THMS2_MOUSE
ID THMS2_MOUSE Reviewed; 663 AA.
AC Q91YX0; Q3U5K5;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Protein THEMIS2 {ECO:0000305};
DE AltName: Full=Induced by contact to basement membrane 1 protein {ECO:0000303|PubMed:20644716};
DE Short=Protein ICB-1;
DE AltName: Full=Thymocyte-expressed molecule involved in selection protein 2;
GN Name=Themis2 {ECO:0000312|MGI:MGI:2446213};
GN Synonyms=Icb1 {ECO:0000303|PubMed:20644716};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Brain, and 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 [4]
RP TISSUE SPECIFICITY.
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 [5]
RP IDENTIFICATION.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [7]
RP FUNCTION, INTERACTION WITH GRB2; LYN AND VAV1, DEVELOPMENTAL STAGE,
RP PHOSPHORYLATION AT TYR-660, AND MUTAGENESIS OF TYR-660.
RX PubMed=20644716; DOI=10.1371/journal.pone.0011465;
RA Peirce M.J., Brook M., Morrice N., Snelgrove R., Begum S., Lanfrancotti A.,
RA Notley C., Hussell T., Cope A.P., Wait R.;
RT "Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage
RT Toll-like receptor signaling and cytokine production.";
RL PLoS ONE 5:E11465-E11465(2010).
RN [8]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH LAT; GRB2 AND
RP VAV1.
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 [9]
RP TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=24907343; DOI=10.4049/jimmunol.1400943;
RA Hartweger H., Schweighoffer E., Davidson S., Peirce M.J., Wack A.,
RA Tybulewicz V.L.;
RT "Themis2 is not required for B cell development, activation, and antibody
RT responses.";
RL J. Immunol. 193:700-707(2014).
RN [10]
RP TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND
RP INTERACTION WITH GRB2; LYN AND PLCG2.
RX PubMed=27992403; DOI=10.1038/ni.3642;
RA Cheng D., Deobagkar-Lele M., Zvezdova E., Choi S., Uehara S., Baup D.,
RA Bennett S.C., Bull K.R., Crockford T.L., Ferry H., Warzecha C.,
RA Marcellin M., de Peredo A.G., Lesourne R., Anzilotti C., Love P.E.,
RA Cornall R.J.;
RT "Themis2 lowers the threshold for B cell activation during positive
RT selection.";
RL Nat. Immunol. 18:205-213(2017).
CC -!- FUNCTION: May constitute a control point in macrophage inflammatory
CC response, promoting LPS-induced TLR4-mediated TNF production
CC (PubMed:20644716). Determines the threshold for activation of B cells
CC by low-affinity and low-avidity ligands via PLCG2 activation and its
CC downstream pathways (PubMed:27992403). {ECO:0000269|PubMed:20644716,
CC ECO:0000269|PubMed:27992403}.
CC -!- SUBUNIT: Interacts with VAV1 (PubMed:20644716, PubMed:22732588).
CC Interacts with LAT (PubMed:22732588). Interacts constitutively with
CC GRB2, LYN and PLCG2; these interactions increase the activation of
CC PLCG2 and its downstream pathways following B cell receptor stimulation
CC (PubMed:27992403, PubMed:20644716, PubMed:22732588).
CC {ECO:0000269|PubMed:20644716, ECO:0000269|PubMed:22732588,
CC ECO:0000269|PubMed:27992403}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22732588}. Cytoplasm
CC {ECO:0000269|PubMed:22732588}.
CC -!- TISSUE SPECIFICITY: Expressed in both developing and mature B-cells
CC with high expression in immature, follicular and B1 B cells
CC (PubMed:27992403, PubMed:19597499, PubMed:24907343). Also expressed in
CC macrophages and dendritic cells (PubMed:19597499). Down-regulated in
CC splenocytes of mice developing arthritis in a collagen-induced model,
CC not in those of mice failing to develop the disease. Transiently down-
CC regulated in splenocytes of mice infected with influenza virus
CC (PubMed:19597499). {ECO:0000269|PubMed:19597499,
CC ECO:0000269|PubMed:24907343, ECO:0000269|PubMed:27992403}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during the differentiation of bone
CC marrow precursors into macrophages. {ECO:0000269|PubMed:20644716}.
CC -!- INDUCTION: Up-regulated by pro-inflammatory stimuli, such as IFNG (at
CC protein level). Down-regulated by anti-inflammatory stimuli, such as
CC TGFB1 and dexamethasone (at protein level).
CC -!- PTM: Phosphorylation at Tyr-660 is induced by LPS (PubMed:20644716).
CC Phosphorylated by Src kinases (Lck or Fyn) following BCR engagement
CC (PubMed:20644716). {ECO:0000269|PubMed:20644716}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice for Themis2 are viable
CC and produced at the expected ratio (PubMed:24907343). Mice show normal
CC B cell development, activation, or Ab responses (PubMed:24907343).
CC {ECO:0000269|PubMed:24907343}.
CC -!- SIMILARITY: Belongs to the themis family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH13712.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK150471; BAE29588.1; -; mRNA.
DR EMBL; AK153536; BAE32073.1; -; mRNA.
DR EMBL; AK155536; BAE33313.1; -; mRNA.
DR EMBL; AK171009; BAE42180.1; -; mRNA.
DR EMBL; AL627130; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL671190; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013712; AAH13712.1; ALT_INIT; mRNA.
DR EMBL; BC151122; AAI51123.1; -; mRNA.
DR EMBL; BC151126; AAI51127.1; -; mRNA.
DR CCDS; CCDS18735.1; -.
DR RefSeq; NP_001028480.1; NM_001033308.2.
DR AlphaFoldDB; Q91YX0; -.
DR BioGRID; 231027; 1.
DR STRING; 10090.ENSMUSP00000036945; -.
DR iPTMnet; Q91YX0; -.
DR PhosphoSitePlus; Q91YX0; -.
DR EPD; Q91YX0; -.
DR jPOST; Q91YX0; -.
DR MaxQB; Q91YX0; -.
DR PaxDb; Q91YX0; -.
DR PeptideAtlas; Q91YX0; -.
DR PRIDE; Q91YX0; -.
DR ProteomicsDB; 259383; -.
DR Antibodypedia; 30867; 107 antibodies from 21 providers.
DR Ensembl; ENSMUST00000045154; ENSMUSP00000036945; ENSMUSG00000037731.
DR GeneID; 230787; -.
DR KEGG; mmu:230787; -.
DR UCSC; uc008vbv.1; mouse.
DR CTD; 9473; -.
DR MGI; MGI:2446213; Themis2.
DR VEuPathDB; HostDB:ENSMUSG00000037731; -.
DR eggNOG; ENOG502QSJR; Eukaryota.
DR GeneTree; ENSGT00530000063770; -.
DR HOGENOM; CLU_022319_0_0_1; -.
DR InParanoid; Q91YX0; -.
DR OMA; DASHPAD; -.
DR OrthoDB; 337909at2759; -.
DR PhylomeDB; Q91YX0; -.
DR TreeFam; TF333479; -.
DR BioGRID-ORCS; 230787; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Themis2; mouse.
DR PRO; PR:Q91YX0; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q91YX0; protein.
DR Bgee; ENSMUSG00000037731; Expressed in granulocyte and 116 other tissues.
DR Genevisible; Q91YX0; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0050864; P:regulation of B cell activation; IMP:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
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 Cytoplasm; Immunity; Inflammatory response; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..663
FT /note="Protein THEMIS2"
FT /id="PRO_0000084144"
FT REGION 2..237
FT /note="CABIT 1"
FT REGION 238..515
FT /note="CABIT 2"
FT REGION 545..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 559..591
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 622..644
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 596
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5TEJ8"
FT MOD_RES 660
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:20644716"
FT MUTAGEN 552
FT /note="P->A: Drastic decrease in GRB2-binding, but no
FT effect on VAV-binding; when associated with A-555. Partial
FT loss of enhancement of LPS-induced TNF production; when
FT associated with A-555."
FT MUTAGEN 555
FT /note="P->A: Drastic decrease in GRB2-binding, but no
FT effect on VAV-binding; when associated with A-552. Partial
FT loss of enhancement of LPS-induced TNF production; when
FT associated with A-552."
FT MUTAGEN 660
FT /note="Y->F: Loss of phosphorylation. Loss of LYN-binding.
FT Slight decrease in GRB2-binding. No effect on VAV-binding.
FT Partial loss of enhancement of LPS-induced TNF production."
FT /evidence="ECO:0000269|PubMed:20644716"
SQ SEQUENCE 663 AA; 74378 MW; C14C53B493D62A13 CRC64;
MEPVPLQDFV SGLDPTSLPR VLRVCSGVYF EGSVYELFGN ECCLSTGDLI KVTHVQLQKV
VCEYPETGQT LELNPNFTGL FSPLTSLRSY RTLEDLVSAM PQNSTRWPIY FKSTQRIVTK
ASVVPEDQPL RLEAVEIHHG IRYARCVQVS KTKELLHLPL SQKGPFWRCK PSAPQTLHQI
LQDPALKDLT LSCPSLPWNS VILKPQYMLQ AIMHMRSSIV KIPSTLEVEV EDVTASSQHI
HFFKPLRLSE VLAGGGPFPL TTEILEVPEG PPVFLSPWVS FLRKGQRLCI YGPASPSWRV
VASSKSRKVP RYFMLSGAYQ GKLKRRPREF STAYDLLGAL QPGRPLRVVA TKDCDGNEEE
NPDFSFLAVG DRLEVLRSGQ VCGTKGQDID VLVCQRLSEQ SGEEEEDLEE IEDEAEDKEQ
ILLPLYLSGS FVEEVNDSRR YNLVDLTAQY SLPCEVKVVT KDTRHPTDPL ASFPGLRLEE
KLTEPFLVVS LDSQPEMCFE IPPRWLDLTV VEAEGQPAQV ARPLSIAPVE ELSEAFYYSL
RKLPASESQA PPPRPPKSQG INKKQQNIQS CKESSVKPQV VEPQKSCPQP QLKAKTLEAL
PKNKSNVYSK ISVHKKDRKP NPQTQNSVLS MKPKTSSSLG KHSTMESHLL PDPDMDDHDY
EEI
