LAT linker for activation of T cells [Homo sapiens (human)] - Gene

Summary

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Official Symbol: LATprovided by HGNC
Official Full Name: linker for activation of T cellsprovided by HGNC
Primary source: HGNC:18874
See related: Ensembl:ENSG00000213658; HPRD:03832; MIM:602354; Vega:OTTHUMG00000131761
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LAT1; pp36
Summary: The protein encoded by this gene is phosphorylated by ZAP-70/Syk protein tyrosine kinases following activation of the T-cell antigen receptor (TCR) signal transduction pathway. This transmembrane protein localizes to lipid rafts and acts as a docking site for SH2 domain-containing proteins. Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 16p11.2

Sequence :: Chromosome: 16; NC_000016.9 (28996147..29002104)

See LAT in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

LAT cleavage may act as a regulator of TCR-mediated activation of T-cells and not only as a transducer of cell death promoting stimuli.
Title: The membrane adaptor LAT is proteolytically cleaved following Fas engagement in a tyrosine phosphorylation-dependent fashion.
Expression of constitutively active Raf transgene enhances lymphoproliferation, indicating a role for the Ras-MAPK pathway in LAT-mediated autoimmune hyperproliferation.
Title: The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity.
Nef employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76
Title: HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulation.
Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2
Title: Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2.
the segment comprising residues 112-126 of human LAT is required for its interaction with Lck.
Title: A negatively charged domain of LAT mediates its interaction with the active form of Lck.
Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRalpha gene expression.
Title: Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression.
Activation of T cell antigen receptors resulted in the recruitment and phosphorylation of linker for activation of T cells (Lat) from subsynaptic vesicles. Studies of Lat mutants confirmed that recruitment preceded Lat phosphorylation.
Title: Pre-existing clusters of the adaptor Lat do not participate in early T cell signaling events.
Data show that MAL regulates membrane order and the distribution of microtubule and transport vesicle docking machinery at the IS and, by doing so, ensures correct protein sorting of Lck and LAT to the cSMAC.
Title: MAL protein controls protein sorting at the supramolecular activation cluster of human T lymphocytes.
PECAM-1-mediated inhibition of GPVI-dependent platelet responses result from recruitment of SHP-2-p85 complexes to tyrosine-phosphorylated PECAM-1, which diminishes the association of PI3K with activatory signaling molecules Gab1 and LAT
Title: Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells.
LAT recruits Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) following T-cell receptor ligation and Akt kinase phosphorylation in Jurkat cells, activating the phosphoinositide 3-hydroxykinase (PI3K) signaling cascade.
Title: Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells.

Submit: New GeneRIF Correction See all (42)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Lck is recuited to a virological synapse (VS) interface and is highly colocalized with gp120 when cells interact with gp120+ICAM-1 bilayers, leading to activate ZAP70, LAT, SLP76, and PLCgamma	PubMed
Nef, p27	nef	HIV-1 Nef inhibits expression of the LAT protein and its recruitment to SLP76-containing microclusters (MCs)	PubMed
	nef	HIV-1 Nef induces localization of LAT mainly from the plasma membrane to the intracellular membrane compartment	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_055202.1		PLCG1	BIND	PubMed	LAT interacts with an unspecified isoform of PLC-gamma-1.
NP_055202.1			BIND	PubMed	LAT interacts with the Grb2/Sos1 complex.
NP_055202.1			BIND	PubMed	LAT interacts with the Gads/SLP-76 complex.
O43561	P22681	CBL	HPRD	PubMed
O43561	Q9BZW8	CD244	HPRD	PubMed
O43561	P01730	CD4	HPRD	PubMed
O43561	P01732	CD8A	HPRD	PubMed
O43561	P12314	FCGR1A	HPRD	PubMed
O43561	P12318	FCGR2A	HPRD	PubMed
O43561	Q9UQC2	GAB2	HPRD	PubMed
O43561	Q13588	GRAP	HPRD	PubMed
O43561	O75791	GRAP2	HPRD	PubMed
O43561	P62993	GRB2	HPRD	PubMed
O43561	Q08881	ITK	HPRD	PubMed
O43561	P06239	LCK	HPRD	PubMed
O43561	Q13094	LCP2	HPRD	PubMed
O43561	Q92918	MAP4K1	HPRD	PubMed
O43561	P19174	PLCG1	HPRD	PubMed
O43561	P16885	PLCG2	HPRD	PubMed
O43561	P18031	PTPN1	HPRD	PubMed
O43561	Q12913	PTPRJ	HPRD	PubMed
O43561	P78314	SH3BP2	HPRD	PubMed
O43561	Q15464	SHB	HPRD	PubMed
O43561	Q13239	SLA	HPRD	PubMed
O43561	P43405	SYK	HPRD	PubMed
O43561	P15498	VAV1	HPRD	PubMed
O43561	P43403	ZAP70	HPRD	PubMed
BioGRID:117971	BioGRID:106715	ALB	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117971	BioGRID:107315	CBL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:107357	CD247	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:107354	CD3E	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:128126	CLYBL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:108503	FCGR1A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:108506	FCGR2A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:108810	FYN	BioGRID	PubMed	Biochemical Activity
BioGRID:117971	BioGRID:115181	GAB2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:115973	GRAP	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:117971	BioGRID:114799	GRAP2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:117971	BioGRID:109142	GRB2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:117971	BioGRID:109907	ITK	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:117971	BioGRID:110124	LCK	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Co-fractionation
BioGRID:117971	BioGRID:116354	MAP4K1	BioGRID	PubMed	Affinity Capture-Western; Co-fractionation
BioGRID:117971	BioGRID:111313	PIK3R1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:117971	BioGRID:111351	PLCG1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-fractionation; FRET; Reconstituted Complex
BioGRID:117971	BioGRID:111759	PTPRJ	BioGRID	PubMed	Biochemical Activity
BioGRID:117971	BioGRID:112350	SH3BP2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:117971	BioGRID:112358	SHB	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:112394	SLA	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:112537	SOS1	BioGRID	PubMed	Co-localization
BioGRID:117971	BioGRID:115546	SPRY1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:112717	SYK	BioGRID	PubMed	Biochemical Activity
BioGRID:117971	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117971	BioGRID:116078	USP19	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117971	BioGRID:113252	VAV1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:117971	BioGRID:113367	ZAP70	BioGRID	PubMed	Biochemical Activity; Co-localization
BioGRID:117971	BioGRID:116549	ZHX2	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Adaptive Immune System, organism-specific biosystem (from REACTOME)
Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
DAP12 interactions, organism-specific biosystem (from REACTOME)
DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
DAP12 signaling, organism-specific biosystem (from REACTOME)
DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
Fc epsilon RI signaling pathway, organism-specific biosystem (from KEGG)
Fc epsilon RI signaling pathway, organism-specific biosystemFc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation...
Fc epsilon RI signaling pathway, conserved biosystem (from KEGG)
Fc epsilon RI signaling pathway, conserved biosystemFc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation...
Fc gamma R-mediated phagocytosis, organism-specific biosystem (from KEGG)
Fc gamma R-mediated phagocytosis, organism-specific biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
Fc gamma R-mediated phagocytosis, conserved biosystem (from KEGG)
Fc gamma R-mediated phagocytosis, conserved biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem (from Pathway Interaction Database)
Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem
Fc-epsilon receptor I signaling in mast cells
GPVI-mediated activation cascade, organism-specific biosystem (from REACTOME)
GPVI-mediated activation cascade, organism-specific biosystemThe GPVI receptor is a complex of the GPVI protein with Fc epsilon R1 gamma (FcR). The Src family kinases Fyn and Lyn constitutively associate with the GPVI-FcR complex in platelets and initiate plat...
Generation of second messenger molecules, organism-specific biosystem (from REACTOME)
Generation of second messenger molecules, organism-specific biosystemIn addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have be...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
Signaling events mediated by PTP1B, organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by PTP1B, organism-specific biosystem
Signaling events mediated by PTP1B
T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
T cell receptor signaling pathway, conserved biosystem (from KEGG)
T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
TCR Signaling Pathway, organism-specific biosystem (from WikiPathways)
TCR Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
TCR signaling, organism-specific biosystem (from REACTOME)
TCR signaling, organism-specific biosystemThe TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen p...
TCR signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
TCR signaling in naive CD8+ T cells, organism-specific biosystem
TCR signaling in naive CD8+ T cells

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

L17705 (e-PCR)
- UniSTS:66091

SHGC-61115 (e-PCR)
- UniSTS:68505

Homology

Homologs of the LAT gene: The LAT gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
SH3/SH2 adaptor activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
Ras protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
T cell activation	TAS Traceable Author Statement more info	PubMed
T cell receptor signaling pathway	TAS Traceable Author Statement more info
blood coagulation	TAS Traceable Author Statement more info
calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
immune response	IDA Inferred from Direct Assay more info	PubMed
innate immune response	TAS Traceable Author Statement more info
integrin-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
mast cell degranulation	IEA Inferred from Electronic Annotation more info
platelet activation	TAS Traceable Author Statement more info
regulation of T cell activation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
immunological synapse	IDA Inferred from Direct Assay more info	PubMed
integral to membrane	IDA Inferred from Direct Assay more info	PubMed
membrane raft	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
signalosome	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: linker for activation of T-cells family member 1

Names: linker for activation of T-cells family member 1; p36-38; 36 kDa phospho-tyrosine adapter protein; 36 kDa phospho-tyrosine adaptor protein; linker for activation of T cells, transmembrane adaptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001014987.1 → NP_001014987.1 linker for activation of T-cells family member 1 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (b) is shorter at the N-terminus compared to isoform d.

Source sequence(s)

AJ223280, BC011563, BI769296

Consensus CDS

CCDS32425.1

UniProtKB/Swiss-Prot

O43561

Related

ENSP00000378841, OTTHUMP00000254830, ENST00000395456, OTTHUMT00000433233
NM_001014988.1 → NP_001014988.1 linker for activation of T-cells family member 1 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence and uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 4. The resulting isoform (c) is shorter at the N- terminus and lacks an internal aa compared to isoform d.

Source sequence(s)

AJ223280, BC011563, BI769296, BI911769

Consensus CDS

CCDS45455.1

UniProtKB/TrEMBL

G5E9K3

UniProtKB/Swiss-Prot

O43561
NM_001014989.1 → NP_001014989.2 linker for activation of T-cells family member 1 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) encodes the longest isoform (d).

Source sequence(s)

BC011563

Consensus CDS

CCDS53999.1

UniProtKB/TrEMBL

B7WPI0

UniProtKB/Swiss-Prot

O43561

Related

ENSP00000378845, OTTHUMP00000162564, ENST00000395461, OTTHUMT00000254689
NM_014387.3 → NP_055202.1 linker for activation of T-cells family member 1 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR and coding sequence and contains an internal in-frame segment compared to variant 4. The resulting isoform (a) is shorter at the N-terminus and contains an internal segment compared to isoform d.

Source sequence(s)

AF036906, AJ223280, BC011563, BI769296

Consensus CDS

CCDS10647.1

UniProtKB/Swiss-Prot

O43561

Related

ENSP00000354119, OTTHUMP00000162563, ENST00000360872, OTTHUMT00000254688

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p10 Primary Assembly

Range

28996147..29002104

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

26864020..26869977

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018927.1 Alternate CHM1_1.0

Range

29892256..29898213

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01045680.1 (4722..10679)	None
genomic	AC109460.3 (117378..123335)	None
genomic	AMYH01007480.1 (43632..49589)	None
genomic	CH471267.1	EAW52024.1
		EAW52025.1
		EAW52026.1
		EAW52027.1
		EAW52028.1
		EAW52029.1
		EAW52030.1
		EAW52031.1
mRNA	AF036905.1	AAC39636.1
mRNA	AF036906.1	AAC39637.1
mRNA	AJ223280.1	CAA11218.1
mRNA	AK093815.1	None
mRNA	AK307342.1	None
mRNA	BC011563.1	AAH11563.1
mRNA	BI769296.1	None
mRNA	BI911769.1	None
mRNA	FN432831.1	CBA11532.1
mRNA	FN432832.1	CBA11533.1
mRNA	FN432833.1	CBA11534.1
mRNA	FN432834.1	CBA11535.1