Reviewed, UniProtKB/Swiss-Prot O43187 (IRAK2_HUMAN)

Names and origin

Protein names

Recommended name:
    Interleukin-1 receptor-associated kinase-like 2
      Short name=IRAK-2

Gene names

Name:

IRAK2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	625 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization. Ref.4 Ref.5
Subunit structure	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. Ref.4
Tissue specificity	Expressed in spleen, thymus, prostate, lung, liver, skeletal muscle, kidney, pancreas and peripheral blood leukocytes. Ref.4
Domain	The protein kinase domain is predicted to be catalytically inactive.
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.
Caution	Asn-335 is present instead of the conserved Asp which is expected to be an active site residue. This enzyme has been shown to be catalytically inactive.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Gene Ontology (GO)
Biological process	I-kappaB kinase/NF-kappaB cascade Ref.4 Traceable author statement. Source: ProtInc MyD88-dependent toll-like receptor signaling pathway Ref.5 Traceable author statement. Source: UniProtKB inflammatory response Ref.4 Traceable author statement. Source: ProtInc interleukin-1-mediated signaling pathway Ref.5 Inferred from mutant phenotype. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Ref.5 Inferred from mutant phenotype. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Ref.5 Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Ref.4 Traceable author statement. Source: ProtInc regulation of cytokine-mediated signaling pathway Ref.5 Inferred from mutant phenotype. Source: UniProtKB response to cytokine stimulus Ref.5 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro NF-kappaB-inducing kinase activity Ref.4 Traceable author statement. Source: ProtInc protein heterodimerization activity Ref.5 Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Ref.5 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-447733,EBI-447733
IRAK1	P51617	1	EBI-447733,EBI-358664
IRAK3	Q9Y616	1	EBI-447733,EBI-447690
MYD88	Q99836	1	EBI-447733,EBI-447677
TIRAP	P58753	1	EBI-447733,EBI-528644
TRAF6	Q9Y4K3	1	EBI-447733,EBI-359276

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 625	625	Interleukin-1 receptor-associated kinase-like 2		PRO_0000086032
Regions
	Domain	13 – 94	82	Death
	Domain	210 – 489	280	Protein kinase
Natural variations
	Natural variant	43	1	R → Q Ref.6		VAR_041342
	Natural variant	47	1	S → Y: dbSNP rs11465864. Ref.6		VAR_030527
	Natural variant	99	1	I → V Ref.6		VAR_041343
	Natural variant	147	1	R → T Ref.6		VAR_041344
	Natural variant	214	1	R → G Ref.6		VAR_041345
	Natural variant	249	1	S → L in a lung adenocarcinoma sample; somatic mutation. Ref.6		VAR_041346
	Natural variant	392	1	L → V: dbSNP rs3844283. Ref.6		VAR_030528
	Natural variant	421	1	P → T in a lung adenocarcinoma sample; somatic mutation. Ref.6		VAR_041347
	Natural variant	431	1	D → E: dbSNP rs708035. Ref.4 Ref.6 Ref.1		VAR_030529
	Natural variant	439	1	L → V: dbSNP rs11465927. Ref.6		VAR_030530
	Natural variant	469	1	D → N Ref.6		VAR_041348
	Natural variant	503	1	L → I: dbSNP rs9854688. Ref.6		VAR_030531
	Natural variant	566	1	R → W Ref.6		VAR_041349
	Natural variant	574	1	D → H: dbSNP rs11465930.		VAR_030532

Sequences

	Sequence		Length	Mass (Da)
	O43187-1 [UniParc]. Last modified February 6, 2007. Version 2. Checksum: 715C954BC9452710	FASTA	625	69,433
	10 20 30 40 50 60 MACYIYQLPS WVLDDLCRNM DALSEWDWME FASYVITDLT QLRKIKSMER VQGVSITREL 70 80 90 100 110 120 LWWWGMRQAT VQQLVDLLCR LELYRAAQII LNWKPAPEIR CPIPAFPDSV KPEKPLAASV 130 140 150 160 170 180 RKAEDEQEEG QPVRMATFPG PGSSPARAHQ PAFLQPPEED APHSLRSDLP TSSDSKDFST 190 200 210 220 230 240 SIPKQEKLLS LAGDSLFWSE ADVVQATDDF NQNRKISQGT FADVYRGHRH GKPFVFKKLR 250 260 270 280 290 300 ETACSSPGSI ERFFQAELQI CLRCCHPNVL PVLGFCAARQ FHSFIYPYMA NGSLQDRLQG 310 320 330 340 350 360 QGGSDPLPWP QRVSICSGLL CAVEYLHGLE IIHSNVKSSN VLLDQNLTPK LAHPMAHLCP 370 380 390 400 410 420 VNKRSKYTMM KTHLLRTSAA YLPEDFIRVG QLTKRVDIFS CGIVLAEVLT GIPAMDNNRS 430 440 450 460 470 480 PVYLKDLLLS DIPSSTASLC SRKTGVENVM AKEICQKYLE KGAGRLPEDC AEALATAACL 490 500 510 520 530 540 CLRRRNTSLQ EVCGSVAAVE ERLRGRETLL PWSGLSEGTG SSSNTPEETD DVDNSSLDAS 550 560 570 580 590 600 SSMSVAPWAG AATPLLPTEN GEGRLRVIVG READSSSEAC VGLEPPQDVT ETSWQIEINE 610 620 AKRKLMENIL LYKEEKVDSI ELFGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of Exon 13 and the 3'UTR region of human IRAK-2 and characterisation of the full length gene." Rosati O., Martin M.U. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-431.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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].
[4]	"IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling." Muzio M., Ni J., Feng P., Dixit V.M. Science 278:1612-1615(1997) [PubMed: 9374458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-590, FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TRAF6; MYD88 AND IL1R1, VARIANT GLU-431. Tissue: Endothelial cell.
[5]	"IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family." Wesche H., Gao X., Li X., Kirschning C.J., Stark G.R., Cao Z. J. Biol. Chem. 274:19403-19410(1999) [PubMed: 10383454] [Abstract] Cited for: FUNCTION.
[6]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-43; TYR-47; VAL-99; THR-147; GLY-214; LEU-249; VAL-392; THR-421; GLU-431; VAL-439; ASN-469; ILE-503 AND TRP-566.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ496794 mRNA. Translation: CAD43180.3. AK299033 mRNA. Translation: BAG61108.1. BC125184 mRNA. Translation: AAI25185.1. AF026273 mRNA. Translation: AAB87669.1.
IPI	IPI00304986.
RefSeq	NP_001561.3.
UniGene	Hs.449207
3D structure databases
HSSP	HSSP built from PDB template 1D2Z based on UniProtKB Q05652.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43187. 7 interactions.
Proteomic databases
PeptideAtlas	O43187.
PRIDE	O43187.
Genome annotation databases
Ensembl	ENSG00000134070. Homo sapiens. [Contig view]
GeneID	3656.
KEGG	hsa:3656.
Organism-specific databases
GeneCards	GC03P010181.
H-InvDB	HIX0030702.
HGNC	HGNC:6113. IRAK2.
HPA	CAB013483.
MIM	603304. gene.
PharmGKB	PA29913.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O43187.
HOVERGEN	O43187.
OMA	O43187. THLFQAS.
Enzyme and pathway databases
BRENDA	2.7.10.2. 247.
Gene expression databases
ArrayExpress	O43187.
Bgee	O43187.
CleanEx	HS_IRAK2.
Family and domain databases
InterPro	IPR000488. Death. IPR011029. DEATH-like. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
Pfam	PF00531. Death. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
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	14303.
SOURCE	Search...

Entry information

Entry name

IRAK2_HUMAN

Accession

Primary (citable) accession number: O43187
Secondary accession number(s): B4DQZ6, Q08AG6, Q5K546

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	February 6, 2007
Last modified:	June 16, 2009
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)