EKS-HOS-00412

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00412

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TKL/IRAK	419.8	2.7E-125	212	518	307

Status

Reviewed

Ensembl Protein

ENSP00000358997

UniProt Accession

P51617; D3DWW3; D3DWW4; Q7Z5V4; Q96C06; Q96RL2;

Protein Name

Interleukin-1 receptor-associated kinase 1

Protein Synonyms/Alias

IRAK-1;

Gene Name

IRAK1

Gene Synonyms/Alias

IRAK1; IRAK;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000184216	ENSP00000392662	ENST00000429936
ENSG00000184216	ENSP00000358997	ENST00000369980
ENSG00000184216	ENSP00000399974	ENST00000444230
ENSG00000184216	ENSP00000403730	ENST00000443220
ENSG00000184216	ENSP00000377291	ENST00000393687
ENSG00000184216	ENSP00000377287	ENST00000393682
ENSG00000184216	ENSP00000406249	ENST00000437278
ENSG00000184216	ENSP00000410953	ENST00000444254
ENSG00000184216	ENSP00000358991	ENST00000369974
ENSG00000184216	ENSP00000358990	ENST00000369973
ENSG00000184216	ENSP00000411809	ENST00000455690

Organism

Homo sapiens

Functional Description

Serine/threonine-protein kinase that plays a criticalrole in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor- signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.

Protein Length

712

Protein Sequence
(FASTA)

MAGGPGPGEP AAPGAQHFLY EVPPWVMCRF YKVMDALEPA DWCQFAALIV RDQTELRLCE 60

RSGQRTASVL WPWINRNARV ADLVHILTHL QLLRARDIIT AWHPPAPLPS PGTTAPRPSS 120

IPAPAEAEAW SPRKLPSSAS TFLSPAFPGS QTHSGPELGL VPSPASLWPP PPSPAPSSTK 180

PGPESSVSLL QGARPFPFCW PLCEISRGTH NFSEELKIGE GGFGCVYRAV MRNTVYAVKR 240

LKENADLEWT AVKQSFLTEV EQLSRFRHPN IVDFAGYCAQ NGFYCLVYGF LPNGSLEDRL 300

HCQTQACPPL SWPQRLDILL GTARAIQFLH QDSPSLIHGD IKSSNVLLDE RLTPKLGDFG 360

LARFSRFAGS SPSQSSMVAR TQTVRGTLAY LPEEYIKTGR LAVDTDTFSF GVVVLETLAG 420

QRAVKTHGAR TKYLKDLVEE EAEEAGVALR STQSTLQAGL AADAWAAPIA MQIYKKHLDP 480

RPGPCPPELG LGLGQLACCC LHRRAKRRPP MTQVYERLEK LQAVVAGVPG HSEAASCIPP 540

SPQENSYVSS TGRAHSGAAP WQPLAAPSGA SAQAAEQLQR GPNQPVESDE SLGGLSAALR 600

SWHLTPSCPL DPAPLREAGC PQGDTAGESS WGSGPGSRPT AVEGLALGSS ASSSSEPPQI 660

IINPARQKMV QKLALYEDGA LDSLQLLSSS SLPGLGLEQD RQGPEESDEF QS 712

Nucleotide Sequence
(FASTA)

ATGGCCGGGG GGCCGGGCCC GGGGGAGCCC GCAGCCCCCG GCGCCCAGCA CTTCTTGTAC 60

GAGGTGCCGC CCTGGGTCAT GTGCCGCTTC TACAAAGTGA TGGACGCCCT GGAGCCCGCC 120

GACTGGTGCC AGTTCGCCGC CCTGATCGTG CGCGACCAGA CCGAGCTGCG GCTGTGCGAG 180

CGCTCCGGGC AGCGCACGGC CAGCGTCCTG TGGCCCTGGA TCAACCGCAA CGCCCGTGTG 240

GCCGACCTCG TGCACATCCT CACGCACCTG CAGCTGCTCC GTGCGCGGGA CATCATCACA 300

GCCTGGCACC CTCCCGCCCC GCTTCCGTCC CCAGGCACCA CTGCCCCGAG GCCCAGCAGC 360

ATCCCTGCAC CCGCCGAGGC CGAGGCCTGG AGCCCCCGGA AGTTGCCATC CTCAGCCTCC 420

ACCTTCCTCT CCCCAGCTTT TCCAGGCTCC CAGACCCATT CAGGGCCTGA GCTCGGCCTG 480

GTCCCAAGCC CTGCTTCCCT GTGGCCTCCA CCGCCATCTC CAGCCCCTTC TTCTACCAAG 540

CCAGGCCCAG AGAGCTCAGT GTCCCTCCTG CAGGGAGCCC GCCCCTTTCC GTTTTGCTGG 600

CCCCTCTGTG AGATTTCCCG GGGCACCCAC AACTTCTCGG AGGAGCTCAA GATCGGGGAG 660

GGTGGCTTTG GGTGCGTGTA CCGGGCGGTG ATGAGGAACA CGGTGTATGC TGTGAAGAGG 720

CTGAAGGAGA ACGCTGACCT GGAGTGGACT GCAGTGAAGC AGAGCTTCCT GACCGAGGTG 780

GAGCAGCTGT CCAGGTTTCG TCACCCAAAC ATTGTGGACT TTGCTGGCTA CTGTGCTCAG 840

AACGGCTTCT ACTGCCTGGT GTACGGCTTC CTGCCCAACG GCTCCCTGGA GGACCGTCTC 900

CACTGCCAGA CCCAGGCCTG CCCACCTCTC TCCTGGCCTC AGCGACTGGA CATCCTTCTG 960

GGTACAGCCC GGGCAATTCA GTTTCTACAT CAGGACAGCC CCAGCCTCAT CCATGGAGAC 1020

ATCAAGAGTT CCAACGTCCT TCTGGATGAG AGGCTGACAC CCAAGCTGGG AGACTTTGGC 1080

CTGGCCCGGT TCAGCCGCTT TGCCGGGTCC AGCCCCAGCC AGAGCAGCAT GGTGGCCCGG 1140

ACACAGACAG TGCGGGGCAC CCTGGCCTAC CTGCCCGAGG AGTACATCAA GACGGGAAGG 1200

CTGGCTGTGG ACACGGACAC CTTCAGCTTT GGGGTGGTAG TGCTAGAGAC CTTGGCTGGT 1260

CAGAGGGCTG TGAAGACGCA CGGTGCCAGG ACCAAGTATC TGAAAGACCT GGTGGAAGAG 1320

GAGGCTGAGG AGGCTGGAGT GGCTTTGAGA AGCACCCAGA GCACACTGCA AGCAGGTCTG 1380

GCTGCAGATG CCTGGGCTGC TCCCATCGCC ATGCAGATCT ACAAGAAGCA CCTGGACCCC 1440

AGGCCCGGGC CCTGCCCACC TGAGCTGGGC CTGGGCCTGG GCCAGCTGGC CTGCTGCTGC 1500

CTGCACCGCC GGGCCAAAAG GAGGCCTCCT ATGACCCAGG TGTACGAGAG GCTAGAGAAG 1560

CTGCAGGCAG TGGTGGCGGG GGTGCCCGGG CATTCGGAGG CCGCCAGCTG CATCCCCCCT 1620

TCCCCGCAGG AGAACTCCTA CGTGTCCAGC ACTGGCAGAG CCCACAGTGG GGCTGCTCCA 1680

TGGCAGCCCC TGGCAGCGCC ATCAGGAGCC AGTGCCCAGG CAGCAGAGCA GCTGCAGAGA 1740

GGCCCCAACC AGCCCGTGGA GAGTGACGAG AGCCTAGGCG GCCTCTCTGC TGCCCTGCGC 1800

TCCTGGCACT TGACTCCAAG CTGCCCTCTG GACCCAGCAC CCCTCAGGGA GGCCGGCTGT 1860

CCTCAGGGGG ACACGGCAGG AGAATCGAGC TGGGGGAGTG GCCCAGGATC CCGGCCCACA 1920

GCCGTGGAAG GACTGGCCCT TGGCAGCTCT GCATCATCGT CGTCAGAGCC ACCGCAGATT 1980

ATCATCAACC CTGCCCGACA GAAGATGGTC CAGAAGCTGG CCCTGTACGA GGATGGGGCC 2040

CTGGACAGCC TGCAGCTGCT GTCGTCCAGC TCCCTCCCAG GCTTGGGCCT GGAACAGGAC 2100

AGGCAGGGGC CCGAAGAAAG TGATGAATTT CAGAGCTGA 2139

Domain Profile

S: 1     fsednrigeGgfgevyrgelkntavavkklkeeadlslkelkqsfltElkvlarfrHdni  60

         fse+ +igeGgfg+vyr+ ++nt++avk+lke+adl+++++kqsfltE+++l+rfrH+ni

Q: 212   FSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNI  271

         899*********************************************************

S: 61    lellgysaeseklcLvYqymknGsLedrLqcq.kgsepLsWpqRlsillGtaraiefLHe  119

         ++++gy+a+++++cLvY++++nGsLedrL+cq ++++pLsWpqRl+illGtarai+fLH+

Q: 272   VDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQtQACPPLSWPQRLDILLGTARAIQFLHQ  331

         ********************************99**************************

S: 120   aspslihgdiksaNiLLDekltpKlgDfglar...fapesekqsstvlrtskvrgtlaYl  176

         +spslihgdiks+N+LLDe+ltpKlgDfglar   fa++s++qss+v+rt++vrgtlaYl

Q: 332   DSPSLIHGDIKSSNVLLDERLTPKLGDFGLARfsrFAGSSPSQSSMVARTQTVRGTLAYL  391

         ********************************98899***********************

S: 177   peefirvgqltvkvDvySfGiVllEvltGlra.vdedrktkyLkdllkeeieeekv....  231

         pee+i++g+l+v++D++SfG+V+lE+l+G+ra ++++++tkyLkdl++ee+ee++v

Q: 392   PEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAvKTHGARTKYLKDLVEEEAEEAGValrs  451

         ********************************77899***********************

S: 232   ....................eilekfldkkagkleeellealielalaclaekakkrPtm  271

                             +i++k+ld ++g++++el   l +la++cl+++ak+rP+m

Q: 452   tqstlqaglaadawaapiamQIYKKHLDPRPGPCPPELGLGLGQLACCCLHRRAKRRPPM  511

         ************************************************************

S: 272   sqvlell  278

         +qv+e+l

Q: 512   TQVYERL  518

         ****987

Domain Sequence
(FASTA)

FSEELKIGEG GFGCVYRAVM RNTVYAVKRL KENADLEWTA VKQSFLTEVE QLSRFRHPNI 60

VDFAGYCAQN GFYCLVYGFL PNGSLEDRLH CQTQACPPLS WPQRLDILLG TARAIQFLHQ 120

DSPSLIHGDI KSSNVLLDER LTPKLGDFGL ARFSRFAGSS PSQSSMVART QTVRGTLAYL 180

PEEYIKTGRL AVDTDTFSFG VVVLETLAGQ RAVKTHGART KYLKDLVEEE AEEAGVALRS 240

TQSTLQAGLA ADAWAAPIAM QIYKKHLDPR PGPCPPELGL GLGQLACCCL HRRAKRRPPM 300

TQVYERL 307

Keyword

Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Immunity; Innate immunity; Kinase; Lipid droplet; Magnesium; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Erinaceus europaeus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0010008	; C:endosome membrane
GO:0045323	; C:interleukin-1 receptor complex
GO:0005811	; C:lipid particle
GO:0005634	; C:nucleus
GO:0005524	; F:ATP binding
GO:0004704	; F:NF-kappaB-inducing kinase activity
GO:0042803	; F:protein homodimerization activity
GO:0004842	; F:ubiquitin-protein ligase activity
GO:0000187	; P:activation of MAPK activity
GO:0007250	; P:activation of NF-kappaB-inducing kinase activity
GO:0045087	; P:innate immune response
GO:0070498	; P:interleukin-1-mediated signaling pathway
GO:0007254	; P:JNK cascade
GO:0031663	; P:lipopolysaccharide-mediated signaling pathway
GO:0002755	; P:MyD88-dependent toll-like receptor signaling pathway
GO:0032088	; P:negative regulation of NF-kappaB transcription factor activity
GO:0048011	; P:nerve growth factor receptor signaling pathway
GO:0070423	; P:nucleotide-binding oligomerization domain containing signaling pathway
GO:0043123	; P:positive regulation of I-kappaB kinase/NF-kappaB cascade
GO:0051092	; P:positive regulation of NF-kappaB transcription factor activity
GO:0045893	; P:positive regulation of transcription, DNA-dependent
GO:0046777	; P:protein autophosphorylation
GO:0051259	; P:protein oligomerization
GO:0001959	; P:regulation of cytokine-mediated signaling pathway
GO:0032494	; P:response to peptidoglycan
GO:0008063	; P:Toll signaling pathway
GO:0034130	; P:toll-like receptor 1 signaling pathway
GO:0034134	; P:toll-like receptor 2 signaling pathway
GO:0034138	; P:toll-like receptor 3 signaling pathway
GO:0034142	; P:toll-like receptor 4 signaling pathway
GO:0007178	; P:transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0035666	; P:TRIF-dependent toll-like receptor signaling pathway

KEGG

hsa:3654

;

InterPros

IPR000488	; Death.
IPR011029	; DEATH-like.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00531	; Death; 1.
PF00069	; Pkinase; 1.

SMARTs

Prosites

PS50017	; DEATH_DOMAIN; FALSE_NEG.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013