AK033707 mRNA. Translation: BAC28438.1.
    AK078062 mRNA. Translation: BAC37114.1.
    AK148248 mRNA. Translation: BAE28437.1.
    AK150056 mRNA. Translation: BAE29271.1.
    AK151428 mRNA. Translation: BAE30392.1.
    AK152682 mRNA. Translation: BAE31414.1.
    AK154715 mRNA. Translation: BAE32783.1.
    BC085324 mRNA. Translation: AAH85324.1.
    CCDSiCCDS20430.1. [Q8CFA1-1]
    CCDS51873.1. [Q8CFA1-2]
    RefSeqiNP_001107025.1. NM_001113553.1. [Q8CFA1-2]
    NP_751893.3. NM_172161.4. [Q8CFA1-1]
    XP_006505388.1. XM_006505325.1. [Q8CFA1-4]
    UniGeneiMm.152142.

    Genome annotation databases

    EnsembliENSMUST00000059286; ENSMUSP00000055073; ENSMUSG00000060477. [Q8CFA1-1]
    ENSMUST00000089022; ENSMUSP00000086416; ENSMUSG00000060477. [Q8CFA1-2]
    ENSMUST00000089023; ENSMUSP00000086417; ENSMUSG00000060477. [Q8CFA1-3]
    ENSMUST00000113024; ENSMUSP00000108647; ENSMUSG00000060477. [Q8CFA1-4]
    GeneIDi108960.
    KEGGimmu:108960.
    UCSCiuc009dhc.3. mouse. [Q8CFA1-1]
    uc009dhe.3. mouse. [Q8CFA1-2]
    uc012eqf.2. mouse. [Q8CFA1-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ440756 mRNA. Translation: CAD29447.2 .
    AY162378 mRNA. Translation: AAO24761.1 .
    AY162379 mRNA. Translation: AAO24762.1 .
    AY162380 mRNA. Translation: AAO24763.1 .
    AY162381 mRNA. Translation: AAO24764.1 .
    AK028733 mRNA. Translation: BAC26088.1 .
    AK033707 mRNA. Translation: BAC28438.1 .
    AK078062 mRNA. Translation: BAC37114.1 .
    AK148248 mRNA. Translation: BAE28437.1 .
    AK150056 mRNA. Translation: BAE29271.1 .
    AK151428 mRNA. Translation: BAE30392.1 .
    AK152682 mRNA. Translation: BAE31414.1 .
    AK154715 mRNA. Translation: BAE32783.1 .
    BC085324 mRNA. Translation: AAH85324.1 .
    CCDSi CCDS20430.1. [Q8CFA1-1 ]
    CCDS51873.1. [Q8CFA1-2 ]
    RefSeqi NP_001107025.1. NM_001113553.1. [Q8CFA1-2 ]
    NP_751893.3. NM_172161.4. [Q8CFA1-1 ]
    XP_006505388.1. XM_006505325.1. [Q8CFA1-4 ]
    UniGenei Mm.152142.

    3D structure databases

    ProteinModelPortali Q8CFA1.
    SMRi Q8CFA1. Positions 2-94, 195-498.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 224495. 2 interactions.
    DIPi DIP-49685N.
    IntActi Q8CFA1. 4 interactions.

    PTM databases

    PhosphoSitei Q8CFA1.

    Proteomic databases

    PRIDEi Q8CFA1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000059286 ; ENSMUSP00000055073 ; ENSMUSG00000060477 . [Q8CFA1-1 ]
    ENSMUST00000089022 ; ENSMUSP00000086416 ; ENSMUSG00000060477 . [Q8CFA1-2 ]
    ENSMUST00000089023 ; ENSMUSP00000086417 ; ENSMUSG00000060477 . [Q8CFA1-3 ]
    ENSMUST00000113024 ; ENSMUSP00000108647 ; ENSMUSG00000060477 . [Q8CFA1-4 ]
    GeneIDi 108960.
    KEGGi mmu:108960.
    UCSCi uc009dhc.3. mouse. [Q8CFA1-1 ]
    uc009dhe.3. mouse. [Q8CFA1-2 ]
    uc012eqf.2. mouse. [Q8CFA1-3 ]

    Organism-specific databases

    CTDi 3656.
    MGIi MGI:2429603. Irak2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00530000063073.
    HOVERGENi HBG052145.
    InParanoidi Q8CFA1.
    KOi K04731.
    OMAi LSEWDWM.
    OrthoDBi EOG747PHP.
    PhylomeDBi Q8CFA1.
    TreeFami TF328924.

    Enzyme and pathway databases

    Reactomei REACT_198536. IRAK2 mediated activation of TAK1 complex.
    REACT_198690. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
    REACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
    REACT_211125. NOD1/2 Signaling Pathway.
    REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_224208. Interleukin-1 signaling.

    Miscellaneous databases

    ChiTaRSi IRAK2. mouse.
    NextBioi 361524.
    PROi Q8CFA1.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8CFA1.
    CleanExi MM_IRAK2.
    Genevestigatori Q8CFA1.

    Family and domain databases

    Gene3Di 1.10.533.10. 1 hit.
    InterProi IPR011029. DEATH-like_dom.
    IPR000488. Death_domain.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    [Graphical view ]
    Pfami PF00531. Death. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification and characterization of murine IRAK-2."
      Rosati O., Martin M.U.
      Biochem. Biophys. Res. Commun. 297:52-58(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Strain: BALB/c.
    2. "The murine IRAK2 gene encodes four alternatively spliced isoforms, two of which are inhibitory."
      Hardy M.P., O'Neill L.A.
      J. Biol. Chem. 279:27699-27708(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
      Strain: C57BL/6.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Strain: C57BL/6J and NOD.
      Tissue: Bone marrow, Cecum, Medulla oblongata and Skin.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
      Tissue: Trophoblast stem cell.

    Entry informationi

    Entry nameiIRAK2_MOUSE
    AccessioniPrimary (citable) accession number: Q8CFA1
    Secondary accession number(s): Q3U3K2
    , Q3U7F5, Q3UFX2, Q5U404, Q6YBR8, Q6YBR9, Q6YBS0, Q6YBS1, Q8C5M0, Q8CC82, Q8CEA0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 6, 2007
    Last sequence update: June 1, 2003
    Last modified: October 1, 2014
    This is version 94 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    Asn-333 is present instead of the conserved Asp which is expected to be an active site residue.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3