EKS-MUM-00440

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00440

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TKL/IRAK	377.5	1.0E-112	188	454	267

Status

Reviewed

Ensembl Protein

ENSMUSP00000074471

UniProt Accession

Q8R4K2; Q80WW1;

Protein Name

Interleukin-1 receptor-associated kinase 4

Protein Synonyms/Alias

IRAK-4;

Gene Name

Irak4

Gene Synonyms/Alias

Irak4;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000059883	ENSMUSP00000074471	ENSMUST00000074936
ENSMUSG00000059883	ENSMUSP00000104871	ENSMUST00000109248

Organism

Mus musculus

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 to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. 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 NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections (By similarity).

Protein Length

459

Protein Sequence
(FASTA)

MNKPLTPSTY IRNLNVGILR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ FHIRRFEALL 60

QTGKSPTCEL LFDWGTTNCT VGDLVDLLVQ IELFAPATLL LPDAVPQTVK SLPPREAATV 120

AQTHGPCQEK DRTSVMPMPK LEHSCEPPDS SSPDNRSVES SDTRFHSFSF HELKSITNNF 180

DEQPASAGGN RMGEGGFGVV YKGCVNNTIV AVKKLGAMVE ISTEELKQQF DQEIKVMATC 240

QHENLVELLG FSSDSDNLCL VYAYMPNGSL LDRLSCLDGT PPLSWHTRCK VAQGTANGIR 300

FLHENHHIHR DIKSANILLD KDFTAKISDF GLARASARLA QTVMTSRIVG TTAYMAPEAL 360

RGEITPKSDI YSFGVVLLEL ITGLAAVDEN REPQLLLDIK EEIEDEEKTI EDYTDEKMSD 420

ADPASVEAMY SAASQCLHEK KNRRPDIAKV QQLLQEMSA 459

Nucleotide Sequence
(FASTA)

ATGAACAAGC CGTTGACACC ATCGACATAC ATACGCAACC TTAATGTGGG GATCCTTAGG 60

AAGCTGTCGG ATTTTATTGA TCCTCAAGAA GGGTGGAAGA AATTAGCAGT AGCTATCAAA 120

AAGCCGTCCG GCGACGACAG ATACAATCAG TTCCATATAA GGAGATTCGA AGCCTTACTT 180

CAGACCGGGA AGAGCCCCAC CTGTGAACTG CTGTTTGACT GGGGCACCAC GAACTGCACA 240

GTTGGCGACC TTGTGGATCT ACTGGTCCAG ATTGAGCTGT TTGCCCCCGC CACTCTCCTG 300

CTGCCGGATG CCGTTCCCCA AACCGTCAAA AGCCTGCCTC CTAGAGAAGC GGCAACAGTG 360

GCACAAACAC ACGGGCCTTG TCAGGAAAAG GACAGGACAT CCGTAATGCC TATGCCGAAG 420

CTAGAACACA GCTGCGAGCC ACCGGACTCC TCAAGCCCAG ACAACAGAAG TGTAGAGTCC 480

AGCGACACTC GGTTCCACAG CTTCTCGTTC CATGAACTGA AGAGCATCAC AAACAACTTC 540

GACGAGCAAC CCGCGTCTGC CGGTGGCAAC CGGATGGGAG AGGGGGGATT TGGAGTGGTG 600

TACAAGGGCT GTGTGAACAA CACCATCGTG GCGGTGAAGA AGCTCGGAGC GATGGTTGAA 660

ATCAGTACTG AAGAACTAAA GCAACAGTTT GATCAAGAAA TTAAAGTAAT GGCAACGTGT 720

CAGCACGAGA ACCTGGTGGA GCTGCTCGGC TTCTCCAGCG ACAGCGACAA CCTGTGCTTA 780

GTGTATGCTT ACATGCCCAA CGGGTCCTTG CTGGACAGAC TGTCCTGCCT GGATGGTACA 840

CCACCGCTTT CCTGGCACAC AAGGTGCAAG GTTGCTCAGG GGACAGCAAA TGGCATCAGG 900

TTTCTGCATG AAAATCATCA CATTCATAGA GATATTAAAA GTGCAAATAT CTTACTAGAC 960

AAAGACTTTA CTGCCAAAAT ATCTGACTTT GGGCTTGCAC GGGCTTCGGC AAGGCTAGCG 1020

CAGACGGTCA TGACCAGCCG AATCGTGGGC ACAACGGCTT ACATGGCACC CGAAGCTTTG 1080

CGGGGAGAAA TAACACCCAA ATCTGACATC TACAGCTTCG GCGTGGTTCT GTTGGAGCTG 1140

ATAACCGGGC TGGCGGCTGT GGATGAAAAC CGTGAACCTC AACTACTGCT GGATATTAAA 1200

GAAGAGATTG AAGATGAAGA GAAGACGATT GAAGATTACA CGGATGAGAA GATGAGCGAT 1260

GCGGACCCTG CTTCGGTGGA AGCAATGTAC TCTGCTGCTA GCCAGTGTCT GCATGAGAAG 1320

AAAAACAGAC GGCCAGACAT TGCAAAGGTT CAACAGCTGC TACAAGAGAT GTCTGCTTAA 1380

Domain Profile

S: 3     ednrigeGgfgevyrgelkntavavkklkeeadlslkelkqsfltElkvlarfrHdnile  62

          +nr+geGgfg+vy+g+++nt+vavkkl +++++s++elkq+f++E+kv+a+++H+n++e

Q: 188   GGNRMGEGGFGVVYKGCVNNTIVAVKKLGAMVEISTEELKQQFDQEIKVMATCQHENLVE  247

         579*********************************************************

S: 63    llgysaeseklcLvYqymknGsLedrLqcqkgsepLsWpqRlsillGtaraiefLHeasp  122

         llg+s++s++lcLvY+ym+nGsL drL+c +g++pLsW++R+++++Gta++i+fLHe+

Q: 248   LLGFSSDSDNLCLVYAYMPNGSLLDRLSCLDGTPPLSWHTRCKVAQGTANGIRFLHEN--  305

         **********************************************************..

S: 123   slihgdiksaNiLLDekltpKlgDfglarfapesekqsstvlrtskvrgtlaYlpeefir  182

         ++ih+diksaNiLLD+++t+K++Dfglar   +s++ ++tv+ ts+++gt+aY+++e++r

Q: 306   HHIHRDIKSANILLDKDFTAKISDFGLAR---ASARLAQTVM-TSRIVGTTAYMAPEALR  361

         *****************************...9999*****9.*****************

S: 183   vgqltvkvDvySfGiVllEvltGlravdedrktkyLkdllkeeieeekveilekfldkka  242

          g++t k+D+ySfG+VllE++tGl avde+r+++ L+d+ keeie+e+ +++e+++d+k+

Q: 362   -GEITPKSDIYSFGVVLLELITGLAAVDENREPQLLLDI-KEEIEDEE-KTIEDYTDEKM  418

         .*************************************9.********.9**********

S: 243   gkleeellealielalaclaekakkrPtmsqvlell  278

         ++++++++ea++++a++cl+ek+++rP++++v++ll

Q: 419   SDADPASVEAMYSAASQCLHEKKNRRPDIAKVQQLL  454

         *********************************986

Domain Sequence
(FASTA)

GGNRMGEGGF GVVYKGCVNN TIVAVKKLGA MVEISTEELK QQFDQEIKVM ATCQHENLVE 60

LLGFSSDSDN LCLVYAYMPN GSLLDRLSCL DGTPPLSWHT RCKVAQGTAN GIRFLHENHH 120

IHRDIKSANI LLDKDFTAKI SDFGLARASA RLAQTVMTSR IVGTTAYMAP EALRGEITPK 180

SDIYSFGVVL LELITGLAAV DENREPQLLL DIKEEIEDEE KTIEDYTDEK MSDADPASVE 240

AMYSAASQCL HEKKNRRPDI AKVQQLL 267

Keyword

3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm; Immunity; Innate immunity; Kinase; Magnesium; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Choloepus hoffmanni"; ?>Ciona intestinalis"; ?>Danio rerio"; ?>Dasypus novemcinctus"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sorex araneus"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tarsius syrichta"; ?>Tetraodon nigroviridis"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005524	; F:ATP binding
GO:0000287	; F:magnesium ion binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0001816	; P:cytokine production
GO:0019221	; P:cytokine-mediated signaling pathway
GO:0045087	; P:innate immune response
GO:0007254	; P:JNK cascade
GO:0048661	; P:positive regulation of smooth muscle cell proliferation
GO:0045944	; P:positive regulation of transcription from RNA polymerase II promoter

KEGG

mmu:266632

;

InterPros

IPR000488	; Death.
IPR011029	; DEATH-like.
IPR017428	; Interleukin-1_rcpt-assoc_kin4.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.

Pfam

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

SMARTs

Prosites

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

Prints

Created Date

20-Feb-2013