IRAK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: IRAK1_MOUSE
• UniProt AC: Q62406
• Protein Name: Interleukin-1 receptor-associated kinase 1
• Gene Name: Irak1
• Organism: Mus musculus (Mouse).
• Sequence Length: 710
• Subcellular Localization: Cytoplasm. Nucleus. Lipid droplet . Translocates to the nucleus when sumoylated (By similarity). RSAD2/viperin recruits it to the lipid droplet..
• Protein Description: Serine/threonine-protein kinase that plays a critical role 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 (By similarity)..
• Protein Sequence: MAGGPGPGEPVVPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSEQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPVVPPSTAAPRPSSISAGSEAGDWSPRKLQSSASTFLSPAFPGSQTHSESELLQVPLPVSLGPPLPSSAPSSTKSSPESPVSGLQRAHPSPFCWPFCEISQGTCNFSEELRIGEGGFGCVYRAVMRNTTYAVKRLKEEADLEWTMVKQSFLTEVEQLSRFRHPNIVDFAGYCAESGLYCLVYGFLPNGSLEDQLHLQTQACSPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLMPKLGDFGLARFSRFAGAKASQSSTVARTSTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVILETLAGQRAVRTQGAKTKYLKDLIEDEAEEAGVTLKSTQPTLWVGVATDAWAAPIAAQIYKKHLDSRPGPCPPQLGLALAQLACCCMHRRAKKRPPMTQVYKRLEGLQAGPPWELEVAGHGSPSPQENSYMSTTGSAQSGDEPWQPLVVTTRAPAQAAQQLQRSPNQPVESDESVPGLSATLHSWHLTPGSHPSPASFREASCTQGGTTRESSVRSSPGFQPTTMEGSPTGSSSLLSSEPPQIIINPARQKMVQKLALYEEGVLDSLQLLSSGFFPGLDLEPEKSQGPEESDEFQS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
66	Phosphorylation	CERSEQRTASVLWPW HHHCCCHHHHHHHHH	23.99	14684752
120	Phosphorylation	TAAPRPSSISAGSEA CCCCCCCCCCCCCCC	24.20	25777480
125	Phosphorylation	PSSISAGSEAGDWSP CCCCCCCCCCCCCCC	24.80	25777480
131	Phosphorylation	GSEAGDWSPRKLQSS CCCCCCCCCHHCHHC	21.40	26824392
185	Phosphorylation	STKSSPESPVSGLQR CCCCCCCCCCCCCCC	33.70	27841257
188	Phosphorylation	SSPESPVSGLQRAHP CCCCCCCCCCCCCCC	36.85	30635358
209	Phosphorylation	FCEISQGTCNFSEEL CEEECCCCCCCCCCE	9.17	-
371	Ubiquitination	FSRFAGAKASQSSTV HHHHCCCCCCCCCCC	47.88	-
375	Phosphorylation	AGAKASQSSTVARTS CCCCCCCCCCCCCCH	26.02	-
381	Phosphorylation	QSSTVARTSTVRGTL CCCCCCCCHHCCCCE	21.00	25338131
382	Phosphorylation	SSTVARTSTVRGTLA CCCCCCCHHCCCCEE	21.25	29514104
387	Phosphorylation	RTSTVRGTLAYLPEE CCHHCCCCEEECCHH	9.54	-
553	Phosphorylation	STTGSAQSGDEPWQP CCCCCCCCCCCCCCC	48.18	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
66	T	Phosphorylation	Kinase	PRKCI	P41743	GPS
66	T	Phosphorylation	Kinase	PRKCI	Q62074	Uniprot
209	T	Phosphorylation	Kinase	IRAK4	Q8R4K2	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Peli1	Q8C669	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
63	K	ubiquitylation	Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'.	-
209	T	Phosphorylation	Following recruitment on the activated receptor complex, phosphorylated on Thr-209, probably by IRAK4, resulting in a conformational change of the kinase domain, allowing further phosphorylations to take place.	-
387	T	Phosphorylation	Thr-387 phosphorylation in the activation loop is required to achieve full enzymatic activity (By similarity).	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of IRAK1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ECSIT_MOUSE	Ecsit	genetic	10465784
BCL10_MOUSE	Bcl10	physical	16831874
TRAF6_MOUSE	Traf6	physical	21460221
IRAK1_MOUSE	Irak1	physical	21460221
IRF5_MOUSE	Irf5	physical	18824541
STAT3_MOUSE	Stat3	physical	15465816
KPCE_MOUSE	Prkce	physical	20044140
TOLIP_MOUSE	Tollip	physical	19273233
NR0B2_MOUSE	Nr0b2	physical	19104650
PELI2_MOUSE	Peli2	physical	12370331

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.