LCK_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: LCK_MOUSE
• UniProt AC: P06240
• Protein Name: Proto-oncogene tyrosine-protein kinase LCK
• Gene Name: Lck
• Organism: Mus musculus (Mouse).
• Sequence Length: 509
• Subcellular Localization: Cytoplasm . Cell membrane ; Lipid-anchor ; Cytoplasmic side . Present in lipid rafts in an inactive form.
• Protein Description: Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP (By similarity). Interacts with UNC119; this interaction plays a crucial role in activation of LCK (By similarity)..
• Protein Sequence: MGCVCSSNPEDDWMENIDVCENCHYPIVPLDSKISLPIRNGSEVRDPLVTYEGSLPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKHYKIRNLDNGGFYISPRITFPGLHDLVRHYTNASDGLCTKLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHPRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLNVNKLLDMAAQIAEGMAFIEEQNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYHLMMLCWKERPEDRPTFDYLRSVLDDFFTATEGQYQPQP

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	------MGCVCSSNP ------CCCCCCCCC	16.74	7980442
3	S-palmitoylation	-----MGCVCSSNPE -----CCCCCCCCCC	2.42	8524258
5	S-palmitoylation	---MGCVCSSNPEDD ---CCCCCCCCCCCC	4.25	8524258
35	Phosphorylation	VPLDSKISLPIRNGS EECCCCCEEEECCCC	31.65	22817900
42	Phosphorylation	SLPIRNGSEVRDPLV EEEECCCCCCCCCEE	36.15	22817900
59	Phosphorylation	EGSLPPASPLQDNLV CCCCCCCCCCCCCEE	31.73	22817900
94	Phosphorylation	QLRILEQSGEWWKAQ EEEEEEECCCCEEEE	29.33	28833060
102	Phosphorylation	GEWWKAQSLTTGQEG CCCEEEEECCCCCCC	32.32	25266776
121	Phosphorylation	NFVAKANSLEPEPWF HHEEECCCCCCCCCH	38.68	27600695
158	Phosphorylation	FLIRESESTAGSFSL EEEEECCCCCCEEEE	32.60	28833060
159	Phosphorylation	LIRESESTAGSFSLS EEEECCCCCCEEEEE	30.87	28833060
162	Phosphorylation	ESESTAGSFSLSVRD ECCCCCCEEEEEEEE	14.81	-
164	Phosphorylation	ESTAGSFSLSVRDFD CCCCCEEEEEEEEEC	22.79	19060867
192	Phosphorylation	NLDNGGFYISPRITF ECCCCCEEECCCEEC	12.08	20438120
194	Phosphorylation	DNGGFYISPRITFPG CCCCEEECCCEECCC	9.21	27600695
198	Phosphorylation	FYISPRITFPGLHDL EEECCCEECCCHHHH	25.67	28833060
394	Phosphorylation	RLIEDNEYTAREGAK HHHCCCCCCCCCCCC	16.38	7521333
395	Phosphorylation	LIEDNEYTAREGAKF HHCCCCCCCCCCCCC	17.04	27566939
499	Phosphorylation	SVLDDFFTATEGQYQ HHHHHHHHHCCCCCC	32.44	28833060
505	Phosphorylation	FTATEGQYQPQP--- HHHCCCCCCCCC---	32.77	7521333

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
59	S	Phosphorylation	Kinase	ERK-SUBFAMILY	-	GPS
394	Y	Phosphorylation	Kinase	LCK	P06240	PSP
505	Y	Phosphorylation	Kinase	CSK	P41241	Uniprot
505	Y	Phosphorylation	Kinase	LCK	P06240	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of LCK_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 LCK_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CYLD_MOUSE	Cyld	physical	16501569
SOCS6_MOUSE	Socs6	physical	20007709
LCK_HUMAN	LCK	physical	20360068
P85A_MOUSE	Pik3r1	physical	9115297
CBL_MOUSE	Cbl	physical	9115297
DLG1_MOUSE	Dlg1	physical	15699074
ZAP70_MOUSE	Zap70	physical	15699074
WASP_MOUSE	Was	physical	15699074
AES_HUMAN	AES	physical	26496610
APOE_HUMAN	APOE	physical	26496610
ATP5I_HUMAN	ATP5I	physical	26496610
MEN1_HUMAN	MEN1	physical	26496610
SPAST_HUMAN	SPAST	physical	26496610
YES_HUMAN	YES1	physical	26496610
CDK13_HUMAN	CDK13	physical	26496610
C2CD5_HUMAN	C2CD5	physical	26496610
HPS5_HUMAN	HPS5	physical	26496610
CAMP2_HUMAN	CAMSAP2	physical	26496610
NELFD_HUMAN	NELFCD	physical	26496610
ZBED8_HUMAN	ZBED8	physical	26496610
PHF5A_HUMAN	PHF5A	physical	26496610
ESCO1_HUMAN	ESCO1	physical	26496610
NSE2_HUMAN	NSMCE2	physical	26496610
CBLB_MOUSE	Cblb	physical	26416283

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Palmitoylation

"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-5, MYRISTOYLATION AT GLY-2, ANDMUTAGENESIS OF GLY-2; CYS-3 AND CYS-5.
PubMed: 7980442

"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-5, AND MUTAGENESIS OF CYS-3 AND CYS-5.
PubMed: 8413237

Phosphorylation

"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.;
Nat. Biotechnol. 23:94-101(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-394, AND MASSSPECTROMETRY.
PubMed: 15592455