dbPTM

FYN_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	FYN_MOUSE
UniProt AC	P39688
Protein Name	Tyrosine-protein kinase Fyn
Gene Name	Fyn
Organism	Mus musculus (Mouse).
Sequence Length	537
Subcellular Localization	Cytoplasm. Nucleus. Cell membrane. Present and active in lipid rafts. Palmitoylation is crucial for proper trafficking (By similarity)..
Protein Description	Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1 (By similarity)..
Protein Sequence	MGCVQCKDKEAAKLTEERDGSLNQSSGYRYGTDPTPQHYPSFGVTSIPNYNNFHAAGGQGLTVFGGVNSSSHTGTLRTRGGTGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVDSIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLCCRLVVPCHKGMPRLTDLSVKTKDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQGFLEDYFTATEPQYQPGENL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Myristoylation	------MGCVQCKDK ------CCCEECCCH	21.94	8655574
2	N-myristoyl glycine	------MGCVQCKDK ------CCCEECCCH	21.94	-
3	S-palmitoylation	-----MGCVQCKDKE -----CCCEECCCHH	1.52	7518463
6	S-palmitoylation	--MGCVQCKDKEAAK --CCCEECCCHHHHH	2.84	7980442
13	Ubiquitination	CKDKEAAKLTEERDG CCCHHHHHCCHHCCC	64.09	27667366
15	Phosphorylation	DKEAAKLTEERDGSL CHHHHHCCHHCCCCC	34.78	28833060
21	Phosphorylation	LTEERDGSLNQSSGY CCHHCCCCCCCCCCC	28.56	25521595
21 (in isoform 2)	Phosphorylation	-	28.56	19144319
25	Phosphorylation	RDGSLNQSSGYRYGT CCCCCCCCCCCCCCC	25.34	26824392
26	Phosphorylation	DGSLNQSSGYRYGTD CCCCCCCCCCCCCCC	30.04	26824392
28	Phosphorylation	SLNQSSGYRYGTDPT CCCCCCCCCCCCCCC	11.56	18515860
50	Phosphorylation	GVTSIPNYNNFHAAG CCCCCCCCCCCCCCC	13.21	29514104
91	Phosphorylation	VTLFVALYDYEARTE EEEEEEEEECCCCCC	13.52	-
150	Phosphorylation	SIQAEEWYFGKLGRK CCCCHHHHCCCCCCH	13.01	25338131
165	Phosphorylation	DAERQLLSFGNPRGT HHHHHHHHCCCCCCE	39.43	28418008
182	Ubiquitination	IRESETTKGAYSLSI EEECCCCCCEEEEEE	44.95	27667366
185	Phosphorylation	SETTKGAYSLSIRDW CCCCCCEEEEEEEEH	20.86	25521595
186	Phosphorylation	ETTKGAYSLSIRDWD CCCCCEEEEEEEEHH	18.33	23737553
188	Phosphorylation	TKGAYSLSIRDWDDM CCCEEEEEEEEHHHC	15.05	25367039
213	Phosphorylation	RKLDNGGYYITTRAQ EECCCCCEEEEEHHH	7.97	25521595
214	Phosphorylation	KLDNGGYYITTRAQF ECCCCCEEEEEHHHH	8.61	21082442
216	Phosphorylation	DNGGYYITTRAQFET CCCCEEEEEHHHHHH	8.29	19060867
217	Phosphorylation	NGGYYITTRAQFETL CCCEEEEEHHHHHHH	17.91	20415495
254	Phosphorylation	HKGMPRLTDLSVKTK CCCCCCCCCCCEECC	35.85	19131326
257	Phosphorylation	MPRLTDLSVKTKDVW CCCCCCCCEECCCHH	25.11	22817900
267 (in isoform 2)	Phosphorylation	-	23.59	27600695
320	Methylation	EEAQIMKKLKHDKLV HHHHHHHHCCCCCEE	45.44	-
322	Methylation	AQIMKKLKHDKLVQL HHHHHHCCCCCEEEE	59.65	-
339	Phosphorylation	VVSEEPIYIVTEYMS EECCCCEEEEEEECC	10.47	-
393	Phosphorylation	YIHRDLRSANILVGN HHCCCHHHCCEEECC	32.72	22817900
417 (in isoform 2)	Phosphorylation	-	46.39	19144319
420	Phosphorylation	RLIEDNEYTARQGAK HHHCCCCCCCCCCCC	16.38	18515860
421	Phosphorylation	LIEDNEYTARQGAKF HHCCCCCCCCCCCCC	14.80	27566939
440	Phosphorylation	TAPEAALYGRFTIKS CCCCHHHHCCEEECC	11.09	20116462
461	Phosphorylation	ILLTELVTKGRVPYP HHHHHHHHCCCCCCC	40.17	22871156
525	Phosphorylation	GFLEDYFTATEPQYQ HHHHHHHCCCCCCCC	26.83	25293948
527	Phosphorylation	LEDYFTATEPQYQPG HHHHHCCCCCCCCCC	45.18	25293948
531	Phosphorylation	FTATEPQYQPGENL- HCCCCCCCCCCCCC-	27.65	18809727

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
420	Y	Phosphorylation	Kinase	FYN	P39688	GPS
531	Y	Phosphorylation	Kinase	CSK	P41241	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
3	C	Palmitoylation	8413237
Palmitoylation at Cys-3 and Cys-6, probably by ZDHHC21, regulates subcellular location.
6	C	Palmitoylation	8413237
Palmitoylation at Cys-3 and Cys-6, probably by ZDHHC21, regulates subcellular location.
15	T	Phosphorylation	22685302
Ultraviolet B (UVB) strongly increase phosphorylation at Thr-15 and kinase activity, and promotes translocation from the cytoplasm to the nucleus.

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 FYN_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ENOA_MOUSE	Eno1	physical	18854310
CBL_MOUSE	Cbl	physical	8551236
KHDR1_MOUSE	Khdrbs1	physical	10844001
CBL_MOUSE	Cbl	physical	9890970
P85A_MOUSE	Pik3r1	physical	9115297
DIAP1_MOUSE	Diap1	physical	18194650
ZN106_MOUSE	Zfp106	physical	9507006
CBL_MOUSE	Cbl	physical	8635998
CBL_MOUSE	Cbl	physical	9210408
NCK1_MOUSE	Nck1	physical	16966330

Drug and Disease Associations

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

Regulatory Network of FYN_MOUSE

Related Literatures of Post-Translational Modification

Myristoylation
Reference	PubMed
"Multiple features of the p59fyn src homology 4 domain define a motiffor immune-receptor tyrosine-based activation motif (ITAM) binding andfor plasma membrane localization."; Gauen L.K.T., Linder M.E., Shaw A.S.; J. Cell Biol. 133:1007-1015(1996). Cited for: MYRISTOYLATION AT GLY-2.	8655574 [Abstract]
Palmitoylation
Reference	PubMed
"Palmitoylation of p59fyn is reversible and sufficient for plasmamembrane association."; Wolven A., Okamura H., Rosenblatt Y., Resh M.D.; Mol. Biol. Cell 8:1159-1173(1997). Cited for: PALMITOYLATION AT CYS-3, AND MUTAGENESIS OF CYS-3.	9201723 [Abstract]
"Palmitoylation of multiple Src-family kinases at a homologous N-terminal motif."; Koegl M., Zlatkine P., Ley S.C., Courtneidge S.A., Magee A.I.; Biochem. J. 303:749-753(1994). Cited for: PALMITOYLATION AT CYS-3 AND CYS-6, AND MUTAGENESIS OF GLY-2; CYS-3 ANDCYS-6.	7980442 [Abstract]
"Palmitylation of an amino-terminal cysteine motif of protein tyrosinekinases p56lck and p59fyn mediates interaction with glycosyl-phosphatidylinositol-anchored proteins."; Shenoy-Scaria A.M., Timson L.K., Kwong J., Shaw A.S., Lublin D.M.; Mol. Cell. Biol. 13:6385-6392(1993). Cited for: PALMITOYLATION AT CYS-3 AND CYS-6, AND MUTAGENESIS OF CYS-3 AND CYS-6.	8413237 [Abstract]
Phosphorylation
Reference	PubMed
"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry."; Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; Mol. Cell. Proteomics 8:904-912(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-254 AND SER-257, ANDMASS SPECTROMETRY.	19131326 [Abstract]
"The phagosomal proteome in interferon-gamma-activated macrophages."; Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.; Immunity 30:143-154(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-420, AND MASSSPECTROMETRY.	19144319 [Abstract]
"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain."; Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; J. Proteome Res. 7:311-318(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185 AND TYR-531, ANDMASS SPECTROMETRY.	18034455 [Abstract]
"Differential effects of expression of the CD45 tyrosine proteinphosphatase on the tyrosine phosphorylation of the lck, fyn, and c-srctyrosine protein kinases."; Hurley T.R., Hyman R., Sefton B.M.; Mol. Cell. Biol. 13:1651-1656(1993). Cited for: PHOSPHORYLATION AT TYR-531, AUTOPHOSPHORYLATION AT TYR-420, AND ENZYMEREGULATION.	8441403 [Abstract]

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