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P06239

- LCK_HUMAN

UniProt

P06239 - LCK_HUMAN

Protein

Tyrosine-protein kinase Lck

Gene

LCK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 201 (01 Oct 2014)
      Sequence version 6 (23 Jan 2007)
      Previous versions | rss
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    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 tyrosines 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.7 Publications

    Catalytic activityi

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

    Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei273 – 2731ATPPROSITE-ProRule annotation
    Active sitei364 – 3641Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi251 – 2599ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. antigen binding Source: Ensembl
    2. ATPase binding Source: UniProtKB
    3. ATP binding Source: UniProtKB-KW
    4. CD4 receptor binding Source: UniProtKB
    5. CD8 receptor binding Source: UniProtKB
    6. glycoprotein binding Source: UniProtKB
    7. identical protein binding Source: IntAct
    8. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    9. phosphatidylinositol 3-kinase binding Source: UniProtKB
    10. protein binding Source: UniProtKB
    11. protein C-terminus binding Source: UniProtKB
    12. protein kinase binding Source: UniProtKB
    13. protein phosphatase binding Source: UniProtKB
    14. protein serine/threonine phosphatase activity Source: UniProtKB
    15. protein tyrosine kinase activity Source: UniProtKB
    16. SH2 domain binding Source: UniProtKB

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. aging Source: Ensembl
    3. B cell receptor signaling pathway Source: Ensembl
    4. blood coagulation Source: Reactome
    5. cellular zinc ion homeostasis Source: UniProtKB
    6. dephosphorylation Source: GOC
    7. epidermal growth factor receptor signaling pathway Source: Reactome
    8. Fc-epsilon receptor signaling pathway Source: Reactome
    9. fibroblast growth factor receptor signaling pathway Source: Reactome
    10. hemopoiesis Source: UniProtKB
    11. innate immune response Source: Reactome
    12. leukocyte migration Source: Reactome
    13. neurotrophin TRK receptor signaling pathway Source: Reactome
    14. phosphatidylinositol-mediated signaling Source: Reactome
    15. platelet activation Source: Reactome
    16. positive regulation of gamma-delta T cell differentiation Source: Ensembl
    17. positive regulation of gene expression Source: Ensembl
    18. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
    19. positive regulation of T cell activation Source: UniProtKB
    20. positive regulation of T cell receptor signaling pathway Source: UniProtKB
    21. positive regulation of tyrosine phosphorylation of Stat5 protein Source: Ensembl
    22. positive regulation of uterine smooth muscle contraction Source: Ensembl
    23. protein autophosphorylation Source: Ensembl
    24. protein phosphorylation Source: UniProtKB
    25. regulation of defense response to virus by virus Source: Reactome
    26. regulation of lymphocyte activation Source: UniProtKB
    27. release of sequestered calcium ion into cytosol Source: UniProtKB
    28. response to drug Source: UniProtKB
    29. response to hydrogen peroxide Source: Ensembl
    30. response to mechanical stimulus Source: Ensembl
    31. response to zinc ion Source: Ensembl
    32. T cell costimulation Source: Reactome
    33. T cell differentiation Source: UniProtKB
    34. T cell receptor signaling pathway Source: Reactome
    35. viral process Source: Reactome

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Host-virus interaction

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 2681.
    ReactomeiREACT_11068. Nef and signal transduction.
    REACT_111040. Signaling by SCF-KIT.
    REACT_111225. Regulation of KIT signaling.
    REACT_11166. Nef Mediated CD4 Down-regulation.
    REACT_12519. PECAM1 interactions.
    REACT_12555. Downstream TCR signaling.
    REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
    REACT_12596. Translocation of ZAP-70 to Immunological synapse.
    REACT_12623. Generation of second messenger molecules.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147814. DAP12 signaling.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_19183. CD28 co-stimulation.
    REACT_19238. CD28 dependent Vav1 pathway.
    REACT_19324. PD-1 signaling.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_19405. CTLA4 inhibitory signaling.
    REACT_27283. Interleukin-2 signaling.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinkiP06239.

    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
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:6524. LCK.

    Subcellular locationi

    Cytoplasm 1 Publication. Cell membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side 1 Publication
    Note: Present in lipid rafts in an inactive form.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. endocytic vesicle Source: Ensembl
    3. extracellular vesicular exosome Source: UniProt
    4. immunological synapse Source: MGI
    5. membrane raft Source: UniProtKB
    6. pericentriolar material Source: UniProtKB
    7. plasma membrane Source: BHF-UCL

    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi59 – 591S → E: Allows interaction with SQSTM1. 1 Publication
    Mutagenesisi154 – 1541R → K: No effect on interaction with SQSTM1. 1 Publication

    Keywords - Diseasei

    Disease mutation, Proto-oncogene

    Organism-specific databases

    Orphaneti280142. Severe combined immunodeficiency due to LCK deficiency.
    PharmGKBiPA30307.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 509508Tyrosine-protein kinase LckPRO_0000088124Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineBy similarity
    Lipidationi3 – 31S-palmitoyl cysteineBy similarity
    Lipidationi5 – 51S-palmitoyl cysteineBy similarity
    Modified residuei102 – 1021Phosphoserine2 Publications
    Modified residuei159 – 1591Phosphothreonine2 Publications
    Modified residuei162 – 1621Phosphoserine2 Publications
    Modified residuei194 – 1941Phosphoserine2 Publications
    Modified residuei394 – 3941Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei505 – 5051Phosphotyrosine; by CSK9 Publications

    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.9 Publications
    Myristoylation is required prior to palmitoylation.By similarity
    Palmitoylation regulates subcellular location.By similarity

    Keywords - PTMi

    Lipoprotein, Myristate, Palmitate, Phosphoprotein

    Proteomic databases

    MaxQBiP06239.
    PaxDbiP06239.
    PRIDEiP06239.

    PTM databases

    PhosphoSiteiP06239.

    Expressioni

    Tissue specificityi

    Expressed specifically in lymphoid cells.

    Gene expression databases

    ArrayExpressiP06239.
    BgeeiP06239.
    CleanExiHS_LCK.
    GenevestigatoriP06239.

    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, FYB 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. Binds to HIV-1 Nef through its SH3 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.10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-1348,EBI-1348
    P225757EBI-1348,EBI-866709From a different organism.
    Q9YJQ82EBI-1348,EBI-7709835From a different organism.
    ADAM15Q134443EBI-1348,EBI-77818
    ARP102757EBI-1348,EBI-608057
    BCL3P207493EBI-1348,EBI-958997
    CD4P017302EBI-1348,EBI-353826
    GAB1Q1348010EBI-1348,EBI-517684
    HSP90AB1P082382EBI-1348,EBI-352572
    KHDRBS1Q076665EBI-1348,EBI-1364
    KITP107218EBI-1348,EBI-1379503
    LATO435612EBI-1348,EBI-1222766
    MED28Q9H2044EBI-1348,EBI-514199
    METP085813EBI-1348,EBI-1039152
    NR3C1P041503EBI-1348,EBI-493507
    PRKCQQ047592EBI-1348,EBI-374762
    PTPN22Q9Y2R25EBI-1348,EBI-1211241
    PTPN6P293505EBI-1348,EBI-78260
    PTPRCP085757EBI-1348,EBI-1341
    SH2D2AQ9NP3112EBI-1348,EBI-490630
    SYKP434057EBI-1348,EBI-78302
    UBCP0CG482EBI-1348,EBI-3390054
    ZAP70P434032EBI-1348,EBI-1211276

    Protein-protein interaction databases

    BioGridi110124. 82 interactions.
    DIPiDIP-553N.
    IntActiP06239. 64 interactions.
    MINTiMINT-110378.

    Structurei

    Secondary structure

    1
    509
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi12 – 154
    Beta strandi21 – 233
    Beta strandi24 – 274
    Turni60 – 634
    Beta strandi65 – 706
    Beta strandi76 – 794
    Beta strandi87 – 926
    Beta strandi95 – 1028
    Turni103 – 1053
    Beta strandi108 – 1125
    Helixi113 – 1153
    Beta strandi116 – 1183
    Beta strandi128 – 1314
    Helixi134 – 1418
    Beta strandi151 – 1555
    Beta strandi157 – 1593
    Beta strandi163 – 1719
    Turni172 – 1743
    Beta strandi175 – 18511
    Turni187 – 1893
    Beta strandi191 – 1944
    Beta strandi199 – 2013
    Helixi202 – 21110
    Beta strandi216 – 2183
    Turni233 – 2353
    Beta strandi237 – 2393
    Helixi242 – 2443
    Beta strandi245 – 25410
    Beta strandi257 – 2648
    Turni265 – 2673
    Beta strandi268 – 2758
    Turni277 – 2793
    Helixi282 – 29413
    Beta strandi303 – 3075
    Beta strandi309 – 3113
    Beta strandi313 – 3175
    Helixi324 – 3274
    Helixi331 – 3344
    Helixi338 – 35720
    Helixi367 – 3693
    Beta strandi370 – 3723
    Beta strandi378 – 3803
    Helixi383 – 3853
    Helixi386 – 3894
    Beta strandi390 – 3923
    Beta strandi393 – 3953
    Turni404 – 4063
    Helixi409 – 4146
    Helixi419 – 43416
    Turni435 – 4373
    Helixi446 – 4549
    Helixi467 – 47610
    Helixi481 – 4833
    Helixi487 – 50014

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP06239.
    SMRiP06239. Positions 7-35, 64-509.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP06239.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini61 – 12161SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini127 – 22498SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini245 – 498254Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 7271Interactions with CD4 and CD8By similarityAdd
    BLAST
    Regioni154 – 24289Interaction with PTPRHAdd
    BLAST

    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
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain, SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    HOVERGENiHBG008761.
    KOiK05856.
    OMAiEYMENDT.
    OrthoDBiEOG7GTT2V.
    PhylomeDBiP06239.
    TreeFamiTF351634.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. 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.
    [Graphical view]

    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. Align

    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

    MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKGTLLIRN GSEVRDPLVT    50
    YEGSNPPASP LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA 100
    QSLTTGQEGF IPFNFVAKAN SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS 150
    FLIRESESTA GSFSLSVRDF DQNQGEVVKH YKIRNLDNGG FYISPRITFP 200
    GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER 250
    LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHQRL 300
    VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE 350
    GMAFIEERNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA 400
    KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI 450
    QNLERGYRMV RPDNCPEELY QLMRLCWKER PEDRPTFDYL RSVLEDFFTA 500
    TEGQYQPQP 509
    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

    Sequence cautioni

    The sequence CAI22320.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence CAI22321.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti29 – 291P → R in AAA59502. (PubMed:3265417)Curated
    Sequence conflicti35 – 351T → R in AAA59502. (PubMed:3265417)Curated
    Sequence conflicti87 – 871Q → P in CAA31884. (PubMed:3265417)Curated
    Sequence conflicti87 – 871Q → P in AAA59502. (PubMed:3265417)Curated
    Sequence conflicti206 – 2116VRHYTN → ASAITPI in CAA28691. (PubMed:3493153)Curated
    Sequence conflicti254 – 2541G → A in AAA59502. (PubMed:3265417)Curated
    Sequence conflicti258 – 26710EVWMGYYNGH → RCGWGTTTGT in CAA28691. (PubMed:3493153)Curated
    Sequence conflicti282 – 2865PDAFL → AGRLP in CAA28691. (PubMed:3493153)Curated
    Sequence conflicti375 – 3751T → A in CAA28165. (PubMed:3489486)Curated
    Sequence conflicti472 – 4721L → H in CAA29667. (PubMed:2835736)Curated
    Sequence conflicti504 – 5096QYQPQP → STA in CAA28691. (PubMed:3493153)Curated

    Mass spectrometryi

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti28 – 281V → L in leukemia. 1 Publication
    VAR_013463
    Natural varianti201 – 2011G → S.
    Corresponds to variant rs11567841 [ dbSNP | Ensembl ].
    VAR_051697
    Natural varianti232 – 2321P → PQKP in leukemia.
    VAR_013464
    Natural varianti353 – 3531A → V in leukemia. 1 Publication
    VAR_013465
    Natural varianti447 – 4471P → L in leukemia. 1 Publication
    VAR_013466

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei321 – 3211N → NDTLLDSQLEEKGLGASPWG NLGQQLLLLPT in isoform 3. 1 PublicationVSP_016049
    Alternative sequencei348 – 36316IAEGM…NYIHR → VRRLGRGAGQGNRPVT in isoform Short. 1 PublicationVSP_005000Add
    BLAST
    Alternative sequencei364 – 509146Missing in isoform Short. 1 PublicationVSP_005001Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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. Translation: CAI22320.1. Different initiation.
    AL121991 Genomic DNA. Translation: CAI22321.1. Different initiation.
    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]
    GeneIDi3932.
    KEGGihsa:3932.
    UCSCiuc001bux.3. human. [P06239-1]
    uc001buz.3. human. [P06239-3]

    Polymorphism databases

    DMDMi125474.

    Keywords - Coding sequence diversityi

    Alternative splicing, Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia

    Lck entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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. Translation: CAI22320.1 . Different initiation.
    AL121991 Genomic DNA. Translation: CAI22321.1 . Different initiation.
    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 .
    CCDSi CCDS359.1. [P06239-1 ]
    PIRi JQ0152. OKHULK.
    RefSeqi NP_001036236.1. NM_001042771.2. [P06239-1 ]
    NP_005347.3. NM_005356.4. [P06239-1 ]
    UniGenei Hs.470627.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1BHF X-ray 1.80 A 119-226 [» ]
    1BHH X-ray 1.90 A 119-226 [» ]
    B 124-226 [» ]
    1CWD X-ray 2.25 L 127-222 [» ]
    1CWE X-ray 2.30 A/C 127-222 [» ]
    1FBZ X-ray 2.40 A/B 123-226 [» ]
    1H92 NMR - A 59-120 [» ]
    1IJR X-ray 2.20 A 124-226 [» ]
    1KIK NMR - A 64-120 [» ]
    1LCJ X-ray 1.80 A 119-226 [» ]
    1LCK X-ray 2.50 A 53-226 [» ]
    B 502-509 [» ]
    1LKK X-ray 1.00 A 122-226 [» ]
    1LKL X-ray 1.80 A 123-226 [» ]
    1Q68 NMR - B 7-35 [» ]
    1Q69 NMR - B 7-35 [» ]
    1QPC X-ray 1.60 A 231-509 [» ]
    1QPD X-ray 2.00 A 231-509 [» ]
    1QPE X-ray 2.00 A 231-509 [» ]
    1QPJ X-ray 2.20 A 231-509 [» ]
    1X27 X-ray 2.70 A/B/C/D/E/F 64-226 [» ]
    2IIM X-ray 1.00 A 59-119 [» ]
    2OF2 X-ray 2.00 A 231-501 [» ]
    2OF4 X-ray 2.70 A 231-501 [» ]
    2OFU X-ray 2.00 A 229-501 [» ]
    2OFV X-ray 2.00 A/B 232-498 [» ]
    2OG8 X-ray 2.30 A/B 237-499 [» ]
    2PL0 X-ray 2.80 A 225-509 [» ]
    2ZM1 X-ray 2.10 A 225-509 [» ]
    2ZM4 X-ray 2.70 A 225-509 [» ]
    2ZYB X-ray 2.55 A 225-509 [» ]
    3AC1 X-ray 1.99 A 225-509 [» ]
    3AC2 X-ray 2.10 A 225-509 [» ]
    3AC3 X-ray 2.55 A 225-509 [» ]
    3AC4 X-ray 2.70 A 225-509 [» ]
    3AC5 X-ray 2.50 A 225-509 [» ]
    3AC8 X-ray 2.30 A 225-509 [» ]
    3ACJ X-ray 2.20 A 225-509 [» ]
    3ACK X-ray 2.60 A 225-509 [» ]
    3AD4 X-ray 2.20 A 225-509 [» ]
    3AD5 X-ray 2.00 A 225-509 [» ]
    3AD6 X-ray 2.15 A 225-509 [» ]
    3B2W X-ray 2.30 A 226-502 [» ]
    3BRH X-ray 2.20 C/D 391-397 [» ]
    3BYM X-ray 2.00 A 230-501 [» ]
    3BYO X-ray 2.00 A 231-501 [» ]
    3BYS X-ray 2.20 A 225-501 [» ]
    3BYU X-ray 2.30 A 225-501 [» ]
    3KMM X-ray 2.80 A 229-509 [» ]
    3KXZ X-ray 2.37 A 225-509 [» ]
    3LCK X-ray 1.70 A 231-501 [» ]
    3MPM X-ray 1.95 A 237-501 [» ]
    4C3F X-ray 1.72 A 237-501 [» ]
    4D8K X-ray 2.36 A 53-226 [» ]
    ProteinModelPortali P06239.
    SMRi P06239. Positions 7-35, 64-509.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110124. 82 interactions.
    DIPi DIP-553N.
    IntActi P06239. 64 interactions.
    MINTi MINT-110378.

    Chemistry

    BindingDBi P06239.
    ChEMBLi CHEMBL2363074.
    DrugBanki DB01254. Dasatinib.
    GuidetoPHARMACOLOGYi 2053.

    PTM databases

    PhosphoSitei P06239.

    Polymorphism databases

    DMDMi 125474.

    Proteomic databases

    MaxQBi P06239.
    PaxDbi P06239.
    PRIDEi P06239.

    Protocols and materials databases

    DNASUi 3932.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000333070 ; ENSP00000328213 ; ENSG00000182866 . [P06239-3 ]
    ENST00000336890 ; ENSP00000337825 ; ENSG00000182866 . [P06239-1 ]
    GeneIDi 3932.
    KEGGi hsa:3932.
    UCSCi uc001bux.3. human. [P06239-1 ]
    uc001buz.3. human. [P06239-3 ]

    Organism-specific databases

    CTDi 3932.
    GeneCardsi GC01P032716.
    H-InvDB HIX0019954.
    HGNCi HGNC:6524. LCK.
    HPAi CAB003816.
    HPA003494.
    MIMi 153390. gene.
    neXtProti NX_P06239.
    Orphaneti 280142. Severe combined immunodeficiency due to LCK deficiency.
    PharmGKBi PA30307.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOVERGENi HBG008761.
    KOi K05856.
    OMAi EYMENDT.
    OrthoDBi EOG7GTT2V.
    PhylomeDBi P06239.
    TreeFami TF351634.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 2681.
    Reactomei REACT_11068. Nef and signal transduction.
    REACT_111040. Signaling by SCF-KIT.
    REACT_111225. Regulation of KIT signaling.
    REACT_11166. Nef Mediated CD4 Down-regulation.
    REACT_12519. PECAM1 interactions.
    REACT_12555. Downstream TCR signaling.
    REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
    REACT_12596. Translocation of ZAP-70 to Immunological synapse.
    REACT_12623. Generation of second messenger molecules.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147814. DAP12 signaling.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_19183. CD28 co-stimulation.
    REACT_19238. CD28 dependent Vav1 pathway.
    REACT_19324. PD-1 signaling.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_19405. CTLA4 inhibitory signaling.
    REACT_27283. Interleukin-2 signaling.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinki P06239.

    Miscellaneous databases

    ChiTaRSi LCK. human.
    EvolutionaryTracei P06239.
    GeneWikii Lck.
    GenomeRNAii 3932.
    NextBioi 15441.
    PROi P06239.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P06239.
    Bgeei P06239.
    CleanExi HS_LCK.
    Genevestigatori P06239.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi 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.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases."
      Koga Y., Caccia N., Toyonaga B., Spolski R., Yanagi Y., Yoshikai Y., Mak T.W.
      Eur. J. Immunol. 16:1643-1646(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Structure and expression of lck transcripts in human lymphoid cells."
      Perlmutter R.M., Marth J.D., Lewis D.B., Peet R., Ziegler S.F., Wilson C.B.
      J. Cell. Biochem. 38:117-126(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons."
      Rouer E., van Huynh T., de Souza S.L., Lang M.C., Fischer S., Benarous R.
      Gene 84:105-113(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia."
      Wright D.D., Sefton B.M., Kamps M.P.
      Mol. Cell. Biol. 14:2429-2437(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-28; GLN-LYS-PRO-232 INS; VAL-353 AND LEU-447, PHOSPHORYLATION AT TYR-394 AND TYR-505.
      Tissue: Leukemia.
    5. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), ALTERNATIVE SPLICING.
      Tissue: Leukemic T-cell.
    6. "No association between lck gene polymorphisms and protein level in type 1 diabetes."
      Nervi S., Nicodeme S., Gartioux C., Atlan C., Lathrop M., Reviron D., Naquet P., Matsuda F., Imbert J., Vialettes B.
      Diabetes 51:3326-3330(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Lymph.
    10. "Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line."
      Garvin A.M., Pawar S., Marth J.D., Perlmutter R.M.
      Mol. Cell. Biol. 8:3058-3064(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
    11. "Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells."
      Takadera T., Leung S., Gernone A., Koga Y., Takihara Y., Miyamoto N.G., Mak T.W.
      Mol. Cell. Biol. 9:2173-2180(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
    12. "Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects."
      Boncristiano M., Majolini M.B., D'Elios M.M., Pacini S., Valensin S., Ulivieri C., Amedei A., Falini B., Del Prete G., Telford J.L., Baldari C.T.
      Eur. J. Immunol. 30:2632-2638(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-509.
      Tissue: Peripheral blood lymphocyte.
    13. "Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines."
      Veillette A., Foss F.M., Sausville E.A., Bolen J.B., Rosen N.
      Oncogene Res. 1:357-374(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 368-509.
    14. "Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA."
      Trevillyan J.M., Lin Y., Chen S.J., Phillips C.A., Canna C., Linna T.J.
      Biochim. Biophys. Acta 888:286-295(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 375-509.
    15. "The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity."
      Bergman M., Mustelin T., Oetken C., Partanen J., Flint N.A., Amrein K.E., Autero M., Burn P., Alitalo K.
      EMBO J. 11:2919-2924(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-505.
    16. "The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase from T lymphocytes."
      Vogel L.B., Fujita D.J.
      Mol. Cell. Biol. 13:7408-7417(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PI3K.
    17. "p70 phosphorylation and binding to p56lck is an early event in interleukin-2-induced onset of cell cycle progression in T-lymphocytes."
      Vogel L.B., Fujita D.J.
      J. Biol. Chem. 270:2506-2511(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KHDRBS1.
    18. "Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region."
      Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J.
      Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SQSTM1, MUTAGENESIS OF SER-59 AND ARG-154.
    19. "Detection of a physical and functional interaction between Csk and Lck which involves the SH2 domain of Csk and is mediated by autophosphorylation of Lck on tyrosine 394."
      Bougeret C., Delaunay T., Romero F., Jullien P., Sabe H., Hanafusa H., Benarous R., Fischer S.
      J. Biol. Chem. 271:7465-7472(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-505 BY CSK, AUTOPHOSPHORYLATION.
    20. "Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen-activated protein kinase, inhibiting kinase activity."
      Greenway A.L., Azad A., Mills J., McPhee D.A.
      J. Virol. 70:6701-6708(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIV-1 NEF.
    21. "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site."
      Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W.
      Oncogene 14:2619-2631(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXL.
    22. "Lck protein tyrosine kinase is a key regulator of T-cell activation and a target for signal intervention by Herpesvirus saimiri and other viral gene products."
      Isakov N., Biesinger B.
      Eur. J. Biochem. 267:3413-3421(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    23. "Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells."
      Yasuda K., Nagafuku M., Shima T., Okada M., Yagi T., Yamada T., Minaki Y., Kato A., Tani-Ichi S., Hamaoka T., Kosugi A.
      J. Immunol. 169:2813-2817(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    24. "Cluster analysis of an extensive human breast cancer cell line protein expression map database."
      Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J.
      Proteomics 2:212-223(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: MASS SPECTROMETRY.
      Tissue: Mammary cancer.
    25. "LIME: a new membrane raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling."
      Brdickova N., Brdicka T., Angelisova P., Horvath O., Spicka J., Hilgert I., Paces J., Simeoni L., Kliche S., Merten C., Schraven B., Horejsi V.
      J. Exp. Med. 198:1453-1462(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LIME1.
    26. "LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation."
      Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.
      J. Exp. Med. 198:1463-1473(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LIME1.
    27. "Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function."
      Ito T., Okazawa H., Maruyama K., Tomizawa K., Motegi S., Ohnishi H., Kuwano H., Kosugi A., Matozaki T.
      J. Biol. Chem. 278:34854-34863(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTPRH.
    28. "Unc119, a novel activator of Lck/Fyn, is essential for T cell activation."
      Gorska M.M., Stafford S.J., Cen O., Sur S., Alam R.
      J. Exp. Med. 199:369-379(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UNC119.
    29. "T cell activation-induced CrkII binding to the Zap70 protein tyrosine kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine 315."
      Gelkop S., Gish G.D., Babichev Y., Pawson T., Isakov N.
      J. Immunol. 175:8123-8132(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF ZAP70.
    30. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
      Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
      Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    31. Cited for: DEPHOSPHORYLATION BY PTN22.
    32. "Regulation of Ly49D/DAP12 signal transduction by Src-family kinases and CD45."
      Mason L.H., Willette-Brown J., Taylor L.S., McVicar D.W.
      J. Immunol. 176:6615-6623(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF TYROBP.
    33. "Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes."
      Hjorthaug H.S., Aasheim H.C.
      Eur. J. Immunol. 37:2326-2336(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPHA1; PTK2B AND PI3-KINASE.
    34. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    35. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    36. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-159; SER-162; SER-194 AND TYR-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    37. "Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm."
      Goh Y.M., Cinghu S., Hong E.T., Lee Y.S., Kim J.H., Jang J.W., Li Y.H., Chi X.Z., Lee K.S., Wee H., Ito Y., Oh B.C., Bae S.C.
      J. Biol. Chem. 285:10122-10129(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF RUNX3.
    38. "The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems."
      Collins M., Tremblay M., Chapman N., Curtiss M., Rothman P.B., Houtman J.C.
      J. Leukoc. Biol. 87:691-701(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PTK2B/PYK2 PHOSPHORYLATION.
    39. "RhoH modulates pre-TCR and TCR signalling by regulating LCK."
      Wang H., Zeng X., Fan Z., Lim B.
      Cell. Signal. 23:249-258(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF RHOH.
    40. "T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice."
      Wiede F., Shields B.J., Chew S.H., Kyparissoudis K., van Vliet C., Galic S., Tremblay M.L., Russell S.M., Godfrey D.I., Tiganis T.
      J. Clin. Invest. 121:4758-4774(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN TCR SIGNALING, PHOSPHORYLATION, DEPHOSPHORYLATION AT TYR-394 BY PTPN2.
    41. Cited for: FUNCTION IN PHOSPHORYLATION OF MAPT.
    42. "Feedback circuits monitor and adjust Basal lck-dependent events in T cell receptor signaling."
      Schoenborn J.R., Tan Y.X., Zhang C., Shokat K.M., Weiss A.
      Sci. Signal. 4:RA59-RA59(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    43. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    44. "Structure of the regulatory domains of the Src-family tyrosine kinase Lck."
      Eck M.J., Atweell S.K., Shoelson S.E., Harrison S.C.
      Nature 368:764-769(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 53-226.
    45. "The crystal structures of the SH2 domain of p56lck complexed with two phosphonopeptides suggest a gated peptide binding site."
      Mikol V., Baumann G., Keller T.H., Manning U.M., Zurini M.G.M.
      J. Mol. Biol. 246:344-355(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 127-221.
    46. "Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0-A and 1.8-A resolution."
      Tong L., Warren T.C., King J., Betageri R., Rose J., Jakes S.
      J. Mol. Biol. 256:601-610(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 122-226.
    47. "Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation."
      Yamaguchi H., Hendrickson W.A.
      Nature 384:484-489(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 231-501.
    48. "Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding."
      Tong L., Warren T.C., Lukas S., Schembri-King J., Betageri R., Proudfoot J.R., Jakes S.
      J. Biol. Chem. 273:20238-20242(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 119-226.

    Entry informationi

    Entry nameiLCK_HUMAN
    AccessioniPrimary (citable) accession number: P06239
    Secondary accession number(s): D3DPP8
    , P07100, Q12850, Q13152, Q5TDH8, Q5TDH9, Q7RTZ3, Q96DW4, Q9NYT8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 201 of the entry and version 6 of the sequence. [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. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3