dbPTM

IRAK4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IRAK4_HUMAN
UniProt AC	Q9NWZ3
Protein Name	Interleukin-1 receptor-associated kinase 4
Gene Name	IRAK4
Organism	Homo sapiens (Human).
Sequence Length	460
Subcellular Localization	Cytoplasm .
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. [PubMed: 17878374 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.]
Protein Sequence	MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MNKPITPS -------CCCCCCHH	15.24	22814378
3	Acetylation	-----MNKPITPSTY -----CCCCCCHHHH	36.18	19608861
3	Ubiquitination	-----MNKPITPSTY -----CCCCCCHHHH	36.18	19608861
6	Phosphorylation	--MNKPITPSTYVRC --CCCCCCHHHHHHH	21.51	18691976
8	Phosphorylation	MNKPITPSTYVRCLN CCCCCCHHHHHHHCC	24.58	-
33	Ubiquitination	IDPQEGWKKLAVAIK CCHHHCHHHHEEEEE	49.09	-
34	Malonylation	DPQEGWKKLAVAIKK CHHHCHHHHEEEEEC	34.86	26320211
34	2-Hydroxyisobutyrylation	DPQEGWKKLAVAIKK CHHHCHHHHEEEEEC	34.86	-
34	Acetylation	DPQEGWKKLAVAIKK CHHHCHHHHEEEEEC	34.86	19608861
114	Phosphorylation	KTANTLPSKEAITVQ CCCCCCCCCCCEEEE	46.36	24719451
115	Ubiquitination	TANTLPSKEAITVQQ CCCCCCCCCCEEEEC	49.58	-
136	Phosphorylation	DKDRTLMTPVQNLEQ CCCCCCEEECHHHHH	24.34	28555341
144	Phosphorylation	PVQNLEQSYMPPDSS ECHHHHHHCCCCCCC	17.64	27080861
145	Phosphorylation	VQNLEQSYMPPDSSS CHHHHHHCCCCCCCC	17.21	20873877
150	Phosphorylation	QSYMPPDSSSPENKS HHCCCCCCCCCCCCC	38.19	30278072
151	Phosphorylation	SYMPPDSSSPENKSL HCCCCCCCCCCCCCC	58.24	30278072
152	Phosphorylation	YMPPDSSSPENKSLE CCCCCCCCCCCCCCE	39.94	30278072
157	Phosphorylation	SSSPENKSLEVSDTR CCCCCCCCCEEECCE	41.15	21815630
167	Phosphorylation	VSDTRFHSFSFYELK EECCEEEECEEEEEE	21.63	27251275
169	Phosphorylation	DTRFHSFSFYELKNV CCEEEECEEEEEEEC	29.90	27251275
208	Phosphorylation	YKGYVNNTTVAVKKL EEEEECCEEHHHHHH	19.90	-
209	Phosphorylation	KGYVNNTTVAVKKLA EEEECCEEHHHHHHH	14.48	-
280	Phosphorylation	RLSCLDGTPPLSWHM HHHCCCCCCCCCHHH	22.77	24719451
284	Phosphorylation	LDGTPPLSWHMRCKI CCCCCCCCHHHHHHH	22.25	24719451
313	Ubiquitination	HHIHRDIKSANILLD CCCCCCHHHHCHHHC	48.05	-
336	Phosphorylation	DFGLARASEKFAQTV HHHHHHHHHHHHHHH	35.45	-
338	Ubiquitination	GLARASEKFAQTVMT HHHHHHHHHHHHHHH	43.43	-
342	Phosphorylation	ASEKFAQTVMTSRIV HHHHHHHHHHHHCCC	14.60	28060719
345	Phosphorylation	KFAQTVMTSRIVGTT HHHHHHHHHCCCCCC	15.54	30576142
346	Phosphorylation	FAQTVMTSRIVGTTA HHHHHHHHCCCCCCC	11.25	19663824
352	Phosphorylation	TSRIVGTTAYMAPEA HHCCCCCCCCCCHHH	15.17	22468782
354	Phosphorylation	RIVGTTAYMAPEALR CCCCCCCCCCHHHHC	7.54	23612710
365	Phosphorylation	EALRGEITPKSDIYS HHHCCCCCCHHHHHH	21.99	30576142
400	Sumoylation	PQLLLDIKEEIEDEE CHHHHHHHHHHHCHH	49.30	-
416	Ubiquitination	TIEDYIDKKMNDADS HHHHHHHHHHCCCCC	44.35	-
423	Phosphorylation	KKMNDADSTSVEAMY HHHCCCCCCCHHHHH	25.05	28450419
424	Phosphorylation	KMNDADSTSVEAMYS HHCCCCCCCHHHHHH	37.02	28450419
425	Phosphorylation	MNDADSTSVEAMYSV HCCCCCCCHHHHHHH	23.16	28450419
430	Phosphorylation	STSVEAMYSVASQCL CCCHHHHHHHHHHHH	13.67	28450419
431	Phosphorylation	TSVEAMYSVASQCLH CCHHHHHHHHHHHHH	9.72	28450419
434	Phosphorylation	EAMYSVASQCLHEKK HHHHHHHHHHHHHHH	21.19	28450419
460	Acetylation	LLQEMTAS------- HHHHHHCC-------	31.43	19608861

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
6	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
8	S	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
114	S	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
150	S	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
151	S	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
152	S	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
208	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
209	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
342	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
345	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
346	S	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP
352	T	Phosphorylation	Kinase	IRAK4	Q9NWZ3	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of IRAK4_HUMAN !!

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 IRAK4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
IRAK1_HUMAN	IRAK1	physical	11960013
TRAF6_HUMAN	TRAF6	physical	11960013
PELI1_HUMAN	PELI1	physical	17675297
PELI2_HUMAN	PELI2	physical	17675297
PELI3_HUMAN	PELI3	physical	17675297
MYD88_HUMAN	MYD88	physical	18221795
TIRAP_HUMAN	TIRAP	physical	18221795
IRAK1_HUMAN	IRAK1	physical	18221795
PELI1_HUMAN	PELI1	physical	17997719
TLR4_HUMAN	TLR4	physical	21220427
PELI1_HUMAN	PELI1	physical	19264966
IRAK1_HUMAN	IRAK1	physical	21903422
IRAK2_HUMAN	IRAK2	physical	21903422
H11_HUMAN	HIST1H1A	physical	15927069
H15_HUMAN	HIST1H1B	physical	15927069
H12_HUMAN	HIST1H1C	physical	15927069
H13_HUMAN	HIST1H1D	physical	15927069
H14_HUMAN	HIST1H1E	physical	15927069
H1T_HUMAN	HIST1H1T	physical	15927069
4EBP1_HUMAN	EIF4EBP1	physical	15927069
MBP_HUMAN	MBP	physical	15927069
PELI1_HUMAN	PELI1	physical	21204785
IRAK1_HUMAN	IRAK1	physical	12538665
MYD88_HUMAN	MYD88	physical	12538665
MYD88_HUMAN	MYD88	physical	12860405
IRAK1_HUMAN	IRAK1	physical	12860405
PELI2_HUMAN	PELI2	physical	12860405
IRAK1_HUMAN	IRAK1	physical	16024789
TRAF6_HUMAN	TRAF6	physical	23381138
SASH1_HUMAN	SASH1	physical	23776175
IRAK1_HUMAN	IRAK1	physical	24735611
MYD88_HUMAN	MYD88	physical	24735611

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
610799	Recurrent isolated invasive pneumococcal disease 1 (IPD1)
607676	IRAK4 deficiency (IRAK4D)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of IRAK4_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-3 AND LYS-34, ANDMASS SPECTROMETRY.	19608861 [Abstract]
Phosphorylation
Reference	PubMed
"Cutting Edge: IL-1 receptor-associated kinase 4 structures revealnovel features and multiple conformations."; Kuglstatter A., Villasenor A.G., Shaw D., Lee S.W., Tsing S., Niu L.,Song K.W., Barnett J.W., Browner M.F.; J. Immunol. 178:2641-2645(2007). Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 160-460 IN COMPLEX WITH ATPANALOGS, PHOSPHORYLATION AT THR-342; THR-345 AND SER-346, ANDBIOPHYSICOCHEMICAL PROPERTIES.	17312103 [Abstract]
"Crystal structures of IRAK-4 kinase in complex with inhibitors: aserine/threonine kinase with tyrosine as a gatekeeper."; Wang Z., Liu J., Sudom A., Ayres M., Li S., Wesche H., Powers J.P.,Walker N.P.C.; Structure 14:1835-1844(2006). Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 154-460 IN COMPLEX WITHINHIBITORS, AND PHOSPHORYLATION AT THR-345 AND SER-346.	17161373 [Abstract]
"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-152, AND MASSSPECTROMETRY.	18691976 [Abstract]