LAT: Linker for Activation of T Cells
A critical adaptor protein in T-cell receptor signaling and immune regulation
Gene Information Card
| Symbol | LAT |
|---|---|
| Full Name | Linker for activation of T cells |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 27040 ncbi.nlm.nih.gov/gene/27040 |
| Ensembl ID | ENSG00000167658 |
| UniProt ID | O43561 |
| OMIM ID | 602354 |
| HGNC ID | 6514 |
| Aliases | p36-38, LAT1, pp36 |
Description
LAT (Linker for activation of T cells) encodes a transmembrane adaptor protein that is essential for T-cell receptor (TCR) signaling. Upon TCR engagement, LAT is phosphorylated by ZAP-70 and recruits multiple downstream signaling molecules, including GRB2, PLCG1, and GADS, leading to calcium mobilization, MAPK activation, and cytoskeletal reorganization. LAT is critical for T-cell development, activation, and homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune lymphoproliferative syndrome (ALPS) type IV | Loss-of-function mutations in LAT impair TCR signaling, leading to defective apoptosis and accumulation of autoreactive T cells. | OMIM #602354; PMID: 19210544 |
| Severe combined immunodeficiency (SCID) with T-cell lymphopenia | Homozygous missense mutations in LAT disrupt T-cell development and function. | OMIM #602354; PMID: 19864675 |
| Rheumatoid arthritis (susceptibility) | Polymorphisms in LAT are associated with altered immune signaling and increased risk. | GWAS catalog; PMID: 24390342 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thymus | 45.2 | High |
| Spleen | 32.1 | High |
| Lymph node | 28.7 | High |
| Peripheral blood mononuclear cells | 22.5 | Medium |
| Lung | 8.3 | Low |
| Small intestine | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 58.4 | High expression; model for TCR signaling |
| Raji (Burkitt lymphoma) | 3.2 | Low expression; B-cell line |
| HEK293 (embryonic kidney) | 1.5 | Very low; not immune lineage |
| THP-1 (monocytic leukemia) | 12.0 | Moderate; myeloid lineage |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Leu76Phe) | Missense | Rare | Loss of function; impairs LAT phosphorylation and downstream signaling |
| c.301G>A (p.Gly101Ser) | Missense | Rare | Loss of function; associated with SCID |
| c.350T>C (p.Ile117Thr) | Missense | Rare | Dominant-negative effect; linked to ALPS type IV |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Leu76Phe, p.Gly101Ser) impair LAT phosphorylation and recruitment of signaling molecules, leading to defective T-cell activation and immunodeficiency.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in LAT.
Dominant Negative (DN)
p.Ile117Thr mutation acts as dominant-negative, disrupting wild-type LAT function and causing autoimmune lymphoproliferative syndrome.
View complete mutation data：
Gene Ontology (GO)
| • signal transduction (GO:0007165) | • plasma membrane (GO:0005886) |
| • signal transducer activity (GO:0004871) | • intracellular signal transduction (GO:0035556) |
| • T cell receptor signaling pathway (GO:0050852) | • cytoplasm (GO:0005737) |
Pathways
• T-cell receptor signaling pathway (KEGG hsa04660)
• Fc epsilon RI signaling pathway (KEGG hsa04664)
• Natural killer cell mediated cytotoxicity (KEGG hsa04650)
• Adaptive immune system (Reactome R-HSA-1280218)
Protein Summary
LAT is a 36-38 kDa transmembrane adaptor protein predominantly expressed in T cells, NK cells, and mast cells. It contains a short extracellular domain, a transmembrane region, and a long cytoplasmic tail with multiple tyrosine phosphorylation sites. Upon TCR activation, LAT is phosphorylated by ZAP-70 and serves as a docking platform for SH2 domain-containing proteins, including GRB2, PLCG1, GADS, and SLP-76. This assembly is essential for calcium flux, MAPK activation, and cytoskeletal changes required for T-cell proliferation and effector functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LATS2 Knockout HEK293 Cell Line | EDJ-KQ1084 | Human | 26524 | Details Get a Quote |
| LAT Knockout HEK293 Cell Line | EDJ-KQ1209 | Human | 27040 | Details Get a Quote |
| LATS1 Knockout HEK293 Cell Line | EDJ-KQ1375 | Human | 9113 | Details Get a Quote |
| PLAT Knockout HEK293 Cell Line | EDJ-KQ1465 | Human | 5327 | Details Get a Quote |
| DLAT Knockout HEK293 Cell Line | EDJ-KQ3308 | Human | 1737 | Details Get a Quote |
| LAT2 Knockout HEK293 Cell Line | EDJ-KQ6012 | Human | 7462 | Details Get a Quote |
| LCLAT1 Knockout HEK293 Cell Line | EDJ-KQ11734 | Human | 253558 | Details Get a Quote |
| LAT Knockout HeLa Cell Line | EDJ-KQ19172 | Human | 27040 | Details Get a Quote |
| PLAT Knockout A-549 Cell Line | EDJ-KQ21030 | Human | 5327 | Details Get a Quote |
| PLAT Knockout HCT 116 Cell Line | EDJ-KQ21031 | Human | 5327 | Details Get a Quote |
| PLAT Knockout HeLa Cell Line | EDJ-KQ21032 | Human | 5327 | Details Get a Quote |
| LCLAT1 Knockout A-549 Cell Line | EDJ-KQ40103 | Human | 253558 | Details Get a Quote |
| LCLAT1 Knockout HeLa Cell Line | EDJ-KQ40105 | Human | 253558 | Details Get a Quote |
| LATS1 Knockout A-549 Cell Line | EDJ-KQ19530 | Human | 9113 | Details Get a Quote |
| LATS2 Knockout A-549 Cell Line | EDJ-KQ20234 | Human | 26524 | Details Get a Quote |
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