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Protein

Tyrosine-protein kinase Lck

Gene

LCK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 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. 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).8 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Activity regulationi

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei273ATPPROSITE-ProRule annotation1
Active sitei364Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi251 – 259ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processHost-virus interaction
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-114604 GPVI-mediated activation cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-1433559 Regulation of KIT signaling
R-HSA-164944 Nef and signal transduction
R-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-210990 PECAM1 interactions
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491 DAP12 signaling
R-HSA-389356 CD28 co-stimulation
R-HSA-389357 CD28 dependent PI3K/Akt signaling
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-389948 PD-1 signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9020558 Interleukin-2 signaling
SignaLinkiP06239
SIGNORiP06239

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Lck (EC:2.7.10.2)
Alternative name(s):
Leukocyte C-terminal Src kinase
Short name:
LSK
Lymphocyte cell-specific protein-tyrosine kinase
Protein YT16
Proto-oncogene Lck
T cell-specific protein-tyrosine kinase
p56-LCK
Gene namesi
Name:LCK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000182866.16
HGNCiHGNC:6524 LCK
MIMi153390 gene
neXtProtiNX_P06239

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
Immunodeficiency 22 (IMD22)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by T-cell dysfunction. Affected individuals present with lymphopenia, recurrent infections, severe diarrhea, and failure to thrive.
See also OMIM:615758
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071291341L → P in IMD22. 1 PublicationCorresponds to variant dbSNP:rs587777335EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi59S → E: Allows interaction with SQSTM1. 1 Publication1
Mutagenesisi154R → K: No effect on interaction with SQSTM1. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi3932
MalaCardsiLCK
MIMi615758 phenotype
OpenTargetsiENSG00000182866
Orphaneti280142 Severe combined immunodeficiency due to LCK deficiency
PharmGKBiPA30307

Chemistry databases

ChEMBLiCHEMBL258
DrugBankiDB06925 3-(2-AMINOQUINAZOLIN-6-YL)-4-METHYL-N-[3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE
DB01254 Dasatinib
DB09079 Nintedanib
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB08901 Ponatinib
DB02010 Staurosporine
GuidetoPHARMACOLOGYi2053

Polymorphism and mutation databases

BioMutaiLCK
DMDMi125474

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000881242 – 509Tyrosine-protein kinase LckAdd BLAST508

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteineBy similarity1
Lipidationi5S-palmitoyl cysteineBy similarity1
Modified residuei102PhosphoserineCombined sources1
Modified residuei159PhosphothreonineCombined sources1
Modified residuei162PhosphoserineCombined sources1
Modified residuei192PhosphotyrosineBy similarity1
Modified residuei194PhosphoserineCombined sources1
Modified residuei394Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei505Phosphotyrosine; by CSKCombined sources3 Publications1

Post-translational modificationi

Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cell receptor signaling.4 Publications
Myristoylation is required prior to palmitoylation.By similarity
Palmitoylation regulates subcellular location.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Proteomic databases

EPDiP06239
MaxQBiP06239
PaxDbiP06239
PeptideAtlasiP06239
PRIDEiP06239
ProteomicsDBi51874
51875 [P06239-2]
51876 [P06239-3]

PTM databases

iPTMnetiP06239
PhosphoSitePlusiP06239
SwissPalmiP06239

Expressioni

Tissue specificityi

Expressed specifically in lymphoid cells.

Gene expression databases

BgeeiENSG00000182866 Expressed in 144 organ(s), highest expression level in thymus
CleanExiHS_LCK
ExpressionAtlasiP06239 baseline and differential
GenevisibleiP06239 HS

Organism-specific databases

HPAiCAB003816
HPA003494

Interactioni

Subunit structurei

Binds to the cytoplasmic domain of cell surface receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB1 and to other protein kinases including CDK1, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocyte migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70. Interacts with UNC119; this interaction plays a crucial role in activation of LCK. Interacts with CEACAM1 (via cytoplasmic domain); mediates CEACAM1 phosphorylation resulting in PTPN6 recruitment that dephosphorylates TCR stimulation-induced CD247 and ZAP70 (PubMed:18424730).10 Publications
(Microbial infection) Interacts with herpes simplex virus 1 UL46; this interaction activates LCK.1 Publication
(Microbial infection) Interacts with HIV-1 Nef through its SH3 domain.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110124, 89 interactors
CORUMiP06239
DIPiDIP-553N
ELMiP06239
IntActiP06239, 86 interactors
MINTiP06239
STRINGi9606.ENSP00000337825

Chemistry databases

BindingDBiP06239

Structurei

Secondary structure

1509
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP06239
SMRiP06239
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06239

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 121SH3PROSITE-ProRule annotationAdd BLAST61
Domaini127 – 224SH2PROSITE-ProRule annotationAdd BLAST98
Domaini245 – 498Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 72Interactions with CD4 and CD8By similarityAdd BLAST71
Regioni154 – 242Interaction with PTPRH1 PublicationAdd BLAST89

Domaini

The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOVERGENiHBG008761
InParanoidiP06239
KOiK05856
OMAiNPEDDWM
OrthoDBiEOG091G0D46
PhylomeDBiP06239
TreeFamiTF351634

Family and domain databases

CDDicd10362 SH2_Src_Lck, 1 hit
cd12005 SH3_Lck, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR035850 Lck_SH2
IPR035749 Lck_SH3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 1 hit
PS50002 SH3, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform Long (identifier: P06239-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKGTLLIRN GSEVRDPLVT
60 70 80 90 100
YEGSNPPASP LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA
110 120 130 140 150
QSLTTGQEGF IPFNFVAKAN SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS
160 170 180 190 200
FLIRESESTA GSFSLSVRDF DQNQGEVVKH YKIRNLDNGG FYISPRITFP
210 220 230 240 250
GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER
260 270 280 290 300
LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHQRL
310 320 330 340 350
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE
360 370 380 390 400
GMAFIEERNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA
410 420 430 440 450
KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI
460 470 480 490 500
QNLERGYRMV RPDNCPEELY QLMRLCWKER PEDRPTFDYL RSVLEDFFTA

TEGQYQPQP
Length:509
Mass (Da):58,001
Last modified:January 23, 2007 - v6
Checksum:i44BFF0D43FFB420D
GO
Isoform Short (identifier: P06239-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     348-363: IAEGMAFIEERNYIHR → VRRLGRGAGQGNRPVT
     364-509: Missing.

Note: No experimental confirmation available.
Show »
Length:363
Mass (Da):40,866
Checksum:iAC4AF1AB58D32577
GO
Isoform 3 (identifier: P06239-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     321-321: N → NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT

Note: No experimental confirmation available.
Show »
Length:539
Mass (Da):61,190
Checksum:iD1024F47D18B289C
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q573B4Q573B4_HUMAN
Tyrosine-protein kinase
LCK
516Annotation score:
E9PJ92E9PJ92_HUMAN
Tyrosine-protein kinase
LCK
319Annotation score:
E9PAP0E9PAP0_HUMAN
Tyrosine-protein kinase Lck
LCK
285Annotation score:
F8W6B9F8W6B9_HUMAN
Tyrosine-protein kinase Lck
LCK
137Annotation score:
E9PKQ8E9PKQ8_HUMAN
Tyrosine-protein kinase Lck
LCK
200Annotation score:
E9PQ10E9PQ10_HUMAN
Tyrosine-protein kinase Lck
LCK
149Annotation score:
E9PI33E9PI33_HUMAN
Tyrosine-protein kinase Lck
LCK
167Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29P → R in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti35T → R in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti87Q → P in CAA31884 (PubMed:3265417).Curated1
Sequence conflicti87Q → P in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti206 – 211VRHYTN → ASAITPI in CAA28691 (PubMed:3493153).Curated6
Sequence conflicti254G → A in AAA59502 (PubMed:3265417).Curated1
Sequence conflicti258 – 267EVWMGYYNGH → RCGWGTTTGT in CAA28691 (PubMed:3493153).Curated10
Sequence conflicti282 – 286PDAFL → AGRLP in CAA28691 (PubMed:3493153).Curated5
Sequence conflicti375T → A in CAA28165 (PubMed:3489486).Curated1
Sequence conflicti472L → H in CAA29667 (PubMed:2835736).Curated1
Sequence conflicti504 – 509QYQPQP → STA in CAA28691 (PubMed:3493153).Curated6

Mass spectrometryi

Molecular mass is 57869.42 Da from positions 2 - 509. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01346328V → L Found in leukemia. 1 Publication1
Natural variantiVAR_051697201G → S. Corresponds to variant dbSNP:rs11567841Ensembl.1
Natural variantiVAR_013464232P → PQKP in leukemia. 1
Natural variantiVAR_071291341L → P in IMD22. 1 PublicationCorresponds to variant dbSNP:rs587777335EnsemblClinVar.1
Natural variantiVAR_013465353A → V Found in leukemia. 1 Publication1
Natural variantiVAR_013466447P → L Found in leukemia. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016049321N → NDTLLDSQLEEKGLGASPWG NLGQQLLLLPT in isoform 3. 1 Publication1
Alternative sequenceiVSP_005000348 – 363IAEGM…NYIHR → VRRLGRGAGQGNRPVT in isoform Short. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_005001364 – 509Missing in isoform Short. 1 PublicationAdd BLAST146

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05027 mRNA Translation: CAA28691.1
X13529 mRNA Translation: CAA31884.1
M36881 mRNA Translation: AAA59502.1
X14055, X14053, X14054 Genomic DNA Translation: CAA32211.1
U07236 mRNA Translation: AAA18225.1
U23852 mRNA Translation: AAC50287.1
BN000073 Genomic DNA Translation: CAD55807.1
AL121991 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07543.1
CH471059 Genomic DNA Translation: EAX07546.1
BC013200 mRNA Translation: AAH13200.1
M21510 Genomic DNA Translation: AAA59501.1 Different termination.
M26692 Genomic DNA Translation: AAA59503.1
AF228313 mRNA Translation: AAF34794.1
X06369 mRNA Translation: CAA29667.1
X04476 mRNA Translation: CAA28165.1
CCDSiCCDS359.1 [P06239-1]
PIRiJQ0152 OKHULK
RefSeqiNP_001036236.1, NM_001042771.2 [P06239-1]
NP_005347.3, NM_005356.4 [P06239-1]
UniGeneiHs.470627

Genome annotation databases

EnsembliENST00000333070; ENSP00000328213; ENSG00000182866 [P06239-3]
ENST00000336890; ENSP00000337825; ENSG00000182866 [P06239-1]
ENST00000619559; ENSP00000477713; ENSG00000182866 [P06239-1]
GeneIDi3932
KEGGihsa:3932
UCSCiuc001bux.3 human [P06239-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

Lck entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05027 mRNA Translation: CAA28691.1
X13529 mRNA Translation: CAA31884.1
M36881 mRNA Translation: AAA59502.1
X14055, X14053, X14054 Genomic DNA Translation: CAA32211.1
U07236 mRNA Translation: AAA18225.1
U23852 mRNA Translation: AAC50287.1
BN000073 Genomic DNA Translation: CAD55807.1
AL121991 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07543.1
CH471059 Genomic DNA Translation: EAX07546.1
BC013200 mRNA Translation: AAH13200.1
M21510 Genomic DNA Translation: AAA59501.1 Different termination.
M26692 Genomic DNA Translation: AAA59503.1
AF228313 mRNA Translation: AAF34794.1
X06369 mRNA Translation: CAA29667.1
X04476 mRNA Translation: CAA28165.1
CCDSiCCDS359.1 [P06239-1]
PIRiJQ0152 OKHULK
RefSeqiNP_001036236.1, NM_001042771.2 [P06239-1]
NP_005347.3, NM_005356.4 [P06239-1]
UniGeneiHs.470627

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BHFX-ray1.80A119-226[»]
1BHHX-ray1.90A119-226[»]
B124-226[»]
1CWDX-ray2.25L127-222[»]
1CWEX-ray2.30A/C127-222[»]
1FBZX-ray2.40A/B123-226[»]
1H92NMR-A59-120[»]
1IJRX-ray2.20A124-226[»]
1KIKNMR-A64-120[»]
1LCJX-ray1.80A119-226[»]
1LCKX-ray2.50A53-226[»]
B502-509[»]
1LKKX-ray1.00A122-226[»]
1LKLX-ray1.80A123-226[»]
1Q68NMR-B7-35[»]
1Q69NMR-B7-35[»]
1QPCX-ray1.60A231-509[»]
1QPDX-ray2.00A231-509[»]
1QPEX-ray2.00A231-509[»]
1QPJX-ray2.20A231-509[»]
1X27X-ray2.70A/B/C/D/E/F64-226[»]
2IIMX-ray1.00A59-119[»]
2OF2X-ray2.00A231-501[»]
2OF4X-ray2.70A231-501[»]
2OFUX-ray2.00A229-501[»]
2OFVX-ray2.00A/B232-498[»]
2OG8X-ray2.30A/B237-499[»]
2PL0X-ray2.80A225-509[»]
2ZM1X-ray2.10A225-509[»]
2ZM4X-ray2.70A225-509[»]
2ZYBX-ray2.55A225-509[»]
3AC1X-ray1.99A225-509[»]
3AC2X-ray2.10A225-509[»]
3AC3X-ray2.55A225-509[»]
3AC4X-ray2.70A225-509[»]
3AC5X-ray2.50A225-509[»]
3AC8X-ray2.30A225-509[»]
3ACJX-ray2.20A225-509[»]
3ACKX-ray2.60A225-509[»]
3AD4X-ray2.20A225-509[»]
3AD5X-ray2.00A225-509[»]
3AD6X-ray2.15A225-509[»]
3B2WX-ray2.30A226-502[»]
3BRHX-ray2.20C/D391-397[»]
3BYMX-ray2.00A230-501[»]
3BYOX-ray2.00A231-501[»]
3BYSX-ray2.20A225-501[»]
3BYUX-ray2.30A225-501[»]
3KMMX-ray2.80A229-509[»]
3KXZX-ray2.37A225-509[»]
3LCKX-ray1.70A231-501[»]
3MPMX-ray1.95A237-501[»]
4C3FX-ray1.72A237-501[»]
4D8KX-ray2.36A53-226[»]
5MTMX-ray2.40A118-231[»]
5MTNX-ray2.85A118-231[»]
ProteinModelPortaliP06239
SMRiP06239
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110124, 89 interactors
CORUMiP06239
DIPiDIP-553N
ELMiP06239
IntActiP06239, 86 interactors
MINTiP06239
STRINGi9606.ENSP00000337825

Chemistry databases

BindingDBiP06239
ChEMBLiCHEMBL258
DrugBankiDB06925 3-(2-AMINOQUINAZOLIN-6-YL)-4-METHYL-N-[3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE
DB01254 Dasatinib
DB09079 Nintedanib
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB08901 Ponatinib
DB02010 Staurosporine
GuidetoPHARMACOLOGYi2053

PTM databases

iPTMnetiP06239
PhosphoSitePlusiP06239
SwissPalmiP06239

Polymorphism and mutation databases

BioMutaiLCK
DMDMi125474

Proteomic databases

EPDiP06239
MaxQBiP06239
PaxDbiP06239
PeptideAtlasiP06239
PRIDEiP06239
ProteomicsDBi51874
51875 [P06239-2]
51876 [P06239-3]

Protocols and materials databases

DNASUi3932
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000333070; ENSP00000328213; ENSG00000182866 [P06239-3]
ENST00000336890; ENSP00000337825; ENSG00000182866 [P06239-1]
ENST00000619559; ENSP00000477713; ENSG00000182866 [P06239-1]
GeneIDi3932
KEGGihsa:3932
UCSCiuc001bux.3 human [P06239-1]

Organism-specific databases

CTDi3932
DisGeNETi3932
EuPathDBiHostDB:ENSG00000182866.16
GeneCardsiLCK
H-InvDBiHIX0019954
HGNCiHGNC:6524 LCK
HPAiCAB003816
HPA003494
MalaCardsiLCK
MIMi153390 gene
615758 phenotype
neXtProtiNX_P06239
OpenTargetsiENSG00000182866
Orphaneti280142 Severe combined immunodeficiency due to LCK deficiency
PharmGKBiPA30307
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOVERGENiHBG008761
InParanoidiP06239
KOiK05856
OMAiNPEDDWM
OrthoDBiEOG091G0D46
PhylomeDBiP06239
TreeFamiTF351634

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-114604 GPVI-mediated activation cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-1433559 Regulation of KIT signaling
R-HSA-164944 Nef and signal transduction
R-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-210990 PECAM1 interactions
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491 DAP12 signaling
R-HSA-389356 CD28 co-stimulation
R-HSA-389357 CD28 dependent PI3K/Akt signaling
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-389948 PD-1 signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9020558 Interleukin-2 signaling
SignaLinkiP06239
SIGNORiP06239

Miscellaneous databases

ChiTaRSiLCK human
EvolutionaryTraceiP06239
GeneWikiiLck
GenomeRNAii3932
PROiPR:P06239
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182866 Expressed in 144 organ(s), highest expression level in thymus
CleanExiHS_LCK
ExpressionAtlasiP06239 baseline and differential
GenevisibleiP06239 HS

Family and domain databases

CDDicd10362 SH2_Src_Lck, 1 hit
cd12005 SH3_Lck, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR035850 Lck_SH2
IPR035749 Lck_SH3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 1 hit
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLCK_HUMAN
AccessioniPrimary (citable) accession number: P06239
Secondary accession number(s): D3DPP8
, P07100, Q12850, Q13152, Q5TDH8, Q5TDH9, Q7RTZ3, Q96DW4, Q9NYT8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 245 of the entry and version 6 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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