dbPTM

ITK_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	ITK_HUMAN
UniProt AC	Q08881
Protein Name	Tyrosine-protein kinase ITK/TSK
Gene Name	ITK
Organism	Homo sapiens (Human).
Sequence Length	620
Subcellular Localization	Cytoplasm . Nucleus . Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.
Protein Description	Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. [PubMed: 12186560]
Protein Sequence	MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISIPCHYKYPFQVVHDNYLLYVFAPDRESRQRWVLALKEETRNNNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDPTKNASKKPLPPTPEDNRRPLWEPEETVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEKSPNNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCIKHYHIKETNDNPKRYYVAEKYVFDSIPLLINYHQHNGGGLVTRLRYPVCFGRQKAPVTAGLRYGKWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAESGL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
13	Ubiquitination	LLEEQLIKKSQQKRR HHHHHHHHHHHHHCC	55.77	22505724
14	Ubiquitination	LEEQLIKKSQQKRRT HHHHHHHHHHHHCCC	46.64	-
22	Phosphorylation	SQQKRRTSPSNFKVR HHHHCCCCCCCCEEE	25.23	-
25	Ubiquitination	KRRTSPSNFKVRFFV HCCCCCCCCEEEEEE	44.11	22505724
27	Ubiquitination	RTSPSNFKVRFFVLT CCCCCCCEEEEEEEE	36.43	24816145
40	Phosphorylation	LTKASLAYFEDRHGK EEHHHHHHHHCCCCC	16.88	27642862
47	Ubiquitination	YFEDRHGKKRTLKGS HHHCCCCCCEEECCE	32.72	29967540
50	Phosphorylation	DRHGKKRTLKGSIEL CCCCCCEEECCEEEE	41.52	-
52	Ubiquitination	HGKKRTLKGSIELSR CCCCEEECCEEEEEE	50.42	29967540
58	Phosphorylation	LKGSIELSRIKCVEI ECCEEEEEEEEEEEE	21.12	23612710
61	Ubiquitination	SIELSRIKCVEIVKS EEEEEEEEEEEEEEC	30.99	-
67	Ubiquitination	IKCVEIVKSDISIPC EEEEEEEECCCCCCC	48.34	29967540
90	Phosphorylation	VHDNYLLYVFAPDRE EECCEEEEEECCCHH	7.30	-
104	Ubiquitination	ESRQRWVLALKEETR HHHHHHHHHHHHHHC	3.52	22505724
107	Ubiquitination	QRWVLALKEETRNNN HHHHHHHHHHHCCCC	48.15	29967540
110	Phosphorylation	VLALKEETRNNNSLV HHHHHHHHCCCCCCC	39.53	29978859
115	Phosphorylation	EETRNNNSLVPKYHP HHHCCCCCCCCCCCC	32.63	-
117	Ubiquitination	TRNNNSLVPKYHPNF HCCCCCCCCCCCCCC	3.74	22505724
119	Ubiquitination	NNNSLVPKYHPNFWM CCCCCCCCCCCCCCC	49.03	29967540
120	Phosphorylation	NNSLVPKYHPNFWMD CCCCCCCCCCCCCCC	19.21	27642862
126	Ubiquitination	KYHPNFWMDGKWRCC CCCCCCCCCCCEEEH	4.21	22505724
129	Ubiquitination	PNFWMDGKWRCCSQL CCCCCCCCEEEHHHH	27.48	22505724
133	Ubiquitination	MDGKWRCCSQLEKLA CCCCEEEHHHHHHHH	1.87	24816145
138	Ubiquitination	RCCSQLEKLATGCAQ EEHHHHHHHHHCCCC	52.60	22505724
141	Phosphorylation	SQLEKLATGCAQYDP HHHHHHHHCCCCCCC	43.14	26552605
146	Phosphorylation	LATGCAQYDPTKNAS HHHCCCCCCCCCCCC	12.83	28796482
149	Phosphorylation	GCAQYDPTKNASKKP CCCCCCCCCCCCCCC	33.75	26074081
150	Ubiquitination	CAQYDPTKNASKKPL CCCCCCCCCCCCCCC	56.77	22505724
153	Phosphorylation	YDPTKNASKKPLPPT CCCCCCCCCCCCCCC	51.08	26074081
154	Ubiquitination	DPTKNASKKPLPPTP CCCCCCCCCCCCCCC	56.87	29967540
155	Ubiquitination	PTKNASKKPLPPTPE CCCCCCCCCCCCCCC	49.65	29967540
160	Phosphorylation	SKKPLPPTPEDNRRP CCCCCCCCCCCCCCC	37.05	23684312
166	Ubiquitination	PTPEDNRRPLWEPEE CCCCCCCCCCCCCCC	36.60	22505724
180	Phosphorylation	ETVVIALYDYQTNDP CEEEEEEEECCCCCH	12.00	12573241
182	Phosphorylation	VVIALYDYQTNDPQE EEEEEEECCCCCHHH	12.04	-
184	Phosphorylation	IALYDYQTNDPQELA EEEEECCCCCHHHHH	35.05	-
198	Phosphorylation	ALRRNEEYCLLDSSE HHHCCCCEEEECCCE	5.13	28796482
203	Phosphorylation	EEYCLLDSSEIHWWR CCEEEECCCEEEEEE	29.82	-
219	Ubiquitination	QDRNGHEGYVPSSYL ECCCCCCCCCCHHHE	24.06	24816145
220	Phosphorylation	DRNGHEGYVPSSYLV CCCCCCCCCCHHHEE	13.25	28796482
223	Phosphorylation	GHEGYVPSSYLVEKS CCCCCCCHHHEEECC	22.90	28796482
224	Phosphorylation	HEGYVPSSYLVEKSP CCCCCCHHHEEECCC	19.20	28796482
225	Phosphorylation	EGYVPSSYLVEKSPN CCCCCHHHEEECCCC	21.07	28796482
229	Ubiquitination	PSSYLVEKSPNNLET CHHHEEECCCCCCHH	64.83	22505724
236	Phosphorylation	KSPNNLETYEWYNKS CCCCCCHHHHHHHHC	29.88	28796482
237	Phosphorylation	SPNNLETYEWYNKSI CCCCCHHHHHHHHCC	8.62	28796482
240	Phosphorylation	NLETYEWYNKSISRD CCHHHHHHHHCCCHH	10.77	29978859
242	Ubiquitination	ETYEWYNKSISRDKA HHHHHHHHCCCHHHH	33.21	22505724
243	Phosphorylation	TYEWYNKSISRDKAE HHHHHHHCCCHHHHH	23.35	28787133
248	Ubiquitination	NKSISRDKAEKLLLD HHCCCHHHHHHHHHH	58.28	29967540
251	Ubiquitination	ISRDKAEKLLLDTGK CCHHHHHHHHHHCCC	49.66	22505724
258	Ubiquitination	KLLLDTGKEGAFMVR HHHHHCCCCCEEEEE	55.88	24816145
267	Phosphorylation	GAFMVRDSRTAGTYT CEEEEECCCCCEEEE	22.44	29759185
272	Phosphorylation	RDSRTAGTYTVSVFT ECCCCCEEEEEEEEE	17.35	29978859
273	Phosphorylation	DSRTAGTYTVSVFTK CCCCCEEEEEEEEEE	12.29	29978859
274	Phosphorylation	SRTAGTYTVSVFTKA CCCCEEEEEEEEEEE	13.22	29978859
276	Phosphorylation	TAGTYTVSVFTKAVV CCEEEEEEEEEEEHH	12.06	29978859
279	Phosphorylation	TYTVSVFTKAVVSEN EEEEEEEEEEHHCCC	18.88	29759185
291	Ubiquitination	SENNPCIKHYHIKET CCCCCCEEEEEEECC	44.84	22505724
296	Acetylation	CIKHYHIKETNDNPK CEEEEEEECCCCCCC	45.21	19608861
296	Ubiquitination	CIKHYHIKETNDNPK CEEEEEEECCCCCCC	45.21	19608861
303	Ubiquitination	KETNDNPKRYYVAEK ECCCCCCCEEEEEEE	60.32	29967540
336	Phosphorylation	GLVTRLRYPVCFGRQ CCEEEEECCEECCCC	12.47	25147952
344	Ubiquitination	PVCFGRQKAPVTAGL CEECCCCCCCCEECC	53.98	24816145
353	Phosphorylation	PVTAGLRYGKWVIDP CCEECCCCCCEEECH	28.27	-
372	Ubiquitination	FVQEIGSGQFGLVHL EEEEECCCCCEEEEE	22.94	22505724
391	Ubiquitination	NKDKVAIKTIREGAM CCCCEEEHHHHHCCC	28.32	29967540
394	Ubiquitination	KVAIKTIREGAMSEE CEEEHHHHHCCCCHH	41.34	22505724
398	Ubiquitination	KTIREGAMSEEDFIE HHHHHCCCCHHHHHH	8.34	22505724
412	Ubiquitination	EEAEVMMKLSHPKLV HHHHHHHHCCCHHHH	28.83	29967540
497	Ubiquitination	VGENQVIKVSDFGMT CCCCCEEEEECCCCC	36.51	22505724
499	Phosphorylation	ENQVIKVSDFGMTRF CCCEEEEECCCCCEE	23.40	-
504	Phosphorylation	KVSDFGMTRFVLDDQ EEECCCCCEEEECCC	22.72	-
512	Phosphorylation	RFVLDDQYTSSTGTK EEEECCCCCCCCCCC	18.65	19605366
513	Phosphorylation	FVLDDQYTSSTGTKF EEECCCCCCCCCCCC	15.57	28796482
514	Phosphorylation	VLDDQYTSSTGTKFP EECCCCCCCCCCCCC	22.44	28796482
515	Phosphorylation	LDDQYTSSTGTKFPV ECCCCCCCCCCCCCC	24.05	26552605
516	Phosphorylation	DDQYTSSTGTKFPVK CCCCCCCCCCCCCCE	48.95	26552605
518	Phosphorylation	QYTSSTGTKFPVKWA CCCCCCCCCCCCEEC	29.60	26552605
519	Ubiquitination	YTSSTGTKFPVKWAS CCCCCCCCCCCEECC	49.36	22505724
523	Ubiquitination	TGTKFPVKWASPEVF CCCCCCCEECCCCEE	36.96	22505724
559	Phosphorylation	FSEGKIPYENRSNSE HHCCCCCCCCCCCCC	29.34	28464451
563	Phosphorylation	KIPYENRSNSEVVED CCCCCCCCCCCEEEE	57.18	30576142
565	Phosphorylation	PYENRSNSEVVEDIS CCCCCCCCCEEEEHH	32.77	21082442
585	Phosphorylation	YKPRLASTHVYQIMN CCCCHHHHHHHHHHH	15.11	-
588	Phosphorylation	RLASTHVYQIMNHCW CHHHHHHHHHHHHHH	5.68	-

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
180	Y	Phosphorylation	Kinase	BTK	Q06187	PSP
180	Y	Phosphorylation	Kinase	ITK	Q08881	PSP
180	Y	Phosphorylation	Kinase	TEC	P42680	PSP
512	Y	Phosphorylation	Kinase	LCK	P06239	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	SMURF1	Q9HCE7	PMID:20804422

Functions of PTM Sites

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
IMA1_HUMAN	KPNA2	physical	11581171
SOCS1_HUMAN	SOCS1	physical	10022833
PPIA_HUMAN	PPIA	physical	11830645
WASP_HUMAN	WAS	physical	8892607
PLCG1_HUMAN	PLCG1	physical	10586033
LCP2_HUMAN	LCP2	physical	10636929
FYN_HUMAN	FYN	physical	10636929
SRC_HUMAN	SRC	physical	10636929
GRB2_HUMAN	GRB2	physical	10636929
KHDR1_HUMAN	KHDRBS1	physical	12163161
ITK_HUMAN	ITK	physical	12163161
PLCG1_HUMAN	PLCG1	physical	12163161
LAT_HUMAN	LAT	physical	12186560
KHDR1_HUMAN	KHDRBS1	physical	8985255
GRB2_HUMAN	GRB2	physical	8985255
HNRPK_HUMAN	HNRNPK	physical	8810341
WASP_HUMAN	WAS	physical	8810341
KHDR1_HUMAN	KHDRBS1	physical	8810341
CBL_HUMAN	CBL	physical	8810341
FYN_HUMAN	FYN	physical	8810341
LCP2_HUMAN	LCP2	physical	12190313
IBTK_HUMAN	IBTK	physical	18596081
SPR2A_HUMAN	SPRR2A	physical	18155796
NSUN6_HUMAN	NSUN6	physical	26344197
DC1I2_HUMAN	DYNC1I2	physical	28514442
HS90B_HUMAN	HSP90AB1	physical	28514442
G3PT_HUMAN	GAPDHS	physical	28514442
CDC37_HUMAN	CDC37	physical	28514442

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
613011	Lymphoproliferative syndrome 1 (LPFS1)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB06589	Pazopanib

Regulatory Network of ITK_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 LYS-296, AND MASS SPECTROMETRY.	19608861 [Abstract]
Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-512 AND SER-565, ANDMASS SPECTROMETRY.	19690332 [Abstract]
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry."; Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.; Mol. Cell. Proteomics 6:537-547(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-512 AND SER-565, ANDMASS SPECTROMETRY.	17192257 [Abstract]
"Identification of phosphorylation sites within the SH3 domains of Tecfamily tyrosine kinases."; Nore B.F., Mattsson P.T., Antonsson P., Backesjo C.-M., Westlund A.,Lennartsson J., Hansson H., Low P., Ronnstrand L., Smith C.I.E.; Biochim. Biophys. Acta 1645:123-132(2003). Cited for: PROTEIN SEQUENCE OF 171-192, AND PHOSPHORYLATION AT TYR-180.	12573241 [Abstract]