T22D3_MOUSE
ID T22D3_MOUSE Reviewed; 137 AA.
AC Q9Z2S7; B1AVF3; C6EX03; Q3UNI6; Q8K160; Q9EQN0; Q9EQN1; Q9EQN2;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=TSC22 domain family protein 3;
DE AltName: Full=Glucocorticoid-induced leucine zipper protein;
DE AltName: Full=TSC22-related-inducible leucine zipper 3;
DE Short=Tilz3;
GN Name=Tsc22d3; Synonyms=Dsip1, Dsipi, Gilz;
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] (ISOFORMS 1 AND 2), AND INDUCTION.
RC STRAIN=C3H/HeN; TISSUE=Thymus;
RX PubMed=9430225; DOI=10.1016/s1074-7613(00)80398-2;
RA D'Adamio F., Zollo O., Moraca R., Ayroldi E., Bruscoli S., Bartoli A.,
RA Cannarile L., Migliorati G., Riccardi C.;
RT "A new dexamethasone-induced gene of the leucine zipper family protects T
RT lymphocytes from TCR/CD3-activated cell death.";
RL Immunity 7:803-812(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, INTERACTION WITH MYOD1
RP AND HDAC1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND INDUCTION.
RC STRAIN=DBA/2J; TISSUE=Myoblast;
RX PubMed=20124407; DOI=10.1074/jbc.m109.070136;
RA Bruscoli S., Donato V., Velardi E., Di Sante M., Migliorati G., Donato R.,
RA Riccardi C.;
RT "Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit
RT myogenic differentiation and mediate anti-myogenic effects of
RT glucocorticoids.";
RL J. Biol. Chem. 285:10385-10396(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RA Ershler M.A., Belyavsky A.V., Visser J.W.M.;
RT "Identification and characterization of a family of leucine zipper genes
RT related to TSC22.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ, and C57BL/6J; 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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Liver;
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=11468175; DOI=10.1182/blood.v98.3.743;
RA Ayroldi E., Migliorati G., Bruscoli S., Marchetti C., Zollo O.,
RA Cannarile L., D'Adamio F., Riccardi C.;
RT "Modulation of T-cell activation by the glucocorticoid-induced leucine
RT zipper factor via inhibition of nuclear factor kappa B.";
RL Blood 98:743-753(2001).
RN [8]
RP HOMODIMERIZATION, AND INTERACTION WITH JUN AND FOS.
RX PubMed=11397794; DOI=10.1074/jbc.m101522200;
RA Mittelstadt P.R., Ashwell J.D.;
RT "Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ.";
RL J. Biol. Chem. 276:29603-29610(2001).
RN [9]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=12393603; DOI=10.1182/blood-2002-02-0538;
RA Berrebi D., Bruscoli S., Cohen N., Foussat A., Migliorati G.,
RA Bouchet-Delbos L., Maillot M.-C., Portier A., Couderc J., Galanaud P.,
RA Peuchmaur M., Riccardi C., Emilie D.;
RT "Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages:
RT an anti-inflammatory and immunosuppressive mechanism shared by
RT glucocorticoids and IL-10.";
RL Blood 101:729-738(2003).
RN [10]
RP INDUCTION.
RX PubMed=15031210; DOI=10.1182/blood-2003-12-4295;
RA Asselin-Labat M.-L., David M., Biola-Vidamment A., Lecoeuche D.,
RA Zennaro M.-C., Bertoglio J., Pallardy M.;
RT "GILZ, a new target for the transcription factor FoxO3, protects T
RT lymphocytes from interleukin-2 withdrawal-induced apoptosis.";
RL Blood 104:215-223(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-125 AND THR-128,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40 (ISOFORM 3),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73 (ISOFORM 4), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, and Testis;
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).
CC -!- FUNCTION: Protects T-cells from IL2 deprivation-induced apoptosis
CC through the inhibition of FOXO3A transcriptional activity that leads to
CC the down-regulation of the pro-apoptotic factor BCL2L11. In
CC macrophages, plays a role in the anti-inflammatory and
CC immunosuppressive effects of glucocorticoids and IL10. In T-cells,
CC inhibits anti-CD3-induced NFKB1 nuclear translocation. In vitro,
CC suppresses AP1 and NFKB1 DNA-binding activities (By similarity).
CC Isoform 1 and isoform 4 inhibit myogenic differentiation and mediate
CC anti-myogenic effects of glucocorticoids by binding and regulating
CC MYOD1 and HDAC1 transcriptional activity resulting in reduced
CC expression of MYOG. {ECO:0000250, ECO:0000269|PubMed:20124407}.
CC -!- SUBUNIT: Can form homodimers, however it is likely to function as a
CC monomer. Interacts with AP1 and NFKB1 (By similarity). Isoform 1 and
CC isoform 4 interact with MYOD1. Isoform 1 interacts with HDAC1; this
CC interaction affects HDAC1 activity on MYOG promoter and thus inhibits
CC MYOD1 transcriptional activity. {ECO:0000250,
CC ECO:0000269|PubMed:11397794, ECO:0000269|PubMed:20124407}.
CC -!- INTERACTION:
CC Q9Z2S7-3; Q8CFI0: Nedd4l; NbExp=2; IntAct=EBI-15771036, EBI-8046183;
CC Q9Z2S7-3; Q99N57: Raf1; NbExp=2; IntAct=EBI-15771036, EBI-397757;
CC Q9Z2S7-3; Q9WVC6: Sgk1; NbExp=2; IntAct=EBI-15771036, EBI-15591730;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Nucleus.
CC Note=Localization depends on differentiation status of myoblasts. In
CC undifferentiated myoblasts, isoform 1 localizes to the cytoplasm, but
CC in differentiating myoblasts, isoform 1 is localized to the nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm. Nucleus.
CC Note=Localization depends on differentiation status of myoblasts. In
CC undifferentiated myoblasts, isoform 4 localizes to the cytoplasm, but
CC in differentiating myoblasts, isoform 4 is localized to the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Tilz3b;
CC IsoId=Q9Z2S7-1; Sequence=Displayed;
CC Name=2; Synonyms=Tilz3a;
CC IsoId=Q9Z2S7-2; Sequence=VSP_012690;
CC Name=3; Synonyms=Tilz3c;
CC IsoId=Q9Z2S7-3; Sequence=VSP_012691;
CC Name=4; Synonyms=Long Gilz, L-Gilz;
CC IsoId=Q9Z2S7-4; Sequence=VSP_055016;
CC -!- TISSUE SPECIFICITY: Constitutively expressed in lung, intestine, kidney
CC and liver, most probably by resident cells from the macrophage lineage.
CC Expression inversely correlates with T-cell activation, being higher in
CC resting cells and lower in cells activated by TCR/CD3 triggering.
CC Isoform 1 and isoform 4 are expressed in spleen and skeletal muscle (at
CC protein level). Isoform 1 is expressed in thymus, lymph nodes, bone
CC marrow, spleen, lung and skeletal muscle. {ECO:0000269|PubMed:11468175,
CC ECO:0000269|PubMed:12393603, ECO:0000269|PubMed:20124407}.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 and isoform 4 are expressed in
CC differentiating myoblasts at a time of myotube formation.
CC {ECO:0000269|PubMed:20124407}.
CC -!- INDUCTION: By glucocorticoids in lymphoid cells and upon IL4, IL10,
CC IL13 or glucocorticoid treatment in monocyte/macrophage cells.
CC Transiently induced by IL2 deprivation in T-cells. Isoform 1 and
CC isoform 4 expression is up-regulated by the synthetic glucocorticoid
CC dexamethasone in differentiating myoblasts.
CC {ECO:0000269|PubMed:12393603, ECO:0000269|PubMed:15031210,
CC ECO:0000269|PubMed:20124407, ECO:0000269|PubMed:9430225}.
CC -!- DOMAIN: The leucine-zipper is involved in homodimerization.
CC -!- SIMILARITY: Belongs to the TSC-22/Dip/Bun family. {ECO:0000305}.
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DR EMBL; AF024519; AAD01789.1; -; mRNA.
DR EMBL; EU818782; ACJ09091.1; -; mRNA.
DR EMBL; AF201287; AAG41220.1; -; mRNA.
DR EMBL; AF201288; AAG41221.1; -; mRNA.
DR EMBL; AF201289; AAG41222.1; -; mRNA.
DR EMBL; AK083389; BAC38897.1; -; mRNA.
DR EMBL; AK144196; BAE25761.1; -; mRNA.
DR EMBL; AL683809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028813; AAH28813.1; -; mRNA.
DR CCDS; CCDS30440.1; -. [Q9Z2S7-1]
DR CCDS; CCDS41150.1; -. [Q9Z2S7-3]
DR RefSeq; NP_001070832.1; NM_001077364.1. [Q9Z2S7-3]
DR RefSeq; NP_034416.3; NM_010286.4. [Q9Z2S7-1]
DR RefSeq; XP_006528562.1; XM_006528499.3. [Q9Z2S7-3]
DR RefSeq; XP_006528563.1; XM_006528500.3. [Q9Z2S7-3]
DR RefSeq; XP_006528564.1; XM_006528501.3.
DR RefSeq; XP_006528566.1; XM_006528503.3. [Q9Z2S7-2]
DR RefSeq; XP_006528567.1; XM_006528504.3. [Q9Z2S7-3]
DR RefSeq; XP_006528568.1; XM_006528505.3. [Q9Z2S7-3]
DR AlphaFoldDB; Q9Z2S7; -.
DR SMR; Q9Z2S7; -.
DR BioGRID; 199919; 5.
DR DIP; DIP-48844N; -.
DR IntAct; Q9Z2S7; 8.
DR STRING; 10090.ENSMUSP00000108620; -.
DR iPTMnet; Q9Z2S7; -.
DR PhosphoSitePlus; Q9Z2S7; -.
DR REPRODUCTION-2DPAGE; IPI00265379; -.
DR EPD; Q9Z2S7; -.
DR jPOST; Q9Z2S7; -.
DR MaxQB; Q9Z2S7; -.
DR PaxDb; Q9Z2S7; -.
DR PeptideAtlas; Q9Z2S7; -.
DR PRIDE; Q9Z2S7; -.
DR ProteomicsDB; 263227; -. [Q9Z2S7-1]
DR ProteomicsDB; 263228; -. [Q9Z2S7-2]
DR ProteomicsDB; 263229; -. [Q9Z2S7-3]
DR ProteomicsDB; 263230; -. [Q9Z2S7-4]
DR Antibodypedia; 29322; 453 antibodies from 32 providers.
DR DNASU; 14605; -.
DR Ensembl; ENSMUST00000055738; ENSMUSP00000062589; ENSMUSG00000031431. [Q9Z2S7-1]
DR Ensembl; ENSMUST00000112996; ENSMUSP00000108620; ENSMUSG00000031431. [Q9Z2S7-3]
DR GeneID; 14605; -.
DR KEGG; mmu:14605; -.
DR UCSC; uc009ukz.2; mouse. [Q9Z2S7-1]
DR UCSC; uc009ulb.1; mouse. [Q9Z2S7-3]
DR CTD; 1831; -.
DR MGI; MGI:1196284; Tsc22d3.
DR VEuPathDB; HostDB:ENSMUSG00000031431; -.
DR eggNOG; KOG4797; Eukaryota.
DR GeneTree; ENSGT00940000156656; -.
DR HOGENOM; CLU_148757_0_0_1; -.
DR InParanoid; Q9Z2S7; -.
DR OMA; YQSPMEV; -.
DR OrthoDB; 1602203at2759; -.
DR PhylomeDB; Q9Z2S7; -.
DR TreeFam; TF329224; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 14605; 2 hits in 70 CRISPR screens.
DR ChiTaRS; Tsc22d3; mouse.
DR PRO; PR:Q9Z2S7; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9Z2S7; protein.
DR Bgee; ENSMUSG00000031431; Expressed in hindlimb stylopod muscle and 251 other tissues.
DR ExpressionAtlas; Q9Z2S7; baseline and differential.
DR Genevisible; Q9Z2S7; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0070236; P:negative regulation of activation-induced cell death of T cells; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:InterPro.
DR GO; GO:0006970; P:response to osmotic stress; IDA:MGI.
DR InterPro; IPR000580; TSC-22_Dip_Bun.
DR Pfam; PF01166; TSC22; 1.
DR PROSITE; PS01289; TSC22; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..137
FT /note="TSC22 domain family protein 3"
FT /id="PRO_0000219371"
FT REGION 1..60
FT /note="AP1-binding"
FT REGION 76..97
FT /note="Leucine-zipper"
FT REGION 101..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99576"
FT MOD_RES 125
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 128
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..57
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9430225, ECO:0000303|Ref.3"
FT /id="VSP_012690"
FT VAR_SEQ 1..40
FT /note="MNTEMYQTPMEVAVYQLHNFSISFFSSLLGGDVVSVKLDN -> MAQPKTEC
FT RSPVGLDCCNCCLDLANRCELQKEKSGESPGSPFVSNFRQLQEKLVFENLNTDKLNNIM
FT RQDSMEPVVRDPCYLINEGICNRNIDQTMLSILLFFH (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_012691"
FT VAR_SEQ 1..40
FT /note="MNTEMYQTPMEVAVYQLHNFSISFFSSLLGGDVVSVKLDN -> MESQKASS
FT AGAHLPAAPDLPEQAAAAAASKPEKMAQPKTECRSPVGLDCCNCCLDLANRCELQKEKS
FT GESPGSPFVSNFRQLQEKLVFENLNTDKLNNIMRQDSMEPVVRDPCYLINEGICNRNID
FT QTMLSILLFFH (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:20124407"
FT /id="VSP_055016"
FT CONFLICT 22
FT /note="I -> T (in Ref. 1; AAD01789)"
FT /evidence="ECO:0000305"
FT CONFLICT 33
FT /note="V -> L (in Ref. 3; AAG41221)"
FT /evidence="ECO:0000305"
FT MOD_RES Q9Z2S7-3:40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES Q9Z2S7-4:73
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 137 AA; 15177 MW; A11D7B69037F111E CRC64;
MNTEMYQTPM EVAVYQLHNF SISFFSSLLG GDVVSVKLDN SASGASVVAL DNKIEQAMDL
VKNHLMYAVR EEVEVLKEQI RELLEKNSQL ERENTLLKTL ASPEQLEKFQ SRLSPEEPAP
EAPETPETPE APGGSAV
