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Q8CFA1

- IRAK2_MOUSE

UniProt

Q8CFA1 - IRAK2_MOUSE

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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

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 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
Complete GO annotation...

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.
ExpressionAtlasiQ8CFA1. baseline and differential.
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, 200-470.
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

        10         20         30         40         50
MACYIYQLPS WVLDDLCRNI DTLSEWDWMQ FASYVITDLT QLRKIKSMER
60 70 80 90 100
VQGVSITREL LWWWSMRQAT VQQLVDLLCH LELYRAAQIV LSWKPVPEST
110 120 130 140 150
SPLPAFPEAV KPGAVATSRR NLKDEQEKVR PVKPRSLLDT GPIMAGAQRQ
160 170 180 190 200
RPCEMDAPCS LKTDAPDSPQ SKYCSTSTSA PKQERLLGLP GDRLFWSEAD
210 220 230 240 250
VVQATEDFDQ SHRISEGTFA DIYQGQRNGV AFAFKKLREV AGSSPGSMDR
260 270 280 290 300
FLQAEMQLCL RCCHANVLPL LGFCTGRQFH SLIYPYMANG SLHDRLWAQG
310 320 330 340 350
NSDMLPWPQR ASICSGLLLA VEHLHSLDII HSNVKSANVL LDQHLNPKLA
360 370 380 390 400
HPVAHPHPDN KKTKYTVMRT HLFQASAAYL PEHFIRVGQL TKQVDIFSCG
410 420 430 440 450
IVLAEVLTGI PAMDKDRSPV YLKDLLLSEI PNSTSSVCSR KTSMGKAVVK
460 470 480 490 500
EICQRHVEKR AGLLPEACEE AWATAVSVCL RRRNASVEEA RVSLAGVEEQ
510 520 530 540 550
LRGQLSLPWS RVSEATGSSS NTPEETDDVD NSSLSVPSLV MMASCPGAAS
560 570 580 590 600
SPLFTGHGAA QPSTSGRQEA DSSSEACTGP QTPQNATETS WKIEINEAKR
610 620
RLMENIVLYK EERLDSSELF GP
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, 200-470.
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.
ExpressionAtlasi Q8CFA1. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 95 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