LYN_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: LYN_MOUSE
• UniProt AC: P25911
• Protein Name: Tyrosine-protein kinase Lyn
• Gene Name: Lyn
• Organism: Mus musculus (Mouse).
• Sequence Length: 512
• Subcellular Localization: Cell membrane. Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Golgi apparatus. Membrane ; Lipid-anchor . Accumulates in the nucleus by inhibition of Crm1-mediated nuclear export. Nuclear accumulation is increased by inhibition of its kinase activ
• Protein Description: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation..
• Protein Sequence: MGCIKSKRKDNLNDDEVDSKTQPVRNTDRTIYVRDPTSNKQQRPVPEFHLLPGQRFQTKDPEEQGDIVVALYPYDGIHPDDLSFKKGEKMKVLEEHGEWWKAKSLSSKREGFIPSNYVAKVNTLETEEWFFKDITRKDAERQLLAPGNSAGAFLIRESETLKGSFSLSVRDYDPMHGDVIKHYKIRSLDNGGYYISPRITFPCISDMIKHYQKQSDGLCRRLEKACISPKPQKPWDKDAWEIPRESIKLVKKLGAGQFGEVWMGYYNNSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEFMAKGSLLDFLKSDEGGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGCFTIKSDVWSFGILLYEIVTYGKIPYPGRTNADVMSALSQGYRMPRMENCPDELYDIMKMCWKEKAEERPTFDYLQSVLDDFYTATEGQYQQQP

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Myristoylation	------MGCIKSKRK ------CCCCCCCCC	23.12	-
3	S-palmitoylation	-----MGCIKSKRKD -----CCCCCCCCCC	3.23	-
9	Ubiquitination	GCIKSKRKDNLNDDE CCCCCCCCCCCCCCC	55.49	22790023
9 (in isoform 2)	Ubiquitination	-	55.49	22790023
19	O-linked_Glycosylation	LNDDEVDSKTQPVRN CCCCCCCCCCCCCCC	42.66	29187734
19	Phosphorylation	LNDDEVDSKTQPVRN CCCCCCCCCCCCCCC	42.66	25521595
19 (in isoform 2)	Phosphorylation	-	42.66	24704852
20	Ubiquitination	NDDEVDSKTQPVRNT CCCCCCCCCCCCCCC	46.87	22790023
20 (in isoform 2)	Ubiquitination	-	46.87	-
21	Phosphorylation	DDEVDSKTQPVRNTD CCCCCCCCCCCCCCC	41.90	29176673
21 (in isoform 2)	Phosphorylation	-	41.90	26745281
30	Phosphorylation	PVRNTDRTIYVRDPT CCCCCCCEEEEECCC	21.33	24719451
32	Phosphorylation	RNTDRTIYVRDPTSN CCCCCEEEEECCCCC	6.71	26026062
37	Phosphorylation	TIYVRDPTSNKQQRP EEEEECCCCCCCCCC	49.58	25367039
106	Phosphorylation	WWKAKSLSSKREGFI HHHHHCCCCCCCCCC	40.69	24719451
166	Phosphorylation	ETLKGSFSLSVRDYD CCCCCEEEEEEEECC	22.79	21183079
172	Phosphorylation	FSLSVRDYDPMHGDV EEEEEEECCCCCCCE	16.04	26026062
187	Phosphorylation	IKHYKIRSLDNGGYY EEEEEEEECCCCCEE	43.48	22499769
192 (in isoform 2)	Ubiquitination	-	20.51	-
193	Phosphorylation	RSLDNGGYYISPRIT EECCCCCEEECCCEE	10.06	22499769
194	Phosphorylation	SLDNGGYYISPRITF ECCCCCEEECCCEEC	9.74	25168779
196	Phosphorylation	DNGGYYISPRITFPC CCCCEEECCCEECCC	7.63	22499769
203	S-palmitoylation	SPRITFPCISDMIKH CCCEECCCHHHHHHH	3.98	28526873
213 (in isoform 2)	Ubiquitination	-	44.60	22790023
213	Ubiquitination	DMIKHYQKQSDGLCR HHHHHHHHHCCCHHH	44.60	22790023
228	Phosphorylation	RLEKACISPKPQKPW HHHHHHCCCCCCCCC	27.10	-
265	Phosphorylation	FGEVWMGYYNNSTKV CCEEEEEEECCCCEE	6.21	25367039
266	Phosphorylation	GEVWMGYYNNSTKVA CEEEEEEECCCCEEE	11.35	25367039
269	Phosphorylation	WMGYYNNSTKVAVKT EEEEECCCCEEEEEE	26.43	25367039
270	Phosphorylation	MGYYNNSTKVAVKTL EEEECCCCEEEEEEC	31.49	25367039
281	Phosphorylation	VKTLKPGTMSVQAFL EEECCCCCEEHHHHH	18.14	28576409
306	Phosphorylation	HDKLVRLYAVVTKEE HCCCEEEEEEECCCC	6.18	-
316	Phosphorylation	VTKEEPIYIITEFMA ECCCCCEEEEEEHHH	9.29	26032504
319	Phosphorylation	EEPIYIITEFMAKGS CCCEEEEEEHHHCCC	17.38	25367039
376	Phosphorylation	RAANVLVSESLMCKI HHHCCEECHHHHHHH	19.80	29472430
376 (in isoform 2)	Phosphorylation	-	19.80	19144319
378	Phosphorylation	ANVLVSESLMCKIAD HCCEECHHHHHHHHH	17.56	29472430
397	Phosphorylation	RVIEDNEYTAREGAK EEEECCCEECCCCCC	16.38	25521595
398	Phosphorylation	VIEDNEYTAREGAKF EEECCCEECCCCCCC	17.04	21082442
419	S-palmitoylation	PEAINFGCFTIKSDV CCCCCCCCEEECCCH	2.08	28526873
460	Phosphorylation	MSALSQGYRMPRMEN HHHHHCCCCCCCCCC	8.97	26026062
473	Phosphorylation	ENCPDELYDIMKMCW CCCCHHHHHHHHHHH	11.02	22817900
487 (in isoform 2)	Phosphorylation	-	27.36	19144319
489	Phosphorylation	EKAEERPTFDYLQSV HHHHHCCCHHHHHHH	35.05	25367039
492	Phosphorylation	EERPTFDYLQSVLDD HHCCCHHHHHHHHHH	11.49	23984901
495	Phosphorylation	PTFDYLQSVLDDFYT CCHHHHHHHHHHHHH	23.27	23737553
501	Phosphorylation	QSVLDDFYTATEGQY HHHHHHHHHHCCCCC	11.49	26745281
502	Phosphorylation	SVLDDFYTATEGQYQ HHHHHHHHHCCCCCC	27.39	26745281
504	Phosphorylation	LDDFYTATEGQYQQQ HHHHHHHCCCCCCCC	32.61	26745281
508	Phosphorylation	YTATEGQYQQQP--- HHHCCCCCCCCC---	21.10	26824392

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
397	Y	Phosphorylation	Kinase	LYN	P25911	PSP
508	Y	Phosphorylation	Kinase	CSK	P41241	Uniprot
508	Y	Phosphorylation	Kinase	LYN	P25911	GPS
508	Y	Phosphorylation	Kinase	MATK	P41242	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Cbl	P22682	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Nedd4	P46935	PMID:22199232

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of LYN_MOUSE !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of LYN_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PHAG1_MOUSE	Pag1	physical	16920712
CBL_MOUSE	Cbl	physical	8627181
KHDR1_MOUSE	Khdrbs1	physical	10844001
CBL_MOUSE	Cbl	physical	9890970
CBL_MOUSE	Cbl	physical	8635998
DOK1_MOUSE	Dok1	physical	10823839

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"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 SER-19 AND TYR-508, AND MASSSPECTROMETRY.
PubMed: 19144319

"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-193; TYR-194 ANDTYR-508, AND MASS SPECTROMETRY.
PubMed: 18034455

"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 TYR-193 AND TYR-194, ANDMASS SPECTROMETRY.
PubMed: 17947660

"Positive and negative regulation of mast cell activation by Lyn viathe FcepsilonRI.";
Xiao W., Nishimoto H., Hong H., Kitaura J., Nunomura S.,Maeda-Yamamoto M., Kawakami Y., Lowell C.A., Ra C., Kawakami T.;
J. Immunol. 175:6885-6892(2005).
Cited for: FUNCTION IN FCER1 SIGNALING; PHOSPHORYLATION OF SYK; MS4A2/FCER1B;INPP5D/SHIP AND PTPN6/SHP-1; ACTIVATION OF AKT1; MAPK1/ERK2 ANDMAPK3/ERK1, PHOSPHORYLATION AT TYR-397, AND INTERACTION WITHMS4A2/FCER1B.
PubMed: 16272347

"CD45 negatively regulates lyn activity by dephosphorylating bothpositive and negative regulatory tyrosine residues in immature Bcells.";
Katagiri T., Ogimoto M., Hasegawa K., Arimura Y., Mitomo K., Okada M.,Clark M.R., Mizuno K., Yakura H.;
J. Immunol. 163:1321-1326(1999).
Cited for: PHOSPHORYLATION AT TYR-397 AND TYR-508, DEPHOSPHORYLATION BYPTPRC/CD45, AND ENZYME REGULATION.
PubMed: 10415030