O54957 (LAT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Lat

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	242 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Adaptive immunity Immunity Mast cell degranulation
Cellular component	Cell membrane Membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras 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 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 mast cell degranulation Inferred from electronic annotation. Source: UniProtKB-KW 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_component	immunological synapse Inferred from direct assay PubMed 14635057. Source: MGI integral to plasma membrane Traceable author statement PubMed 9729044. Source: MGI signalosome Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	SH3/SH2 adaptor activity Inferred from sequence or structural similarity. Source: HGNC receptor signaling protein activity Traceable author statement Ref.1. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 242	242	Linker for activation of T-cells family member 1		PRO_0000083326
Regions
	Topological domain	1 – 4	4	Extracellular Potential
	Transmembrane	5 – 28	24	Helical; Signal-anchor for type III membrane protein; Potential
	Topological domain	29 – 242	214	Cytoplasmic Potential
	Region	136 – 139	4	Interaction with PLCG1 By similarity
	Region	175 – 178	4	Interaction with GRB2, GRAP2 and PIK3R1 By similarity
	Region	195 – 198	4	Interaction with GRB2, GRAP2 and PIK3R1 By similarity
Amino acid modifications
	Modified residue	40	1	Phosphothreonine By similarity
	Modified residue	41	1	Phosphoserine By similarity
	Modified residue	44	1	Phosphoserine By similarity
	Modified residue	87	1	Phosphoserine By similarity
	Modified residue	104	1	Phosphoserine By similarity
	Modified residue	109	1	Phosphoserine By similarity
	Modified residue	175	1	Phosphotyrosine By similarity
	Modified residue	199	1	Phosphoserine By similarity
	Modified residue	215	1	Phosphoserine By similarity
	Modified residue	235	1	Phosphotyrosine By similarity
	Lipidation	27	1	S-palmitoyl cysteine Ref.5 Ref.7
	Lipidation	30	1	S-palmitoyl cysteine Ref.5 Ref.7

Sequences

	Sequence		Length	Mass (Da)
	O54957 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 6AC25F7AE6E1A5C1	FASTA	242	26,015
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00119939.
RefSeq	NP_034819.1. NM_010689.2.
UniGene	Mm.10280.
3D structure databases
ProteinModelPortal	O54957.
ModBase	Search...
Protein-protein interaction databases
IntAct	O54957. 3 interactions.
MINT	MINT-8202415.
PTM databases
PhosphoSite	O54957.
Proteomic databases
PRIDE	O54957.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000032997; ENSMUSP00000032997; ENSMUSG00000030742.
GeneID	16797.
KEGG	mmu:16797.
UCSC	uc009jqx.1. mouse.
Organism-specific databases
CTD	27040.
MGI	MGI:1342293. Lat.
Phylogenomic databases
eggNOG	NOG41822.
HOGENOM	HOG000081810.
HOVERGEN	HBG018198.
InParanoid	O54957.
KO	K07362.
OMA	MESGEDY.
OrthoDB	EOG4Z8XXN.
Gene expression databases
ArrayExpress	O54957.
Bgee	O54957.
CleanEx	MM_LAT.
Genevestigator	O54957.
GermOnline	ENSMUSG00000030742. Mus musculus.
Family and domain databases
InterPro	IPR008359. Linker_for_activat_Tcells_prot. [Graphical view]
PRINTS	PR01781. LATPROTEIN.
ProtoNet	Search...
Other
NextBio	290670.
SOURCE	Search...

Entry information

Entry name

LAT_MOUSE

Accession

Primary (citable) accession number: O54957

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	June 1, 1998
Last modified:	May 29, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program