O43187 (IRAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	625 AA.
Sequence status	Complete.
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
Ligand	ATP-binding Nucleotide-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Traceable author statement Ref.4. Source: ProtInc JNK cascade Traceable author statement. Source: Reactome MyD88-dependent toll-like receptor signaling pathway Traceable author statement Ref.5. Source: BHF-UCL TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome activation of MAPK activity Traceable author statement. Source: Reactome inflammatory response Traceable author statement Ref.4. Source: ProtInc innate immune response Traceable author statement. Source: Reactome interleukin-1-mediated signaling pathway Inferred from mutant phenotype Ref.5. Source: BHF-UCL lipopolysaccharide-mediated signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.5. Source: BHF-UCL nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.5. Source: BHF-UCL regulation of cytokine-mediated signaling pathway Inferred from mutant phenotype Ref.5. Source: BHF-UCL toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cell surface Inferred from direct assay PubMed 12493773. Source: UniProtKB cytosol Traceable author statement. Source: Reactome endosome membrane Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	2	EBI-447733,EBI-365961
IRAK1	P51617	3	EBI-447733,EBI-358664
IRAK3	Q9Y616	3	EBI-447733,EBI-447690
Sarm1	Q6PDS3	2	EBI-447733,EBI-6117196	From a different organism.
STT3A	P46977	2	EBI-447733,EBI-719212
TARDBP	Q13148	2	EBI-447733,EBI-372899
TIRAP	P58753	2	EBI-447733,EBI-528644
TOLLIP	Q9H0E2	2	EBI-447733,EBI-74615
TRAF6	Q9Y4K3	3	EBI-447733,EBI-359276
ZC3H12A	Q5D1E8	2	EBI-447733,EBI-747793

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

Nucleotide binding

216 – 224

9

ATP By similarity

Nucleotide binding

337 – 340

4

ATP By similarity

Sites

Binding site

237

1

ATP By similarity

Natural variations

Natural variant

43

1

R → Q. Ref.7
Corresponds to variant rs34945585 [ dbSNP | Ensembl ].

VAR_041342

Natural variant

47

1

S → Y. Ref.7
Corresponds to variant rs11465864 [ dbSNP | Ensembl ].

VAR_030527

Natural variant

99

1

I → V. Ref.7
Corresponds to variant rs55898544 [ dbSNP | Ensembl ].

VAR_041343

Natural variant

147

1

R → T. Ref.7
Corresponds to variant rs56053222 [ dbSNP | Ensembl ].

VAR_041344

Natural variant

214

1

R → G. Ref.7
Corresponds to variant rs35060588 [ dbSNP | Ensembl ].

VAR_041345

Natural variant

249

1

S → L in a lung adenocarcinoma sample; somatic mutation. Ref.7

VAR_041346

Natural variant

392

1

L → V. Ref.7
Corresponds to variant rs3844283 [ dbSNP | Ensembl ].

VAR_030528

Natural variant

421

1

P → T in a lung adenocarcinoma sample; somatic mutation. Ref.7

VAR_041347

Natural variant

431

1

D → E. Ref.1 Ref.4 Ref.7
Corresponds to variant rs708035 [ dbSNP | Ensembl ].

VAR_030529

Natural variant

439

1

L → V. Ref.7
Corresponds to variant rs11465927 [ dbSNP | Ensembl ].

VAR_030530

Natural variant

469

1

D → N. Ref.7
Corresponds to variant rs56242986 [ dbSNP | Ensembl ].

VAR_041348

Natural variant

503

1

L → I. Ref.7
Corresponds to variant rs9854688 [ dbSNP | Ensembl ].

VAR_030531

Natural variant

566

1

R → W. Ref.7
Corresponds to variant rs55740652 [ dbSNP | Ensembl ].

VAR_041349

Natural variant

574

1

D → H.
Corresponds to variant rs11465930 [ dbSNP | Ensembl ].

VAR_030532

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

625

Helix Strand Turn

Details...

Helix

5 – 7

3

Helix

10 – 16

7

Turn

17 – 22

6

Helix

25 – 32

8

Turn

33 – 36

4

Helix

39 – 47

9

Helix

48 – 50

3

Helix

56 – 65

10

Turn

66 – 68

3

Helix

72 – 76

5

Turn

77 – 81

5

Helix

84 – 87

4

Turn

88 – 91

4

Sequences

	Sequence		Length	Mass (Da)
	O43187 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling." Lin S.-C., Lo Y.-C., Wu H. Nature 465:885-890(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 2-112.
[7]	"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] [Europe PMC] [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

EMBL
GenBank
DDBJ

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. NM_001570.3.

UniGene

Hs.449207.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MOP	X-ray	3.40	K/L/M/N	2-112	[»]

ProteinModelPortal

O43187.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31800N.

IntAct

O43187. 30 interactions.

MINT

MINT-97184.

STRING

9606.ENSP00000256458.

PTM databases

PhosphoSite

O43187.

Proteomic databases

PaxDb

O43187.

PeptideAtlas

O43187.

PRIDE

O43187.

Protocols and materials databases

DNASU

3656.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256458; ENSP00000256458; ENSG00000134070.

GeneID

3656.

KEGG

hsa:3656.

UCSC

uc003bve.1. human.

Organism-specific databases

CTD

3656.

GeneCards

GC03P010206.

HGNC

HGNC:6113. IRAK2.

HPA

CAB013483.

MIM

603304. gene.

neXtProt

NX_O43187.

PharmGKB

PA29913.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000113102.

HOVERGEN

HBG052145.

InParanoid

O43187.

KO

K04731.

OMA

PWSGLSE.

OrthoDB

EOG4R23TT.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Reactome

REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

Bgee

O43187.

CleanEx

HS_IRAK2.

Genevestigator

O43187.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.

InterPro

IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
[Graphical view]

Pfam

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

SUPFAM

SSF47986. DEATH_like. 1 hit.
SSF56112. Kinase_like. 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

EvolutionaryTrace

O43187.

GenomeRNAi

3656.

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:	May 1, 2013
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.