LAT_HUMAN
ID LAT_HUMAN Reviewed; 262 AA.
AC O43561; B7WPI0; C7C5T6; G5E9K3; O43919;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 195.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 32-47
RP AND 219-233, PHOSPHORYLATION AT TYR-200, IDENTIFICATION BY MASS
RP SPECTROMETRY, MUTAGENESIS OF TYR-200 AND TYR-220, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PIK3R1; GRB2; GRAP AND PLCG1.
RC TISSUE=Leukemia;
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 [MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=9529333; DOI=10.1084/jem.187.7.1157;
RA Weber J.R., Orstavik S., Torgersen K.M., Danbolt N.C., Berg S.F.,
RA Ryan J.C., Tasken K., Imboden J.B., Vaage J.T.;
RT "Molecular cloning of the cDNA encoding pp36, a tyrosine-phosphorylated
RT adaptor protein selectively expressed by T cells and natural killer
RT cells.";
RL J. Exp. Med. 187:1157-1161(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Bone marrow;
RA Muschen M.;
RT "Inactivation of pre-B cell receptor-mediated tumor suppression by aberrant
RT splicing in Ph+ acute lymphoblastic leukemia.";
RL Submitted (JUL-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
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 [7]
RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-26 AND CYS-29, AND MUTAGENESIS
RP OF CYS-26 AND CYS-29.
RX PubMed=9729044; DOI=10.1016/s1074-7613(00)80606-8;
RA Zhang W., Trible R.P., Samelson L.E.;
RT "LAT palmitoylation: its essential role in membrane microdomain targeting
RT and tyrosine phosphorylation during T cell activation.";
RL Immunity 9:239-246(1998).
RN [8]
RP INTERACTION WITH SHB.
RX PubMed=10488157; DOI=10.1074/jbc.274.39.28050;
RA Lindholm C.K., Gylfe E., Zhang W., Samelson L.E., Welsh M.;
RT "Requirement of the Src homology 2 domain protein Shb for T cell receptor-
RT dependent activation of the interleukin-2 gene nuclear factor for
RT activation of T cells element in Jurkat T cells.";
RL J. Biol. Chem. 274:28050-28057(1999).
RN [9]
RP FUNCTION IN NK CELLS, AND INTERACTION WITH PLCG1.
RX PubMed=10072481;
RA Jevremovic D., Billadeau D.D., Schoon R.A., Dick C.J., Irvin B.J.,
RA Zhang W., Samelson L.E., Abraham R.T., Leibson P.J.;
RT "A role for the adaptor protein LAT in human NK cell-mediated
RT cytotoxicity.";
RL J. Immunol. 162:2453-2456(1999).
RN [10]
RP INTERACTION WITH GRB2; GRAP2 AND PLCG1.
RX PubMed=10811803; DOI=10.1074/jbc.m000404200;
RA Zhang W., Trible R.P., Zhu M., Liu S.K., McGlade C.J., Samelson L.E.;
RT "Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated
RT LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell antigen
RT receptor-mediated signaling.";
RL J. Biol. Chem. 275:23355-23361(2000).
RN [11]
RP INTERACTION WITH FCGR1A.
RX PubMed=10781611; DOI=10.1074/jbc.m909462199;
RA Tridandapani S., Lyden T.W., Smith J.L., Carter J.E., Coggeshall K.M.,
RA Anderson C.L.;
RT "The adapter protein LAT enhances fcgamma receptor-mediated signal
RT transduction in myeloid cells.";
RL J. Biol. Chem. 275:20480-20487(2000).
RN [12]
RP PHOSPHORYLATION, AND INTERACTION WITH LCP2; SKAP2; GRB2; PLCG2 AND CBL.
RX PubMed=10942756; DOI=10.1074/jbc.m001439200;
RA Asazuma N., Wilde J.I., Berlanga O., Leduc M., Leo A., Schweighoffer E.,
RA Tybulewicz V., Bon C., Liu S.K., McGlade C.J., Schraven B., Watson S.P.;
RT "Interaction of linker for activation of T cells with multiple adapter
RT proteins in platelets activated by the glycoprotein VI-selective ligand,
RT convulxin.";
RL J. Biol. Chem. 275:33427-33434(2000).
RN [13]
RP INTERACTION WITH PIK3R1 AND PLCG1, AND MUTAGENESIS OF TYR-161.
RX PubMed=11368773; DOI=10.1042/0264-6021:3560461;
RA Paz P.E., Wang S., Clarke H., Lu X., Stokoe D., Abo A.;
RT "Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of
RT T cells) required for recruitment and activation of signalling proteins in
RT T cells.";
RL Biochem. J. 356:461-471(2001).
RN [14]
RP PROBABLE DEPHOSPHORYLATION BY PTPRJ.
RX PubMed=11259588; DOI=10.1128/mcb.21.7.2393-2403.2001;
RA Baker J.E., Majeti R., Tangye S.G., Weiss A.;
RT "Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor
RT signal transduction is associated with reduced LAT and phospholipase
RT Cgamma1 phosphorylation.";
RL Mol. Cell. Biol. 21:2393-2403(2001).
RN [15]
RP PHOSPHORYLATION BY ITK.
RX PubMed=12186560; DOI=10.1021/bi025554o;
RA Perez-Villar J.J., Whitney G.S., Sitnick M.T., Dunn R.J., Venkatesan S.,
RA O'Day K., Schieven G.L., Lin T.A., Kanner S.B.;
RT "Phosphorylation of the linker for activation of T-cells by Itk promotes
RT recruitment of Vav.";
RL Biochemistry 41:10732-10740(2002).
RN [16]
RP PROBABLE DEPHOSPHORYLATION BY PTPRJ.
RX PubMed=12913111; DOI=10.1083/jcb.200303040;
RA Lin J., Weiss A.;
RT "The tyrosine phosphatase CD148 is excluded from the immunologic synapse
RT and down-regulates prolonged T cell signaling.";
RL J. Cell Biol. 162:673-682(2003).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [18]
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 [19]
RP TISSUE SPECIFICITY.
RX PubMed=16160011; DOI=10.1182/blood-2005-06-2273;
RA Tedoldi S., Paterson J.C., Hansmann M.-L., Natkunam Y., Rudiger T.,
RA Angelisova P., Du M.Q., Roberton H., Roncador G., Sanchez L., Pozzobon M.,
RA Masir N., Barry R., Pileri S., Mason D.Y., Marafioti T., Horejsi V.;
RT "Transmembrane adaptor molecules: a new category of lymphoid-cell
RT markers.";
RL Blood 107:213-221(2006).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84; SER-101 AND SER-224, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-39; SER-40; SER-41; SER-43;
RP SER-101; SER-106; SER-240; SER-241 AND TYR-255, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP INVOLVEMENT IN IMD52.
RX PubMed=27242165; DOI=10.1084/jem.20151110;
RA Keller B., Zaidman I., Yousefi O.S., Hershkovitz D., Stein J., Unger S.,
RA Schachtrup K., Sigvardsson M., Kuperman A.A., Shaag A., Schamel W.W.,
RA Elpeleg O., Warnatz K., Stepensky P.;
RT "Early onset combined immunodeficiency and autoimmunity in patients with
RT loss-of-function mutation in LAT.";
RL J. Exp. Med. 213:1185-1199(2016).
RN [24]
RP INVOLVEMENT IN IMD52.
RX PubMed=27522155; DOI=10.1016/j.jaci.2016.05.036;
RA Bacchelli C., Moretti F.A., Carmo M., Adams S., Stanescu H.C., Pearce K.,
RA Madkaikar M., Gilmour K.C., Nicholas A.K., Woods C.G., Kleta R.,
RA Beales P.L., Qasim W., Gaspar H.B.;
RT "Mutations in linker for activation of T cells (LAT) lead to a novel form
RT of severe combined immunodeficiency.";
RL J. Allergy Clin. Immunol. 139:634-642(2017).
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:10072481}.
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, SKAP2 and CLNK (By similarity). Interacts
CC with FCGR1A. Interacts with GRB2, PLCG1 and THEMIS upon TCR activation
CC in thymocytes (By similarity). Interacts with THEMIS2 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:O54957}.
CC -!- INTERACTION:
CC O43561; P00533: EGFR; NbExp=3; IntAct=EBI-1222766, EBI-297353;
CC O43561; P62993: GRB2; NbExp=7; IntAct=EBI-1222766, EBI-401755;
CC O43561; P06239: LCK; NbExp=2; IntAct=EBI-1222766, EBI-1348;
CC O43561; P27986: PIK3R1; NbExp=4; IntAct=EBI-1222766, EBI-79464;
CC O43561; P19174: PLCG1; NbExp=7; IntAct=EBI-1222766, EBI-79387;
CC O43561; P18031: PTPN1; NbExp=3; IntAct=EBI-1222766, EBI-968788;
CC O43561; O43765: SGTA; NbExp=3; IntAct=EBI-1222766, EBI-347996;
CC O43561-2; Q96BI3: APH1A; NbExp=3; IntAct=EBI-8070286, EBI-2606935;
CC O43561-2; P07307-3: ASGR2; NbExp=3; IntAct=EBI-8070286, EBI-12808270;
CC O43561-2; Q9BXK5: BCL2L13; NbExp=3; IntAct=EBI-8070286, EBI-747430;
CC O43561-2; J3KQ12: BSCL2; NbExp=3; IntAct=EBI-8070286, EBI-11532900;
CC O43561-2; P49069: CAMLG; NbExp=3; IntAct=EBI-8070286, EBI-1748958;
CC O43561-2; P09693: CD3G; NbExp=3; IntAct=EBI-8070286, EBI-3862428;
CC O43561-2; P19397: CD53; NbExp=3; IntAct=EBI-8070286, EBI-6657396;
CC O43561-2; Q9H305: CDIP1; NbExp=3; IntAct=EBI-8070286, EBI-2876678;
CC O43561-2; P57739: CLDN2; NbExp=3; IntAct=EBI-8070286, EBI-751440;
CC O43561-2; O00501: CLDN5; NbExp=3; IntAct=EBI-8070286, EBI-18400628;
CC O43561-2; O95471: CLDN7; NbExp=3; IntAct=EBI-8070286, EBI-740744;
CC O43561-2; Q5JRM2: CXorf66; NbExp=3; IntAct=EBI-8070286, EBI-12823659;
CC O43561-2; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-8070286, EBI-2680384;
CC O43561-2; O15552: FFAR2; NbExp=3; IntAct=EBI-8070286, EBI-2833872;
CC O43561-2; O14843: FFAR3; NbExp=3; IntAct=EBI-8070286, EBI-17762181;
CC O43561-2; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-8070286, EBI-3918971;
CC O43561-2; P48165: GJA8; NbExp=3; IntAct=EBI-8070286, EBI-17458373;
CC O43561-2; P08034: GJB1; NbExp=3; IntAct=EBI-8070286, EBI-17565645;
CC O43561-2; O75712: GJB3; NbExp=3; IntAct=EBI-8070286, EBI-3908586;
CC O43561-2; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-8070286, EBI-712073;
CC O43561-2; Q96P66: GPR101; NbExp=3; IntAct=EBI-8070286, EBI-17935713;
CC O43561-2; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-8070286, EBI-11955647;
CC O43561-2; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-8070286, EBI-13345167;
CC O43561-2; O15529: GPR42; NbExp=3; IntAct=EBI-8070286, EBI-18076404;
CC O43561-2; P62993-1: GRB2; NbExp=3; IntAct=EBI-8070286, EBI-15787932;
CC O43561-2; Q96MG2: JSRP1; NbExp=3; IntAct=EBI-8070286, EBI-11305455;
CC O43561-2; Q8N5Z5: KCTD17; NbExp=3; IntAct=EBI-8070286, EBI-743960;
CC O43561-2; P43628: KIR2DL3; NbExp=3; IntAct=EBI-8070286, EBI-8632435;
CC O43561-2; A8MZ59: LEUTX; NbExp=3; IntAct=EBI-8070286, EBI-17490413;
CC O43561-2; Q86WI0: LHFPL1; NbExp=3; IntAct=EBI-8070286, EBI-18268016;
CC O43561-2; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-8070286, EBI-2820517;
CC O43561-2; Q9BXW4: MAP1LC3C; NbExp=3; IntAct=EBI-8070286, EBI-2603996;
CC O43561-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-8070286, EBI-16439278;
CC O43561-2; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-8070286, EBI-11956541;
CC O43561-2; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-8070286, EBI-373355;
CC O43561-2; Q6N075: MFSD5; NbExp=3; IntAct=EBI-8070286, EBI-3920969;
CC O43561-2; Q9Y676: MRPS18B; NbExp=3; IntAct=EBI-8070286, EBI-750085;
CC O43561-2; Q9GZW8: MS4A7; NbExp=3; IntAct=EBI-8070286, EBI-721391;
CC O43561-2; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-8070286, EBI-3923617;
CC O43561-2; Q8N183: NDUFAF2; NbExp=3; IntAct=EBI-8070286, EBI-2682365;
CC O43561-2; P35372-10: OPRM1; NbExp=3; IntAct=EBI-8070286, EBI-12807478;
CC O43561-2; Q16378: PRR4; NbExp=3; IntAct=EBI-8070286, EBI-738624;
CC O43561-2; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-8070286, EBI-3920694;
CC O43561-2; O43765: SGTA; NbExp=3; IntAct=EBI-8070286, EBI-347996;
CC O43561-2; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-8070286, EBI-744081;
CC O43561-2; Q15849: SLC14A2; NbExp=3; IntAct=EBI-8070286, EBI-1573290;
CC O43561-2; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-8070286, EBI-17595455;
CC O43561-2; Q9BZV2: SLC19A3; NbExp=3; IntAct=EBI-8070286, EBI-3923779;
CC O43561-2; Q9BXS9-3: SLC26A6; NbExp=3; IntAct=EBI-8070286, EBI-12814225;
CC O43561-2; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-8070286, EBI-17295964;
CC O43561-2; Q86UW2: SLC51B; NbExp=5; IntAct=EBI-8070286, EBI-12266756;
CC O43561-2; P03973: SLPI; NbExp=3; IntAct=EBI-8070286, EBI-355293;
CC O43561-2; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-8070286, EBI-17280858;
CC O43561-2; Q8N9I0: SYT2; NbExp=3; IntAct=EBI-8070286, EBI-8032987;
CC O43561-2; Q8WY91: THAP4; NbExp=3; IntAct=EBI-8070286, EBI-726691;
CC O43561-2; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-8070286, EBI-13351685;
CC O43561-2; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-8070286, EBI-10982110;
CC O43561-2; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-8070286, EBI-3923061;
CC O43561-2; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-8070286, EBI-11742770;
CC O43561-2; Q9UBN6: TNFRSF10D; NbExp=3; IntAct=EBI-8070286, EBI-1044859;
CC O43561-2; Q9NXF8-2: ZDHHC7; NbExp=3; IntAct=EBI-8070286, EBI-12948063;
CC O43561-2; P08487: PLCG1; Xeno; NbExp=4; IntAct=EBI-8070286, EBI-8013886;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9489702,
CC ECO:0000269|PubMed:9729044}; Single-pass type III membrane protein
CC {ECO:0000269|PubMed:9489702, ECO:0000269|PubMed:9729044}. Note=Present
CC in lipid rafts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Long;
CC IsoId=O43561-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=O43561-2; Sequence=VSP_004303;
CC Name=3;
CC IsoId=O43561-3; Sequence=VSP_054758, VSP_004303;
CC Name=4;
CC IsoId=O43561-4; Sequence=VSP_054759, VSP_004303;
CC Name=5;
CC IsoId=O43561-5; Sequence=VSP_054759;
CC -!- TISSUE SPECIFICITY: Expressed in thymus, T-cells, NK cells, mast cells
CC and, at lower levels, in spleen. Present in T-cells but not B-cells (at
CC protein level). {ECO:0000269|PubMed:16160011,
CC ECO:0000269|PubMed:9489702}.
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.
CC -!- PTM: Palmitoylation of Cys-26 and Cys-29 is required for raft targeting
CC and efficient phosphorylation. {ECO:0000269|PubMed:9729044}.
CC -!- DISEASE: Immunodeficiency 52 (IMD52) [MIM:617514]: An autosomal
CC recessive primary immunodeficiency characterized by T-cell
CC abnormalities, resulting in severe combined immunodeficiency,
CC autoimmune disease, progressive lymphopenia and hypogammaglobulinemia,
CC and lymphoproliferation with splenomegaly. Patients develop severe
CC recurrent infections from infancy. {ECO:0000269|PubMed:27242165,
CC ECO:0000269|PubMed:27522155}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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.
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DR EMBL; AF036906; AAC39637.1; -; mRNA.
DR EMBL; AF036905; AAC39636.1; -; mRNA.
DR EMBL; AJ223280; CAA11218.1; -; mRNA.
DR EMBL; FN432832; CBA11533.1; -; mRNA.
DR EMBL; AC109460; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471267; EAW52027.1; -; Genomic_DNA.
DR EMBL; CH471267; EAW52028.1; -; Genomic_DNA.
DR EMBL; BC011563; AAH11563.1; -; mRNA.
DR CCDS; CCDS10647.1; -. [O43561-1]
DR CCDS; CCDS32425.1; -. [O43561-2]
DR CCDS; CCDS45455.1; -. [O43561-4]
DR CCDS; CCDS53999.1; -. [O43561-3]
DR RefSeq; NP_001014987.1; NM_001014987.1. [O43561-2]
DR RefSeq; NP_001014988.1; NM_001014988.1. [O43561-4]
DR RefSeq; NP_001014989.2; NM_001014989.1. [O43561-3]
DR RefSeq; NP_055202.1; NM_014387.3. [O43561-1]
DR AlphaFoldDB; O43561; -.
DR BioGRID; 117971; 113.
DR CORUM; O43561; -.
DR DIP; DIP-29231N; -.
DR IntAct; O43561; 80.
DR MINT; O43561; -.
DR ChEMBL; CHEMBL5779; -.
DR GlyGen; O43561; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; O43561; -.
DR PhosphoSitePlus; O43561; -.
DR SwissPalm; O43561; -.
DR BioMuta; LAT; -.
DR jPOST; O43561; -.
DR MassIVE; O43561; -.
DR MaxQB; O43561; -.
DR PeptideAtlas; O43561; -.
DR PRIDE; O43561; -.
DR ProteomicsDB; 33964; -.
DR ProteomicsDB; 49052; -. [O43561-1]
DR ProteomicsDB; 49053; -. [O43561-2]
DR ProteomicsDB; 6302; -.
DR ProteomicsDB; 7609; -.
DR Antibodypedia; 2621; 1034 antibodies from 47 providers.
DR CPTC; O43561; 1 antibody.
DR DNASU; 27040; -.
DR Ensembl; ENST00000360872.9; ENSP00000354119.5; ENSG00000213658.13. [O43561-1]
DR Ensembl; ENST00000395456.7; ENSP00000378841.3; ENSG00000213658.13. [O43561-2]
DR Ensembl; ENST00000395461.7; ENSP00000378845.3; ENSG00000213658.13. [O43561-3]
DR Ensembl; ENST00000454369.6; ENSP00000398793.2; ENSG00000213658.13. [O43561-4]
DR Ensembl; ENST00000564277.5; ENSP00000457036.1; ENSG00000213658.13. [O43561-4]
DR Ensembl; ENST00000566177.5; ENSP00000456761.1; ENSG00000213658.13. [O43561-5]
DR GeneID; 27040; -.
DR KEGG; hsa:27040; -.
DR MANE-Select; ENST00000395456.7; ENSP00000378841.3; NM_001014987.2; NP_001014987.1. [O43561-2]
DR UCSC; uc002dsb.4; human. [O43561-1]
DR CTD; 27040; -.
DR DisGeNET; 27040; -.
DR GeneCards; LAT; -.
DR HGNC; HGNC:18874; LAT.
DR HPA; ENSG00000213658; Tissue enriched (lymphoid).
DR MalaCards; LAT; -.
DR MIM; 602354; gene.
DR MIM; 617514; phenotype.
DR neXtProt; NX_O43561; -.
DR OpenTargets; ENSG00000213658; -.
DR Orphanet; 504523; Severe combined immunodeficiency due to LAT deficiency.
DR PharmGKB; PA38728; -.
DR VEuPathDB; HostDB:ENSG00000213658; -.
DR GeneTree; ENSGT00390000014223; -.
DR HOGENOM; CLU_093883_0_0_1; -.
DR InParanoid; O43561; -.
DR OMA; WGPSWAR; -.
DR OrthoDB; 1328822at2759; -.
DR PhylomeDB; O43561; -.
DR TreeFam; TF337741; -.
DR PathwayCommons; O43561; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-2424491; DAP12 signaling. [O43561-2]
DR Reactome; R-HSA-2454202; Fc epsilon receptor (FCERI) signaling. [O43561-2]
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. [O43561-2]
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. [O43561-2]
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [O43561-2]
DR SignaLink; O43561; -.
DR SIGNOR; O43561; -.
DR BioGRID-ORCS; 27040; 18 hits in 1085 CRISPR screens.
DR ChiTaRS; LAT; human.
DR GeneWiki; Linker_of_activated_T_cells; -.
DR GenomeRNAi; 27040; -.
DR Pharos; O43561; Tbio.
DR PRO; PR:O43561; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O43561; protein.
DR Bgee; ENSG00000213658; Expressed in granulocyte and 93 other tissues.
DR ExpressionAtlas; O43561; baseline and differential.
DR Genevisible; O43561; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0008180; C:COP9 signalosome; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0001772; C:immunological synapse; IDA:HGNC-UCL.
DR GO; GO:0016021; C:integral component of membrane; IDA:HGNC-UCL.
DR GO; GO:0045121; C:membrane raft; TAS:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IDA:HGNC-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:HGNC-UCL.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IDA:HGNC-UCL.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:HGNC-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:HGNC-UCL.
DR GO; GO:0002260; P:lymphocyte homeostasis; IEA:Ensembl.
DR GO; GO:0043303; P:mast cell degranulation; IEA:UniProtKB-KW.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEP:CACAO.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:HGNC-UCL.
DR GO; GO:0050863; P:regulation of T cell activation; IMP:HGNC-UCL.
DR GO; GO:0042110; P:T cell activation; TAS:UniProtKB.
DR DisProt; DP01126; -.
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; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Immunity; Lipoprotein; Mast cell degranulation;
KW Membrane; Palmitate; Phosphoprotein; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..262
FT /note="Linker for activation of T-cells family member 1"
FT /id="PRO_0000083325"
FT TOPO_DOM 1..4
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..27
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 69..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..164
FT /note="Interaction with PLCG1"
FT REGION 200..203
FT /note="Interaction with GRB2, GRAP2 and PIK3R1"
FT /evidence="ECO:0000269|PubMed:10811803"
FT REGION 206..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..223
FT /note="Interaction with GRB2, GRAP2 and PIK3R1"
FT /evidence="ECO:0000269|PubMed:10811803"
FT COMPBIAS 69..83
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 39
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54957"
FT MOD_RES 110
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 156
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 161
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 200
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9489702"
FT MOD_RES 220
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 255
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT LIPID 26
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:9729044"
FT LIPID 29
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:9729044"
FT VAR_SEQ 1
FT /note="M -> MEATAASWQVAVPVLGGASRPLGPRGAASLLRAPLQM (in
FT isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054758"
FT VAR_SEQ 83
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_054759"
FT VAR_SEQ 114..142
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9489702, ECO:0000303|PubMed:9529333"
FT /id="VSP_004303"
FT MUTAGEN 26
FT /note="C->A: Reduces palmitoylation; abolishes localization
FT to lipid rafts."
FT /evidence="ECO:0000269|PubMed:9729044"
FT MUTAGEN 29
FT /note="C->A: Reduces palmitoylation; impairs localization
FT to lipid rafts."
FT /evidence="ECO:0000269|PubMed:9729044"
FT MUTAGEN 161
FT /note="Y->F: Abolishes interaction with PLCG1."
FT /evidence="ECO:0000269|PubMed:11368773"
FT MUTAGEN 200
FT /note="Y->F: Abolishes interaction with GRB2 and PIK3R1;
FT when associated with F-220."
FT /evidence="ECO:0000269|PubMed:9489702"
FT MUTAGEN 220
FT /note="Y->F: Abolishes interaction with GRB2 and PIK3R1;
FT when associated with F-200."
FT /evidence="ECO:0000269|PubMed:9489702"
SQ SEQUENCE 262 AA; 27930 MW; BCD80AE7DCA64153 CRC64;
MEEAILVPCV LGLLLLPILA MLMALCVHCH RLPGSYDSTS SDSLYPRGIQ FKRPHTVAPW
PPAYPPVTSY PPLSQPDLLP IPRSPQPLGG SHRTPSSRRD SDGANSVASY ENEGASGIRG
AQAGWGVWGP SWTRLTPVSL PPEPACEDAD EDEDDYHNPG YLVVLPDSTP ATSTAAPSAP
ALSTPGIRDS AFSMESIDDY VNVPESGESA EASLDGSREY VNVSQELHPG AAKTEPAALS
SQEAEEVEEE GAPDYENLQE LN
