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O54957 (LAT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Lat
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length242 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3

Subunit structure

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. Ref.4 Ref.8

Subcellular location

Cell membrane; Single-pass type III membrane protein. Note: Present in lipid rafts.

Tissue specificity

Expressed in T-cells and mast cells. Ref.3

Post-translational modification

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. Ref.5 Ref.7

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.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
Mast cell degranulation
   Cellular componentCell membrane
Membrane
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   PTMLipoprotein
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRas protein signal transduction

Inferred from sequence or structural similarity. Source: HGNC

calcium-mediated signaling

Inferred from sequence or structural similarity. Source: HGNC

cellular defense response

Traceable author statement PubMed 9729044. Source: MGI

gene expression

Inferred from mutant phenotype PubMed 16002666. Source: MGI

homeostasis of number of cells

Inferred from mutant phenotype PubMed 23793062. Source: MGI

immune response

Inferred from sequence or structural similarity. Source: HGNC

inflammatory response

Inferred from mutant phenotype PubMed 16002666. Source: MGI

integrin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: HGNC

intracellular signal transduction

Inferred from sequence or structural similarity. Source: HGNC

lymphocyte homeostasis

Inferred from mutant phenotype PubMed 23776175. Source: MGI

mast cell degranulation

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of signal transduction

Inferred from sequence or structural similarity. Source: GOC

regulation of T cell activation

Inferred from sequence or structural similarity. Source: HGNC

transmembrane receptor protein tyrosine kinase signaling pathway

Traceable author statement Ref.1. Source: MGI

   Cellular_componentCOP9 signalosome

Inferred from direct assay Ref.8. Source: UniProtKB

cell-cell junction

Inferred from direct assay PubMed 23793062. Source: MGI

immunological synapse

Inferred from direct assay PubMed 14635057. Source: MGI

integral component of plasma membrane

Traceable author statement PubMed 9729044. Source: MGI

mast cell granule

Inferred from electronic annotation. Source: GOC

   Molecular_functionSH3/SH2 adaptor activity

Inferred from sequence or structural similarity. Source: HGNC

protein binding

Inferred from physical interaction PubMed 21487392Ref.8. Source: IntAct

receptor signaling protein activity

Traceable author statement Ref.1. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Grb2Q606312EBI-6390034,EBI-1688
Plcg1Q620772EBI-6390034,EBI-300133

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 242242Linker for activation of T-cells family member 1
PRO_0000083326

Regions

Topological domain1 – 44Extracellular Potential
Transmembrane5 – 2824Helical; Signal-anchor for type III membrane protein; Potential
Topological domain29 – 242214Cytoplasmic Potential
Region136 – 1394Interaction with PLCG1 By similarity
Region175 – 1784Interaction with GRB2, GRAP2 and PIK3R1 By similarity
Region195 – 1984Interaction with GRB2, GRAP2 and PIK3R1 By similarity

Amino acid modifications

Modified residue401Phosphothreonine By similarity
Modified residue411Phosphoserine By similarity
Modified residue441Phosphoserine By similarity
Modified residue871Phosphoserine By similarity
Modified residue1041Phosphoserine By similarity
Modified residue1091Phosphoserine By similarity
Modified residue1751Phosphotyrosine By similarity
Modified residue1991Phosphoserine By similarity
Modified residue2151Phosphoserine By similarity
Modified residue2351Phosphotyrosine By similarity
Lipidation271S-palmitoyl cysteine Ref.5 Ref.7
Lipidation301S-palmitoyl cysteine Ref.5 Ref.7

Sequences

Sequence LengthMass (Da)Tools
O54957 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 6AC25F7AE6E1A5C1

FASTA24226,015
        10         20         30         40         50         60 
MEADALSPVG LGLLLLPFLV TLLAALCVRC RELPVSYDST STESLYPRSI LIKPPQITVP 

        70         80         90        100        110        120 
RTPAVSYPLV TSFPPLRQPD LLPIPRSPQP LGGSHRMPSS QQNSDDANSV ASYENQEPAC 

       130        140        150        160        170        180 
KNVDADEDED DYPNGYLVVL PDSSPAAVPV VSSAPVPSNP DLGDSAFSVE SCEDYVNVPE 

       190        200        210        220        230        240 
SEESAEASLD GSREYVNVSP EQQPVTRAEL ASVNSQEVED EGEEEGVDGE EAPDYENLQE 


LN 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF036907 mRNA. Translation: AAC40054.1.
BC013337 mRNA. Translation: AAH13337.1.
CCDSCCDS21825.1.
RefSeqNP_034819.1. NM_010689.2.
UniGeneMm.10280.

3D structure databases

ProteinModelPortalO54957.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201112. 1 interaction.
IntActO54957. 5 interactions.
MINTMINT-8202415.

PTM databases

PhosphoSiteO54957.

Proteomic databases

PRIDEO54957.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032997; ENSMUSP00000032997; ENSMUSG00000030742.
GeneID16797.
KEGGmmu:16797.
UCSCuc009jqx.1. mouse.

Organism-specific databases

CTD27040.
MGIMGI:1342293. Lat.

Phylogenomic databases

eggNOGNOG41822.
HOGENOMHOG000081810.
HOVERGENHBG018198.
InParanoidO54957.
KOK07362.
OMAGSHRMPS.
OrthoDBEOG7FJH24.
PhylomeDBO54957.
TreeFamTF337741.

Gene expression databases

ArrayExpressO54957.
BgeeO54957.
CleanExMM_LAT.
GenevestigatorO54957.

Family and domain databases

InterProIPR008359. Linker_for_activat_Tcells_prot.
[Graphical view]
PANTHERPTHR15586. PTHR15586. 1 hit.
PfamPF15234. LAT. 1 hit.
[Graphical view]
PRINTSPR01781. LATPROTEIN.
ProtoNetSearch...

Other

NextBio290670.
PROO54957.
SOURCESearch...

Entry information

Entry nameLAT_MOUSE
AccessionPrimary (citable) accession number: O54957
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

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