LCK
entrez
3932
canonical
uniprot
P06239
canonical
ensembl
ENSG00000182866
resolver
ensp
ENSP00000337825
resolver
ensp
ENSP00000431517
resolver
ensp
ENSP00000435605
resolver
ensp
ENSP00000555256
resolver
ensp
ENSP00000585449
resolver
ensp
ENSP00000585451
resolver
ensp
ENSP00000585452
resolver
enst
ENST00000482949
resolver
enst
ENST00000495610
resolver
enst
ENST00000915390
resolver
enst
ENST00000915392
resolver
enst
ENST00000915393
resolver
genesymbol
LCK
resolver
hgnc
HGNC:6524
resolver
uniprot
A0A0S2Z3Y4
resolver
uniprot
A0A0S2Z3Y8
resolver
uniprot
A0ACM8QMS7
resolver
uniprot
D3DPP8
resolver
uniprot
E9PJ92
resolver
uniprot
E9PKQ8
resolver
uniprot
P07100
resolver
uniprot
Q12850
resolver
uniprot
Q13152
resolver
uniprot
Q573B4
resolver
uniprot
Q5TDH8
resolver
uniprot
Q5TDH9
resolver
uniprot
Q7RTZ3
resolver
uniprot
Q96DW4
resolver
uniprot
Q9NYT8
resolver
uniprot_entry
A0A0S2Z3Y8_HUMAN
resolver
uniprot_entry
A0ACM8QMS7_HUMAN
resolver
uniprot_entry
E9PJ92_HUMAN
resolver
uniprot_entry
E9PKQ8_HUMAN
resolver
uniprot_entry
LCK_HUMAN
resolver
uniprot_entry
Q573B4_HUMAN
resolver
uniprot_sec
A0A0S2Z3Y4
resolver
uniprot_sec
D3DPP8
resolver
uniprot_sec
P07100
resolver
uniprot_sec
Q12850
resolver
uniprot_sec
Q13152
resolver
uniprot_sec
Q5TDH8
resolver
uniprot_sec
Q5TDH9
resolver
uniprot_sec
Q7RTZ3
resolver
uniprot_sec
Q96DW4
resolver
uniprot_sec
Q9NYT8
resolver
activity_regulation
ACTIVITY REGULATION: The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation. {ECO:0000269|PubMed:21917715}.
uniprot
proteins
amino_acid_sequence
MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKHYKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKERPEDRPTFDYLRSVLEDFFTATEGQYQPQP
uniprot
proteins
disease_involvement
DISEASE: Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.; DISEASE: Immunodeficiency 22 (IMD22) [MIM:615758]: A primary immunodeficiency characterized by T-cell dysfunction. Affected individuals present with lymphopenia, recurrent infections, severe diarrhea, and failure to thrive. {ECO:0000269|PubMed:22985903}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
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 (PubMed:2470098). Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways (PubMed:2470098). Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors (PubMed:2470098). 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 (PubMed:2470098). 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 (PubMed:2470098, PubMed:40592325). 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. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:40592325}.
uniprot
proteins
mass_dalton
58001
uniprot
proteins
mutagenesis
MUTAGEN 59; /note="S->E: Allows interaction with SQSTM1."; /evidence="ECO:0000269|PubMed:8618896"; MUTAGEN 99; /note="K->R: Abolishes UBR2-mediated 'Lys-63'-linked ubiquitination. Abolishes UBR2-mediated 'Lys-63'-linked ubiquitination and autophosphorylation of Tyr-394; when associated with R-276."; /evidence="ECO:0000269|PubMed:38225265"; MUTAGEN 154; /note="R->K: No effect on interaction with SQSTM1."; /evidence="ECO:0000269|PubMed:8618896"; MUTAGEN 273; /note="K->R: Abolished autoinhibition; when associated with F-505."; /evidence="ECO:0000269|PubMed:40592325"; MUTAGEN 276; /note="K->R: Abolishes UBR2-mediated 'Lys-63'-linked ubiquitination. Abolishes UBR2-mediated 'Lys-63'-linked ubiquitination and autophosphorylation of Tyr-394; when associated with R-99."; /evidence="ECO:0000269|PubMed:38225265"; MUTAGEN 394; /note="Y->F: Abolishes autophosphorylation."; /evidence="ECO:0000269|PubMed:38225265"; MUTAGEN 505; /note="Y->F: Abolished autoinhibition; when associated with R-273."; /evidence="ECO:0000269|PubMed:40592325
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity (PubMed:40592325). Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cell receptor signaling. Dephosphorylation at Tyr-394 by DUSP22 negatively regulates T-cell receptor signaling (PubMed:24714587, PubMed:38225265). {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:24714587, ECO:0000269|PubMed:38225265, ECO:0000269|PubMed:40592325, ECO:0000269|PubMed:8139546, ECO:0000269|PubMed:8631775}.; PTM: Myristoylation is required prior to palmitoylation. {ECO:0000250}.; PTM: Palmitoylation regulates association with the plasma membrane and could be mediated by ZDHHC2. {ECO:0000269|PubMed:22034844}.; PTM: 'Lys-63'-linked ubiquitinated at Lys-99 and Lys-276 by UBR2; this modification is required for autophosphorylation at Tyr-394. {ECO:0000269|PubMed:38225265}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
SRC subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10848956
uniprot
proteins
pubmed
11009097
uniprot
proteins
pubmed
11840567
uniprot
proteins
pubmed
11978774
uniprot
proteins
pubmed
12007789
uniprot
proteins
pubmed
12218089
uniprot
proteins
pubmed
12401726
uniprot
proteins
pubmed
12837766
uniprot
proteins
pubmed
14610044
uniprot
proteins
pubmed
14610046
uniprot
proteins
pubmed
14757743
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
16339550
uniprot
proteins
pubmed
1639064
uniprot
proteins
pubmed
16461343
uniprot
proteins
pubmed
16709819
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17634955
uniprot
proteins
pubmed
18424730
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20028775
uniprot
proteins
pubmed
20100835
uniprot
proteins
pubmed
20851766
uniprot
proteins
pubmed
21269457
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21917715
uniprot
proteins
pubmed
22034844
uniprot
proteins
pubmed
22080863
uniprot
proteins
pubmed
22985903
uniprot
proteins
pubmed
23946459
uniprot
proteins
pubmed
2470098
uniprot
proteins
pubmed
24714587
uniprot
proteins
pubmed
2558056
uniprot
proteins
pubmed
27335501
uniprot
proteins
pubmed
2787474
uniprot
proteins
pubmed
2835736
uniprot
proteins
pubmed
2850479
uniprot
proteins
pubmed
3265417
uniprot
proteins
pubmed
3489486
uniprot
proteins
pubmed
3493153
uniprot
proteins
pubmed
38225265
uniprot
proteins
pubmed
38614099
uniprot
proteins
pubmed
40592325
uniprot
proteins
pubmed
7495859
uniprot
proteins
pubmed
7504174
uniprot
proteins
pubmed
7512222
uniprot
proteins
pubmed
7532720
uniprot
proteins
pubmed
7852312
uniprot
proteins
pubmed
8139546
uniprot
proteins
pubmed
8604142
uniprot
proteins
pubmed
8618896
uniprot
proteins
pubmed
8631775
uniprot
proteins
pubmed
8794306
uniprot
proteins
pubmed
8945479
uniprot
proteins
pubmed
9178760
uniprot
proteins
pubmed
9685372
uniprot
proteins
sequence_length
509
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12218089, ECO:0000269|PubMed:22034844}; Lipid-anchor {ECO:0000269|PubMed:12218089, ECO:0000269|PubMed:22034844}; Cytoplasmic side {ECO:0000269|PubMed:12218089, ECO:0000269|PubMed:22034844}. Cytoplasm, cytosol {ECO:0000269|PubMed:12218089, ECO:0000269|PubMed:22034844}. Note=Present in lipid rafts in an inactive form. {ECO:0000269|PubMed:12218089}.
uniprot
proteins