dbPTM

IRAK1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IRAK1_HUMAN
UniProt AC	P51617
Protein Name	Interleukin-1 receptor-associated kinase 1
Gene Name	IRAK1
Organism	Homo sapiens (Human).
Sequence Length	712
Subcellular Localization	Cytoplasm . Nucleus . Lipid droplet. Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity)..
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..
Protein Sequence	MAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLDPRPGPCPPELGLGLGQLACCCLHRRAKRRPPMTQVYERLEKLQAVVAGVPGHSEAASCIPPSPQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
66	Phosphorylation	CERSGQRTASVLWPW HHHCCCCCHHHHHHH	18.52	12138165
100	Phosphorylation	LRARDIITAWHPPAP HHHHHHHHHCCCCCC	24.83	22817900
110	Phosphorylation	HPPAPLPSPGTTAPR CCCCCCCCCCCCCCC	43.58	26471730
113	Phosphorylation	APLPSPGTTAPRPSS CCCCCCCCCCCCCCC	24.14	29978859
114	Phosphorylation	PLPSPGTTAPRPSSI CCCCCCCCCCCCCCC	40.35	29978859
117	Methylation	SPGTTAPRPSSIPAP CCCCCCCCCCCCCCC	41.07	115480459
119	Phosphorylation	GTTAPRPSSIPAPAE CCCCCCCCCCCCCCC	42.02	23312004
120	Phosphorylation	TTAPRPSSIPAPAEA CCCCCCCCCCCCCCH	34.96	23312004
131	Phosphorylation	PAEAEAWSPRKLPSS CCCHHCCCCCCCCCC	23.13	23898821
134	Ubiquitination	AEAWSPRKLPSSAST HHCCCCCCCCCCCCC	69.04	18326498
144	Phosphorylation	SSASTFLSPAFPGSQ CCCCCCCCCCCCCCC	15.25	-
163	Phosphorylation	PELGLVPSPASLWPP CCCCCCCCHHHHCCC	26.14	-
173	Phosphorylation	SLWPPPPSPAPSSTK HHCCCCCCCCCCCCC	39.19	-
180	Ubiquitination	SPAPSSTKPGPESSV CCCCCCCCCCCHHHH	50.34	-
209	Phosphorylation	LCEISRGTHNFSEEL HHHHCCCCCCCCCCE	16.73	22817900
217	Acetylation	HNFSEELKIGEGGFG CCCCCCEECCCCCCC	52.52	25953088
227	Phosphorylation	EGGFGCVYRAVMRNT CCCCCHHHHHHHHCH	9.27	29496907
234	Phosphorylation	YRAVMRNTVYAVKRL HHHHHHCHHHHHHHH	12.43	29691806
236	Phosphorylation	AVMRNTVYAVKRLKE HHHHCHHHHHHHHHH	12.02	29691806
239	Acetylation	RNTVYAVKRLKENAD HCHHHHHHHHHHCCC	43.79	30589541
239	Ubiquitination	RNTVYAVKRLKENAD HCHHHHHHHHHHCCC	43.79	-
242	Ubiquitination	VYAVKRLKENADLEW HHHHHHHHHCCCCCC	53.61	-
253	Ubiquitination	DLEWTAVKQSFLTEV CCCCHHHHHHHHHHH	37.45	-
342 (in isoform 1)	Ubiquitination	-	53.20	21890473
342 (in isoform 2)	Ubiquitination	-	53.20	21890473
342	Ubiquitination	SLIHGDIKSSNVLLD CCCCCCCCCCCEEEC	53.20	21890473
342	Ubiquitination	SLIHGDIKSSNVLLD CCCCCCCCCCCEEEC	53.20	21890473
355 (in isoform 1)	Ubiquitination	-	60.92	21890473
355 (in isoform 2)	Ubiquitination	-	60.92	21890473
355	Ubiquitination	LDERLTPKLGDFGLA ECCCCCCCCCHHHHH	60.92	21890473
355	Ubiquitination	LDERLTPKLGDFGLA ECCCCCCCCCHHHHH	60.92	21890473
368 (in isoform 3)	Ubiquitination	-	18.82	21890473
370	Phosphorylation	RFSRFAGSSPSQSSM HHHHCCCCCCCCCHH	35.33	29978859
371	Phosphorylation	FSRFAGSSPSQSSMV HHHCCCCCCCCCHHH	27.87	21712546
373	Phosphorylation	RFAGSSPSQSSMVAR HCCCCCCCCCHHHEE	44.64	29978859
375	Phosphorylation	AGSSPSQSSMVARTQ CCCCCCCCHHHEEEH	25.41	30576142
376	Phosphorylation	GSSPSQSSMVARTQT CCCCCCCHHHEEEHH	15.05	29396449
381	Phosphorylation	QSSMVARTQTVRGTL CCHHHEEEHHHCCCE	20.89	-
381 (in isoform 3)	Ubiquitination	-	20.89	21890473
387	Phosphorylation	RTQTVRGTLAYLPEE EEHHHCCCEECCCHH	9.54	22817900
390	Phosphorylation	TVRGTLAYLPEEYIK HHCCCEECCCHHHHH	26.38	29496907
395	Phosphorylation	LAYLPEEYIKTGRLA EECCCHHHHHCCCEE	13.17	29496907
397 (in isoform 1)	Ubiquitination	-	43.98	21890473
397	Ubiquitination	YLPEEYIKTGRLAVD CCCHHHHHCCCEEEC	43.98	21890473
397 (in isoform 2)	Ubiquitination	-	43.98	21890473
397	Ubiquitination	YLPEEYIKTGRLAVD CCCHHHHHCCCEEEC	43.98	21890473
397	Malonylation	YLPEEYIKTGRLAVD CCCHHHHHCCCEEEC	43.98	26320211
423 (in isoform 3)	Ubiquitination	-	10.16	21890473
431 (in isoform 4)	Phosphorylation	-	24.41	-
435	Ubiquitination	GARTKYLKDLVEEEA CCCHHHHHHHHHHHH	46.02	-
512	Phosphorylation	AKRRPPMTQVYERLE HHCCCCHHHHHHHHH	22.21	25003641
515	Phosphorylation	RPPMTQVYERLEKLQ CCCHHHHHHHHHHHH	5.87	-
541	Phosphorylation	AASCIPPSPQENSYV HHHCCCCCCCCCCCC	33.58	26657352
556	Phosphorylation	SSTGRAHSGAAPWQP CCCCCCCCCCCCCCC	29.19	22617229
568	Phosphorylation	WQPLAAPSGASAQAA CCCCCCCCCHHHHHH	42.12	16094384
591	Phosphorylation	QPVESDESLGGLSAA CCCCCCCCCCHHHHH	36.99	28555341
601	Phosphorylation	GLSAALRSWHLTPSC HHHHHHHHCCCCCCC	21.50	30108239
605	Phosphorylation	ALRSWHLTPSCPLDP HHHHCCCCCCCCCCC	10.56	30108239
607	Phosphorylation	RSWHLTPSCPLDPAP HHCCCCCCCCCCCCC	24.11	30108239
650	Phosphorylation	EGLALGSSASSSSEP CCEECCCCCCCCCCC	30.30	-
653	Phosphorylation	ALGSSASSSSEPPQI ECCCCCCCCCCCCEE	37.28	-
688	Phosphorylation	LDSLQLLSSSSLPGL CHHHHHHHCCCCCCC	36.44	28348404
689	Phosphorylation	DSLQLLSSSSLPGLG HHHHHHHCCCCCCCC	24.74	28348404
690	Phosphorylation	SLQLLSSSSLPGLGL HHHHHHCCCCCCCCC	32.30	28348404
691	Phosphorylation	LQLLSSSSLPGLGLE HHHHHCCCCCCCCCC	40.30	28348404

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	Uniprot
66	T	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
100	T	Phosphorylation	Kinase	AKT1	P31749	PSP
100	T	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
100	T	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
209	T	Phosphorylation	Kinase	IRAK1	P51617	PSP
209	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	Uniprot
376	S	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
387	T	Phosphorylation	Kinase	IRAK1	P51617	PSP
387	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	TRAF6	Q9Y4K3	PMID:18347055
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	PELI1	Q96FA3	PMID:16884718
-	K	Ubiquitination	E3 ubiquitin ligase	PELI3	Q8N2H9	PMID:12874243

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
63	K	ubiquitylation	16690127
Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'.
209	T	Phosphorylation	14625308
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	14625308
Thr-387 phosphorylation in the activation loop is required to achieve full enzymatic activity.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of IRAK1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KPCZ_HUMAN	PRKCZ	physical	11937546
TRAF6_HUMAN	TRAF6	physical	11518704
IKBP1_HUMAN	IRAK1BP1	physical	11096118
IKKB_HUMAN	IKBKB	physical	11096118
IKKA_HUMAN	CHUK	physical	11096118
TRAF6_HUMAN	TRAF6	physical	10920205
TRAF6_HUMAN	TRAF6	physical	11259596
IRAK1_HUMAN	IRAK1	physical	11259596
MYD88_HUMAN	MYD88	physical	11544529
NEMO_HUMAN	IKBKG	physical	18180283
IKKA_HUMAN	CHUK	physical	18180283
IKKB_HUMAN	IKBKB	physical	18180283
BCL10_HUMAN	BCL10	physical	16831874
TRAF6_HUMAN	TRAF6	physical	11287640
PELI1_HUMAN	PELI1	physical	17997719
PP2AA_HUMAN	PPP2CA	physical	21708940
TRAF6_HUMAN	TRAF6	physical	21220427
TNAP3_HUMAN	TNFAIP3	physical	21220427
PELI1_HUMAN	PELI1	physical	19264966
TRAF6_HUMAN	TRAF6	physical	20043910
TRI32_HUMAN	TRIM32	physical	21903422
BAG3_HUMAN	BAG3	physical	21903422
COQ8A_HUMAN	ADCK3	physical	21903422
CCD47_HUMAN	CCDC47	physical	21903422
IQEC1_HUMAN	IQSEC1	physical	21903422
IRAK2_HUMAN	IRAK2	physical	21903422
MAGD1_HUMAN	MAGED1	physical	21903422
PJA1_HUMAN	PJA1	physical	21903422
PP2BB_HUMAN	PPP3CB	physical	21903422
MIRO1_HUMAN	RHOT1	physical	21903422
U520_HUMAN	SNRNP200	physical	21903422
TADBP_HUMAN	TARDBP	physical	21903422
TOM70_HUMAN	TOMM70A	physical	21903422
YTDC2_HUMAN	YTHDC2	physical	21903422
RSAD2_MOUSE	Rsad2	physical	21435586
TRAF6_HUMAN	TRAF6	physical	19716405
IRAK1_HUMAN	IRAK1	physical	18524972
IRAK1_HUMAN	IRAK1	physical	14625308
TRAF6_HUMAN	TRAF6	physical	14625308
TOLIP_HUMAN	TOLLIP	physical	17276401
MYD88_HUMAN	MYD88	physical	17276401
IRAK4_HUMAN	IRAK4	physical	17276401
TOLIP_HUMAN	TOLLIP	physical	16107720
CAV1_HUMAN	CAV1	physical	16107720
PELI1_HUMAN	PELI1	physical	21204785
TRAF6_HUMAN	TRAF6	physical	12242293
IL1R1_HUMAN	IL1R1	physical	12242293
M3K7_HUMAN	MAP3K7	physical	12242293
IRAK1_HUMAN	IRAK1	physical	11397809
TOLIP_HUMAN	TOLLIP	physical	11397809
TRAF4_HUMAN	TRAF4	physical	16052631
IRF7_HUMAN	IRF7	physical	15767370
TRAF6_HUMAN	TRAF6	physical	17785851
IRAK4_HUMAN	IRAK4	physical	17785851
FBW1A_HUMAN	BTRC	physical	22851693
FBW1B_HUMAN	FBXW11	physical	22851693
CUL1_HUMAN	CUL1	physical	22851693
HS90A_HUMAN	HSP90AA1	physical	15647277
CDC37_HUMAN	CDC37	physical	15647277
HSP74_HUMAN	HSPA4	physical	15647277
STIP1_HUMAN	STIP1	physical	15647277
H31T_HUMAN	HIST3H3	physical	18276832
PELI3_HUMAN	PELI3	physical	12874243
PELI2_HUMAN	PELI2	physical	12860405
NAL12_HUMAN	NLRP12	physical	16203735
IRAK2_HUMAN	IRAK2	physical	12138165
IRAK3_HUMAN	IRAK3	physical	12138165
STAT3_HUMAN	STAT3	physical	15465816
KPCD_HUMAN	PRKCD	physical	21804018
TRAF6_HUMAN	TRAF6	physical	19166926
IRAK1_HUMAN	IRAK1	physical	19166926
IRAK3_HUMAN	IRAK3	physical	19166926
IRAK4_HUMAN	IRAK4	physical	19166926
IRAK1_HUMAN	IRAK1	physical	16951688
MYD88_HUMAN	MYD88	physical	16951688
TRAF6_HUMAN	TRAF6	physical	16951688
IRAK4_HUMAN	IRAK4	physical	16951688
PELI1_HUMAN	PELI1	physical	16951688
STAT1_HUMAN	STAT1	physical	12856330
IL1R1_MOUSE	Il1r1	physical	9426216
IRAK1_HUMAN	IRAK1	physical	16024789
IRAK4_HUMAN	IRAK4	physical	16024789
TRAF6_HUMAN	TRAF6	physical	16024789
MYD88_HUMAN	MYD88	physical	16024789
VASP_HUMAN	VASP	physical	20044140
HSP7C_HUMAN	HSPA8	physical	15647277
F10A1_HUMAN	ST13	physical	15647277
TRAF6_HUMAN	TRAF6	physical	23244239
PINK1_HUMAN	PINK1	physical	23244239
TRAF6_HUMAN	TRAF6	physical	23381138
PELI1_HUMAN	PELI1	physical	16884718
PELI2_HUMAN	PELI2	physical	16884718
PELI3_HUMAN	PELI3	physical	16884718
SASH1_HUMAN	SASH1	physical	23776175
RNF31_HUMAN	RNF31	physical	24491438
AIFM1_HUMAN	AIFM1	physical	25852190
AT1A1_HUMAN	ATP1A1	physical	25852190
ATPB_HUMAN	ATP5B	physical	25852190
BAG2_HUMAN	BAG2	physical	25852190
CALU_HUMAN	CALU	physical	25852190
TCPB_HUMAN	CCT2	physical	25852190
TCPG_HUMAN	CCT3	physical	25852190
TCPD_HUMAN	CCT4	physical	25852190
TCPE_HUMAN	CCT5	physical	25852190
TCPZ_HUMAN	CCT6A	physical	25852190
TCPH_HUMAN	CCT7	physical	25852190
TCPQ_HUMAN	CCT8	physical	25852190
DNJA1_HUMAN	DNAJA1	physical	25852190
DNJA2_HUMAN	DNAJA2	physical	25852190
DNJA3_HUMAN	DNAJA3	physical	25852190
EF2_HUMAN	EEF2	physical	25852190
EMD_HUMAN	EMD	physical	25852190
1A02_HUMAN	HLA-A	physical	25852190
1A03_HUMAN	HLA-A	physical	25852190
1A01_HUMAN	HLA-A	physical	25852190
1A26_HUMAN	HLA-A	physical	25852190
HNRPF_HUMAN	HNRNPF	physical	25852190
HSPB1_HUMAN	HSPB1	physical	25852190
MIC60_HUMAN	IMMT	physical	25852190
LMNA_HUMAN	LMNA	physical	25852190
RCN1_HUMAN	RCN1	physical	25852190
SC16A_HUMAN	SEC16A	physical	25852190
DIC_HUMAN	SLC25A10	physical	25852190
CMC2_HUMAN	SLC25A13	physical	25852190
GTR1_HUMAN	SLC2A1	physical	25852190
LAT1_HUMAN	SLC7A5	physical	25852190
CHIP_HUMAN	STUB1	physical	25852190
TCPA_HUMAN	TCP1	physical	25852190
TIM50_HUMAN	TIMM50	physical	25852190
OPTN_HUMAN	OPTN	physical	28882891
TRAF6_HUMAN	TRAF6	physical	28882891

Drug and Disease Associations

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

Regulatory Network of IRAK1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131 AND SER-371, ANDMASS SPECTROMETRY.	18691976 [Abstract]
"Quantitative phosphoproteome analysis using a dendrimer conjugationchemistry and tandem mass spectrometry."; Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J.,Bodenmiller B., Watts J.D., Hood L., Aebersold R.; Nat. Methods 2:591-598(2005). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568, AND MASSSPECTROMETRY.	16094384 [Abstract]
"Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter ininterleukin-1 signaling."; Kollewe C., Mackensen A.C., Neumann D., Knop J., Cao P., Li S.,Wesche H., Martin M.U.; J. Biol. Chem. 279:5227-5236(2004). Cited for: PHOSPHORYLATION AT THR-209 AND THR-387, DOMAIN, AND MUTAGENESIS OFTHR-209 AND THR-387.	14625308 [Abstract]
"Regulation of interleukin receptor-associated kinase (IRAK)phosphorylation and signaling by iota protein kinase C."; Mamidipudi V., Lin C., Seibenhener M.L., Wooten M.W.; J. Biol. Chem. 279:4161-4165(2004). Cited for: FUNCTION, AND PHOSPHORYLATION AT THR-66.	14684752 [Abstract]

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