Human Gene LAT (ENST00000395456.7) from GENCODE V44
  Description: Homo sapiens linker for activation of T cells (LAT), transcript variant 2, mRNA. (from RefSeq NM_001014987)
RefSeq Summary (NM_001014987): 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].
Gencode Transcript: ENST00000395456.7
Gencode Gene: ENSG00000213658.13
Transcript (Including UTRs)
   Position: hg38 chr16:28,985,052-28,990,784 Size: 5,733 Total Exon Count: 12 Strand: +
Coding Region
   Position: hg38 chr16:28,985,418-28,990,012 Size: 4,595 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:28,985,052-28,990,784)mRNA (may differ from genome)Protein (233 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: LAT_HUMAN
DESCRIPTION: RecName: Full=Linker for activation of T-cells family member 1; AltName: Full=36 kDa phospho-tyrosine adapter protein; Short=pp36; AltName: Full=p36-38;
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.
SUBUNIT: 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, SKAP2 and CLNK (By similarity). Interacts with FCGR1A. Interacts with GRB2, PLCG1 and THEMIS upon TCR activation in thymocytes (By similarity).
INTERACTION: P06239:LCK; NbExp=2; IntAct=EBI-1222766, EBI-1348; P19174:PLCG1; NbExp=2; IntAct=EBI-1222766, EBI-79387;
SUBCELLULAR LOCATION: Cell membrane; Single-pass type III membrane protein. Note=Present in lipid rafts.
TISSUE SPECIFICITY: Expressed in thymus, T-cells, NK cells, mast cells and, at lower levels, in spleen. Present in T-cells but not B-cells (at protein level).
PTM: 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.
PTM: Palmitoylation of Cys-26 and Cys-29 is required for raft targeting and efficient phosphorylation.
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.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: LAT
Diseases sorted by gene-association score: immunodeficiency 52* (900), cranial nerve palsy (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 25.71 RPKM in Spleen
Total median expression: 440.08 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -186.20366-0.509 Picture PostScript Text
3' UTR -220.10603-0.365 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008359 - Linker_for_activat_Tcells_prot

ModBase Predicted Comparative 3D Structure on O43561
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005070 SH3/SH2 adaptor activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005515 protein binding
GO:0019901 protein kinase binding

Biological Process:
GO:0000165 MAPK cascade
GO:0002250 adaptive immune response
GO:0002260 lymphocyte homeostasis
GO:0002376 immune system process
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007165 signal transduction
GO:0007229 integrin-mediated signaling pathway
GO:0007265 Ras protein signal transduction
GO:0009967 positive regulation of signal transduction
GO:0010467 gene expression
GO:0019722 calcium-mediated signaling
GO:0035556 intracellular signal transduction
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042110 T cell activation
GO:0043303 mast cell degranulation
GO:0045860 positive regulation of protein kinase activity
GO:0048872 homeostasis of number of cells
GO:0050852 T cell receptor signaling pathway
GO:0050863 regulation of T cell activation

Cellular Component:
GO:0001772 immunological synapse
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0005911 cell-cell junction
GO:0008180 COP9 signalosome
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0042629 mast cell granule
GO:0045121 membrane raft


-  Descriptions from all associated GenBank mRNAs
  AB209402 - Homo sapiens mRNA for spinster variant protein.
BC011563 - Homo sapiens linker for activation of T cells, mRNA (cDNA clone MGC:20145 IMAGE:4644259), complete cds.
AK307342 - Homo sapiens cDNA, FLJ97290.
AJ223280 - Homo sapiens mRNA for tyrosine-phosphorylated protein of 36 kD (pp36) (LAT gene).
AF036906 - Homo sapiens linker for activation of T cells (LAT) mRNA, alternatively spliced form, complete cds.
JD477729 - Sequence 458753 from Patent EP1572962.
AF036905 - Homo sapiens linker for activation of T cells (LAT) mRNA, complete cds.
JD221795 - Sequence 202819 from Patent EP1572962.
KJ893590 - Synthetic construct Homo sapiens clone ccsbBroadEn_02984 LAT gene, encodes complete protein.
FN432831 - Homo sapiens mRNA for linker for activation of T-cells family member 1 (LAT gene), transcript variant Ins27.
FN432832 - Homo sapiens mRNA for linker for activation of T-cells family member 1 (LAT gene), transcript variant Del3.
FN432833 - Homo sapiens mRNA for linker for activation of T-cells family member 1 (LAT gene), transcript variant Del30.
FN432834 - Homo sapiens mRNA for linker for activation of T-cells family member 1 (LAT gene), transcript variant Del116.
JD027469 - Sequence 8493 from Patent EP1572962.
AK093815 - Homo sapiens cDNA FLJ36496 fis, clone THYMU2018819.
JD056709 - Sequence 37733 from Patent EP1572962.
JD075859 - Sequence 56883 from Patent EP1572962.
JD161430 - Sequence 142454 from Patent EP1572962.
JD424930 - Sequence 405954 from Patent EP1572962.
JD479470 - Sequence 460494 from Patent EP1572962.
JD355644 - Sequence 336668 from Patent EP1572962.
JD070843 - Sequence 51867 from Patent EP1572962.
JD532559 - Sequence 513583 from Patent EP1572962.
JD196490 - Sequence 177514 from Patent EP1572962.
JD494282 - Sequence 475306 from Patent EP1572962.
JD540469 - Sequence 521493 from Patent EP1572962.
JD231463 - Sequence 212487 from Patent EP1572962.
JD420464 - Sequence 401488 from Patent EP1572962.
JD173117 - Sequence 154141 from Patent EP1572962.
JD221583 - Sequence 202607 from Patent EP1572962.
JD142070 - Sequence 123094 from Patent EP1572962.
JD528379 - Sequence 509403 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04650 - Natural killer cell mediated cytotoxicity
hsa04660 - T cell receptor signaling pathway
hsa04664 - Fc epsilon RI signaling pathway
hsa04666 - Fc gamma R-mediated phagocytosis

BioCarta from NCI Cancer Genome Anatomy Project
h_mcmPathway - CDK Regulation of DNA Replication

Reactome (by CSHL, EBI, and GO)

Protein O43561 (Reactome details) participates in the following event(s):

R-HSA-202245 Phosphorylation of TBSMs in LAT
R-HSA-434836 Syk/Lck phosphorylate LAT
R-HSA-202212 Recruitment of PLC-gamma1 to LAT
R-HSA-202325 Recruitment of Gads to LAT
R-HSA-213406 Disassociation of PLC-gamma1 from LAT
R-HSA-202241 Recruitment of SLP-76 to Gads
R-HSA-202216 Phosphorylation of SLP-76
R-HSA-202331 Recruitment of PLC-gamma1 to SLP-76
R-HSA-202375 Recruitment of ITK to SLP-76
R-HSA-213407 Disassociation of PLC-gamma1 from SLP-76
R-HSA-202248 Phosphorylation of PLC-gamma1
R-HSA-202433 Generation of second messenger molecules
R-HSA-114604 GPVI-mediated activation cascade
R-HSA-202403 TCR signaling
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-1280218 Adaptive Immune System
R-HSA-109582 Hemostasis
R-HSA-168256 Immune System
R-HSA-2395801 Phosphorylation of LAT by p-SYK
R-HSA-2730843 Phosphorylation of LAT by p-SYK
R-HSA-2396599 Recruitment of GRB2:SOS to p-5Y-LAT
R-HSA-2396561 Recruitment of GADS:SLP-76 to p-5Y-LAT
R-HSA-2424485 Release of p-PLCG1
R-HSA-2424481 Recruitment of VAV and BTK to p-SLP-76
R-HSA-2730892 Recruitment of VAV to p-SLP-76
R-HSA-2396594 Phosphorylation of SLP-76 by p-SYK
R-HSA-2730851 Phosphorylation of SLP-76 by p-SYK
R-HSA-2396606 Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT
R-HSA-2424477 SOS mediated nucleotide exchange of RAS (SHC)
R-HSA-2424487 Phosphorylation of PLC-gamma by p-BTK/p-SYK
R-HSA-2424484 Phosphorylation of BTK by p-SYK
R-HSA-2424486 Phosphorylation and activation of VAV2/VAV3 by SYK
R-HSA-2730888 Phosphorylation of PLC-gamma
R-HSA-2730858 Autophosphorylation of BTK/ITK
R-HSA-2730840 Activation of RAC1 by VAV
R-HSA-2730841 Phosphorylation and activation of VAV
R-HSA-2730885 Recruitment of TEC kinases to p-SLP-76
R-HSA-2730833 Phosphorylation of TEC kinases by p-SYK
R-HSA-2730889 Recruitment of PAK to the membrane by binding active RAC1
R-HSA-2730856 Autophosphorylation of PAK
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-2424476 Activation of RAC1 by VAV2/3
R-HSA-2730847 Hydrolysis of PIP2 by PLCG
R-HSA-2424491 DAP12 signaling
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-2172127 DAP12 interactions
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000395456.1, ENST00000395456.2, ENST00000395456.3, ENST00000395456.4, ENST00000395456.5, ENST00000395456.6, LAT_HUMAN, NM_001014987, O43561, O43919, uc002dsb.1, uc002dsb.2, uc002dsb.3, uc002dsb.4, uc002dsb.5
UCSC ID: ENST00000395456.7
RefSeq Accession: NM_001014987
Protein: O43561 (aka LAT_HUMAN)
CCDS: CCDS32425.1, CCDS45455.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.