ID T22D4_MOUSE Reviewed; 387 AA.
AC Q9EQN3; Q99PD5; Q9D2V9;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 02-OCT-2024, entry version 149.
DE RecName: Full=TSC22 domain family protein 4 {ECO:0000250|UniProtKB:Q9Y3Q8};
DE AltName: Full=TSC22-related-inducible leucine zipper protein 2;
GN Name=Tsc22d4 {ECO:0000250|UniProtKB:Q9Y3Q8};
GN Synonyms=Thg1-pit {ECO:0000303|PubMed:11707329};
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], DEVELOPMENTAL STAGE, AND INDUCTION BY TGF-BETA.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=11707329; DOI=10.1016/s0378-1119(01)00715-6;
RA Fiorenza M.T., Mukhopadhyay M., Westphal H.;
RT "Expression screening for Lhx3 downstream genes identifies Thg-1pit as a
RT novel mouse gene involved in pituitary development.";
RL Gene 278:125-130(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Spleen;
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP TISSUE SPECIFICITY, AND INDUCTION BY HYPEROSMOTIC STRESS.
RX PubMed=17147695; DOI=10.1111/j.1742-4658.2006.05569.x;
RA Fiol D.F., Mak S.K., Kueltz D.;
RT "Specific TSC22 domain transcripts are hypertonically induced and
RT alternatively spliced to protect mouse kidney cells during osmotic
RT stress.";
RL FEBS J. 274:109-124(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; THR-183; SER-187;
RP SER-189; SER-219; THR-223; SER-254; SER-258 AND SER-271, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Spleen, and
RC 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).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=20878296; DOI=10.1007/s12311-010-0211-8;
RA Canterini S., Bosco A., Carletti V., Fuso A., Curci A., Mangia F.,
RA Fiorenza M.T.;
RT "Subcellular TSC22D4 localization in cerebellum granule neurons of the
RT mouse depends on development and differentiation.";
RL Cerebellum 11:28-40(2012).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY WASTING-ASSOCIATED LIVER
RP METABOLISM.
RX PubMed=23307490; DOI=10.1002/emmm.201201869;
RA Jones A., Friedrich K., Rohm M., Schaefer M., Algire C., Kulozik P.,
RA Seibert O., Mueller-Decker K., Sijmonsma T., Strzoda D., Sticht C.,
RA Gretz N., Dallinga-Thie G.M., Leuchs B., Koegl M., Stremmel W., Diaz M.B.,
RA Herzig S.;
RT "TSC22D4 is a molecular output of hepatic wasting metabolism.";
RL EMBO Mol. Med. 5:294-308(2013).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27827363; DOI=10.1038/ncomms13267;
RA Ekim Uestuenel B., Friedrich K., Maida A., Wang X., Krones-Herzig A.,
RA Seibert O., Sommerfeld A., Jones A., Sijmonsma T.P., Sticht C., Gretz N.,
RA Fleming T., Nawroth P.P., Stremmel W., Rose A.J., Berriel-Diaz M.,
RA Blueher M., Herzig S.;
RT "Control of diabetic hyperglycaemia and insulin resistance through
RT TSC22D4.";
RL Nat. Commun. 7:13267-13267(2016).
CC -!- FUNCTION: Binds DNA and acts as a transcriptional repressor
CC (PubMed:27827363). Involved in the regulation of systematic glucose
CC homeostasis and insulin sensitivity, via transcriptional repression of
CC downstream insulin signaling targets such as OBP2A/LCN13
CC (PubMed:27827363). Acts as a negative regulator of lipogenic gene
CC expression in hepatocytes and thereby mediates the control of very low-
CC density lipoprotein release (PubMed:23307490). May play a role in
CC neurite elongation and survival (PubMed:20878296).
CC {ECO:0000269|PubMed:20878296, ECO:0000269|PubMed:23307490,
CC ECO:0000269|PubMed:27827363}.
CC -!- SUBUNIT: Forms a homodimer or heterodimer (By similarity). Forms a
CC heterodimer with TSC22D1 isoforms 1 and 2 (By similarity). Interacts
CC with NRBP1 (By similarity). {ECO:0000250|UniProtKB:Q9Y3Q8}.
CC -!- INTERACTION:
CC Q9EQN3; Q9Z0X1: Aifm1; NbExp=4; IntAct=EBI-7821198, EBI-773597;
CC Q9EQN3; P62500: Tsc22d1; NbExp=2; IntAct=EBI-7821198, EBI-8296837;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20878296}. Cytoplasm
CC {ECO:0000269|PubMed:20878296}. Cell projection, dendrite
CC {ECO:0000269|PubMed:20878296}. Synapse {ECO:0000269|PubMed:20878296}.
CC Note=Localizes away from the nucleus to neurite processes and synaptic
CC termini as cerebellar granular neurons differentiate (PubMed:20878296).
CC Accumulates in the cytoplasm of differentiated Purkinje cells
CC (PubMed:20878296). Localized to both the cytoplasm and nucleus in
CC immature cerebellar granular neurons and atrophic Purkinje cells
CC (PubMed:20878296). {ECO:0000269|PubMed:20878296}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver (at protein level)
CC (PubMed:23307490, PubMed:27827363). Expressed in Purkinje cells and
CC proliferating cerebellar granular neurons (at protein level)
CC (PubMed:20878296). Expressed in the cortex, medulla and papilla of the
CC kidney. {ECO:0000269|PubMed:17147695, ECO:0000269|PubMed:20878296,
CC ECO:0000269|PubMed:23307490, ECO:0000269|PubMed:27827363}.
CC -!- DEVELOPMENTAL STAGE: Expression starts at 8.5 dpc and undergoes a
CC second peak of activation at 12.5 dpc (PubMed:11707329). At 12.5 dpc,
CC expression encompasses the entire central nervous system, with highest
CC levels in the dorsal root and trigeminal ganglia (PubMed:11707329).
CC Expressed in the granule neurons and Purkinje cells in the external and
CC internal granular layers of the cerebellum from postnatal day 6
CC (PubMed:20878296). {ECO:0000269|PubMed:11707329,
CC ECO:0000269|PubMed:20878296}.
CC -!- INDUCTION: Induced by TGF-beta treatment (PubMed:11707329). Induced by
CC a wasting-associated liver metabolism as a result of a methionine-
CC choline deficient diet or cancer-induced cachectic phenotype
CC (PubMed:23307490). Induced by renal hyperosmotic stress
CC (PubMed:17147695). {ECO:0000269|PubMed:11707329,
CC ECO:0000269|PubMed:17147695, ECO:0000269|PubMed:23307490}.
CC -!- MISCELLANEOUS: Involved in the development of hyperglycaemia and
CC insulin resistance in diabetic mouse models (PubMed:27827363). May be
CC involved in altered hepatic lipid handling as part of cancer-induced
CC cachexia (PubMed:23307490). {ECO:0000269|PubMed:23307490,
CC ECO:0000269|PubMed:27827363}.
CC -!- SIMILARITY: Belongs to the TSC-22/Dip/Bun family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK02018.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF315352; AAK02018.1; ALT_FRAME; mRNA.
DR EMBL; AF201286; AAG41219.1; -; mRNA.
DR EMBL; BC018544; AAH18544.1; -; mRNA.
DR EMBL; BC023761; AAH23761.1; -; mRNA.
DR EMBL; BC145721; AAI45722.1; -; mRNA.
DR EMBL; BC145723; AAI45724.1; -; mRNA.
DR EMBL; AK018735; BAB31377.1; -; mRNA.
DR EMBL; AK143608; BAE25460.1; -; mRNA.
DR EMBL; CH466529; EDL19240.1; -; Genomic_DNA.
DR CCDS; CCDS19776.1; -.
DR RefSeq; NP_076399.4; NM_023910.6.
DR AlphaFoldDB; Q9EQN3; -.
DR SMR; Q9EQN3; -.
DR BioGRID; 219663; 3.
DR IntAct; Q9EQN3; 5.
DR MINT; Q9EQN3; -.
DR STRING; 10090.ENSMUSP00000098108; -.
DR GlyGen; Q9EQN3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9EQN3; -.
DR PhosphoSitePlus; Q9EQN3; -.
DR jPOST; Q9EQN3; -.
DR PaxDb; 10090-ENSMUSP00000098107; -.
DR ProteomicsDB; 263231; -.
DR Pumba; Q9EQN3; -.
DR Antibodypedia; 1818; 168 antibodies from 26 providers.
DR DNASU; 78829; -.
DR Ensembl; ENSMUST00000100539.10; ENSMUSP00000098107.4; ENSMUSG00000029723.17.
DR GeneID; 78829; -.
DR KEGG; mmu:78829; -.
DR UCSC; uc009adu.2; mouse.
DR CTD; 81628; -.
DR VEuPathDB; HostDB:ENSMUSG00000029723; -.
DR eggNOG; KOG4797; Eukaryota.
DR GeneTree; ENSGT00940000161400; -.
DR HOGENOM; CLU_052826_0_0_1; -.
DR InParanoid; Q9EQN3; -.
DR OMA; PYHRGRW; -.
DR OrthoDB; 2965073at2759; -.
DR TreeFam; TF338725; -.
DR BioGRID-ORCS; 78829; 2 hits in 79 CRISPR screens.
DR ChiTaRS; Tsc22d4; mouse.
DR PRO; PR:Q9EQN3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9EQN3; protein.
DR Bgee; ENSMUSG00000029723; Expressed in granulocyte and 272 other cell types or tissues.
DR ExpressionAtlas; Q9EQN3; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; IMP:UniProtKB.
DR CDD; cd21941; ZIP_TSC22D4; 1.
DR Gene3D; 1.20.5.490; Single helix bin; 1.
DR InterPro; IPR000580; TSC22/Bun.
DR InterPro; IPR047862; TSC22/BUN_CS.
DR InterPro; IPR042553; TSC22D4.
DR PANTHER; PTHR47610; TSC22 DOMAIN FAMILY PROTEIN 4; 1.
DR PANTHER; PTHR47610:SF1; TSC22 DOMAIN FAMILY PROTEIN 4; 1.
DR Pfam; PF01166; TSC22; 1.
DR SUPFAM; SSF58026; Delta-sleep-inducing peptide immunoreactive peptide; 1.
DR PROSITE; PS01289; TSC22; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; Synapse; Transcription; Transcription regulation.
FT CHAIN 1..387
FT /note="TSC22 domain family protein 4"
FT /id="PRO_0000219375"
FT REGION 1..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..357
FT /note="Leucine-zipper"
FT REGION 368..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..48
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..212
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 57
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q8"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q8"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 183
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 223
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q8"
FT CONFLICT 97
FT /note="E -> K (in Ref. 1; AAK02018)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="Q -> H (in Ref. 2; AAG41219)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 387 AA; 39979 MW; D4160FA3AB2DFB90 CRC64;
MSGGKKKSSF QITSVTTDYE GPGSPGASDS PVPPALAGPP PRLPNGDPNP DPGGRGTPRN
GSPPPGAPAS RFRVVKLPQG LGEPYRRGRW TCVDVYERDL EPPSFGRLLE GIRGASGGTG
GRSLDSRLEL ASLGISTPIP QPGLSQGPTS WLRPPPTSPG PQARSFTGGL GQLAGPGKAK
VETPPLSASP PQQRPPGPGT GDSAQTLPSL RVEVESGGSA AATPPLSRRR DGAVRLRMEL
VAPAETGKVP PTDSRPNSPA LYFDASLVHK SPDPFGAAAA QSLSLARSML AISGHLDSDD
DSGSGSLVGI DNKIEQAMDL VKSHLMFAVR EEVEVLKEQI RDLAERNAAL EQENGLLRAL
ASPEQLAQLP SSGLPRLGPS APNGPSI
//
