LAT_MOUSE
ID LAT_MOUSE Reviewed; 242 AA.
AC O54957;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Linker for activation of T-cells family member 1;
DE AltName: Full=36 kDa phospho-tyrosine adapter protein;
DE Short=pp36;
DE AltName: Full=p36-38;
GN Name=Lat;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thymus;
RX PubMed=9489702; DOI=10.1016/s0092-8674(00)80901-0;
RA Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.;
RT "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to
RT cellular activation.";
RL Cell 92:83-92(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION IN MAST CELLS, AND TISSUE SPECIFICITY.
RX PubMed=10843385; DOI=10.1016/s1074-7613(00)80204-6;
RA Saitoh S., Arudchandran R., Manetz T.S., Zhang W., Sommers C.L., Love P.E.,
RA Rivera J., Samelson L.E.;
RT "LAT is essential for Fc(epsilon)RI-mediated mast cell activation.";
RL Immunity 12:525-535(2000).
RN [4]
RP INTERACTION WITH CLNK.
RX PubMed=11463797; DOI=10.1074/jbc.m106390200;
RA Goitsuka R., Tatsuno A., Ishiai M., Kurosaki T., Kitamura D.;
RT "MIST functions through distinct domains in immunoreceptor signaling in the
RT presence and absence of LAT.";
RL J. Biol. Chem. 276:36043-36050(2001).
RN [5]
RP PALMITOYLATION.
RX PubMed=12626544; DOI=10.4049/jimmunol.170.6.2932;
RA Van Laethem F., Liang X., Andris F., Urbain J., Vandenbranden M.,
RA Ruysschaert J.-M., Resh M.D., Stulnig T.M., Leo O.;
RT "Glucocorticoids alter the lipid and protein composition of membrane rafts
RT of a murine T cell hybridoma.";
RL J. Immunol. 170:2932-2939(2003).
RN [6]
RP REVIEW ON FUNCTION IN T-CELLS.
RX PubMed=14696041; DOI=10.1002/bies.10384;
RA Sommers C.L., Samelson L.E., Love P.E.;
RT "LAT: a T lymphocyte adapter protein that couples the antigen receptor to
RT downstream signaling pathways.";
RL Bioessays 26:61-67(2004).
RN [7]
RP PALMITOYLATION AT CYS-27 AND CYS-30.
RX PubMed=19592663; DOI=10.4049/jimmunol.0803921;
RA Hundt M., Harada Y., De Giorgio L., Tanimura N., Zhang W., Altman A.;
RT "Palmitoylation-dependent plasma membrane transport but lipid raft-
RT independent signaling by linker for activation of T cells.";
RL J. Immunol. 183:1685-1694(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-44; SER-109; SER-112;
RP SER-199; SER-212 AND SER-215, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP INTERACTION WITH THEMIS2.
RX PubMed=22732588; DOI=10.4049/jimmunol.1200123;
RA Lesourne R., Zvezdova E., Song K.D., El-Khoury D., Uehara S., Barr V.A.,
RA Samelson L.E., Love P.E.;
RT "Interchangeability of Themis1 and Themis2 in thymocyte development reveals
RT two related proteins with conserved molecular function.";
RL J. Immunol. 189:1154-1161(2012).
RN [10]
RP INTERACTION WITH GRB2; PLCG1 AND THEMIS.
RC TISSUE=Thymocyte;
RX PubMed=22561606; DOI=10.1038/ni.2301;
RA Wang D., Zheng M., Lei L., Ji J., Yao Y., Qiu Y., Ma L., Lou J., Ouyang C.,
RA Zhang X., He Y., Chi J., Wang L., Kuang Y., Wang J., Cao X., Lu L.;
RT "Tespa1 is involved in late thymocyte development through the regulation of
RT TCR-mediated signaling.";
RL Nat. Immunol. 13:560-568(2012).
CC -!- FUNCTION: Required for TCR (T-cell antigen receptor)- and pre-TCR-
CC mediated signaling, both in mature T-cells and during their
CC development. Involved in FCGR3 (low affinity immunoglobulin gamma Fc
CC region receptor III)-mediated signaling in natural killer cells and
CC FCER1 (high affinity immunoglobulin epsilon receptor)-mediated
CC signaling in mast cells. Couples activation of these receptors and
CC their associated kinases with distal intracellular events such as
CC mobilization of intracellular calcium stores, PKC activation, MAPK
CC activation or cytoskeletal reorganization through the recruitment of
CC PLCG1, GRB2, GRAP2, and other signaling molecules.
CC {ECO:0000269|PubMed:10843385}.
CC -!- SUBUNIT: When phosphorylated, interacts directly with the PIK3R1
CC subunit of phosphoinositide 3-kinase and the SH2 domains of GRB2, GRAP,
CC GRAP2, PLCG1 and PLCG2. Interacts indirectly with CBL, SOS, VAV, and
CC LCP2. Interacts with SHB and SKAP2. Interacts with FCGR1A (By
CC similarity). Interacts with CLNK. Interacts with GRB2, PLCG1 and THEMIS
CC upon TCR activation in thymocytes. Interacts with THEMIS2
CC (PubMed:22732588). {ECO:0000250, ECO:0000269|PubMed:11463797,
CC ECO:0000269|PubMed:22561606, ECO:0000269|PubMed:22732588}.
CC -!- INTERACTION:
CC O54957; Q60631: Grb2; NbExp=5; IntAct=EBI-6390034, EBI-1688;
CC O54957; Q60787: Lcp2; NbExp=8; IntAct=EBI-6390034, EBI-5324248;
CC O54957; Q62077: Plcg1; NbExp=5; IntAct=EBI-6390034, EBI-300133;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type III membrane
CC protein. Note=Present in lipid rafts.
CC -!- TISSUE SPECIFICITY: Expressed in T-cells and mast cells.
CC {ECO:0000269|PubMed:10843385}.
CC -!- PTM: Phosphorylated on tyrosines by ZAP70 upon TCR activation, or by
CC SYK upon other immunoreceptor activation; which leads to the
CC recruitment of multiple signaling molecules. Is one of the most
CC prominently tyrosine-phosphorylated proteins detected following TCR
CC engagement. May be dephosphorylated by PTPRJ. Phosphorylated by ITK
CC leading to the recruitment of VAV1 to LAT-containing complexes (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Palmitoylation of Cys-27 and Cys-30 is required for raft targeting
CC and efficient phosphorylation. {ECO:0000250}.
CC -!- MISCELLANEOUS: Engagement of killer inhibitory receptors (KIR) disrupts
CC the interaction of PLCG1 with LAT and blocks target cell-induced
CC activation of PLC, maybe by inducing the dephosphorylation of LAT.
CC {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF036907; AAC40054.1; -; mRNA.
DR EMBL; BC013337; AAH13337.1; -; mRNA.
DR CCDS; CCDS21825.1; -.
DR RefSeq; NP_034819.1; NM_010689.3.
DR AlphaFoldDB; O54957; -.
DR BioGRID; 201112; 2.
DR ELM; O54957; -.
DR IntAct; O54957; 58.
DR MINT; O54957; -.
DR STRING; 10090.ENSMUSP00000032997; -.
DR iPTMnet; O54957; -.
DR PhosphoSitePlus; O54957; -.
DR SwissPalm; O54957; -.
DR EPD; O54957; -.
DR jPOST; O54957; -.
DR PaxDb; O54957; -.
DR PRIDE; O54957; -.
DR ProteomicsDB; 264977; -.
DR Antibodypedia; 2621; 1034 antibodies from 47 providers.
DR DNASU; 16797; -.
DR Ensembl; ENSMUST00000032997; ENSMUSP00000032997; ENSMUSG00000030742.
DR GeneID; 16797; -.
DR KEGG; mmu:16797; -.
DR UCSC; uc009jqx.1; mouse.
DR CTD; 27040; -.
DR MGI; MGI:1342293; Lat.
DR VEuPathDB; HostDB:ENSMUSG00000030742; -.
DR eggNOG; ENOG502SXAZ; Eukaryota.
DR GeneTree; ENSGT00390000014223; -.
DR HOGENOM; CLU_093883_0_0_1; -.
DR InParanoid; O54957; -.
DR OMA; WGPSWAR; -.
DR OrthoDB; 1328822at2759; -.
DR PhylomeDB; O54957; -.
DR TreeFam; TF337741; -.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2454202; Fc epsilon receptor (FCERI) signaling.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 16797; 0 hits in 58 CRISPR screens.
DR ChiTaRS; Lat; mouse.
DR PRO; PR:O54957; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O54957; protein.
DR Bgee; ENSMUSG00000030742; Expressed in peripheral lymph node and 128 other tissues.
DR ExpressionAtlas; O54957; baseline and differential.
DR Genevisible; O54957; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0001772; C:immunological synapse; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; ISS:HGNC-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:HGNC-UCL.
DR GO; GO:0006968; P:cellular defense response; TAS:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR GO; GO:0006955; P:immune response; ISS:HGNC-UCL.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:HGNC-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:HGNC-UCL.
DR GO; GO:0002260; P:lymphocyte homeostasis; IMP:MGI.
DR GO; GO:0043303; P:mast cell degranulation; IEA:UniProtKB-KW.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IBA:GO_Central.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:HGNC-UCL.
DR GO; GO:0050863; P:regulation of T cell activation; ISS:HGNC-UCL.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:MGI.
DR InterPro; IPR008359; Linker_for_activat_Tcells_prot.
DR PANTHER; PTHR15586; PTHR15586; 1.
DR Pfam; PF15234; LAT; 1.
DR PRINTS; PR01781; LATPROTEIN.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cell membrane; Immunity; Lipoprotein;
KW Mast cell degranulation; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..242
FT /note="Linker for activation of T-cells family member 1"
FT /id="PRO_0000083326"
FT TOPO_DOM 1..4
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..28
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 78..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..139
FT /note="Interaction with PLCG1"
FT /evidence="ECO:0000250"
FT REGION 175..178
FT /note="Interaction with GRB2, GRAP2 and PIK3R1"
FT /evidence="ECO:0000250"
FT REGION 176..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 195..198
FT /note="Interaction with GRB2, GRAP2 and PIK3R1"
FT /evidence="ECO:0000250"
FT COMPBIAS 93..116
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..213
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..242
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 40
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43561"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43561"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43561"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 175
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O43561"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 235
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O43561"
FT LIPID 27
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19592663"
FT LIPID 30
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19592663"
SQ SEQUENCE 242 AA; 26015 MW; 6AC25F7AE6E1A5C1 CRC64;
MEADALSPVG LGLLLLPFLV TLLAALCVRC RELPVSYDST STESLYPRSI LIKPPQITVP
RTPAVSYPLV TSFPPLRQPD LLPIPRSPQP LGGSHRMPSS QQNSDDANSV ASYENQEPAC
KNVDADEDED DYPNGYLVVL PDSSPAAVPV VSSAPVPSNP DLGDSAFSVE SCEDYVNVPE
SEESAEASLD GSREYVNVSP EQQPVTRAEL ASVNSQEVED EGEEEGVDGE EAPDYENLQE
LN
