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

Summary

Official Symbol: LATprovided by HGNC
Official Full Name: linker for activation of T cellsprovided by HGNC
Primary source: HGNC:HGNC:18874
See related: Ensembl:ENSG00000213658 MIM:602354; AllianceGenome:HGNC:18874
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; IMD52
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]
Expression: Broad expression in lymph node (RPKM 29.3), appendix (RPKM 13.0) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p11.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (28984803..28990784)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (29265918..29271899)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (28996124..29002105)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.
Title: Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.
L-type amino acid transporter 1 as a target for inflammatory disease and cancer immunotherapy.
Title: L-type amino acid transporter 1 as a target for inflammatory disease and cancer immunotherapy.
The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions.
Title: The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions.
Retrograde and Anterograde Transport of Lat-Vesicles during the Immunological Synapse Formation: Defining the Finely-Tuned Mechanism.
Title: Retrograde and Anterograde Transport of Lat-Vesicles during the Immunological Synapse Formation: Defining the Finely-Tuned Mechanism.
A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling.
Title: A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling.
The role of prolines and glycine in the transmembrane domain of LAT.
Title: The role of prolines and glycine in the transmembrane domain of LAT.
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.
that LAT1 is not only associated with poor prognosis of ovarian carcinoma, but also associated with chemoresistance in ovarian carcinoma
Title: Significant relationship between the LAT1 expression pattern and chemoresistance in ovarian clear cell carcinoma.
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.
Discovery of a conserved proline-rich motif in LAT that mediates efficient LAT phosphorylation.
Title: Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT.

Submit: New GeneRIF Correction See all GeneRIFs (77)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Severe combined immunodeficiency due to LAT deficiency MedGen: C4479588 OMIM: 617514 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

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	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 Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

L17705 (e-PCR)
- UniSTS:66091

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables molecular condensate scaffold activity	IDA Inferred from Direct Assay more info	PubMed
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	IPI Inferred from Physical Interaction more info	PubMed
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor complex adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in T cell activation	TAS Traceable Author Statement more info	PubMed
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in integrin-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in lymphocyte homeostasis	IEA Inferred from Electronic Annotation more info
involved_in mast cell degranulation	IEA Inferred from Electronic Annotation more info
involved_in membrane raft distribution	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein kinase activity	IEP Inferred from Expression Pattern more info	PubMed
involved_in regulation of T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of T cell activation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of COP9 signalosome	ISS Inferred from Sequence or Structural Similarity more info
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
part_of TCR signalosome	IDA Inferred from Direct Assay more info	PubMed
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
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 membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

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 phospho-tyrosine adaptor protein; 36 kDa phosphotyrosine adapter protein; linker for activation of T cells, transmembrane adaptor; p36-38

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_001014987.2 → NP_001014987.1 linker for activation of T-cells family member 1 isoform b

See identical proteins and their annotated locations for NP_001014987.1

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)

AC109460, AJ223280, BC011563, BI769296

Consensus CDS

CCDS32425.1

UniProtKB/TrEMBL

C7C5T7

Related

ENSP00000378841.3, ENST00000395456.7

Conserved Domains (1) summary

pfam15234
Location:1 → 229

LAT; Linker for activation of T-cells
NM_001014988.2 → NP_001014988.1 linker for activation of T-cells family member 1 isoform c

See identical proteins and their annotated locations for NP_001014988.1

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)

AC109460, AJ223280, BC011563, BI769296, BI911769

Consensus CDS

CCDS45455.1

UniProtKB/TrEMBL

C7C5T7

Related

ENSP00000398793.2, ENST00000454369.6

Conserved Domains (1) summary

pfam15234
Location:1 → 228

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

See identical proteins and their annotated locations for NP_001014989.2

Status: REVIEWED

Description

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

Source sequence(s)

AC109460, BC011563

Consensus CDS

CCDS53999.1

UniProtKB/TrEMBL

C7C5T7

Related

ENSP00000378845.3, ENST00000395461.7

Conserved Domains (1) summary

pfam15234
Location:37 → 269

LAT; Linker for activation of T-cells
NM_014387.4 → NP_055202.1 linker for activation of T-cells family member 1 isoform a

See identical proteins and their annotated locations for NP_055202.1

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)

AC109460, AF036906, AJ223280, BC011563, BI769296

Consensus CDS

CCDS10647.1

UniProtKB/Swiss-Prot

B7WPI0, C7C5T6, G5E9K3, O43561, O43919

UniProtKB/TrEMBL

C7C5T7

Related

ENSP00000354119.5, ENST00000360872.9

Conserved Domains (1) summary

pfam15234
Location:1 → 262

LAT; Linker for activation of T-cells