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
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.
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.
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.
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):