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O54957

- LAT_MOUSE

UniProt

O54957 - LAT_MOUSE

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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

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

GO - Biological processi

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

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 44Extracellular Reviewed prediction
Transmembranei5 – 2824Helical; Signal-anchor for type III membrane protein; Reviewed prediction
Add
BLAST
Topological domaini29 – 242214Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

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

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 1
PRO_0000083326Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi27 – 271S-palmitoyl cysteine2 Publications
Lipidationi30 – 301S-palmitoyl cysteine2 Publications
Modified residuei40 – 401Phosphothreonine By similarity
Modified residuei41 – 411Phosphoserine By similarity
Modified residuei44 – 441Phosphoserine By similarity
Modified residuei87 – 871Phosphoserine By similarity
Modified residuei104 – 1041Phosphoserine By similarity
Modified residuei109 – 1091Phosphoserine By similarity
Modified residuei175 – 1751Phosphotyrosine By similarity
Modified residuei199 – 1991Phosphoserine By similarity
Modified residuei215 – 2151Phosphoserine By similarity
Modified residuei235 – 2351Phosphotyrosine By 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.
Palmitoylation of Cys-27 and Cys-30 is required for raft targeting and efficient phosphorylation By similarity.2 Publications

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.2 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.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni136 – 1394Interaction with PLCG1 By similarity
Regioni175 – 1784Interaction with GRB2, GRAP2 and PIK3R1 By similarity
Regioni195 – 1984Interaction with GRB2, GRAP2 and PIK3R1 By 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...

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 113 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

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