Reviewed, UniProtKB/Swiss-Prot Q8R4K2 (IRAK4_MOUSE)

Names and origin

Protein names

Recommended name:
    Interleukin-1 receptor-associated kinase 4
      Short name=IRAK-4
    EC=2.7.11.1

Gene names

Name:

Irak4

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	459 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for the efficient recruitment of IRAK1 to the IL-1 receptor complex following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization. Phosphorylates IRAK1 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Subunit structure	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. Interacts with IL1RL1 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily. Contains 1 death domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cytokine production Inferred from direct assay. Source: MGI cytokine-mediated signaling pathway Inferred from direct assay. Source: MGI protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW interleukin-1 receptor binding Inferred from physical interaction. Source: MGI magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 459

459

Interleukin-1 receptor-associated kinase 4

PRO_0000086036

Regions

Domain

20 – 104

85

Death

Domain

186 – 454

269

Protein kinase

Nucleotide binding

192 – 200

9

ATP By similarity

Sites

Active site

311

1

Proton acceptor By similarity

Binding site

213

1

ATP By similarity

Amino acid modifications

Modified residue

3

1

N6-acetyllysine By similarity

Modified residue

34

1

N6-acetyllysine By similarity

Modified residue

152

1

Phosphoserine By similarity

Experimental info

Sequence conflict

321

1

K → R in AAH51676. Ref.3

Secondary structure

1

.

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459

Helix Strand Turn

Details...

Helix

11 – 13

3

Helix

16 – 26

11

Helix

28 – 30

3

Helix

31 – 38

8

Beta strand

44 – 48

5

Helix

50 – 58

9

Turn

59 – 63

5

Helix

66 – 74

9

Helix

75 – 77

3

Helix

81 – 90

10

Helix

94 – 100

7

Helix

102 – 104

3

Sequences

	Sequence		Length	Mass (Da)
	Q8R4K2-1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: FC11AD06983B7AEB	FASTA	459	50,872
	10 20 30 40 50 60 MNKPLTPSTY IRNLNVGILR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ FHIRRFEALL 70 80 90 100 110 120 QTGKSPTCEL LFDWGTTNCT VGDLVDLLVQ IELFAPATLL LPDAVPQTVK SLPPREAATV 130 140 150 160 170 180 AQTHGPCQEK DRTSVMPMPK LEHSCEPPDS SSPDNRSVES SDTRFHSFSF HELKSITNNF 190 200 210 220 230 240 DEQPASAGGN RMGEGGFGVV YKGCVNNTIV AVKKLGAMVE ISTEELKQQF DQEIKVMATC 250 260 270 280 290 300 QHENLVELLG FSSDSDNLCL VYAYMPNGSL LDRLSCLDGT PPLSWHTRCK VAQGTANGIR 310 320 330 340 350 360 FLHENHHIHR DIKSANILLD KDFTAKISDF GLARASARLA QTVMTSRIVG TTAYMAPEAL 370 380 390 400 410 420 RGEITPKSDI YSFGVVLLEL ITGLAAVDEN REPQLLLDIK EEIEDEEKTI EDYTDEKMSD 430 440 450 ADPASVEAMY SAASQCLHEK KNRRPDIAKV QQLLQEMSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase." Li S., Strelow A., Fontana E.J., Wesche H. Proc. Natl. Acad. Sci. U.S.A. 99:5567-5572(2002) [PubMed: 11960013] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Skin.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Embryo.
[4]	"Molecular structure of the IL-1R-associated kinase-4 death domain and its implications for TLR signaling." Lasker M.V., Gajjar M.M., Nair S.K. J. Immunol. 175:4175-4179(2005) [PubMed: 16177054] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-113.
[5]	"Solution structure of the death domain of interleukin-1 receptor-associated kinase 4 (IRAK4) from Mus musculus." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-114.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF445803 mRNA. Translation: AAM15773.1.
AK028837 mRNA. Translation: BAC26146.1.
BC051676 mRNA. Translation: AAH51676.1.

IPI

IPI00153899.

RefSeq

NP_084202.2.

UniGene

Mm.422858

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WH4	NMR	-	A	1-114	[»]
2A9I	X-ray	1.70	A	1-113	[»]

SMR

Q8R4K2. Positions 163-458.

ModBase

Search...

Protein-protein interaction databases

STRING

Q8R4K2.

PTM databases

PhosphoSite

Q8R4K2.

Proteomic databases

PRIDE

Q8R4K2.

Genome annotation databases

Ensembl

ENSMUST00000074936; ENSMUSP00000074471; ENSMUSG00000059883; Mus musculus. [Genome view]

GeneID

266632.

KEGG

mmu:266632.

UCSC

uc007xjk.1. mouse.

Organism-specific databases

CTD

266632.

MGI

MGI:2182474. Irak4.

Phylogenomic databases

HOGENOM

HBG713523.

HOVERGEN

Q8R4K2.

InParanoid

Q8R4K2.

OMA

MVEISTE.

PhylomeDB

Q8R4K2.

Enzyme and pathway databases

BRENDA

2.7.11.1. 244.

Gene expression databases

ArrayExpress

Q8R4K2.

Bgee

Q8R4K2.

CleanEx

MM_IRAK4.

Genevestigator

Q8R4K2.

GermOnline

ENSMUSG00000059883. Mus musculus.

Family and domain databases

InterPro

IPR000488. Death.
IPR011029. DEATH-like.
IPR017428. Interleukin-1_rcpt-assoc_kin4.
IPR015787. Interleukin1_rcpt-assoc_kin4_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017442. Se/Thr_prot_kinase-like_dom.
[Graphical view]

PANTHER

PTHR23258:SF428. IRAK4. 1 hit.

Pfam

PF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

PIRSF

PIRSF038189. IRAK4. 1 hit.

PROSITE

PS50017. DEATH_DOMAIN. False negative.
PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

392172.

SOURCE

Search...

Entry information

Entry name

IRAK4_MOUSE

Accession

Primary (citable) accession number: Q8R4K2
Secondary accession number(s): Q80WW1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	June 1, 2002
Last modified:	January 19, 2010
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)