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P42682

- TXK_MOUSE

UniProt

P42682 - TXK_MOUSE

Protein

Tyrosine-protein kinase TXK

Gene

Txk

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.4 Publications

    Catalytic activityi

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

    Enzyme regulationi

    Activated by phosphorylation by FYN.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei299 – 2991ATPPROSITE-ProRule annotation
    Active sitei390 – 3901Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi277 – 2859ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. DNA binding Source: UniProtKB-KW
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. activation of phospholipase C activity Source: UniProtKB
    2. adaptive immune response Source: UniProtKB
    3. cytokine production Source: UniProtKB
    4. interferon-gamma production Source: MGI
    5. interleukin-4 production Source: MGI
    6. NK T cell differentiation Source: MGI
    7. regulation of transcription, DNA-templated Source: UniProtKB-KW
    8. T cell receptor signaling pathway Source: UniProtKB
    9. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Adaptive immunity, Immunity, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, DNA-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 3474.
    ReactomeiREACT_188202. FCERI mediated Ca+2 mobilization.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase TXK (EC:2.7.10.2)
    Alternative name(s):
    PTK-RL-18
    Resting lymphocyte kinase
    Gene namesi
    Name:Txk
    Synonyms:Rlk
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:102960. Txk.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Cell membrane; Peripheral membrane protein
    Note: Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. Translocates into the nucleus and enhances IFN-gamma gene transcription in T-cells.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi16 – 183CCC → SLA: Reduces palmitoylation and leads to nuclear localization. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 527527Tyrosine-protein kinase TXKPRO_0000088176Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei91 – 911Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei420 – 4201Phosphotyrosine; by FYN and autocatalysis2 Publications

    Post-translational modificationi

    Phosphorylated at Tyr-420 by FYN. Autophosphorylation at Tyr-91 is critical for the activation of TXK, leading to the up-regulation of IFN-gamma gene transcription.By similarity
    The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location.1 Publication

    Keywords - PTMi

    Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiP42682.
    PRIDEiP42682.

    PTM databases

    PhosphoSiteiP42682.

    Expressioni

    Tissue specificityi

    Expressed in early thymocytes, T-cells and mast cells.

    Gene expression databases

    ArrayExpressiP42682.
    BgeeiP42682.
    CleanExiMM_TXK.
    GenevestigatoriP42682.

    Interactioni

    Subunit structurei

    Interacts with PARP1 and EEF1A1 By similarity. Interacts with SH2D2A.By similarity2 Publications

    Protein-protein interaction databases

    IntActiP42682. 1 interaction.
    MINTiMINT-4138781.
    STRINGi10090.ENSMUSP00000109234.

    Structurei

    3D structure databases

    ProteinModelPortaliP42682.
    SMRiP42682. Positions 87-526.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini82 – 14261SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini150 – 24697SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini271 – 527257Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi14 – 207Poly-Cys

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC 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.
    GeneTreeiENSGT00640000091251.
    HOGENOMiHOG000233859.
    HOVERGENiHBG008761.
    InParanoidiP42682.
    KOiK08016.
    OrthoDBiEOG7KM5SC.
    PhylomeDBiP42682.
    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.
    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 (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative initiation. Align

    Isoform 1 (identifier: P42682-1) [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

    MILSSYSSFQ SVLCCCCCRC SVQKRQVRTQ ISLSREEELS EKHSQRQRPW    50
    FAKLMGKTQS NRGGVQPSKR KPLPPLPQEP PDERIQVKAL YDFLPREPGN 100
    LALKRAEEYL ILERCDPHWW KARDRFGNEG LIPSNYVTEN RLANLEIYEW 150
    YHKNITRNQT ERLLRQEAKE GAFIVRDSRH LGSYTISVFT RARRHTQSSI 200
    KHYQIKKNDS GQWYITERHL FPSVPELIQY HQYNAAGLIS RLRYPIGLLG 250
    SCLPATSGFS YEKWEIDPSE LAFVKEIGSG QFGVVHLGEW RAHIPVAIKA 300
    INEGSMSEED FIEEAKVMMK LSHSRLVQLY GVCIQQKPLY IVTEFMENGC 350
    LLDYLRERKG QLQKALLLSM CQDICEGMAY LERSCYIHRD LAARNCLVSS 400
    ACVVKISDFG MARYVLDDEY ISSSGAKFPV KWCPPEVFHF NKYSSKSDVW 450
    SFGVLMWEVF TEGKMPFENK SNLQVVEAIS QGFRLYRPHL APMTIYRVMY 500
    SCWHESPKGR PTFAELLQVL TEIAETW 527
    Length:527
    Mass (Da):61,108
    Last modified:November 1, 1995 - v1
    Checksum:iD3A32C09B3A201FA
    GO
    Isoform 2 (identifier: P42682-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-54: Missing.

    Note: Produced by alternative initiation at Met-55 of isoform 1.

    Show »
    Length:473
    Mass (Da):54,741
    Checksum:iAA6C96FBDB8C5AF9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti3 – 42LS → SF in BAA07900. 1 PublicationCurated
    Sequence conflicti6 – 61Y → D in BAA07900. 1 PublicationCurated
    Sequence conflicti272 – 2721A → T in BAA07900. 1 PublicationCurated
    Sequence conflicti497 – 4971R → S in BAA07900. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 5454Missing in isoform 2. CuratedVSP_041923Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U16145 mRNA. Translation: AAC52264.1.
    U19607 mRNA. Translation: AAA86698.1.
    L35268 mRNA. Translation: AAA67039.1.
    D43964 mRNA. Translation: BAA07900.1.
    CCDSiCCDS51514.1. [P42682-1]
    PIRiI49133.
    RefSeqiNP_001116226.1. NM_001122754.2. [P42682-1]
    NP_001276424.1. NM_001289495.1. [P42682-2]
    UniGeneiMm.3264.

    Genome annotation databases

    EnsembliENSMUST00000113604; ENSMUSP00000109234; ENSMUSG00000054892. [P42682-1]
    GeneIDi22165.
    KEGGimmu:22165.
    UCSCiuc008xrx.2. mouse. [P42682-1]

    Keywords - Coding sequence diversityi

    Alternative initiation

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U16145 mRNA. Translation: AAC52264.1 .
    U19607 mRNA. Translation: AAA86698.1 .
    L35268 mRNA. Translation: AAA67039.1 .
    D43964 mRNA. Translation: BAA07900.1 .
    CCDSi CCDS51514.1. [P42682-1 ]
    PIRi I49133.
    RefSeqi NP_001116226.1. NM_001122754.2. [P42682-1 ]
    NP_001276424.1. NM_001289495.1. [P42682-2 ]
    UniGenei Mm.3264.

    3D structure databases

    ProteinModelPortali P42682.
    SMRi P42682. Positions 87-526.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P42682. 1 interaction.
    MINTi MINT-4138781.
    STRINGi 10090.ENSMUSP00000109234.

    PTM databases

    PhosphoSitei P42682.

    Proteomic databases

    PaxDbi P42682.
    PRIDEi P42682.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000113604 ; ENSMUSP00000109234 ; ENSMUSG00000054892 . [P42682-1 ]
    GeneIDi 22165.
    KEGGi mmu:22165.
    UCSCi uc008xrx.2. mouse. [P42682-1 ]

    Organism-specific databases

    CTDi 7294.
    MGIi MGI:102960. Txk.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00640000091251.
    HOGENOMi HOG000233859.
    HOVERGENi HBG008761.
    InParanoidi P42682.
    KOi K08016.
    OrthoDBi EOG7KM5SC.
    PhylomeDBi P42682.
    TreeFami TF351634.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 3474.
    Reactomei REACT_188202. FCERI mediated Ca+2 mobilization.

    Miscellaneous databases

    NextBioi 302102.
    PROi P42682.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P42682.
    Bgeei P42682.
    CleanExi MM_TXK.
    Genevestigatori P42682.

    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.
    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. "The murine form of TXK, a novel TEC kinase expressed in thymus maps to chromosome 5."
      Haire R.N., Litman G.W.
      Mamm. Genome 6:476-480(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6J.
      Tissue: Thymus.
    2. "Murine txk: a protein tyrosine kinase gene regulated by T cell activation."
      Sommers C.L., Huang K., Shores E.W., Grinberg A., Charlick D.A., Kozak C.A., Love P.E.
      Oncogene 11:245-251(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: FVB/N.
      Tissue: Thymus.
    3. "Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage."
      Hu Q., Davidson D., Schwartzberg P.L., Macchiarini F., Lenardo M.J., Bluestone J.A., Matis L.A.
      J. Biol. Chem. 270:1928-1934(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thymus.
    4. Higashitsuji H., Nonoguchi K., Arii S., Furutani M., Kaneko Y., Nakayama H., Fujita J.
      Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6.
      Tissue: Liver.
    5. "RIBP, a novel Rlk/Txk- and Itk-binding adaptor protein that regulates T cell activation."
      Rajagopal K., Sommers C.L., Decker D.C., Mitchell E.O., Korthauer U., Sperling A.I., Kozak C.A., Love P.E., Bluestone J.A.
      J. Exp. Med. 190:1657-1668(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SH2D2A.
    6. "A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection."
      Sommers C.L., Rabin R.L., Grinberg A., Tsay H.C., Farber J., Love P.E.
      J. Exp. Med. 190:1427-1438(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases."
      Debnath J., Chamorro M., Czar M.J., Schaeffer E.M., Lenardo M.J., Varmus H.E., Schwartzberg P.L.
      Mol. Cell. Biol. 19:1498-1507(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE INITIATION (ISOFORM 2), SUBCELLULAR LOCATION, PALMITOYLATION, MUTAGENESIS OF 16-CYS--CYS-18, ENZYME REGULATION.
    8. "Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells."
      Schneider H., Guerette B., Guntermann C., Rudd C.E.
      J. Biol. Chem. 275:3835-3840(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF LCP2.
    9. "Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk."
      Chamorro M., Czar M.J., Debnath J., Cheng G., Lenardo M.J., Varmus H.E., Schwartzberg P.L.
      BMC Immunol. 2:3-3(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FYN, PHOSPHORYLATION AT TYR-420, SUBCELLULAR LOCATION.
    10. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
      Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
      J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-91 AND TYR-420, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Mast cell.
    11. "Selective expression rather than specific function of Txk and Itk regulate Th1 and Th2 responses."
      Sahu N., Venegas A.M., Jankovic D., Mitzner W., Gomez-Rodriguez J., Cannons J.L., Sommers C., Love P., Sher A., Schwartzberg P.L., August A.
      J. Immunol. 181:6125-6131(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk."
      Readinger J.A., Mueller K.L., Venegas A.M., Horai R., Schwartzberg P.L.
      Immunol. Rev. 228:93-114(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.

    Entry informationi

    Entry nameiTXK_MOUSE
    AccessioniPrimary (citable) accession number: P42682
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 135 of the entry and version 1 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3