dbPTM

KSYK_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KSYK_MOUSE
UniProt AC	P48025
Protein Name	Tyrosine-protein kinase SYK
Gene Name	Syk
Organism	Mus musculus (Mouse).
Sequence Length	629
Subcellular Localization	Cell membrane . Cytoplasm, cytosol . Cytoplasmic vesicle, phagosome .
Protein Description	Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response. [PubMed: 26195794]
Protein Sequence	MAGSAVDSANHLTYFFGNITREEAEDYLVQGGMTDGLYLLRQSRNYLGGFALSVAHNRKAHHYTIERELNGTYAISGGRAHASPADLCHYHSQEPDGLICLLKKPFNRPPGVQPKTGPFEDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGNISRDESEQTVLIGSKTNGKFLIRARDNSGSYALCLLHEGKVLHYRIDRDKTGKLSIPEGKKFDTLWQLVEHYSYKPDGLLRVLTVPCQKIGAQMGHPGSPNAHPVTWSPGGIISRIKSYSFPKPGHKKPAPPQGSRPESTVSFNPYEPTGGPWGPDRGLQREALPMDTEVYESPYADPEEIRPKEVYLDRSLLTLEDNELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAEANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGPLNKYLQQNRHIKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYAPECINYYKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPAGCPREMYDLMNLCWTYDVENRPGFTAVELRLRNYYYDVVN

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
14	Phosphorylation	DSANHLTYFFGNITR HHHHHHHHCCCCCCH	11.85	-
27	Phosphorylation	TREEAEDYLVQGGMT CHHHHHHHHHCCCCC	10.57	-
43	Phosphorylation	GLYLLRQSRNYLGGF HHHHHHHCCCCCCCE	18.96	-
46	Phosphorylation	LLRQSRNYLGGFALS HHHHCCCCCCCEEEE	12.96	-
63	Phosphorylation	HNRKAHHYTIERELN CCCCCCCEEEEEECC	10.27	-
73	Phosphorylation	ERELNGTYAISGGRA EEECCCEEEECCCCC	11.88	-
90	Phosphorylation	SPADLCHYHSQEPDG CHHHHCCCCCCCCCC	11.36	-
130	Phosphorylation	KENLIREYVKQTWNL HHHHHHHHHHHHHCC	11.78	18689684
134	Phosphorylation	IREYVKQTWNLQGQA HHHHHHHHHCCCHHH	15.59	25367039
199	Phosphorylation	LIRARDNSGSYALCL EEEEECCCCCEEEEE	33.15	25367039
201	Phosphorylation	RARDNSGSYALCLLH EEECCCCCEEEEEEE	13.67	25367039
202	Phosphorylation	ARDNSGSYALCLLHE EECCCCCEEEEEEEC	13.71	26026062
222	Phosphorylation	YRIDRDKTGKLSIPE EEECCCCCCCCCCCC	43.78	22871156
243	Phosphorylation	LWQLVEHYSYKPDGL HHHHHHHHCCCCCCC	10.53	25367039
244	Phosphorylation	WQLVEHYSYKPDGLL HHHHHHHCCCCCCCE	28.70	25367039
245	Phosphorylation	QLVEHYSYKPDGLLR HHHHHHCCCCCCCEE	21.26	25367039
255	Phosphorylation	DGLLRVLTVPCQKIG CCCEEEEEEEHHHHC	21.39	29176673
270	Phosphorylation	AQMGHPGSPNAHPVT CCCCCCCCCCCCCCC	21.31	22942356
277	Phosphorylation	SPNAHPVTWSPGGII CCCCCCCCCCCCCHH	25.36	25159016
279	Phosphorylation	NAHPVTWSPGGIISR CCCCCCCCCCCHHHH	12.33	25159016
285	Phosphorylation	WSPGGIISRIKSYSF CCCCCHHHHHHCCCC	26.49	25367039
289	Phosphorylation	GIISRIKSYSFPKPG CHHHHHHCCCCCCCC	24.52	25159016
290	Phosphorylation	IISRIKSYSFPKPGH HHHHHHCCCCCCCCC	14.88	25159016
291	Phosphorylation	ISRIKSYSFPKPGHK HHHHHCCCCCCCCCC	42.01	27742792
306	Phosphorylation	KPAPPQGSRPESTVS CCCCCCCCCCCCCEE	39.14	25367039
310	Phosphorylation	PQGSRPESTVSFNPY CCCCCCCCCEEECCC	36.47	17947660
311	Phosphorylation	QGSRPESTVSFNPYE CCCCCCCCEEECCCC	20.64	25367039
313	Phosphorylation	SRPESTVSFNPYEPT CCCCCCEEECCCCCC	21.28	17947660
317	Phosphorylation	STVSFNPYEPTGGPW CCEEECCCCCCCCCC	35.33	28725479
320	Phosphorylation	SFNPYEPTGGPWGPD EECCCCCCCCCCCCC	42.71	25367039
339	Phosphorylation	REALPMDTEVYESPY CCCCCCCCCCCCCCC	22.54	30635358
342	Phosphorylation	LPMDTEVYESPYADP CCCCCCCCCCCCCCH	12.40	20828828
344	Phosphorylation	MDTEVYESPYADPEE CCCCCCCCCCCCHHH	12.91	30635358
346	Phosphorylation	TEVYESPYADPEEIR CCCCCCCCCCHHHHC	32.68	20828828
358	Phosphorylation	EIRPKEVYLDRSLLT HHCCCEEEECCCEEE	12.18	8657103
373	Phosphorylation	LEDNELGSGNFGTVK ECCCCCCCCCCCCCC	43.09	24719451
378	Phosphorylation	LGSGNFGTVKKGYYQ CCCCCCCCCCCHHHH	25.64	-
383	Phosphorylation	FGTVKKGYYQMKKVV CCCCCCHHHHHHHHH	10.21	25367039
384	Phosphorylation	GTVKKGYYQMKKVVK CCCCCHHHHHHHHHH	15.70	25367039
478	Phosphorylation	QVSMGMKYLEESNFV HHHHHHHHHHHCCCC	15.51	-
501	Phosphorylation	VLLVTQHYAKISDFG HEEEEEEEEHHHHCC	10.36	-
519	Phosphorylation	ALRADENYYKAQTHG HHHCCCCCHHCCCCC	12.33	20828828
520	Phosphorylation	LRADENYYKAQTHGK HHCCCCCHHCCCCCC	16.07	20828828
524	Phosphorylation	ENYYKAQTHGKWPVK CCCHHCCCCCCCCCE	37.14	-
540	Phosphorylation	YAPECINYYKFSSKS ECHHHHCEEEECCHH	6.52	22817900
565	Acetylation	EAFSYGQKPYRGMKG HHHHCCCCCCCCCCH	39.39	19814859
573	Phosphorylation	PYRGMKGSEVTAMLE CCCCCCHHHHHHHHH	24.31	-
576	Phosphorylation	GMKGSEVTAMLEKGE CCCHHHHHHHHHCCC	11.42	-
623	Phosphorylation	VELRLRNYYYDVVN- EEEEEHHCEEECCC-	9.29	17947660
624	Phosphorylation	ELRLRNYYYDVVN-- EEEEHHCEEECCC--	9.20	17947660
625	Phosphorylation	LRLRNYYYDVVN--- EEEHHCEEECCC---	7.60	25367039

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
130	Y	Phosphorylation	Kinase	SYK	Q99MN1	PhosphoELM
130	Y	Phosphorylation	Kinase	LYN	P25911	PhosphoELM
130	Y	Phosphorylation	Kinase	SYK	P48025	PSP
290	Y	Phosphorylation	Kinase	SYK	P48025	GPS
291	S	Phosphorylation	Kinase	PRKD1	Q15139	PSP
317	Y	Phosphorylation	Kinase	SYK	P43405	PSP
317	Y	Phosphorylation	Kinase	LYN	P25911	Uniprot
317	Y	Phosphorylation	Kinase	LYN	P07948	PSP
317	Y	Phosphorylation	Kinase	LCK	P06239	PSP
317	Y	Phosphorylation	Kinase	SYK	P48025	PSP
342	Y	Phosphorylation	Kinase	SYK	Q99MN1	PhosphoELM
342	Y	Phosphorylation	Kinase	SYK	P43405	PSP
342	Y	Phosphorylation	Kinase	LCK	P06239	PSP
342	Y	Phosphorylation	Kinase	LYN	P25911	PSP
342	Y	Phosphorylation	Kinase	SYK	P48025	PSP
346	Y	Phosphorylation	Kinase	SYK	Q99MN1	PhosphoELM
346	Y	Phosphorylation	Kinase	SYK	P48025	PSP
346	Y	Phosphorylation	Kinase	SYK	P43405	PSP
346	Y	Phosphorylation	Kinase	LYN	P25911	PSP
346	Y	Phosphorylation	Kinase	LCK	P06239	PSP
358	Y	Phosphorylation	Kinase	SYK	P48025	GPS
358	Y	Phosphorylation	Kinase	SYK	Q99MN1	PhosphoELM
519	Y	Phosphorylation	Kinase	SYK	P48025	PSP
519	Y	Phosphorylation	Kinase	SYK	Q99MN1	PhosphoELM
520	Y	Phosphorylation	Kinase	SYK	Q99MN1	PhosphoELM
520	Y	Phosphorylation	Kinase	SYK	P48025	PSP
624	Y	Phosphorylation	Kinase	SYK	P48025	GPS
625	Y	Phosphorylation	Kinase	SYK	P48025	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Cbl	P22682	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Cblb	Q3TTA7	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Nedd4	P46935	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
291	S	Phosphorylation		-
Phosphorylation on Ser-291 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG (By similarity).

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 KSYK_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
B3AT_MOUSE	Slc4a1	physical	8798454
TRAF3_MOUSE	Traf3	physical	23962979
TRAF6_MOUSE	Traf6	physical	23962979
M3K7_MOUSE	Map3k7	physical	23962979
TBK1_MOUSE	Tbk1	physical	23962979
TLR4_MOUSE	Tlr4	physical	23962979
DOK1_MOUSE	Dok1	physical	10823839

Drug and Disease Associations

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

Regulatory Network of KSYK_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310; SER-313; TYR-317;TYR-342; TYR-346; TYR-519; TYR-520; TYR-540; TYR-623 AND TYR-624, ANDMASS SPECTROMETRY.	17947660 [Abstract]
"Regulation of signaling in B cells through the phosphorylation of Sykon linker region tyrosines. A mechanism for negative signaling by theLyn tyrosine kinase."; Hong J.J., Yankee T.M., Harrison M.L., Geahlen R.L.; J. Biol. Chem. 277:31703-31714(2002). Cited for: PHOSPHORYLATION AT TYR-317; TYR-342 AND TYR-346.	12077122 [Abstract]
"Inhibition of beta 2 integrin receptor and Syk kinase signaling inmonocytes by the Src family kinase Fgr."; Vines C.M., Potter J.W., Xu Y., Geahlen R.L., Costello P.S.,Tybulewicz V.L., Lowell C.A., Chang P.W., Gresham H.D., Willman C.L.; Immunity 15:507-519(2001). Cited for: FUNCTION IN INTEGRIN SIGNALING, PHOSPHORYLATION AT TYR-342; TYR-519AND TYR-520, AND INTERACTION WITH ITGB2 AND FGR.	11672534 [Abstract]

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