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: 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:0000242	Component	Pericentriolar material	IDA	7513706
GO:0001772	Component	Immunological synapse	IDA	20007709
GO:0001784	Function	Phosphotyrosine residue binding	IPI	20624904
GO:0004713	Function	Protein tyrosine kinase activity	EXP	1381360, 9799234, 12923167, 18697750
GO:0004713	Function	Protein tyrosine kinase activity	IBA	21873635
GO:0004713	Function	Protein tyrosine kinase activity	IDA	214242
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	21873635
GO:0004722	Function	Protein serine/threonine phosphatase activity	IDA	8506364
GO:0005102	Function	Signaling receptor binding	IBA	21873635
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:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	12150984
GO:0005886	Component	Plasma membrane	TAS
GO:0006468	Process	Protein phosphorylation	IDA	214242
GO:0006470	Process	Protein dephosphorylation	IEA
GO:0006882	Process	Cellular zinc ion homeostasis	IEP	11739864
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA	16116473
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0008022	Function	Protein C-terminus binding	IPI	16245368
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IMP	8681956
GO:0019901	Function	Protein kinase binding	IPI	8618896
GO:0019903	Function	Protein phosphatase binding	IPI	22080863, 24714587
GO:0030097	Process	Hemopoiesis	NAS	12884910
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030168	Process	Platelet activation	TAS
GO:0030217	Process	T cell differentiation	IBA	21873635
GO:0030217	Process	T cell differentiation	IMP	1579166
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	IBA	21873635
GO:0031295	Process	T cell costimulation	TAS
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IMP	27400149
GO:0042169	Function	SH2 domain binding	IPI	7852312, 8794306
GO:0042493	Process	Response to drug	IDA	16116473
GO:0042608	Function	T cell receptor binding	IPI	8681956
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:0043548	Function	Phosphatidylinositol 3-kinase binding	IPI	7504174
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0045121	Component	Membrane raft	IDA	12150984, 12732664
GO:0050690	Process	Regulation of defense response to virus by virus	TAS
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0050853	Process	B cell receptor signaling pathway	IBA	21873635
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	TAS
GO:0051117	Function	ATPase binding	IPI	15671290
GO:0051209	Process	Release of sequestered calcium ion into cytosol	ISS
GO:0051249	Process	Regulation of lymphocyte activation	NAS	7852312
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:1903039	Process	Positive regulation of leukocyte cell-cell adhesion	IMP	27400149
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

• 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
Disease name	Disease term	dbSNP ID	References
Immunodeficiency	IMMUNODEFICIENCY 22	rs1565678077, rs121908002, rs1421444086, rs1565688667, rs944235493, rs121918314, rs587776713, rs137852678, rs587776714, rs128620188, rs2147483647, rs1569556522, rs137853331, rs137853332, rs179363866, rs483352928, rs121918659, rs111033580, rs111033581, rs74315290, rs193922740, rs193922741, rs104894199, rs483352927, rs104894286, rs1571865049, rs886041032, rs2069709, rs587776822, rs74315444, rs587776823, rs1315265916, rs104893893, rs104893894, rs121434560, rs387906572, rs587776853, rs104893973, rs587776854, rs587776855, rs587776857, rs104893974, rs121912715, rs1393707607, rs113994136, rs387906593, rs587776870, rs387906763, rs387906913, rs199469663, rs199469662, rs199469664, rs193922640, rs193922641, rs193922645, rs398122890, rs387907316, rs397514710, rs398122383, rs397515453, rs397514332, rs398123058, rs397518423, rs587777075, rs199676861, rs77563738, rs587777337, rs28730670, rs587777389, rs587777390, rs587777413, rs587777414, rs587777415, rs587777416, rs267608260, rs267608261, rs587778405, rs587777446, rs587777562, rs587777564, rs587777565, rs869320745, rs587777709, rs606231305, rs672601318, rs727503779, rs727503780, rs730880296, rs786200953, rs375323253, rs794729666, rs886041037, rs886041038, rs796051887, rs796051888, rs749956849, rs199641706, rs775739391, rs869312886, rs869312857, rs879253731, rs879253732, rs201025290, rs770927552, rs878853275, rs878853276, rs878853277, rs878853278, rs1567506566, rs886037920, rs886037921, rs750610248, rs200044623, rs886043118, rs886060531, rs1057519074, rs1057519075, rs1057518744, rs1057519079, rs1057518745, rs1057518746, rs1057518747, rs782178147, rs55729925, rs1064795762, rs1064794957, rs1085307649, rs745463649, rs773694113, rs1192554889, rs779575307, rs1554051075, rs1554051067, rs1554051033, rs1554067182, rs1555167566, rs1555169270, rs1555908409, rs1555719963, rs1554064929, rs768091235, rs1404084330, rs144104577, rs1553238837, rs1553243550, rs1554020278, rs1554066684, rs762678772, rs570768621, rs1443126481, rs1553721236, rs121434258, rs888230251, rs1759915032, rs1759514836, rs138156467, rs1560914625, rs755373718, rs1561423197, rs1560938296, rs200803157, rs766555082, rs201543770, rs114951157, rs775578531, rs201128237, rs778624945, rs1563340753, rs1561772403, rs1484948342, rs777878144, rs1562364898, rs1561254290, rs1569296295, rs1568815169, rs1568822574, rs1571880832, rs934523851, rs1922072844, rs1266114717, rs137869655, rs869320689, rs1571880941, rs1580875488, rs1581303476, rs1448018291, rs1390410878, rs774803573, rs1591278347, rs1602300615, rs1601340933, rs757598952, rs1181595292, rs1408683294, rs1595843113, rs1595848141, rs779560450, rs1595816926, rs1601861196, rs1601861199, rs756541321, rs1594389703, rs1594390415, rs1581401865, rs1236009877, rs753213766, rs778993919, rs1602878106, rs141698985, rs1264504989, rs1580974401, rs2093571190, rs530286781, rs2086875746, rs2089298923, rs1206185362, rs1581573705, rs1596718225, rs1004337827, rs1573613529, rs1574636674, rs1574657735, rs1574657762, rs1574672718, rs1581573640, rs1553657429, rs200666300, rs1578735747, rs1578771211, rs1578793312, rs1578795536, rs1578809101, rs1578811073, rs1578811245, rs1171694504, rs1578971328, rs140800288, rs374333820, rs1584926133, rs1585040113, rs1584409386, rs1379376784, rs1586940273, rs1587143342, rs748910652, rs1592117677, rs758555433, rs1596712783, rs34019455, rs147766868, rs751386365, rs1600631294, rs1489114116, rs1057520578, rs1603007888, rs1603008329, rs1574450161, rs1578735709, rs1403833564, rs1580262965, rs570910902, rs1589866171, rs1578999313, rs1582635229, rs1582637044, rs1580851910, rs1750760771, rs745453685, rs1249197356, rs201840561, rs1940921909, rs1941410085, rs1941465194, rs1321690789, rs1302362911, rs1730552437, rs2052705192, rs1941856970	11351273, 22985903
Severe combined immunodeficiency disease	Combined immunodeficiency, Severe combined immunodeficiency due to LCK deficiency	rs886037607, rs118203993, rs121908714, rs121908739, rs121908740, rs121908735, rs121908721, rs121908722, rs121908156, rs1564414523, rs1564418254, rs1564446526, rs786205074, rs121908157, rs121908159, rs786200884, rs397515357, rs104894562, rs137852624, rs137852625, rs137852626, rs137852627, rs137852507, rs137852509, rs111033619, rs111033620, rs1569480018, rs111033621, rs137852510, rs587776729, rs111033622, rs111033617, rs111033618, rs121917894, rs121917896, rs2133313409, rs121917897, rs28933392, rs104894282, rs104894283, rs104894285, rs121918570, rs121918572, rs730880318, rs104893674, rs730880319, rs104894453, rs104894454, rs104894451, rs137853206, rs777503956, rs267606645, rs267606648, rs397515390, rs193922346, rs193922347, rs193922348, rs193922349, rs193922350, rs137852508, rs193922640, rs193922641, rs193922643, rs193922645, rs193922361, rs193922364, rs193922464, rs148508754, rs193922574, rs113994174, rs606231246, rs397514671, rs397514686, rs397514755, rs199474679, rs199474685, rs199474686, rs199474681, rs150739647, rs267605358, rs886041036, rs587777335, rs587778405, rs145092287, rs587777562, rs606231256, rs200296680, rs786205456, rs786205517, rs774202259, rs786205615, rs878853261, rs786205890, rs782753385, rs746052951, rs869025224, rs869312857, rs869320660, rs869320659, rs869320658, rs879253742, rs886037924, rs886037925, rs750610248, rs886039394, rs761242509, rs886039387, rs886041043, rs886041044, rs886042051, rs886041333, rs749481781, rs1057517747, rs1057519506, rs1057523762, rs1057521062, rs1057520644, rs761583890, rs751635016, rs55729925, rs1064793248, rs1064793347, rs1064794027, rs781410769, rs1555524788, rs1486760100, rs769633203, rs1556330713, rs1555322558, rs1556330234, rs1556330755, rs1556329779, rs1556330552, rs1556329822, rs1556330286, rs1556331272, rs2146178281, rs376610445, rs757797994, rs775704953, rs1555743321, rs1564995660, rs1564995662, rs1556330249, rs144104577, rs886041796, rs1026474882, rs570768621, rs1556330562, rs1556330568, rs780014431, rs778343059, rs1555844617, rs1567629968, rs1567628757, rs1567629943, rs1567632864, rs1567632829, rs1567626023, rs1559328006, rs1561423197, rs1452483770, rs1568400897, rs1569479913, rs1568404443, rs1569480047, rs1563340753, rs368303189, rs1568431262, rs1568431102, rs1561424886, rs1602289943, rs1241698978, rs1569479994, rs1569480082, rs1602289649, rs1573261820, rs770985198, rs1589050343, rs1340132582, rs1589064324, rs1589070600, rs1213680890, rs149316157, rs1599873591, rs755706305, rs1602288051, rs1602289411, rs1602289183, rs1583513256, rs1589136659, rs1380154594, rs1011307501, rs1599876167, rs1569967422, rs1602289631, rs1573262398, rs760191638, rs1592117677, rs1640406042, rs372597855, rs1839558393, rs1839622622, rs1839957089, rs777008519, rs1233957241, rs2092261618, rs1839255008, rs1677695565, rs936493226, rs1162344514, rs991089005	11351273

Unknown
Disease name	Disease term	dbSNP ID	References
Immunologic deficiency syndromes	Immunologic Deficiency Syndromes
Panniculitis	Panniculitis