THMS1_MOUSE
ID THMS1_MOUSE Reviewed; 636 AA.
AC Q8BGW0; Q059Y0; Q3TEM0; Q3UU76; Q8BGP0; Q8C9S6;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Protein THEMIS;
DE AltName: Full=Grb2-associating protein;
DE Short=Gasp;
DE AltName: Full=Protein thylex;
DE AltName: Full=Thymocyte-expressed molecule involved in selection;
GN Name=Themis;
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), FUNCTION, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF THR-512.
RC STRAIN=C57BL/6J; TISSUE=Thymocyte;
RX PubMed=19620281; DOI=10.1128/mcb.00793-09;
RA Kakugawa K., Yasuda T., Miura I., Kobayashi A., Fukiage H., Satoh R.,
RA Matsuda M., Koseki H., Wakana S., Kawamoto H., Yoshida H.;
RT "A novel gene essential for the development of single positive
RT thymocytes.";
RL Mol. Cell. Biol. 29:5128-5135(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, DISRUPTION PHENOTYPE,
RP PHOSPHORYLATION, AND INTERACTION WITH PLCG1 AND ITK.
RX PubMed=19597499; DOI=10.1038/ni.1766;
RA Fu G., Vallee S., Rybakin V., McGuire M.V., Ampudia J., Brockmeyer C.,
RA Salek M., Fallen P.R., Hoerter J.A.H., Munshi A., Huang Y.H., Hu J.,
RA Fox H.S., Sauer K., Acuto O., Gascoigne N.R.J.;
RT "Themis controls thymocyte selection through regulation of T cell antigen
RT receptor-mediated signaling.";
RL Nat. Immunol. 10:848-856(2009).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP PHOSPHORYLATION, AND INTERACTION WITH GRB2.
RX PubMed=19597498; DOI=10.1038/ni.1768;
RA Lesourne R., Uehara S., Lee J., Song K.-D., Li L., Pinkhasov J., Zhang Y.,
RA Weng N.-P., Wildt K.F., Wang L., Bosselut R., Love P.E.;
RT "Themis, a T cell-specific protein important for late thymocyte
RT development.";
RL Nat. Immunol. 10:840-847(2009).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND INTERACTION WITH GRB2.
RX PubMed=19597497; DOI=10.1038/ni.1769;
RA Johnson A.L., Aravind L., Shulzhenko N., Morgun A., Choi S.-Y.,
RA Crockford T.L., Lambe T., Domaschenz H., Kucharska E.M., Zheng L.,
RA Vinuesa C.G., Lenardo M.J., Goodnow C.C., Cornall R.J., Schwartz R.H.;
RT "Themis is a member of a new metazoan gene family and is required for the
RT completion of thymocyte positive selection.";
RL Nat. Immunol. 10:831-839(2009).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP GRB2.
RX PubMed=19805304; DOI=10.1073/pnas.0908593106;
RA Patrick M.S., Oda H., Hayakawa K., Sato Y., Eshima K., Kirikae T.,
RA Iemura S., Shirai M., Abe T., Natsume T., Sasazuki T., Suzuki H.;
RT "Gasp, a Grb2-associating protein, is critical for positive selection of
RT thymocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16345-16350(2009).
RN [9]
RP INTERACTION WITH GRB2; LAT AND PLCG1.
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: Plays a central role in late thymocyte development by
CC controlling both positive and negative T-cell selection. Required to
CC sustain and/or integrate signals required for proper lineage commitment
CC and maturation of T-cells. Regulates T-cell development through T-cell
CC antigen receptor (TCR) signaling and in particular through the
CC regulation of calcium influx and phosphorylation of Erk.
CC {ECO:0000269|PubMed:19597497, ECO:0000269|PubMed:19597498,
CC ECO:0000269|PubMed:19597499, ECO:0000269|PubMed:19620281,
CC ECO:0000269|PubMed:19805304}.
CC -!- SUBUNIT: Interacts with PLCG1, ITK, GRB2, and LAT.
CC {ECO:0000269|PubMed:19597497, ECO:0000269|PubMed:19597498,
CC ECO:0000269|PubMed:19597499, ECO:0000269|PubMed:19805304,
CC ECO:0000269|PubMed:22561606}.
CC -!- INTERACTION:
CC Q8BGW0-1; Q60631-1: Grb2; NbExp=3; IntAct=EBI-15806957, EBI-15532571;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19597497,
CC ECO:0000269|PubMed:19597498, ECO:0000269|PubMed:19620281}. Nucleus
CC {ECO:0000269|PubMed:19597498, ECO:0000269|PubMed:19620281}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8BGW0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BGW0-2; Sequence=VSP_020922;
CC Name=3;
CC IsoId=Q8BGW0-3; Sequence=VSP_020923;
CC Name=4;
CC IsoId=Q8BGW0-4; Sequence=VSP_020919, VSP_020924;
CC Name=5;
CC IsoId=Q8BGW0-5; Sequence=VSP_020920, VSP_020921;
CC -!- TISSUE SPECIFICITY: Expressed in the thymus and to a lesser extent in
CC the spleen but not detectable in non-lymphoid tissues. Highly expressed
CC in thymocytes between the pre-T-cell antigen receptor (pre-TCR) and
CC positive-selection checkpoints and expressed at low level in mature T-
CC cells (at protein level). {ECO:0000269|PubMed:19597497,
CC ECO:0000269|PubMed:19597498, ECO:0000269|PubMed:19597499,
CC ECO:0000269|PubMed:19805304}.
CC -!- INDUCTION: Down-regulated by stimulation through the alpha-beta TCR.
CC {ECO:0000269|PubMed:19597499}.
CC -!- PTM: Phosphorylated on Tyr residues quickly after TCR stimulation.
CC {ECO:0000269|PubMed:19597498, ECO:0000269|PubMed:19597499}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable, are born at the expected
CC Mendelian frequency and present no gross abnormalities. They however
CC display a blockade in late T-cell development with defects in thymocyte
CC selection. The number of transitional CD4(+)CD8(int) thymocytes as well
CC as CD4(+) or CD8(+) single-positive thymocytes is lower. Thymocytes
CC show defective positive selection, resulting in fewer mature
CC thymocytes. Negative selection is also impaired. A greater percentage
CC of T-cells have CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi)
CC memory phenotypes compared to wild-type T-cells.
CC {ECO:0000269|PubMed:19597497, ECO:0000269|PubMed:19597498,
CC ECO:0000269|PubMed:19597499, ECO:0000269|PubMed:19620281,
CC ECO:0000269|PubMed:19805304}.
CC -!- SIMILARITY: Belongs to the themis family. {ECO:0000305}.
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DR EMBL; AB509340; BAH79575.1; -; mRNA.
DR EMBL; AK040594; BAC30638.1; -; mRNA.
DR EMBL; AK041386; BAC30927.1; -; mRNA.
DR EMBL; AK041562; BAC30986.1; -; mRNA.
DR EMBL; AK041622; BAC31008.1; -; mRNA.
DR EMBL; AK088136; BAC40167.1; -; mRNA.
DR EMBL; AK089077; BAC40738.1; -; mRNA.
DR EMBL; AK138701; BAE23752.1; -; mRNA.
DR EMBL; AK169558; BAE41228.1; -; mRNA.
DR EMBL; CH466540; EDL04825.1; -; Genomic_DNA.
DR EMBL; BC125486; AAI25487.1; -; mRNA.
DR EMBL; BC125488; AAI25489.1; -; mRNA.
DR CCDS; CCDS23758.1; -. [Q8BGW0-1]
DR CCDS; CCDS87977.1; -. [Q8BGW0-3]
DR RefSeq; NP_001292592.1; NM_001305663.1. [Q8BGW0-4]
DR RefSeq; NP_848781.1; NM_178666.6. [Q8BGW0-1]
DR AlphaFoldDB; Q8BGW0; -.
DR DIP; DIP-48976N; -.
DR IntAct; Q8BGW0; 6.
DR STRING; 10090.ENSMUSP00000060129; -.
DR iPTMnet; Q8BGW0; -.
DR PhosphoSitePlus; Q8BGW0; -.
DR EPD; Q8BGW0; -.
DR jPOST; Q8BGW0; -.
DR MaxQB; Q8BGW0; -.
DR PaxDb; Q8BGW0; -.
DR PRIDE; Q8BGW0; -.
DR ProteomicsDB; 262812; -. [Q8BGW0-1]
DR ProteomicsDB; 262813; -. [Q8BGW0-2]
DR ProteomicsDB; 262814; -. [Q8BGW0-3]
DR ProteomicsDB; 262815; -. [Q8BGW0-4]
DR ProteomicsDB; 262816; -. [Q8BGW0-5]
DR Antibodypedia; 49883; 248 antibodies from 34 providers.
DR DNASU; 210757; -.
DR Ensembl; ENSMUST00000056097; ENSMUSP00000060129; ENSMUSG00000049109. [Q8BGW0-1]
DR Ensembl; ENSMUST00000060409; ENSMUSP00000055315; ENSMUSG00000049109. [Q8BGW0-2]
DR Ensembl; ENSMUST00000105516; ENSMUSP00000101155; ENSMUSG00000049109. [Q8BGW0-3]
DR GeneID; 210757; -.
DR KEGG; mmu:210757; -.
DR UCSC; uc007eso.2; mouse. [Q8BGW0-5]
DR UCSC; uc007esp.2; mouse. [Q8BGW0-1]
DR UCSC; uc007esq.2; mouse. [Q8BGW0-4]
DR CTD; 387357; -.
DR MGI; MGI:2443552; Themis.
DR VEuPathDB; HostDB:ENSMUSG00000049109; -.
DR eggNOG; ENOG502QSJR; Eukaryota.
DR GeneTree; ENSGT00530000063770; -.
DR HOGENOM; CLU_022319_1_0_1; -.
DR InParanoid; Q8BGW0; -.
DR OMA; KVPVGCQ; -.
DR OrthoDB; 337909at2759; -.
DR PhylomeDB; Q8BGW0; -.
DR TreeFam; TF333479; -.
DR BioGRID-ORCS; 210757; 1 hit in 57 CRISPR screens.
DR ChiTaRS; Themis; mouse.
DR PRO; PR:Q8BGW0; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BGW0; protein.
DR Bgee; ENSMUSG00000049109; Expressed in thymus and 36 other tissues.
DR ExpressionAtlas; Q8BGW0; baseline and differential.
DR Genevisible; Q8BGW0; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0043383; P:negative T cell selection; IMP:UniProtKB.
DR GO; GO:0043368; P:positive T cell selection; IMP:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR InterPro; IPR025946; CABIT_dom.
DR InterPro; IPR039671; THEMIS.
DR PANTHER; PTHR15215; PTHR15215; 1.
DR Pfam; PF12736; CABIT; 2.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cytoplasm; Developmental protein;
KW Immunity; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..636
FT /note="Protein THEMIS"
FT /id="PRO_0000252379"
FT REGION 1..260
FT /note="CABIT 1"
FT REGION 261..520
FT /note="CABIT 2"
FT REGION 583..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 583..603
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 586
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N1K5"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020919"
FT VAR_SEQ 238..262
FT /note="FQKDIVRILPSLDVEVKDITDSYDA -> CKYPLRMLSCVSLHCGIWAREAF
FT RT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020920"
FT VAR_SEQ 263..636
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020921"
FT VAR_SEQ 589..636
FT /note="SHHVDRPKKLPSDESGQDSRAPVGFQNDVADVERQKSKHGPLQPQAPL ->
FT YLSNNKSHDWKPEDDEA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020922"
FT VAR_SEQ 589..636
FT /note="SHHVDRPKKLPSDESGQDSRAPVGFQNDVADVERQKSKHGPLQPQAPL ->
FT DRTPCCC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020923"
FT VAR_SEQ 589..636
FT /note="SHHVDRPKKLPSDESGQDSRAPVGFQNDVADVERQKSKHGPLQPQAPL ->
FT NSSKLKNIKNNKT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020924"
FT MUTAGEN 512
FT /note="T->P: Decreased levels of protein expression in
FT thymocytes. Reduced numbers of CD4 and CD8 single-positive
FT thymocytes as well as reduced numbers of peripheral CD4 and
FT CD8 T-cells."
FT /evidence="ECO:0000269|PubMed:19620281"
FT CONFLICT 152
FT /note="N -> S (in Ref. 2; BAE41228)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 636 AA; 72780 MW; 695B904A539110B8 CRC64;
MALSLEEFVY SLDLRTLPRV LEIQSGIYFE GSVYEMFGNE CCLSTGEVIK ITGLKIKKMM
AEICEGAIGG CESQKPFELP MNFPGLFKVM ADKTPYLSIE EITRTVNIGP SRLGHPCFYH
LKDIKLENLI IKQGEPIRFN SVEEINGETL VNCGVVRNHQ SHSFTLPLSQ EGEFYECEDE
HIYTLKEIVE WKIPKNRTRT VKLTDFSNKW DSTNPFPEDF YGTLILKPVY EIQGVLKFQK
DIVRILPSLD VEVKDITDSY DANWFLQLLS TDDLFEMTSK EFPVVAEVVE ISQGNHLPQS
ILQREKTIVI HKKYQASRIL ASEIRSNFPK RHFLIPISYK GKFKRRPREF PTAYDLQIAK
SRKETLHVVA TKAFHTLHKE LSPVSVGDQF LVHHSETTEV VFEGTRKVNV LTCEKVLNKT
REDAQLPLYM EGGFVEVIHD KKQYQISELC TQFCWPFNVK VAVRDLSIKD DILAATPGLQ
LEEDITDSYL LISDFANPEE CWEIPMSRLN MTVRLVNGSS LPADAGLLQV RSFVEEITEE
QYYMMRRYES SLSHPPPRPP KHPSAEEMKL TLLSLAEERT INLPKSLKSH HVDRPKKLPS
DESGQDSRAP VGFQNDVADV ERQKSKHGPL QPQAPL
