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Protein

Linker for activation of T-cells family member 1

Gene

Lat

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

  • protein kinase binding Source: MGI
  • receptor signaling protein activity Source: MGI
  • SH3/SH2 adaptor activity Source: HGNC

GO - Biological processi

  • calcium-mediated signaling Source: HGNC
  • cellular defense response Source: MGI
  • gene expression Source: MGI
  • homeostasis of number of cells Source: MGI
  • immune response Source: HGNC
  • inflammatory response Source: MGI
  • integrin-mediated signaling pathway Source: HGNC
  • intracellular signal transduction Source: HGNC
  • lymphocyte homeostasis Source: MGI
  • mast cell degranulation Source: UniProtKB-KW
  • positive regulation of signal transduction Source: MGI
  • Ras protein signal transduction Source: HGNC
  • regulation of T cell activation Source: HGNC
  • 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_301936. DAP12 signaling.
REACT_314186. FCERI mediated MAPK activation.
REACT_334692. Generation of second messenger molecules.
REACT_337915. GPVI-mediated activation cascade.
REACT_345245. Fc epsilon receptor (FCERI) signaling.
REACT_348733. FCERI mediated Ca+2 mobilization.

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 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1342293. Lat.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 44ExtracellularSequence Analysis
Transmembranei5 – 2824Helical; Signal-anchor for type III membrane proteinSequence AnalysisAdd
BLAST
Topological domaini29 – 242214CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • COP9 signalosome Source: UniProtKB
  • immunological synapse Source: MGI
  • integral component of membrane Source: MGI
  • integral component of plasma membrane Source: MGI
  • 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 1PRO_0000083326Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi27 – 271S-palmitoyl cysteine1 Publication
Lipidationi30 – 301S-palmitoyl cysteine1 Publication
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

MaxQBiO54957.
PRIDEiO54957.

PTM databases

PhosphoSiteiO54957.

Expressioni

Tissue specificityi

Expressed in T-cells and mast cells.1 Publication

Gene expression databases

BgeeiO54957.
CleanExiMM_LAT.
ExpressionAtlasiO54957. baseline and differential.
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...

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.
OMAiLCVRCRE.
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

        10         20         30         40         50
MEADALSPVG LGLLLLPFLV TLLAALCVRC RELPVSYDST STESLYPRSI
60 70 80 90 100
LIKPPQITVP RTPAVSYPLV TSFPPLRQPD LLPIPRSPQP LGGSHRMPSS
110 120 130 140 150
QQNSDDANSV ASYENQEPAC KNVDADEDED DYPNGYLVVL PDSSPAAVPV
160 170 180 190 200
VSSAPVPSNP DLGDSAFSVE SCEDYVNVPE SEESAEASLD GSREYVNVSP
210 220 230 240
EQQPVTRAEL ASVNSQEVED EGEEEGVDGE EAPDYENLQE LN
Length:242
Mass (Da):26,015
Last modified:June 1, 1998 - v1
Checksum:i6AC25F7AE6E1A5C1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
AF036907 mRNA. Translation: AAC40054.1.
BC013337 mRNA. Translation: AAH13337.1.
CCDSiCCDS21825.1.
RefSeqiNP_034819.1. NM_010689.2.
UniGeneiMm.10280.

3D structure databases

ProteinModelPortaliO54957.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiO54957.

Proteomic databases

MaxQBiO54957.
PRIDEiO54957.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi27040.
MGIiMGI:1342293. Lat.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiREACT_301936. DAP12 signaling.
REACT_314186. FCERI mediated MAPK activation.
REACT_334692. Generation of second messenger molecules.
REACT_337915. GPVI-mediated activation cascade.
REACT_345245. Fc epsilon receptor (FCERI) signaling.
REACT_348733. FCERI mediated Ca+2 mobilization.

Miscellaneous databases

NextBioi290670.
PROiO54957.
SOURCEiSearch...

Gene expression databases

BgeeiO54957.
CleanExiMM_LAT.
ExpressionAtlasiO54957. baseline and differential.
GenevestigatoriO54957.

Family and domain databases

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

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: April 1, 2015
This is version 119 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.