EKS-BOT-00408

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-BOT-00408

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TKL/IRAK	377.2	5.6E-113	190	455	266

Status

Reviewed

Ensembl Protein

ENSBTAP00000028115

UniProt Accession

Q1RMT8;

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
ENSBTAG00000021105	ENSBTAP00000028115	ENSBTAT00000028115

Organism

Bos taurus

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

461

Protein Sequence
(FASTA)

MNKPITASTY VRCLSLGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ FHIRRFEALL 60

QIGKSPTCEL LFDWGTTNCT VGDLVDILVQ NEFFAPASLL LPDAVPKNVN TLPSKVTVVA 120

VQQKPKPLCG KDRTSVISDE NPEQNYVLPD SSSPENTSLE FSDTRFHSFS FFELKDVTNN 180

FDERPISVGG NKMGEGGFGV VYKGYVNNRT VAVKKLAAMV DISTEELKQQ FDQEIKVMAK 240

CQHENLVELL GFSSDGDDLC LVYVYMPNGS LLDRLSCLDG TPPLSWNMRC KIAQGAANGL 300

SYLHENHHIH RDIKSANILL DEDFTAKISD FGLARASEKF AQTVMTSRIV GTTAYMAPEA 360

LRGEITPKSD IYSFGVVLLE IITGLPAVDE HREPQLLLDI KEEIEDEEKT IEDYVDRKMN 420

DIDSTSIETM YSVASQCLHE KKNKRPDIKK VQQLLEEMTG S 461

Nucleotide Sequence
(FASTA)

ATGAACAAAC CCATAACAGC ATCAACATAC GTGCGCTGCC TCAGTCTTGG ACTAATTAGA 60

AAGCTGTCCG ATTTTATTGA TCCTCAAGAA GGATGGAAGA AGTTAGCAGT CGCTATTAAA 120

AAACCATCTG GTGATGATAG ATACAATCAG TTTCACATAA GGAGATTTGA AGCATTACTG 180

CAAATTGGAA AAAGCCCCAC GTGTGAGTTA CTGTTTGACT GGGGCACCAC AAATTGCACA 240

GTTGGTGATC TTGTGGATAT TTTGGTCCAA AATGAGTTTT TTGCCCCTGC AAGTCTTTTG 300

CTACCAGATG CTGTACCCAA AAATGTTAAT ACACTGCCTT CTAAAGTCAC TGTAGTAGCA 360

GTTCAGCAGA AACCGAAGCC CCTCTGTGGC AAAGACAGGA CATCTGTGAT ATCTGATGAG 420

AATCCTGAAC AAAACTATGT GCTACCTGAC TCCTCAAGTC CAGAAAATAC AAGTTTAGAA 480

TTTAGTGATA CACGTTTTCA CAGTTTTTCA TTTTTTGAAT TGAAGGATGT CACAAATAAC 540

TTTGATGAAC GGCCCATTTC TGTTGGTGGT AACAAAATGG GAGAAGGAGG GTTTGGAGTT 600

GTGTATAAAG GCTACGTGAA CAACAGGACT GTAGCAGTGA AGAAGCTTGC AGCAATGGTT 660

GACATTAGTA CTGAAGAACT GAAACAACAA TTTGATCAAG AAATAAAAGT AATGGCAAAG 720

TGTCAACATG AAAACTTAGT AGAATTACTT GGTTTCTCAA GTGATGGAGA TGACCTCTGC 780

TTAGTATATG TTTACATGCC CAATGGTTCA TTGCTGGACA GACTGTCTTG CTTGGATGGT 840

ACTCCCCCAC TCTCTTGGAA CATGAGATGC AAGATTGCCC AGGGTGCAGC TAATGGCCTC 900

AGTTATTTAC ATGAAAACCA TCATATTCAT AGAGATATTA AAAGTGCAAA TATCTTATTA 960

GATGAAGACT TTACAGCCAA AATATCTGAC TTTGGGCTTG CACGGGCTTC TGAGAAGTTT 1020

GCCCAGACAG TCATGACTAG CAGAATTGTG GGAACAACAG CTTATATGGC ACCTGAAGCT 1080

TTGCGAGGAG AAATTACACC CAAATCTGAC ATCTACAGCT TTGGTGTGGT TTTGCTAGAA 1140

ATAATAACTG GACTTCCAGC TGTGGATGAA CACCGTGAAC CTCAGTTATT GCTAGATATT 1200

AAAGAAGAAA TTGAAGATGA AGAAAAGACA ATTGAAGATT ATGTTGATAG GAAGATGAAT 1260

GACATTGATT CCACTTCCAT TGAAACTATG TACTCTGTTG CCAGTCAGTG TCTGCATGAA 1320

AAGAAAAATA AGAGACCAGA CATTAAGAAG GTTCAACAGC TGCTAGAAGA AATGACAGGT 1380

TCTTAA 1386

Domain Profile

S: 4     dnrigeGgfgevyrgelkntavavkklkeeadlslkelkqsfltElkvlarfrHdnilel  63

         +n++geGgfg+vy+g ++n +vavkkl++++d+s++elkq+f++E+kv+a+++H+n++el

Q: 190   GNKMGEGGFGVVYKGYVNNRTVAVKKLAAMVDISTEELKQQFDQEIKVMAKCQHENLVEL  249

         79**********************************************************

S: 64    lgysaeseklcLvYqymknGsLedrLqcqkgsepLsWpqRlsillGtaraiefLHeasps  123

         lg+s+++++lcLvY ym+nGsL drL+c +g++pLsW++R++i++G+a+++++LHe+  +

Q: 250   LGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWNMRCKIAQGAANGLSYLHEN--H  307

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

S: 124   lihgdiksaNiLLDekltpKlgDfglarfapesekqsstvlrtskvrgtlaYlpeefirv  183

         +ih+diksaNiLLDe++t+K++Dfglar   +sek ++tv+ ts+++gt+aY+++e++r

Q: 308   HIHRDIKSANILLDEDFTAKISDFGLAR---ASEKFAQTVM-TSRIVGTTAYMAPEALR-  362

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

S: 184   gqltvkvDvySfGiVllEvltGlravdedrktkyLkdllkeeieeekveilekfldkkag  243

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

Q: 363   GEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDI-KEEIEDEE-KTIEDYVDRKMN  420

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

S: 244   kleeellealielalaclaekakkrPtmsqvlell  278

         ++++++ e+++++a++cl+ek++krP++++v++ll

Q: 421   DIDSTSIETMYSVASQCLHEKKNKRPDIKKVQQLL  455

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

Domain Sequence
(FASTA)

GNKMGEGGFG VVYKGYVNNR TVAVKKLAAM VDISTEELKQ QFDQEIKVMA KCQHENLVEL 60

LGFSSDGDDL CLVYVYMPNG SLLDRLSCLD GTPPLSWNMR CKIAQGAANG LSYLHENHHI 120

HRDIKSANIL LDEDFTAKIS DFGLARASEK FAQTVMTSRI VGTTAYMAPE ALRGEITPKS 180

DIYSFGVVLL EIITGLPAVD EHREPQLLLD IKEEIEDEEK TIEDYVDRKM NDIDSTSIET 240

MYSVASQCLH EKKNKRPDIK KVQQLL 266

Keyword

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"; ?>Caenorhabditis elegans"; ?>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"; ?>Mus musculus"; ?>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

KEGG

bta:533692

;

InterPros

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

Pfam

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