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O54957

- LAT_MOUSE

UniProt

O54957 - LAT_MOUSE

Protein

Linker for activation of T-cells family member 1

Gene

Lat

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Jun 1998)
      Previous versions | rss
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    Functioni

    Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development. Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules.1 Publication

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. receptor signaling protein activity Source: MGI
    3. SH3/SH2 adaptor activity Source: HGNC

    GO - Biological processi

    1. calcium-mediated signaling Source: HGNC
    2. cellular defense response Source: MGI
    3. gene expression Source: MGI
    4. homeostasis of number of cells Source: MGI
    5. immune response Source: HGNC
    6. inflammatory response Source: MGI
    7. integrin-mediated signaling pathway Source: HGNC
    8. intracellular signal transduction Source: HGNC
    9. lymphocyte homeostasis Source: MGI
    10. mast cell degranulation Source: UniProtKB-KW
    11. positive regulation of signal transduction Source: GOC
    12. Ras protein signal transduction Source: HGNC
    13. regulation of T cell activation Source: HGNC
    14. transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI

    Keywords - Biological processi

    Adaptive immunity, Immunity, Mast cell degranulation

    Enzyme and pathway databases

    ReactomeiREACT_188185. DAP12 signaling.
    REACT_188202. FCERI mediated Ca+2 mobilization.
    REACT_188204. Fc epsilon receptor (FCERI) signaling.
    REACT_188530. FCERI mediated MAPK activation.
    REACT_220092. GPVI-mediated activation cascade.
    REACT_225768. Generation of second messenger molecules.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Linker for activation of T-cells family member 1
    Alternative name(s):
    36 kDa phospho-tyrosine adapter protein
    Short name:
    pp36
    p36-38
    Gene namesi
    Name:Lat
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:1342293. Lat.

    Subcellular locationi

    GO - Cellular componenti

    1. cell-cell junction Source: MGI
    2. COP9 signalosome Source: UniProtKB
    3. immunological synapse Source: MGI
    4. integral component of plasma membrane Source: MGI
    5. mast cell granule Source: GOC

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 242242Linker for activation of T-cells family member 1PRO_0000083326Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi27 – 271S-palmitoyl cysteine2 Publications
    Lipidationi30 – 301S-palmitoyl cysteine2 Publications
    Modified residuei40 – 401PhosphothreonineBy similarity
    Modified residuei41 – 411PhosphoserineBy similarity
    Modified residuei44 – 441PhosphoserineBy similarity
    Modified residuei87 – 871PhosphoserineBy similarity
    Modified residuei104 – 1041PhosphoserineBy similarity
    Modified residuei109 – 1091PhosphoserineBy similarity
    Modified residuei175 – 1751PhosphotyrosineBy similarity
    Modified residuei199 – 1991PhosphoserineBy similarity
    Modified residuei215 – 2151PhosphoserineBy similarity
    Modified residuei235 – 2351PhosphotyrosineBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosines by ZAP70 upon TCR activation, or by SYK upon other immunoreceptor activation; which leads to the recruitment of multiple signaling molecules. Is one of the most prominently tyrosine-phosphorylated proteins detected following TCR engagement. May be dephosphorylated by PTPRJ. Phosphorylated by ITK leading to the recruitment of VAV1 to LAT-containing complexes By similarity.By similarity
    Palmitoylation of Cys-27 and Cys-30 is required for raft targeting and efficient phosphorylation.By similarity

    Keywords - PTMi

    Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    PRIDEiO54957.

    PTM databases

    PhosphoSiteiO54957.

    Expressioni

    Tissue specificityi

    Expressed in T-cells and mast cells.1 Publication

    Gene expression databases

    ArrayExpressiO54957.
    BgeeiO54957.
    CleanExiMM_LAT.
    GenevestigatoriO54957.

    Interactioni

    Subunit structurei

    When phosphorylated, interacts directly with the PIK3R1 subunit of phosphoinositide 3-kinase and the SH2 domains of GRB2, GRAP, GRAP2, PLCG1 and PLCG2. Interacts indirectly with CBL, SOS, VAV, and LCP2. Interacts with SHB and SKAP2. Interacts with FCGR1A By similarity. Interacts with CLNK. Interacts with GRB2, PLCG1 and THEMIS upon TCR activation in thymocytes.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Grb2Q606312EBI-6390034,EBI-1688
    Plcg1Q620772EBI-6390034,EBI-300133

    Protein-protein interaction databases

    BioGridi201112. 1 interaction.
    IntActiO54957. 5 interactions.
    MINTiMINT-8202415.

    Structurei

    3D structure databases

    ProteinModelPortaliO54957.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 44ExtracellularSequence Analysis
    Topological domaini29 – 242214CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei5 – 2824Helical; Signal-anchor for type III membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni136 – 1394Interaction with PLCG1By similarity
    Regioni175 – 1784Interaction with GRB2, GRAP2 and PIK3R1By similarity
    Regioni195 – 1984Interaction with GRB2, GRAP2 and PIK3R1By similarity

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG41822.
    HOGENOMiHOG000081810.
    HOVERGENiHBG018198.
    InParanoidiO54957.
    KOiK07362.
    OMAiGSHRMPS.
    OrthoDBiEOG7FJH24.
    PhylomeDBiO54957.
    TreeFamiTF337741.

    Family and domain databases

    InterProiIPR008359. Linker_for_activat_Tcells_prot.
    [Graphical view]
    PANTHERiPTHR15586. PTHR15586. 1 hit.
    PfamiPF15234. LAT. 1 hit.
    [Graphical view]
    PRINTSiPR01781. LATPROTEIN.

    Sequencei

    Sequence statusi: Complete.

    O54957-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEADALSPVG LGLLLLPFLV TLLAALCVRC RELPVSYDST STESLYPRSI    50
    LIKPPQITVP RTPAVSYPLV TSFPPLRQPD LLPIPRSPQP LGGSHRMPSS 100
    QQNSDDANSV ASYENQEPAC KNVDADEDED DYPNGYLVVL PDSSPAAVPV 150
    VSSAPVPSNP DLGDSAFSVE SCEDYVNVPE SEESAEASLD GSREYVNVSP 200
    EQQPVTRAEL ASVNSQEVED EGEEEGVDGE EAPDYENLQE LN 242
    Length:242
    Mass (Da):26,015
    Last modified:June 1, 1998 - v1
    Checksum:i6AC25F7AE6E1A5C1
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF036907 mRNA. Translation: AAC40054.1.
    BC013337 mRNA. Translation: AAH13337.1.
    CCDSiCCDS21825.1.
    RefSeqiNP_034819.1. NM_010689.2.
    UniGeneiMm.10280.

    Genome annotation databases

    EnsembliENSMUST00000032997; ENSMUSP00000032997; ENSMUSG00000030742.
    GeneIDi16797.
    KEGGimmu:16797.
    UCSCiuc009jqx.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF036907 mRNA. Translation: AAC40054.1 .
    BC013337 mRNA. Translation: AAH13337.1 .
    CCDSi CCDS21825.1.
    RefSeqi NP_034819.1. NM_010689.2.
    UniGenei Mm.10280.

    3D structure databases

    ProteinModelPortali O54957.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201112. 1 interaction.
    IntActi O54957. 5 interactions.
    MINTi MINT-8202415.

    PTM databases

    PhosphoSitei O54957.

    Proteomic databases

    PRIDEi O54957.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000032997 ; ENSMUSP00000032997 ; ENSMUSG00000030742 .
    GeneIDi 16797.
    KEGGi mmu:16797.
    UCSCi uc009jqx.1. mouse.

    Organism-specific databases

    CTDi 27040.
    MGIi MGI:1342293. Lat.

    Phylogenomic databases

    eggNOGi NOG41822.
    HOGENOMi HOG000081810.
    HOVERGENi HBG018198.
    InParanoidi O54957.
    KOi K07362.
    OMAi GSHRMPS.
    OrthoDBi EOG7FJH24.
    PhylomeDBi O54957.
    TreeFami TF337741.

    Enzyme and pathway databases

    Reactomei REACT_188185. DAP12 signaling.
    REACT_188202. FCERI mediated Ca+2 mobilization.
    REACT_188204. Fc epsilon receptor (FCERI) signaling.
    REACT_188530. FCERI mediated MAPK activation.
    REACT_220092. GPVI-mediated activation cascade.
    REACT_225768. Generation of second messenger molecules.

    Miscellaneous databases

    NextBioi 290670.
    PROi O54957.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O54957.
    Bgeei O54957.
    CleanExi MM_LAT.
    Genevestigatori O54957.

    Family and domain databases

    InterProi IPR008359. Linker_for_activat_Tcells_prot.
    [Graphical view ]
    PANTHERi PTHR15586. PTHR15586. 1 hit.
    Pfami PF15234. LAT. 1 hit.
    [Graphical view ]
    PRINTSi PR01781. LATPROTEIN.
    ProtoNeti Search...

    Publicationsi

    1. "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation."
      Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.
      Cell 92:83-92(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thymus.
    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].
      Strain: FVB/N.
      Tissue: Salivary gland.
    3. "LAT is essential for Fc(epsilon)RI-mediated mast cell activation."
      Saitoh S., Arudchandran R., Manetz T.S., Zhang W., Sommers C.L., Love P.E., Rivera J., Samelson L.E.
      Immunity 12:525-535(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MAST CELLS, TISSUE SPECIFICITY.
    4. "MIST functions through distinct domains in immunoreceptor signaling in the presence and absence of LAT."
      Goitsuka R., Tatsuno A., Ishiai M., Kurosaki T., Kitamura D.
      J. Biol. Chem. 276:36043-36050(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CLNK.
    5. "Glucocorticoids alter the lipid and protein composition of membrane rafts of a murine T cell hybridoma."
      Van Laethem F., Liang X., Andris F., Urbain J., Vandenbranden M., Ruysschaert J.-M., Resh M.D., Stulnig T.M., Leo O.
      J. Immunol. 170:2932-2939(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION.
    6. "LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways."
      Sommers C.L., Samelson L.E., Love P.E.
      Bioessays 26:61-67(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION IN T-CELLS.
    7. "Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells."
      Hundt M., Harada Y., De Giorgio L., Tanimura N., Zhang W., Altman A.
      J. Immunol. 183:1685-1694(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-27 AND CYS-30.
    8. "Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling."
      Wang D., Zheng M., Lei L., Ji J., Yao Y., Qiu Y., Ma L., Lou J., Ouyang C., Zhang X., He Y., Chi J., Wang L., Kuang Y., Wang J., Cao X., Lu L.
      Nat. Immunol. 13:560-568(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GRB2; PLCG1 AND THEMIS.
      Tissue: Thymocyte.

    Entry informationi

    Entry nameiLAT_MOUSE
    AccessioniPrimary (citable) accession number: O54957
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 2001
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 114 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Engagement of killer inhibitory receptors (KIR) disrupts the interaction of PLCG1 with LAT and blocks target cell-induced activation of PLC, maybe by inducing the dephosphorylation of LAT.By similarity

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

    External Data

    Dasty 3