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Protein Page:
Lck (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
Lck a tyrosine kinase of the Src family that is crucial to antigen-receptor signaling in lymphocytes. plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. 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, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls 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. Binds to the cytoplasmic domain of cell surface receptors, such as CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDC2, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of Sam68 through its SH2 domain. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Overexpression in mice leads to thymic tumors. Aberrant expression is seen in T cell leukemias and colon cancer. The leukemic translocation t(1;7)(p34;q34) has breakpoints at the T cell receptor gene and close to the Lck promoters, can cause increased Lck expression, and in one case, point mutations. A mutated Lck has also been seen in a cell line. One patient with aberrant Lck splicing suffered from SCID-like T cell deficiency. Inhibitor: BMS-279700. Three alternatively spliced isoforms of the human proteinhave been described. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.2; Protein kinase, tyrosine (non-receptor); Kinase, protein; Protein kinase, TK; TK group; Src family
Cellular Component: pericentriolar material; endocytic vesicle; plasma membrane; immunological synapse; cytosol; lipid raft
Molecular Function: protein C-terminus binding; identical protein binding; CD8 receptor binding; non-membrane spanning protein tyrosine kinase activity; protein serine/threonine phosphatase activity; antigen binding; protein kinase binding; protein phosphatase binding; ATPase binding; protein binding; protein-tyrosine kinase activity; protein complex binding; phosphoinositide 3-kinase binding; SH2 domain binding; glycoprotein binding; CD4 receptor binding; ATP binding
Biological Process: peptidyl-tyrosine phosphorylation; viral reproduction; nerve growth factor receptor signaling pathway; protein amino acid autophosphorylation; protein amino acid phosphorylation; T cell receptor signaling pathway; B cell receptor signaling pathway; positive regulation of T cell receptor signaling pathway; hemopoiesis; positive regulation of gamma-delta T cell differentiation; T cell differentiation; aging; regulation of lymphocyte activation; caspase activation; response to drug; epidermal growth factor receptor signaling pathway; platelet activation; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; cellular zinc ion homeostasis; regulation of defense response to virus by virus; response to hydrogen peroxide; positive regulation of tyrosine phosphorylation of Stat5 protein; dephosphorylation; response to zinc ion; response to mechanical stimulus; release of sequestered calcium ion into cytosol; T cell costimulation; innate immune response; positive regulation of T cell activation; blood coagulation; leukocyte migration
Reference #:  P06239 (UniProtKB)
Alt. Names/Synonyms: LCK; LSK; Lymphocyte cell-specific protein-tyrosine kinase; lymphocyte-specific protein tyrosine kinase; p56(LSTRA) protein-tyrosine kinase; p56-LCK; p56lck; pp58lck; Proto-oncogene Lck; proto-oncogene tyrosine-protein kinase LCK; T cell-specific protein-tyrosine kinase; T-lymphocyte specific protein tyrosine kinase p56lck; Tyrosine-protein kinase Lck; YT16
Gene Symbols: LCK
Molecular weight: 58,001 Da
Basal Isoelectric point: 5.23  Predict pI for various phosphorylation states
CST Pathways:  GPCR Signaling to MAPKs  |  T Cell Receptor Signaling  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Lck

Protein Structure Not Found.

Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
cell growth, altered: Y394‑p, Y505‑p
activity, inhibited: Y192‑p, Y505‑p
enzymatic activity, induced: Y394‑p
enzymatic activity, inhibited: Y505‑p
intracellular localization: Y394‑p, Y505‑p
molecular association, regulation: S59‑p, Y192‑p, Y394‑p, Y505‑p
phosphorylation: Y192‑p, Y505‑p
protein conformation: Y394‑p, Y505‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 15 Y25-p DVCENCHyPIVPLDG
0 5 T35-p VPLDGKGtLLIRNGs
2 31 S42-p tLLIRNGsEVRDPLV
0 3 T50-p EVRDPLVtyEGSNPP
0 8 Y51-p VRDPLVtyEGSNPPA
8 7 S59-p EGSNPPAsPLQDNLV
0 1 K84-ub DGDLGFEkGEQLRIL
0 4 S102-p GEWWKAQsLTTGQEG
0 1 S156-p GSFLIREsEstAGsF
1 3 S158-p FLIREsEstAGsFSL
0 1 T159-p LIREsEstAGsFSLS
0 6 S162-p EsEstAGsFSLSVRD
0 1 S164 EstAGsFSLSVRDFD
0 1 K179-ac QNQGEVVkHyKIRNL
0 3 K179-ub QNQGEVVkHyKIRNL
0 1 Y181-p QGEVVkHyKIRNLDN
2 1062 Y192-p NLDNGGFyIsPRItF
1 11 S194-p DNGGFyIsPRItFPG
0 2 T198-p FyIsPRItFPGLHEL
0 1 Y209-p LHELVRHytNAsDGL
0 3 T210-p HELVRHytNAsDGLC
0 1 S213-p VRHytNAsDGLCTRL
0 1 K246-ub EVPRETLkLVERLGA
0 65 Y263-p FGEVWMGyyNGHtKV
0 19 Y264-p GEVWMGyyNGHtKVA
0 1 T268-p MGyyNGHtKVAVKsL
0 3 S274-p HtKVAVKsLKQGSMs
0 1 S281-p sLKQGSMsPDAFLAE
0 4 T375-p ANILVSDtLSCkIAD
0 8 K379-ub VSDtLSCkIADFGLA
34 2967 Y394-p RLIEDNEytAREGAK
1 22 T395-p LIEDNEytAREGAKF
0 43 Y414-p TAPEAINyGtFTIKS
0 5 T416-p PEAINyGtFTIKSDV
0 162 Y470-p DNCPEELyQLMRLCW
0 2 K478-ub QLMRLCWkERPEDRP
0 3 Y489-p EDRPTFDyLRsVLED
0 1 S492-p PTFDyLRsVLEDFFT
0 11 T501-p LEDFFTAtEGQyQPQ
36 807 Y505-p FTAtEGQyQPQP___
2101 : Phospho-Src Family (Tyr416) Antibody
6943 : Phospho-Src Family (Tyr416) (D49G4) Rabbit mAb
2751 : Phospho-Lck (Tyr505) Antibody
  mouse

 
Y25 DVCENCHYPIVPLDS
S35-p VPLDSKIsLPIRNGs
S42-p sLPIRNGsEVRDPLV
T50 EVRDPLVTYEGSLPP
Y51 VRDPLVTYEGSLPPA
S59-p EGSLPPAsPLQDNLV
K84 DGDLGFEKGEQLRIL
S102 GEWWKAQSLTTGQEG
S156 GSFLIRESESTAGSF
S158 FLIRESESTAGSFsL
T159 LIRESESTAGSFsLS
S162 ESESTAGSFsLSVRD
S164-p ESTAGSFsLSVRDFD
K179 QNQGEVVKHYKIRNL
K179 QNQGEVVKHYKIRNL
Y181 QGEVVKHYKIRNLDN
Y192-p NLDNGGFyISPRITF
S194 DNGGFyISPRITFPG
T198 FyISPRITFPGLHDL
Y209 LHDLVRHYTNASDGL
T210 HDLVRHYTNASDGLC
S213 VRHYTNASDGLCTKL
K246 EVPRETLKLVERLGA
Y263 FGEVWMGYYNGHTKV
Y264 GEVWMGYYNGHTKVA
T268 MGYYNGHTKVAVKSL
S274 HTKVAVKSLKQGSMS
S281 SLKQGSMSPDAFLAE
T375 ANILVSDTLSCKIAD
K379 VSDTLSCKIADFGLA
Y394-p RLIEDNEytAREGAK
T395-p LIEDNEytAREGAKF
Y414 TAPEAINYGTFTIKS
T416 PEAINYGTFTIKSDV
Y470 DNCPEELYHLMMLCW
K478 HLMMLCWKERPEDRP
Y489 EDRPTFDYLRSVLDD
S492 PTFDYLRSVLDDFFT
T501 LDDFFTATEGQyQPQ
Y505-p FTATEGQyQPQP___
2101 : Phospho-Src Family (Tyr416) Antibody
6943 : Phospho-Src Family (Tyr416) (D49G4) Rabbit mAb
2751 : Phospho-Lck (Tyr505) Antibody
  rat

 
Y25 DVCENCHYPIVPLDS
T35 VPLDSKSTLPIRTGS
S42 TLPIRTGSEVRDPLV
T50 EVRDPLVTYEGSLPP
Y51 VRDPLVTYEGSLPPA
S59 EGSLPPASPLQDNLV
K84 DGDLGFEKGEQLRIL
S102 GEWWKAQSLTTGQEG
S156 GSFLIRESESTAGSF
S158 FLIRESESTAGSFSL
T159 LIRESESTAGSFSLS
S162 ESESTAGSFSLSVRD
S164 ESTAGSFSLSVRDFD
K179 QNQGEVVKHYKIRNL
K179 QNQGEVVKHYKIRNL
Y181 QGEVVKHYKIRNLDN
Y192-p NLDNGGFyISPRITF
S194 DNGGFyISPRITFPG
T198 FyISPRITFPGLHDL
Y209 LHDLVRHYTNASDGL
T210 HDLVRHYTNASDGLC
S213 VRHYTNASDGLCTKL
K246 EVPRETLKLVERLGA
Y263 FGEVWMGYYNGHTKV
Y264 GEVWMGYYNGHTKVA
T268 MGYYNGHTKVAVKSL
S274 HTKVAVKSLKQGSMS
S281 SLKQGSMSPDAFLAE
T375 ANILVSDTLSCKIAD
K379 VSDTLSCKIADFGLA
Y394-p RLIEDNEyTAREGAK
T395 LIEDNEyTAREGAKF
Y414 TAPEAINYGTFTIKS
T416 PEAINYGTFTIKSDV
Y470 DNCPEELYHLMMLCW
K478 HLMMLCWKERPEDRP
Y489 EDRPTFDYLRSVLDD
S492 PTFDYLRSVLDDFFT
T501 LDDFFTATEGQYQPQ
Y505 FTATEGQYQPQP___
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