Lat linker for activation of T cells [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Latprovided by MGI
Official Full Name: linker for activation of T cellsprovided by MGI
Primary source: MGI:MGI:1342293
See related: Ensembl:ENSMUSG00000030742 AllianceGenome:MGI:1342293
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: pp36; p36-38
Summary: Predicted to enable protein kinase binding activity and signaling receptor complex adaptor activity. Acts upstream of or within gene expression; inflammatory response; and lymphocyte homeostasis. Located in cell-cell junction and immunological synapse. Part of COP9 signalosome. Is expressed in liver and thymus primordium. Used to study IgG4-related disease. Human ortholog(s) of this gene implicated in immunodeficiency 52. Orthologous to human LAT (linker for activation of T cells). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in thymus adult (RPKM 497.8), spleen adult (RPKM 58.8) and 1 other tissue See more
Orthologs: human all
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Genomic context

Location:: 7 F3; 7 69.01 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (125962999..125968877, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (126363827..126369705, complement)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.
Title: Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.
Spontaneous Differentiation of T Follicular Helper Cells in LATY136F Mutant Mice.
Title: Spontaneous Differentiation of T Follicular Helper Cells in LATY136F Mutant Mice.
The pronounced lung lesions developing in LATY136F knock-in mice mimic human IgG4-related lung disease.
Title: The pronounced lung lesions developing in LATY136F knock-in mice mimic human IgG4-related lung disease.
LRCH1 deficiency enhances LAT signalosome formation and CD8(+) T cell responses against tumors and pathogens.
Title: LRCH1 deficiency enhances LAT signalosome formation and CD8(+) T cell responses against tumors and pathogens.
mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.
Title: mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.
Study shows that tyrosine phosphorylation of the T cell adapter protein LAT at position Y132 is a critical kinetic bottleneck for ligand discrimination. The slow phosphorylation of Y132 is governed by a preceding glycine residue (G131) but can be accelerated by substituting this glycine with aspartate or glutamate. Slow phosphorylation of Y132 acts as a proofreading step to facilitate T cell ligand discrimination.
Title: Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.
These data enabled the identification of a negative regulation function for 4.1R in CD8(+) T cells by a direct association between 4.1R and LAT, possibly through inhibiting phosphorylation of LAT and then modulating intracellular signal transduction.
Title: Protein 4.1R negatively regulates CD8(+) T-cell activation by modulating phosphorylation of linker for activation of T cells.
LAT, once internalized, transits through the Golgi-trans-Golgi network (TGN), where it is repolarized to the immune synapse.
Title: Rab6-dependent retrograde traffic of LAT controls immune synapse formation and T cell activation.
LatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with of immunoglobulin G4-related disease (IgG4-RD). The development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. LatY136F knock-in mouse strain represents a promising model for human IgG4-RD.
Title: LatY136F knock-in mouse model for human IgG4-related disease.
this study shows that the site-specific delivery of linker for activation of T cells (LAT) in asthmatic mouse model
Title: LAT alleviates Th2/Treg imbalance in an OVA-induced allergic asthma mouse model through LAT-PLC-γ1 interaction.

Submit: New GeneRIF Correction See all GeneRIFs (59)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (16) 1 citation
Endonuclease-mediated (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables molecular condensate scaffold activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables signaling receptor complex adaptor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in T cell receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in calcium-mediated signaling	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell surface receptor protein tyrosine kinase signaling pathway	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within cellular defense response	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within homeostasis of number of cells	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within immune system process	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in integrin-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lymphocyte homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mast cell degranulation	IEA Inferred from Electronic Annotation more info
involved_in membrane raft distribution	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of T cell activation	ISO Inferred from Sequence Orthology more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of COP9 signalosome	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
part_of TCR signalosome	ISO Inferred from Sequence Orthology more info
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
is_active_in immunological synapse	IBA Inferred from Biological aspect of Ancestor more info
located_in immunological synapse	IDA Inferred from Direct Assay more info	PubMed
located_in immunological synapse	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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

Names: 36 kDa phospho-tyrosine adapter protein; 36 kDa phosphotyrosine adapter protein; linker protein

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_010689.3 → NP_034819.1 linker for activation of T-cells family member 1

See identical proteins and their annotated locations for NP_034819.1

Status: VALIDATED

Source sequence(s)

AC125322, AK134003, BE947351

Consensus CDS

CCDS21825.1

UniProtKB/Swiss-Prot

O54957

UniProtKB/TrEMBL

Q546H1, Q80UR6

Related

ENSMUSP00000032997.7, ENSMUST00000032997.8

Conserved Domains (1) summary

pfam15234
Location:24 → 242

LAT; Linker for activation of T-cells

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000073.7 Reference GRCm39 C57BL/6J

Range

125962999..125968877 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006507396.3 → XP_006507459.3 linker for activation of T-cells family member 1 isoform X1

Conserved Domains (1) summary

pfam15234
Location:137 → 341

LAT; Linker for activation of T-cells
XM_006507398.5 → XP_006507461.1 linker for activation of T-cells family member 1 isoform X4

Conserved Domains (1) summary

pfam15234
Location:8 → 176

LAT; Linker for activation of T-cells
XM_006507397.4 → XP_006507460.2 linker for activation of T-cells family member 1 isoform X2

UniProtKB/TrEMBL

Q80UR6

Conserved Domains (1) summary

pfam15234
Location:24 → 224

LAT; Linker for activation of T-cells
XM_030242172.2 → XP_030098032.1 linker for activation of T-cells family member 1 isoform X3

Conserved Domains (1) summary

pfam15234
Location:137 → 281

LAT; Linker for activation of T-cells