LCK (LCK proto-oncogene, Src family tyrosine kinase)

Gene

• Entrez ID: 3932
• Gene name: LCK proto-oncogene, Src family tyrosine kinase
• Gene symbol: LCK
• Synonyms (NCBI Gene): IMD22, LSK, YT16, p56lck, pp58lck
• Chromosome: 1
• Chromosome location: 1p35.2
• Summary: This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein is a key signaling molecule in the selection and maturation of developing T-cells. It contains N-terminal sites for myristylation and palmitylation, a PTK doma

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587777335	T>C	Pathogenic	Coding sequence variant, missense variant
rs1569967422	->A	Likely-pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017673	hsa-miR-335-5p	Microarray	18185580
MIRT2029138	hsa-miR-1197	CLIP-seq
MIRT2029139	hsa-miR-4436a	CLIP-seq
MIRT2029140	hsa-miR-4700-3p	CLIP-seq
MIRT2029138	hsa-miR-1197	CLIP-seq
MIRT2029139	hsa-miR-4436a	CLIP-seq
MIRT2029140	hsa-miR-4700-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ETS1	Activation	7970721
ETS2	Activation	7970721
MYB	Activation	7970721

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000242	Component	Pericentriolar material	IDA	7513706
GO:0001772	Component	Immunological synapse	IDA	20007709
GO:0001784	Function	Phosphotyrosine residue binding	IPI	20624904
GO:0002429	Process	Immune response-activating cell surface receptor signaling pathway	IEA
GO:0004672	Function	Protein kinase activity	IEA
GO:0004713	Function	Protein tyrosine kinase activity	EXP	1381360, 9799234, 12923167, 18697750
GO:0004713	Function	Protein tyrosine kinase activity	IDA	214242, 8478617
GO:0004713	Function	Protein tyrosine kinase activity	IEA
GO:0004713	Function	Protein tyrosine kinase activity	IMP	8681956
GO:0004713	Function	Protein tyrosine kinase activity	TAS
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IBA
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IDA	8681956, 11606584, 16339550, 38614099
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IEA
GO:0004722	Function	Protein serine/threonine phosphatase activity	IDA	8506364
GO:0005102	Function	Signaling receptor binding	IBA
GO:0005515	Function	Protein binding	IPI	7507203, 7513706, 7852312, 8114715, 8576115, 8650207, 8798676, 9045636, 9175835, 9341123, 10209036, 10318843, 10369126, 10553045, 10656681, 11278465, 11741929, 11978774, 14625311, 14757743, 15536084, 15554700, 15827961, 16051843, 16099425, 16107303, 16195219, 16245368, 16461343, 1683
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IDA	38614099
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	12218089
GO:0005886	Component	Plasma membrane	IDA	12150984
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005911	Component	Cell-cell junction	IEA
GO:0006468	Process	Protein phosphorylation	IDA	214242
GO:0006882	Process	Intracellular zinc ion homeostasis	IEP	11739864
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0007169	Process	Cell surface receptor protein tyrosine kinase signaling pathway	IBA
GO:0009410	Process	Response to xenobiotic stimulus	IDA	16116473
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0016004	Function	Phospholipase activator activity	IDA	11606584
GO:0016020	Component	Membrane	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IMP	8681956
GO:0019901	Function	Protein kinase binding	IPI	8618896
GO:0019903	Function	Protein phosphatase binding	IEA
GO:0019903	Function	Protein phosphatase binding	IPI	22080863, 24714587
GO:0030097	Process	Hemopoiesis	NAS	12884910
GO:0030168	Process	Platelet activation	TAS
GO:0030217	Process	T cell differentiation	IBA
GO:0030217	Process	T cell differentiation	IMP	1579166
GO:0031295	Process	T cell costimulation	TAS
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IMP	27400149
GO:0035556	Process	Intracellular signal transduction	IDA	8681956
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0035556	Process	Intracellular signal transduction	IMP	11606584
GO:0038083	Process	Peptidyl-tyrosine autophosphorylation	IDA	8478617
GO:0038094	Process	Fc-gamma receptor signaling pathway	IDA	8478617
GO:0038094	Process	Fc-gamma receptor signaling pathway	IEA
GO:0042110	Process	T cell activation	IDA	38354704
GO:0042169	Function	SH2 domain binding	IPI	7852312, 8794306
GO:0042492	Process	Gamma-delta T cell differentiation	IEA
GO:0042608	Function	T cell receptor binding	IPI	8681956
GO:0042609	Function	CD4 receptor binding	IEA
GO:0042609	Function	CD4 receptor binding	IPI	7486703
GO:0042610	Function	CD8 receptor binding	IPI	2470098
GO:0042802	Function	Identical protein binding	IPI	17118402, 24463463
GO:0043274	Function	Phospholipase binding	IPI	11606584
GO:0043410	Process	Positive regulation of MAPK cascade	IDA	11368773
GO:0043548	Function	Phosphatidylinositol 3-kinase binding	IPI	7504174
GO:0045121	Component	Membrane raft	IDA	12150984, 12732664
GO:0045588	Process	Positive regulation of gamma-delta T cell differentiation	IEA
GO:0045589	Process	Regulation of regulatory T cell differentiation	IEA
GO:0050852	Process	T cell receptor signaling pathway	IDA	11368773, 35271814, 38614099
GO:0050852	Process	T cell receptor signaling pathway	IDA	8943371, 38614099
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0050853	Process	B cell receptor signaling pathway	IBA
GO:0050853	Process	B cell receptor signaling pathway	IEA
GO:0050856	Process	Regulation of T cell receptor signaling pathway	IEA
GO:0050862	Process	Positive regulation of T cell receptor signaling pathway	NAS	12614355
GO:0050870	Process	Positive regulation of T cell activation	IDA	8943371
GO:0050900	Process	Leukocyte migration	IEA
GO:0050900	Process	Leukocyte migration	TAS
GO:0051117	Function	ATPase binding	IPI	15671290
GO:0051209	Process	Release of sequestered calcium ion into cytosol	IEA
GO:0051209	Process	Release of sequestered calcium ion into cytosol	ISS
GO:0051240	Process	Positive regulation of multicellular organismal process	IEA
GO:0051249	Process	Regulation of lymphocyte activation	NAS	7852312
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0160162	Process	CD27 signaling pathway	IDA	38354704
GO:1903039	Process	Positive regulation of leukocyte cell-cell adhesion	IMP	27400149
GO:1990405	Function	Protein antigen binding	IEA
GO:2001244	Process	Positive regulation of intrinsic apoptotic signaling pathway	IMP	16116473

Other IDs

• MIM: 153390
• HGNC: 6524
• e!Ensembl: ENSG00000182866

Protein

• UniProt ID: P06239
• Protein name: Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK)
• 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 transduc
• PDB: 1BHF, 1BHH, 1CWD, 1CWE, 1FBZ, 1H92, 1IJR, 1KIK, 1LCJ, 1LCK, 1LKK, 1LKL, 1Q68, 1Q69, 1QPC, 1QPD, 1QPE, 1QPJ, 1X27, 2IIM, 2OF2, 2OF4, 2OFU, 2OFV, 2OG8, 2PL0, 2ZM1, 2ZM4, 2ZYB, 3AC1, 3AC2, 3AC3, 3AC4, 3AC5, 3AC8, 3ACJ, 3ACK, 3AD4, 3AD5, 3AD6, 3B2W, 3BRH, 3BYM, 3BYO, 3BYS, 3BYU, 3KMM, 3KXZ, 3LCK, 3MPM, 4C3F
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00018	SH3_1	67 → 113	SH3 domain	Domain
  PF00017	SH2	127 → 209	SH2 domain	Domain
  PF07714	PK_Tyr_Ser-Thr	245 → 494	Protein tyrosine and serine/threonine kinase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed specifically in lymphoid cells.
• Sequence:

  MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASP
  LQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKAN
  SLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKH
  YKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEV
  PRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRL
  VRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNY
  IHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIK
  SDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKER
  PEDRPTFDYLRSVLEDFFTATEGQYQPQP

• Sequence length: 509

Pathways

KEGG:

NF-kappa B signaling pathway
Osteoclast differentiation
Natural killer cell mediated cytotoxicity
Th1 and Th2 cell differentiation
Th17 cell differentiation
T cell receptor signaling pathway
Yersinia infection
Human T-cell leukemia virus 1 infection
PD-L1 expression and PD-1 checkpoint pathway in cancer
Primary immunodeficiency

Reactome:

GPVI-mediated activation cascade
PIP3 activates AKT signaling
Signaling by SCF-KIT
Regulation of KIT signaling
Nef and signal transduction
Nef Mediated CD4 Down-regulation
Downstream TCR signaling
Phosphorylation of CD3 and TCR zeta chains
Translocation of ZAP-70 to Immunological synapse
Generation of second messenger molecules
PECAM1 interactions
Constitutive Signaling by Aberrant PI3K in Cancer
DAP12 signaling
CD28 co-stimulation
CD28 dependent PI3K/Akt signaling
CD28 dependent Vav1 pathway
CTLA4 inhibitory signaling
PD-1 signaling
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
Interleukin-2 signaling

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Severe combined immunodeficiency disease	Likely pathogenic	rs2521644688	RCV002470002
Severe combined immunodeficiency due to LCK deficiency	Pathogenic; Likely pathogenic	rs1640237880, rs587777335, rs2124355238, rs2521638529, rs1640240931, rs2521697784, rs2521643296, rs2521748820, rs1318678254, rs1569967422, rs1640406042	RCV001342141 RCV000114989 RCV001943020 RCV002903252 RCV002954412 RCV003746135 RCV003988799 RCV003988800 RCV003988801 RCV000991355 RCV001051256

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Conflicting classifications of pathogenicity	rs11567841	RCV005901654
LCK-related disorder	Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	rs1223366825, rs764228746, rs375815167, rs2521749804, rs1126767, rs11567841, rs142674647, rs775454062, rs746656319	RCV003900693 RCV003958461 RCV003941211 RCV003412493 RCV003954237 RCV003907949 RCV003905936 RCV003928605 RCV003972986
Lung cancer	Conflicting classifications of pathogenicity	rs11567841	RCV005901657
Malignant tumor of esophagus	Conflicting classifications of pathogenicity	rs11567841	RCV005901655
Melanoma	Conflicting classifications of pathogenicity	rs11567841	RCV005901656

Associations from Text Mining
Disease Name	Relationship Type	References
Acquired Immunodeficiency Syndrome	Inhibit	8823293
Alopecia Areata	Associate	20546884
Anodontia	Associate	14534291
Aortic Aneurysm Abdominal	Stimulate	33858751
Arthritis Rheumatoid	Associate	32840301, 33430905
Breast Neoplasms	Associate	14699120, 23558942, 26126114, 31715586, 32710281
Carcinoma Endometrioid	Associate	33159014
Carcinoma Hepatocellular	Associate	24564241, 32730361, 34218795
Carcinoma Non Small Cell Lung	Associate	17202451, 22457183
Carcinoma Pancreatic Ductal	Associate	33213062
Carcinoma Renal Cell	Associate	31672930, 40612864
Cardiomyopathy Dilated	Associate	36733486
Carotid Artery Diseases	Associate	36316672
Cerebral Hemorrhage	Associate	30836997, 33206327
Cholangiocarcinoma	Associate	36162702
Chromosome Breakage	Associate	8049439
Colitis Ulcerative	Stimulate	9329971
Colonic Neoplasms	Associate	29562499, 7499213
Colorectal Neoplasms	Associate	11180095, 9490199
Coronary Artery Disease	Associate	30015926
COVID 19	Associate	34330510
Craniopharyngioma	Associate	25990246
Crohn Disease	Stimulate	9329971
Death	Associate	24688028
Diabetic Nephropathies	Stimulate	36568106
Drug Related Side Effects and Adverse Reactions	Associate	30333226
Endometrial Neoplasms	Associate	33159014
Fibromatosis Aggressive	Associate	9736021
Fibrosis	Associate	21824427
Glioblastoma	Associate	32237064, 34395626
Hashimoto Disease	Associate	34522174
Head and Neck Neoplasms	Associate	35090306
Hematologic Neoplasms	Associate	36430477
HIV Infections	Associate	12823281
HIV Infections	Inhibit	8823293
Hodgkin Disease	Inhibit	16304050
Hypoxia	Associate	14534291
Hypoxia Brain	Associate	35150959
Idiopathic Pulmonary Fibrosis	Associate	24089408
Infections	Associate	12823281, 21345943
Inflammation	Associate	33858751, 33999861, 37426642
Inflammatory Bowel Diseases	Associate	9329971
Leprosy	Associate	15967991
Leukemia	Associate	1530879, 8611704
Leukemia Lymphocytic Chronic B Cell	Associate	23505068, 29669754, 9558397
Leukemia Prolymphocytic T Cell	Associate	29196709
Leukemia T Cell	Associate	1379847, 1680958, 26210498
Lown Ganong Levine Syndrome	Associate	32710281
Lung Diseases	Associate	17078813
Lung Neoplasms	Associate	24135919
Lupus Erythematosus Systemic	Inhibit	11681490, 12746907, 15085197, 17082661
Lupus Erythematosus Systemic	Associate	19201859, 37426642
Lymphoma	Associate	2779553
Lymphoma	Stimulate	32237064
Lymphoma Follicular	Associate	20208138
Lymphoma Large B Cell Diffuse	Associate	32237064
Lymphoma Large Cell Anaplastic	Associate	20511667
Lymphoma T Cell Peripheral	Associate	23716562
Lymphoproliferative Disorders	Inhibit	24688028
Melanoma	Associate	27335052
Melanoma	Stimulate	36341345
Mitochondrial Diseases	Associate	26210498
Mouth Neoplasms	Associate	34116687
Multiple Myeloma	Inhibit	14717778
Mycosis Fungoides	Associate	10903801, 25779945
Myositis Inclusion Body	Associate	35237874
Nasopharyngeal Carcinoma	Associate	37274867
Neoplasm Metastasis	Associate	11180095, 34116687
Neoplasms	Associate	10478643, 11180095, 1680958, 19272155, 19435912, 22457183, 24155921, 24231767, 26210498, 27335052, 2779553, 28936799, 31515669, 31715586, 31817155, 34116687, 36341345, 36430477, 37773310, 38017109, 7914906, 9490199, 9531350
Neoplasms	Inhibit	34218795
Neuroinflammatory Diseases	Associate	30836997
Nose Diseases	Inhibit	22310933
Obesity	Stimulate	34330510
Obesity	Associate	37063877
Ovarian Neoplasms	Associate	31515669, 37773310
Pancreatic Neoplasms	Associate	33213062
Paraparesis Tropical Spastic	Stimulate	26358743
Paraparesis Tropical Spastic	Associate	40004169
Precursor Cell Lymphoblastic Leukemia Lymphoma	Associate	16467082, 37363966
Precursor T Cell Lymphoblastic Leukemia Lymphoma	Associate	1680958, 23872305, 35805156, 8049439
Primary Ovarian Insufficiency	Associate	37460774
Prostatic Neoplasms	Associate	29938870, 31253147
Prostatitis	Associate	8650201
Pulmonary Disease Chronic Obstructive	Associate	23977094, 33108241
Sarcoidosis	Inhibit	21177920
Sarcoidosis	Associate	24284293
Schizophrenia	Associate	24564241
Scleroderma Systemic	Associate	35663995
Severe Combined Immunodeficiency	Associate	9664084
Sezary Syndrome	Associate	25779945
Urinary Bladder Neoplasms	Associate	32228629, 33204728
Uterine Cervical Neoplasms	Associate	35090306
Uveomeningoencephalitic Syndrome	Associate	35003060
X Linked Combined Immunodeficiency Diseases	Associate	38112969