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Q01621

- LCK_RAT

UniProt

Q01621 - LCK_RAT

Protein

Proto-oncogene tyrosine-protein kinase LCK

Gene

Lck

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 3 (24 Mar 2009)
      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 By similarity. Interacts with UNC119; this interaction plays a crucial role in activation of LCK By similarity.By similarity

    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 By similarity.By similarity

    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: RGD
    2. ATP binding Source: UniProtKB-KW
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    4. protein complex binding Source: RGD
    5. protein tyrosine kinase activity Source: RGD

    GO - Biological processi

    1. aging Source: RGD
    2. apoptotic process Source: RGD
    3. B cell receptor signaling pathway Source: Ensembl
    4. peptidyl-tyrosine phosphorylation Source: RGD
    5. positive regulation of gamma-delta T cell differentiation Source: Ensembl
    6. positive regulation of gene expression Source: Ensembl
    7. positive regulation of tyrosine phosphorylation of Stat5 protein Source: Ensembl
    8. positive regulation of uterine smooth muscle contraction Source: RGD
    9. protein autophosphorylation Source: RGD
    10. regulation of T cell receptor signaling pathway Source: Ensembl
    11. release of sequestered calcium ion into cytosol Source: Ensembl
    12. response to hydrogen peroxide Source: RGD
    13. response to mechanical stimulus Source: RGD
    14. response to metal ion Source: RGD
    15. response to zinc ion Source: RGD

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_195025. Signaling by SCF-KIT.
    REACT_197451. Regulation of KIT signaling.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_212418. DAP12 signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Proto-oncogene tyrosine-protein kinase LCK (EC:2.7.10.2)
    Alternative name(s):
    Lymphocyte cell-specific protein-tyrosine kinase
    p56-LCK
    Gene namesi
    Name:Lck
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 5

    Organism-specific databases

    RGDi2994. Lck.

    Subcellular locationi

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

    GO - Cellular componenti

    1. endocytic vesicle Source: RGD
    2. immunological synapse Source: Ensembl
    3. membrane raft Source: RGD
    4. plasma membrane Source: RGD

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Proviral insertion upstream of the Lck gene causes overexpression, leading to the development of thymic lymphoma.

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 509508Proto-oncogene tyrosine-protein kinase LCKPRO_0000088126Add
    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 – 1021PhosphoserineBy similarity
    Modified residuei159 – 1591PhosphothreonineBy similarity
    Modified residuei162 – 1621PhosphoserineBy similarity
    Modified residuei194 – 1941PhosphoserineBy similarity
    Modified residuei394 – 3941Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei505 – 5051Phosphotyrosine; by CSKBy similarity

    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-cells differentiation By similarity.By similarity
    Myristoylation is required prior to palmitoylation.By similarity
    Palmitoylation regulates subcellular location.By similarity

    Keywords - PTMi

    Lipoprotein, Myristate, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiQ01621.

    PTM databases

    PhosphoSiteiQ01621.

    Expressioni

    Gene expression databases

    ArrayExpressiQ01621.
    GenevestigatoriQ01621.

    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. 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 phosphorylations in presence of a functional ZAP70 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000012936.

    Structurei

    3D structure databases

    ProteinModelPortaliQ01621.
    SMRiQ01621. Positions 7-35, 64-509.
    ModBaseiSearch...
    MobiDBiSearch...

    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 PTPRHBy similarityAdd
    BLAST

    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

    SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00620000087866.
    HOGENOMiHOG000233858.
    HOVERGENiHBG008761.
    InParanoidiQ01621.
    KOiK05856.
    OMAiDIHESCS.
    OrthoDBiEOG7GTT2V.
    PhylomeDBiQ01621.
    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]

    Sequencei

    Sequence statusi: Complete.

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

    Q01621-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGCVCSSNPE DDWMENIDVC ENCHYPIVPL DSKSTLPIRT GSEVRDPLVT    50
    YEGSLPPASP LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA 100
    QSLTTGQEGF IPFNFVAKAN SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS 150
    FLIRESESTA GSFSLSVRDF DQNQGEVVKH YKIRNLDNGG FYISPRITFP 200
    GLHDLVRHYT NASDGLCTKL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER 250
    LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHPRL 300
    VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLNVNK LLDMAAQIAE 350
    GMAFIEEQNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA 400
    KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI 450
    QNLEKGYRMV RPDNCPEELY HLMMLCWKER PEDRPTFDYL RSVLDDFFTA 500
    TEGQYQPQP 509
    Length:509
    Mass (Da):57,890
    Last modified:March 24, 2009 - v3
    Checksum:iB23F3F4BEF3D6654
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CH473968 Genomic DNA. Translation: EDL80546.1.
    BC160881 mRNA. Translation: AAI60881.1.
    Z15029 Genomic DNA. Translation: CAA78748.1.
    PIRiI58370. S24780.
    RefSeqiNP_001094179.1. NM_001100709.1.
    XP_006238995.1. XM_006238933.1.
    UniGeneiRn.22791.

    Genome annotation databases

    EnsembliENSRNOT00000012936; ENSRNOP00000012936; ENSRNOG00000009705.
    GeneIDi313050.
    KEGGirno:313050.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CH473968 Genomic DNA. Translation: EDL80546.1 .
    BC160881 mRNA. Translation: AAI60881.1 .
    Z15029 Genomic DNA. Translation: CAA78748.1 .
    PIRi I58370. S24780.
    RefSeqi NP_001094179.1. NM_001100709.1.
    XP_006238995.1. XM_006238933.1.
    UniGenei Rn.22791.

    3D structure databases

    ProteinModelPortali Q01621.
    SMRi Q01621. Positions 7-35, 64-509.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000012936.

    PTM databases

    PhosphoSitei Q01621.

    Proteomic databases

    PaxDbi Q01621.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000012936 ; ENSRNOP00000012936 ; ENSRNOG00000009705 .
    GeneIDi 313050.
    KEGGi rno:313050.

    Organism-specific databases

    CTDi 3932.
    RGDi 2994. Lck.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00620000087866.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    InParanoidi Q01621.
    KOi K05856.
    OMAi DIHESCS.
    OrthoDBi EOG7GTT2V.
    PhylomeDBi Q01621.
    TreeFami TF351634.

    Enzyme and pathway databases

    Reactomei REACT_195025. Signaling by SCF-KIT.
    REACT_197451. Regulation of KIT signaling.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_212418. DAP12 signaling.

    Miscellaneous databases

    NextBioi 665540.

    Gene expression databases

    ArrayExpressi Q01621.
    Genevestigatori Q01621.

    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. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    2. "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].
      Tissue: Thymus.
    3. "Frequent activation of the lck gene by promoter insertion and aberrant splicing in murine leukemia virus-induced rat lymphomas."
      Shin S., Steffen D.L.
      Oncogene 8:141-149(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
      Strain: Fischer.

    Entry informationi

    Entry nameiLCK_RAT
    AccessioniPrimary (citable) accession number: Q01621
    Secondary accession number(s): B1H265
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: March 24, 2009
    Last modified: October 1, 2014
    This is version 123 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3