UniProtKB - P06240 (LCK_MOUSE)
Proto-oncogene tyrosine-protein kinase LCK
Lck
Functioni
Catalytic activityi
- EC:2.7.10.2PROSITE-ProRule annotation
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 273 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 364 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 251 – 259 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- antigen binding Source: MGI
- ATPase binding Source: MGI
- ATP binding Source: UniProtKB-KW
- CD4 receptor binding Source: UniProtKB
- CD8 receptor binding Source: MGI
- identical protein binding Source: MGI
- non-membrane spanning protein tyrosine kinase activity Source: GO_Central
- phosphatidylinositol 3-kinase binding Source: MGI
- phosphotyrosine residue binding Source: MGI
- protein antigen binding Source: MGI
- protein-containing complex binding Source: MGI
- protein C-terminus binding Source: MGI
- protein kinase binding Source: MGI
- protein phosphatase binding Source: ARUK-UCL
- protein serine/threonine phosphatase activity Source: UniProtKB
- protein tyrosine kinase activity Source: MGI
- SH2 domain binding Source: UniProtKB
- signaling receptor binding Source: GO_Central
- T cell receptor binding Source: MGI
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- B cell receptor signaling pathway Source: MGI
- cell differentiation Source: GO_Central
- cell surface receptor signaling pathway Source: MGI
- cellular zinc ion homeostasis Source: UniProtKB
- innate immune response Source: GO_Central
- peptidyl-tyrosine autophosphorylation Source: GO_Central
- peptidyl-tyrosine phosphorylation Source: MGI
- positive regulation of gamma-delta T cell differentiation Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of heterotypic cell-cell adhesion Source: MGI
- positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of leukocyte cell-cell adhesion Source: MGI
- positive regulation of T cell activation Source: UniProtKB
- positive regulation of tyrosine phosphorylation of STAT protein Source: MGI
- positive regulation of uterine smooth muscle contraction Source: MGI
- protein autophosphorylation Source: MGI
- protein phosphorylation Source: MGI
- regulation of cell population proliferation Source: GO_Central
- regulation of regulatory T cell differentiation Source: MGI
- regulation of T cell receptor signaling pathway Source: MGI
- release of sequestered calcium ion into cytosol Source: UniProtKB
- response to drug Source: UniProtKB
- response to hydrogen peroxide Source: MGI
- response to mechanical stimulus Source: MGI
- response to metal ion Source: MGI
- T cell differentiation Source: UniProtKB
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Keywordsi
Molecular function | Kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 3474 |
Reactomei | R-MMU-114604, GPVI-mediated activation cascade R-MMU-1257604, PIP3 activates AKT signaling R-MMU-1433557, Signaling by SCF-KIT R-MMU-1433559, Regulation of KIT signaling R-MMU-202424, Downstream TCR signaling R-MMU-202427, Phosphorylation of CD3 and TCR zeta chains R-MMU-202430, Translocation of ZAP-70 to Immunological synapse R-MMU-202433, Generation of second messenger molecules R-MMU-210990, PECAM1 interactions R-MMU-2424491, DAP12 signaling R-MMU-389356, CD28 co-stimulation R-MMU-389357, CD28 dependent PI3K/Akt signaling R-MMU-389359, CD28 dependent Vav1 pathway R-MMU-389513, CTLA4 inhibitory signaling R-MMU-389948, PD-1 signaling R-MMU-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-MMU-9020558, Interleukin-2 signaling |
Names & Taxonomyi
Protein namesi | Recommended name: Proto-oncogene 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 p56-LCK |
Gene namesi | Name:Lck Synonyms:Lsk-t |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:96756, Lck |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side 1 Publication
Cytosol
- cytosol 1 Publication
Note: Present in lipid rafts in an inactive form.By similarity
Cytoskeleton
- pericentriolar material Source: UniProtKB
Cytosol
- cytosol Source: Reactome
Plasma Membrane
- extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
- immunological synapse Source: MGI
- plasma membrane Source: MGI
Other locations
- cell-cell junction Source: MGI
- endocytic vesicle Source: MGI
- glutamatergic synapse Source: MGI
- membrane raft Source: UniProtKB
- postsynaptic specialization, intracellular component Source: MGI
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 | G → A: Abolishes myristoylation and palmitoylation. 1 Publication | 1 | |
Mutagenesisi | 3 – 5 | CVC → SVK: Complete loss of interaction with CD4 or CD8. 1 Publication | 3 | |
Mutagenesisi | 3 | C → S: Abolishes plasma membrane association; when associated with S-41. Reduced palmitoylation level. 2 Publications | 1 | |
Mutagenesisi | 5 | C → K: Reduced palmitoylation level. 2 Publications | 1 | |
Mutagenesisi | 5 | C → S: Abolishes plasma membrane association; when associated with S-21. 2 Publications | 1 | |
Mutagenesisi | 20 | C → S: Complete loss of interaction with CD4 or CD8. 1 Publication | 1 | |
Mutagenesisi | 23 | C → S: Complete loss of interaction with CD4 or CD8. 1 Publication | 1 | |
Mutagenesisi | 269 | K → N: Reduced activity. | 1 | |
Mutagenesisi | 270 | V → L: Reduced activity. | 1 | |
Mutagenesisi | 271 | A → S: Reduced activity. | 1 | |
Mutagenesisi | 272 | V → A: Reduced activity. | 1 | |
Mutagenesisi | 273 | K → R: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 274 | S → N: Reduced activity. | 1 | |
Mutagenesisi | 275 | L → M: Reduced activity. | 1 | |
Mutagenesisi | 276 | K → V: Reduced activity. | 1 | |
Mutagenesisi | 505 | Y → F: Causes thymic tumors. 2 Publications | 1 |
Keywords - Diseasei
Proto-oncogeneChemistry databases
ChEMBLi | CHEMBL2480 |
DrugCentrali | P06240 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCurated | |||
ChainiPRO_0000088125 | 2 – 509 | Proto-oncogene tyrosine-protein kinase LCKAdd BLAST | 508 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycine1 Publication | 1 | |
Lipidationi | 3 | S-palmitoyl cysteine2 Publications | 1 | |
Lipidationi | 5 | S-palmitoyl cysteine2 Publications | 1 | |
Modified residuei | 102 | PhosphoserineBy similarity | 1 | |
Modified residuei | 159 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 162 | PhosphoserineBy similarity | 1 | |
Modified residuei | 192 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 194 | PhosphoserineBy similarity | 1 | |
Modified residuei | 394 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 505 | Phosphotyrosine; by CSKBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Lipoprotein, Myristate, Palmitate, PhosphoproteinProteomic databases
EPDi | P06240 |
jPOSTi | P06240 |
MaxQBi | P06240 |
PaxDbi | P06240 |
PRIDEi | P06240 |
PTM databases
iPTMneti | P06240 |
PhosphoSitePlusi | P06240 |
SwissPalmi | P06240 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000000409, Expressed in thymus and 185 other tissues |
ExpressionAtlasi | P06240, baseline and differential |
Genevisiblei | P06240, MM |
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.
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-lymphocytes migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70.
Interacts with CEACAM1 (via cytoplasmic domain); mediates CEACAM1 phosphorylation resulting in PTPN6 recruitment that dephosphorylates TCR stimulation-induced CD247 and ZAP70.
Interacts with FYB2 (By similarity).
Interacts with CD160.
By similarityBinary interactionsi
Hide detailsP06240
GO - Molecular functioni
- ATPase binding Source: MGI
- CD4 receptor binding Source: UniProtKB
- CD8 receptor binding Source: MGI
- identical protein binding Source: MGI
- phosphatidylinositol 3-kinase binding Source: MGI
- phosphotyrosine residue binding Source: MGI
- protein antigen binding Source: MGI
- protein C-terminus binding Source: MGI
- protein kinase binding Source: MGI
- protein phosphatase binding Source: ARUK-UCL
- SH2 domain binding Source: UniProtKB
- signaling receptor binding Source: GO_Central
- T cell receptor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 201120, 30 interactors |
CORUMi | P06240 |
ELMi | P06240 |
IntActi | P06240, 33 interactors |
MINTi | P06240 |
STRINGi | 10090.ENSMUSP00000066209 |
Chemistry databases
BindingDBi | P06240 |
Miscellaneous databases
RNActi | P06240, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 61 – 121 | SH3PROSITE-ProRule annotationAdd BLAST | 61 | |
Domaini | 127 – 224 | SH2PROSITE-ProRule annotationAdd BLAST | 98 | |
Domaini | 245 – 498 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 254 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 72 | Interactions with CD4 and CD8Add BLAST | 71 | |
Regioni | 154 – 242 | Interaction with PTPRHBy similarityAdd BLAST | 89 |
Domaini
Sequence similaritiesi
Keywords - Domaini
SH2 domain, SH3 domainPhylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000161163 |
HOGENOMi | CLU_000288_7_2_1 |
InParanoidi | P06240 |
OMAi | ICEHCNY |
PhylomeDBi | P06240 |
TreeFami | TF351634 |
Family and domain databases
CDDi | cd10362, SH2_Src_Lck, 1 hit cd12005, SH3_Lck, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 1 hit PF00018, SH3_1, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00452, SH3DOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00252, SH2, 1 hit SM00326, SH3, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MGCVCSSNPE DDWMENIDVC ENCHYPIVPL DSKISLPIRN GSEVRDPLVT
60 70 80 90 100
YEGSLPPASP 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
GLHDLVRHYT NASDGLCTKL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER
260 270 280 290 300
LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHPRL
310 320 330 340 350
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLNVNK LLDMAAQIAE
360 370 380 390 400
GMAFIEEQNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA
410 420 430 440 450
KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI
460 470 480 490 500
QNLERGYRMV RPDNCPEELY HLMMLCWKER PEDRPTFDYL RSVLDDFFTA
TEGQYQPQP
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9Q696 | E9Q696_MOUSE | Tyrosine-protein kinase | Lck | 520 | Annotation score: | ||
B2KG65 | B2KG65_MOUSE | Proto-oncogene tyrosine-protein kin... | Lck | 92 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M12056 mRNA Translation: AAB59674.1 X03533 mRNA Translation: CAA27234.1 X03533 mRNA Translation: CAA27235.1 Sequence problems. X03533 mRNA Translation: CAA27236.1 Sequence problems. AK088001 mRNA Translation: BAC40086.1 BC011474 mRNA Translation: AAH11474.1 M21511 Genomic DNA Translation: AAA39422.1 Sequence problems. M18098 Genomic DNA Translation: AAA39421.1 |
CCDSi | CCDS18697.1 |
PIRi | I48845 |
RefSeqi | NP_001155905.1, NM_001162433.1 NP_034823.1, NM_010693.3 XP_006502881.1, XM_006502818.3 |
Genome annotation databases
Ensembli | ENSMUST00000067240; ENSMUSP00000066209; ENSMUSG00000000409 ENSMUST00000102596; ENSMUSP00000099656; ENSMUSG00000000409 |
GeneIDi | 16818 |
KEGGi | mmu:16818 |
UCSCi | uc008uxi.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M12056 mRNA Translation: AAB59674.1 X03533 mRNA Translation: CAA27234.1 X03533 mRNA Translation: CAA27235.1 Sequence problems. X03533 mRNA Translation: CAA27236.1 Sequence problems. AK088001 mRNA Translation: BAC40086.1 BC011474 mRNA Translation: AAH11474.1 M21511 Genomic DNA Translation: AAA39422.1 Sequence problems. M18098 Genomic DNA Translation: AAA39421.1 |
CCDSi | CCDS18697.1 |
PIRi | I48845 |
RefSeqi | NP_001155905.1, NM_001162433.1 NP_034823.1, NM_010693.3 XP_006502881.1, XM_006502818.3 |
3D structure databases
BMRBi | P06240 |
SMRi | P06240 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 201120, 30 interactors |
CORUMi | P06240 |
ELMi | P06240 |
IntActi | P06240, 33 interactors |
MINTi | P06240 |
STRINGi | 10090.ENSMUSP00000066209 |
Chemistry databases
BindingDBi | P06240 |
ChEMBLi | CHEMBL2480 |
DrugCentrali | P06240 |
PTM databases
iPTMneti | P06240 |
PhosphoSitePlusi | P06240 |
SwissPalmi | P06240 |
Proteomic databases
EPDi | P06240 |
jPOSTi | P06240 |
MaxQBi | P06240 |
PaxDbi | P06240 |
PRIDEi | P06240 |
Protocols and materials databases
Antibodypediai | 735, 1646 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000067240; ENSMUSP00000066209; ENSMUSG00000000409 ENSMUST00000102596; ENSMUSP00000099656; ENSMUSG00000000409 |
GeneIDi | 16818 |
KEGGi | mmu:16818 |
UCSCi | uc008uxi.2, mouse |
Organism-specific databases
CTDi | 3932 |
MGIi | MGI:96756, Lck |
Phylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000161163 |
HOGENOMi | CLU_000288_7_2_1 |
InParanoidi | P06240 |
OMAi | ICEHCNY |
PhylomeDBi | P06240 |
TreeFami | TF351634 |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 3474 |
Reactomei | R-MMU-114604, GPVI-mediated activation cascade R-MMU-1257604, PIP3 activates AKT signaling R-MMU-1433557, Signaling by SCF-KIT R-MMU-1433559, Regulation of KIT signaling R-MMU-202424, Downstream TCR signaling R-MMU-202427, Phosphorylation of CD3 and TCR zeta chains R-MMU-202430, Translocation of ZAP-70 to Immunological synapse R-MMU-202433, Generation of second messenger molecules R-MMU-210990, PECAM1 interactions R-MMU-2424491, DAP12 signaling R-MMU-389356, CD28 co-stimulation R-MMU-389357, CD28 dependent PI3K/Akt signaling R-MMU-389359, CD28 dependent Vav1 pathway R-MMU-389513, CTLA4 inhibitory signaling R-MMU-389948, PD-1 signaling R-MMU-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-MMU-9020558, Interleukin-2 signaling |
Miscellaneous databases
BioGRID-ORCSi | 16818, 3 hits in 17 CRISPR screens |
ChiTaRSi | Lck, mouse |
PROi | PR:P06240 |
RNActi | P06240, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000000409, Expressed in thymus and 185 other tissues |
ExpressionAtlasi | P06240, baseline and differential |
Genevisiblei | P06240, MM |
Family and domain databases
CDDi | cd10362, SH2_Src_Lck, 1 hit cd12005, SH3_Lck, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 1 hit PF00018, SH3_1, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00452, SH3DOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00252, SH2, 1 hit SM00326, SH3, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LCK_MOUSE | |
Accessioni | P06240Primary (citable) accession number: P06240 Secondary accession number(s): Q61794 Q91X65 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1988 |
Last sequence update: | January 23, 2007 | |
Last modified: | December 2, 2020 | |
This is version 230 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families