Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Tyrosine-protein kinase Lck  

UniProtKB / Swiss-Prot ID :  LCK_HUMAN

Gene Name (Synonyms) : 
LCK  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note=Present in lipid rafts in an unactive form. 

Protein Function :  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 tyrosines 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. 

Protein Sequence MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALH...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCCEECCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCEEEEEEE...
Protein Variant
LocationDescription
28V -> L (in leukemia). VAR_013463
201G -> S (in dbSNP:rs11567841). VAR_051697
232P -> PQKP (in leukemia). VAR_013464
353A -> V (in leukemia). VAR_013465
447P -> L (in leukemia). VAR_013466
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
2N-myristoyl glycine---MGCGCS
---CCCCCC
19.27HPRD
Link-
3N-palmitoyl cysteine--MGCGCSS
--CCCCCCC
4.85HPRD
Link-
5N-palmitoyl cysteineMGCGCSSHP
CCCCCCCCC
4.36HPRD
Link-
42PhosphoserineIRNGSEVRD
CCCCCCCCC
36.15Phosphositeplus
Link-
42Phosphoserine (MAPK3;MAPK3;MAPK1;MAPK1)IRNGSEVRD
CCCCCCCCC
36.15PhosphoELM
Link-
42Phosphoserine (PRKACA)IRNGSEVRD
CCCCCCCCC
36.15HPRD
Link-
42Phosphoserine (PRKCA)IRNGSEVRD
CCCCCCCCC
36.15HPRD
Link-
59PhosphoserineNPPASPLQD
CCCCCCCCC
31.73PhosphoELM
Link-
59Phosphoserine (MAPK1)NPPASPLQD
CCCCCCCCC
31.73HPRD
Link-
59Phosphoserine (MAPK3)NPPASPLQD
CCCCCCCCC
31.73HPRD
Link-
102PhosphoserineWKAQSLTTG
EEEEECCCC
32.32Phosphositeplus
Link-
102Phosphoserine.WKAQSLTTG
EEEEECCCC
32.32UniProtKB
Link-
133PhosphoserineFKNLSRKDA
CCCCCHHHH
46.83HPRD
Link
158PhosphoserineRESESTAGS
ECCCCCCCC
32.60PhosphoELM
Link
158PhosphoserineRESESTAGS
ECCCCCCCC
32.60Phosphositeplus
Link
159PhosphothreonineESESTAGSF
CCCCCCCCE
30.87Phosphositeplus
Link
159Phosphothreonine.ESESTAGSF
CCCCCCCCE
30.87UniProtKB
Link
162PhosphoserineSTAGSFSLS
CCCCCEEEE
14.81PhosphoELM
Link
162PhosphoserineSTAGSFSLS
CCCCCEEEE
14.81Phosphositeplus
Link
162Phosphoserine.STAGSFSLS
CCCCCEEEE
14.81UniProtKB
Link
179N6-acetyllysineGEVVKHYKI
CCEECEEEE
46.52HPRD
Link
179N6-acetyllysineGEVVKHYKI
CCEECEEEE
46.52Phosphositeplus
Link
179N6-acetyllysine.GEVVKHYKI
CCEECEEEE
46.52UniProtKB
Link
192PhosphotyrosineNGGFYISPR
CCCEEECCC
12.08HPRD
Link
192PhosphotyrosineNGGFYISPR
CCCEEECCC
12.08PhosphoELM
Link
192PhosphotyrosineNGGFYISPR
CCCEEECCC
12.08Phosphositeplus
Link
192Phosphotyrosine (SYK)NGGFYISPR
CCCEEECCC
12.08HPRD
Link
192Phosphotyrosine.NGGFYISPR
CCCEEECCC
12.08UniProtKB
Link
194PhosphoserineGFYISPRIT
CEEECCCCC
9.21PhosphoELM
Link
194PhosphoserineGFYISPRIT
CEEECCCCC
9.21Phosphositeplus
Link
194Phosphoserine.GFYISPRIT
CEEECCCCC
9.21UniProtKB
Link
213PhosphoserineYTNASDGLC
HHCCCCCCE
33.99PhosphoELM
Link
213Phosphoserine.YTNASDGLC
HHCCCCCCE
33.99UniProtKB
Link
394DePhosphotyrosineEDNEYTARE
CCCCEEEEE
16.38HPRD
Link-
394DePhosphotyrosineEDNEYTARE
CCCCEEEEE
16.38HPRD
Link-
394DePhosphotyrosineEDNEYTARE
CCCCEEEEE
16.38HPRD
Link-
394PhosphotyrosineEDNEYTARE
CCCCEEEEE
16.38HPRD
Link-
394PhosphotyrosineEDNEYTARE
CCCCEEEEE
16.38HPRD
Link-
394PhosphotyrosineEDNEYTARE
CCCCEEEEE
16.38Phosphositeplus
Link-
394PhosphotyrosineEDNEYTARE
CCCCEEEEE
16.38SysPTM
Link-
394Phosphotyrosine (FCGR3A)EDNEYTARE
CCCCEEEEE
16.38HPRD
Link-
394Phosphotyrosine (LCK)EDNEYTARE
CCCCEEEEE
16.38HPRD
Link-
394Phosphotyrosine (Lck)EDNEYTARE
CCCCEEEEE
16.38PhosphoELM
Link-
394Phosphotyrosine; by autocatalysis.EDNEYTARE
CCCCEEEEE
16.38UniProtKB
Link-
395PhosphothreonineDNEYTAREG
CCCEEEEEC
17.04Phosphositeplus
Link-
501PhosphothreonineFFTATEGQY
HHHCCCCCC
37.28PhosphoELM
Link-
501PhosphothreonineFFTATEGQY
HHHCCCCCC
37.28Phosphositeplus
Link-
501Phosphothreonine.FFTATEGQY
HHHCCCCCC
37.28UniProtKB
Link-
505DePhosphotyrosineTEGQYQPQP
CCCCCCCCC
32.77HPRD
Link-
505PhosphotyrosineTEGQYQPQP
CCCCCCCCC
32.77HPRD
Link-
505PhosphotyrosineTEGQYQPQP
CCCCCCCCC
32.77HPRD
Link-
505PhosphotyrosineTEGQYQPQP
CCCCCCCCC
32.77Phosphositeplus
Link-
505Phosphotyrosine (CSK)TEGQYQPQP
CCCCCCCCC
32.77HPRD
Link-
505Phosphotyrosine (Lck)TEGQYQPQP
CCCCCCCCC
32.77PhosphoELM
Link-
505Phosphotyrosine; by CSK.TEGQYQPQP
CCCCCCCCC
32.77UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
GCR_HUMANphysical interactionMINT-3373920MINT16888650
GCR_HUMANphysical interactionMINT-3373935MINT16888650
GCR_HUMANcolocalizationMINT-3374072MINT16888650
CD2_HUMANphosphorylation reactionMINT-50662MINT9677430
CBL_HUMANphysical interactionMINT-15515MINT7721825
CBL_HUMANphysical interactionMINT-13718MINT8621719
MK01_HUMANphysical interactionMINT-60780MINT8626561
MK01_HUMANphysical interactionMINT-60779MINT8626561
ZAP70_HUMANphysical interactionMINT-59476MINT10556826
KSYK_HUMANphysical interactionMINT-56730MINT15536084
DLG1_HUMANphysical interactionMINT-68488MINT9341123
DLG1_HUMANphysical interactionMINT-68489MINT9341123
LCP2_HUMANphysical interactionMINT-59474MINT10556826
G3BP1_HUMANphysical interactionMINT-61274MINT15743820
G3BP1_HUMANphysical interactionMINT-61276MINT15743820
ADA15_HUMANphysical interactionMINT-16264MINT11741929
HS90A_HUMANphysical interactionDIP:820EDIP8043579
KHDR1_HUMANphysical interaction
physical interaction
physical interaction
EBI-1375
EBI-518312
EBI-78087
intact7852312
9045636
11278465
CD45_HUMANphysical interactionEBI-1356
intact8576115
MED28_HUMANphysical interaction
physical interaction
phosphorylation
physical interaction
EBI-1206888
EBI-1206783
EBI-1
intact10656681
16899217
16899217
16899217
CD3Z_HUMANphosphorylationEBI-1211674
intact16461343
STAT3_HUMANin vivoHPRD:01080HPRD10825200
CD44_HUMANin vitro
in vivo
HPRD:01080HPRD8576267
CD38_HUMANin vitro
in vivo
HPRD:01080HPRD10636863
UFO_HUMANin vivoHPRD:01080HPRD9178760
CD48_HUMANin vitroHPRD:01080HPRD12007789
CTLA4_HUMANin vitro
in vivo
HPRD:01080HPRD9712716
9973379
EZRI_HUMANin vitro
in vivo
HPRD:01080HPRD1382070
12560083
DAF_HUMANin vivoHPRD:01080HPRD1385527
TNR6_HUMANin vivoHPRD:01080HPRD8864141
TNFL6_HUMANin vivoHPRD:01080HPRD11741599
ESR1_HUMANin vitro
in vivo
HPRD:01080HPRD7539106
RASA1_HUMANin vitro
in vivo
HPRD:01080HPRD1850098
IL2RB_HUMANin vitroHPRD:01080HPRD2047859
10214954
CD5_HUMANin vitro
in vivo
HPRD:01080HPRD7513045
11298344
15144186
LCK_HUMANin vitroHPRD:01080HPRD8879209
8945479
8258691
8405050
15144186
IKBA_HUMANin vitro
in vivo
HPRD:01080HPRD8797825
12429743
9792645
VAV_HUMANin vivoHPRD:01080HPRD10669745
P85A_HUMANin vivoHPRD:01080HPRD7504174
9461588
ZAP70_HUMANin vitro
in vivo
HPRD:01080HPRD10318843
7961936
9685404
15144186
ITK_HUMANin vitro
in vivo
HPRD:01080HPRD9312162
15144186
PLCG2_HUMANin vitroHPRD:01080HPRD12181444
7682059
15144186
KPCT_HUMANin vitro
in vivo
HPRD:01080HPRD10652356
STAT1_HUMANin vitro
in vivo
HPRD:01080HPRD7657660
11294897
10918587
15322115
7543024
11839738
12817007
7690989
12637327
SHC1_HUMANin vivoHPRD:01080HPRD12237775
11075717
10764799
9121430
9446569
10816433
10896916
10921922
9741627
9710204
10482988
LCP2_HUMANin vitro
in vivo
HPRD:01080HPRD8702662
16354835
DOK1_HUMANin vivoHPRD:01080HPRD10799545
SH2B3_HUMANin vitro
in vivo
HPRD:01080HPRD10799879
9169414
DAPP1_HUMANin vitro
in vivo
HPRD:01080HPRD10880360
PPAC_HUMANin vitro
in vivo
HPRD:01080HPRD9038134
CD3E_HUMANin vitro
in vivo
HPRD:01080HPRD11855827
KI2L3_HUMANin vitroHPRD:01080HPRD9751747
KPCD_HUMANin vitroHPRD:01080HPRD11381116
CD79B_HUMANin vitroHPRD:01080HPRD8077654
MUC1_HUMANin vitro
in vivo
HPRD:01080HPRD14766232
CD3Z_HUMANin vivoHPRD:01080HPRD9047237
FAK1_HUMANin vitro
in vivo
HPRD:01080HPRD9257837
STA5A_HUMANin vitroHPRD:01080HPRD10825200
ESR2_HUMANin vitroHPRD:01080HPRD12415108
3BP2_HUMANin vitro
in vivo
HPRD:01080HPRD15751964
LAT_HUMANin vitro
in vivo
HPRD:01080HPRD12359715
12186560
GRAP_HUMANin vitro
in vivo
HPRD:01080HPRD8995379
GAB2_HUMANin vivoHPRD:01080HPRD11572860
LIME1_HUMANin vivoHPRD:01080HPRD14610044
LAX1_HUMANin vivoHPRD:01080HPRD12359715
SH21A_HUMANin vitro
yeast 2-hybrid
HPRD:01080HPRD15096483
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Disease Reference
Kegg disease
H00093 Combined immunodeficiencies (CIDs), including the following nine diseases: X-linked hyper IgM syndro
OMIM disease
Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1
7)(p34
q34) with TCRB.
615758
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, AND MASS SPECTROMETRY.
Phosphorylation
ReferencePubMed
"The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 anddown regulates its catalytic activity.";
Bergman M., Mustelin T., Oetken C., Partanen J., Flint N.A.,Amrein K.E., Autero M., Burn P., Alitalo K.;
EMBO J. 11:2919-2924(1992).
Cited for: PHOSPHORYLATION AT TYR-505.
"Detection of a physical and functional interaction between Csk andLck which involves the SH2 domain of Csk and is mediated byautophosphorylation of Lck on tyrosine 394.";
Bougeret C., Delaunay T., Romero F., Jullien P., Sabe H., Hanafusa H.,Benarous R., Fischer S.;
J. Biol. Chem. 271:7465-7472(1996).
Cited for: PHOSPHORYLATION AT TYR-505 BY CSK, AND AUTOPHOSPHORYLATION.
"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 TYR-505, ANDMASS SPECTROMETRY.
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-192 AND TYR-505, ANDMASS SPECTROMETRY.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162; TYR-192; SER-213;TYR-394; THR-501 AND TYR-505, AND MASS SPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND MASSSPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND MASSSPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-159; SER-162;TYR-192; SER-194 AND TYR-505, AND MASS SPECTROMETRY.
"Oncogenic activation of the Lck protein accompanies translocation ofthe LCK gene in the human HSB2 T-cell leukemia.";
Wright D.D., Sefton B.M., Kamps M.P.;
Mol. Cell. Biol. 14:2429-2437(1994).
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-28; GLN-LYS-PRO-232 INS;VAL-353 AND LEU-447, AND PHOSPHORYLATION AT TYR-394 AND TYR-505.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures