NTAL_MOUSE
ID NTAL_MOUSE Reviewed; 203 AA.
AC Q9JHL0; Q3UYF6; Q9JJ29;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Linker for activation of T-cells family member 2;
DE AltName: Full=Linker for activation of B-cells;
DE AltName: Full=Membrane-associated adapter molecule;
DE AltName: Full=Non-T-cell activation linker;
DE AltName: Full=Williams-Beuren syndrome chromosomal region 15 protein homolog;
GN Name=Lat2; Synonyms=Lab, Ntal, Wbscr15, Wbscr5;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=11124535; DOI=10.1159/000056790;
RA Doyle J.L., DeSilva U., Miller W., Green E.D.;
RT "Divergent human and mouse orthologs of a novel gene (WBSCR15/Wbscr15)
RT reside within the genomic interval commonly deleted in Williams syndrome.";
RL Cytogenet. Cell Genet. 90:285-290(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1 AND
RP 2).
RC STRAIN=129/SvJ;
RX PubMed=11003705; DOI=10.1007/s003350010166;
RA Martindale D.W., Wilson M.D., Wang D., Burke R.D., Chen X., Duronio V.,
RA Koop B.F.;
RT "Comparative genomic sequence analysis of the Williams syndrome region
RT (LIMK1-RFC2) of human chromosome 7q11.23.";
RL Mamm. Genome 11:890-898(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RX PubMed=12514734; DOI=10.1038/ni882;
RA Janssen E., Zhu M., Zhang W., Koonpaew S., Zhang W.;
RT "LAB: a new membrane-associated adaptor molecule in B cell activation.";
RL Nat. Immunol. 4:117-123(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RA Green E.D.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Aorta, Cecum, Embryo, Medulla oblongata, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=129; TISSUE=Mammary tumor;
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 TISSUE SPECIFICITY.
RX PubMed=15539154; DOI=10.1016/j.immuni.2004.09.007;
RA Stork B., Engelke M., Frey J., Horejsi V., Hamm-Baarke A., Schraven B.,
RA Kurosaki T., Wienands J.;
RT "Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-
RT regulating signal circuit in B lymphocytes.";
RL Immunity 21:681-691(2004).
RN [8]
RP TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH GRB2, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15477350; DOI=10.1084/jem.20041223;
RA Zhu M., Liu Y., Koonpaew S., Granillo O., Zhang W.;
RT "Positive and negative regulation of FcepsilonRI-mediated signaling by the
RT adaptor protein LAB/NTAL.";
RL J. Exp. Med. 200:991-1000(2004).
RN [9]
RP FUNCTION, INTERACTION WITH GRB2, AND SUBCELLULAR LOCATION.
RX PubMed=15477348; DOI=10.1084/jem.20041213;
RA Volna P., Lebduska P., Draberova L., Simova S., Heneberg P., Boubelik M.,
RA Bugajev V., Malissen B., Wilson B.S., Horejsi V., Malissen M., Draber P.;
RT "Negative regulation of mast cell signaling and function by the adaptor
RT LAB/NTAL.";
RL J. Exp. Med. 200:1001-1013(2004).
RN [10]
RP DEVELOPMENTAL STAGE, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15899851; DOI=10.1128/mcb.25.11.4455-4465.2005;
RA Wang Y., Horvath O., Hamm-Baarke A., Richelme M., Gregoire C.,
RA Guinamard R., Horejsi V., Angelisova P., Spicka J., Schraven B.,
RA Malissen B., Malissen M.;
RT "Single and combined deletions of the NTAL/LAB and LAT adaptors minimally
RT affect B-cell development and function.";
RL Mol. Cell. Biol. 25:4455-4465(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-59 AND SER-60, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
CC -!- FUNCTION: Involved in FCER1 (high affinity immunoglobulin epsilon
CC receptor)-mediated signaling in mast cells. May also be involved in BCR
CC (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high
CC affinity immunoglobulin gamma Fc receptor I)-mediated signaling in
CC myeloid cells. Couples activation of these receptors and their
CC associated kinases with distal intracellular events through the
CC recruitment of GRB2. {ECO:0000269|PubMed:15477348,
CC ECO:0000269|PubMed:15477350, ECO:0000269|PubMed:15899851}.
CC -!- SUBUNIT: When phosphorylated, interacts with GRB2. May also interact
CC with SOS1, GAB1 and CBL. {ECO:0000269|PubMed:15477348,
CC ECO:0000269|PubMed:15477350}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15477348,
CC ECO:0000269|PubMed:15477350}; Single-pass type III membrane protein
CC {ECO:0000269|PubMed:15477348, ECO:0000269|PubMed:15477350}.
CC Note=Present in lipid rafts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JHL0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JHL0-2; Sequence=VSP_016646;
CC -!- TISSUE SPECIFICITY: Strongly expressed in testis. Expressed in heart,
CC spleen and lung. Present in B-cells and mast cells (at protein level).
CC {ECO:0000269|PubMed:11124535, ECO:0000269|PubMed:15477350,
CC ECO:0000269|PubMed:15539154}.
CC -!- DEVELOPMENTAL STAGE: Hardly expressed in pro-B and pre-B cells.
CC Moderately expressed in immature B-cells, mature B-cells and plasma
CC cells. Highly expressed in transitional B-cells.
CC {ECO:0000269|PubMed:15899851}.
CC -!- PTM: Phosphorylated on tyrosines following cross-linking of BCR in B-
CC cells, high affinity IgG receptor (FCGR1) in myeloid cells, or high
CC affinity IgE receptor (FCER1) in mast cells; which induces the
CC recruitment of GRB2. {ECO:0000269|PubMed:15477350}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit normal T-cell, B-cell and mast cell
CC development and normal humoral response, but have hyperresponsive mast
CC cells. {ECO:0000269|PubMed:15899851}.
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DR EMBL; AF257136; AAF91353.1; -; mRNA.
DR EMBL; AF139987; AAF75558.1; -; Genomic_DNA.
DR EMBL; AF139987; AAF75559.1; -; Genomic_DNA.
DR EMBL; AY190024; AAO63156.1; -; mRNA.
DR EMBL; AF289664; AAF99331.1; -; Genomic_DNA.
DR EMBL; AK134721; BAE22256.1; -; mRNA.
DR EMBL; AK138953; BAE23833.1; -; mRNA.
DR EMBL; AK143533; BAE25422.1; -; mRNA.
DR EMBL; AK162321; BAE36852.1; -; mRNA.
DR EMBL; BC005804; AAH05804.1; -; mRNA.
DR CCDS; CCDS39311.1; -. [Q9JHL0-2]
DR CCDS; CCDS39312.1; -. [Q9JHL0-1]
DR RefSeq; NP_064428.1; NM_020044.3. [Q9JHL0-1]
DR RefSeq; NP_075253.2; NM_022964.4. [Q9JHL0-2]
DR RefSeq; XP_006504513.1; XM_006504450.2. [Q9JHL0-1]
DR RefSeq; XP_006504514.1; XM_006504451.3. [Q9JHL0-1]
DR RefSeq; XP_006504515.1; XM_006504452.2. [Q9JHL0-2]
DR AlphaFoldDB; Q9JHL0; -.
DR CORUM; Q9JHL0; -.
DR STRING; 10090.ENSMUSP00000046900; -.
DR iPTMnet; Q9JHL0; -.
DR PhosphoSitePlus; Q9JHL0; -.
DR SwissPalm; Q9JHL0; -.
DR MaxQB; Q9JHL0; -.
DR PaxDb; Q9JHL0; -.
DR PeptideAtlas; Q9JHL0; -.
DR PRIDE; Q9JHL0; -.
DR ProteomicsDB; 295536; -. [Q9JHL0-1]
DR ProteomicsDB; 295537; -. [Q9JHL0-2]
DR Antibodypedia; 1198; 503 antibodies from 40 providers.
DR DNASU; 56743; -.
DR Ensembl; ENSMUST00000036362; ENSMUSP00000046900; ENSMUSG00000040751. [Q9JHL0-1]
DR Ensembl; ENSMUST00000077636; ENSMUSP00000076824; ENSMUSG00000040751. [Q9JHL0-2]
DR Ensembl; ENSMUST00000200998; ENSMUSP00000143977; ENSMUSG00000040751. [Q9JHL0-1]
DR GeneID; 56743; -.
DR KEGG; mmu:56743; -.
DR UCSC; uc008zwm.2; mouse. [Q9JHL0-1]
DR UCSC; uc008zwo.2; mouse. [Q9JHL0-2]
DR CTD; 7462; -.
DR MGI; MGI:1926479; Lat2.
DR VEuPathDB; HostDB:ENSMUSG00000040751; -.
DR eggNOG; ENOG502SH0N; Eukaryota.
DR GeneTree; ENSGT00390000006821; -.
DR HOGENOM; CLU_099084_0_0_1; -.
DR InParanoid; Q9JHL0; -.
DR OMA; ASCRYQN; -.
DR OrthoDB; 1271896at2759; -.
DR PhylomeDB; Q9JHL0; -.
DR TreeFam; TF336203; -.
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR BioGRID-ORCS; 56743; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Lat2; mouse.
DR PRO; PR:Q9JHL0; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9JHL0; protein.
DR Bgee; ENSMUSG00000040751; Expressed in spleen and 94 other tissues.
DR ExpressionAtlas; Q9JHL0; baseline and differential.
DR Genevisible; Q9JHL0; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; ISS:HGNC-UCL.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; ISS:HGNC-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0042113; P:B cell activation; ISS:HGNC-UCL.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:HGNC-UCL.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:HGNC-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:HGNC-UCL.
DR GO; GO:0043303; P:mast cell degranulation; IEA:UniProtKB-KW.
DR InterPro; IPR031428; LAT2.
DR PANTHER; PTHR15646; PTHR15646; 2.
DR Pfam; PF15703; LAT2; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane; Immunity;
KW Lipoprotein; Mast cell degranulation; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..203
FT /note="Linker for activation of T-cells family member 2"
FT /id="PRO_0000083335"
FT TOPO_DOM 1..6
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..27
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..203
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 171..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 59
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 139
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9GZY6"
FT MOD_RES 160
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9GZY6"
FT MOD_RES 192
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9GZY6"
FT LIPID 26
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 29
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 92..103
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_016646"
FT CONFLICT 114
FT /note="V -> E (in Ref. 5; BAE22256)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 203 AA; 22876 MW; 1B21A87D8FBAE097 CRC64;
MSAELELLWP VSGLLLLLLG ATAWLCVHCS RPGVKRNEKI YEQRNRQENA QSSAAAQTYS
LARQVWPGPQ MDTAPNKSFE RKNKMLFSHL EGPESPRYQN FYKGSNQEPD AAYVDPIPTN
YYNWGCFQKP SEDDDSNSYE NVLVCKPSTP ESGVEDFEDY QNSVSIHQWR ESKRTMGAPM
SLSGSPDEEP DYVNGDVAAA ENI
