LYN_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: LYN_RAT
• UniProt AC: Q07014
• Protein Name: Tyrosine-protein kinase Lyn
• Gene Name: Lyn
• Organism: Rattus norvegicus (Rat).
• 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 (By similarity). Phosphorylates LPXN on 'Tyr-72' (By similarity). Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation..
• Protein Sequence: MGCIKSKRKDNLNDDGVDMKTQPVRNTDRTIYVRDPTSNKQQRPVPESQLLPGQRFQAKDPEEQGDIVVALYPYDGIHPDDLSFKKGEKMKVLEEHGEWWKAKSLSSKREGFIPSNYVAKVNTLETEEWFFKDITRKDAERQLLAPGNSAGAFLIRESETLKGSFSLSVRDYDPMHGDVIKHYKIRSLDNGGYYISPRITFPCISDMIKHYQKQSDGLCRRLEKACISPKPQKPWDKDAWEIPRESIKLVKKLGAGQFGEVWMGYYNNSTKVAVKTLKPGTMSAQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEFMAKGSLLDFLKSDEGSKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGCFTIKSDVWSFGILLYEIVTYGKIPYPGRTNADVMTALSQGYRMPRMENCPDELYDIMKMCWKESAEERPTFDYLQSVLDDFYTATEGQYQQQP

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	-
20	Ubiquitination	NDDGVDMKTQPVRNT CCCCCCCCCCCCCCC	39.27	-
32	Phosphorylation	RNTDRTIYVRDPTSN CCCCCEEEEECCCCC	6.71	-
37	Phosphorylation	TIYVRDPTSNKQQRP EEEEECCCCCCCCCC	49.58	25575281
38	Phosphorylation	IYVRDPTSNKQQRPV EEEECCCCCCCCCCC	47.63	25575281
48	Phosphorylation	QQRPVPESQLLPGQR CCCCCCHHHCCCCCC	21.76	25575281
181	Acetylation	PMHGDVIKHYKIRSL CCCCCEEEEEEEEEC	40.50	22902405
187	Phosphorylation	IKHYKIRSLDNGGYY EEEEEEEECCCCCEE	43.48	28689409
193	Phosphorylation	RSLDNGGYYISPRIT EECCCCCEEECCCEE	10.06	28689409
194	Phosphorylation	SLDNGGYYISPRITF ECCCCCEEECCCEEC	9.74	28689409
196	Phosphorylation	DNGGYYISPRITFPC CCCCEEECCCEECCC	7.63	30181290
213	Acetylation	DMIKHYQKQSDGLCR HHHHHHHHHCCCHHH	44.60	22902405
228	Phosphorylation	RLEKACISPKPQKPW HHHHHHCCCCCCCCC	27.10	-
248	Acetylation	EIPRESIKLVKKLGA CCCHHHHHHHHHHCC	57.41	22902405
306	Phosphorylation	HDKLVRLYAVVTKEE HCCCEEEEEEECCCC	6.18	-
316	Phosphorylation	VTKEEPIYIITEFMA ECCCCCEEEEEEHHH	9.29	22673903
397	Phosphorylation	RVIEDNEYTAREGAK EEEECCCEECCCCCC	16.38	22108457
398	Phosphorylation	VIEDNEYTAREGAKF EEECCCEECCCCCCC	17.04	30181290
460	Phosphorylation	MTALSQGYRMPRMEN HHHHHCCCCCCCCCC	8.97	-
473	Phosphorylation	ENCPDELYDIMKMCW CCCCHHHHHHHHHHH	11.02	-
495	Phosphorylation	PTFDYLQSVLDDFYT CCHHHHHHHHHHHHH	23.27	22673903
501	Phosphorylation	QSVLDDFYTATEGQY HHHHHHHHHHCCCCC	11.49	27097102
502	Phosphorylation	SVLDDFYTATEGQYQ HHHHHHHHHCCCCCC	27.39	27097102
504	Phosphorylation	LDDFYTATEGQYQQQ HHHHHHHCCCCCCCC	32.61	27097102
508	Phosphorylation	YTATEGQYQQQP--- HHHCCCCCCCCC---	21.10	27097102

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	Q07014	GPS
508	Y	Phosphorylation	Kinase	CSK	P32577	Uniprot
508	Y	Phosphorylation	Kinase	LYN	Q07014	GPS
508	Y	Phosphorylation	Kinase	MATK	P41243	Uniprot

Functions of PTM Sites

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

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_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
UBC_RAT	Ubc	physical	14531861
UBC_RAT	Ubc	physical	11137137
LYN_RAT	Lyn	physical	14604964
ENOA_HUMAN	ENO1	physical	14604964
SYUA_HUMAN	SNCA	physical	11744621

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Spontaneous autophosphorylation of Lyn tyrosine kinase at both itsactivation segment and C-terminal tail confers altered substratespecificity.";
Donella-Deana A., Cesaro L., Ruzzene M., Brunati A.M., Marin O.,Pinna L.A.;
Biochemistry 37:1438-1446(1998).
Cited for: PHOSPHORYLATION AT TYR-397 AND TYR-508, CATALYTIC ACTIVITY,AUTOPHOSPHORYLATION, ENZYME REGULATION, AND TISSUE SPECIFICITY.
PubMed: 9477973