UniProtKB - Q64092 (TFE3_MOUSE)
Transcription factor E3
Tfe3
Functioni
Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:16936731, PubMed:29146937).
Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF (PubMed:16936731).
Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFE3 phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:27913603).
Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:27913603).
In association with TFEB, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4+ T-cells and thymus-dependent humoral immunity (PubMed:16936731).
Specifically recognizes the MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer (By similarity).
It also binds very well to a USF/MLTF site. May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937).
Acts as a positive regulator of browning of adipose tissue by promoting expression of target genes; mTOR-dependent phosphorylation promotes cytoplasmic retention of TFE3 and inhibits browning of adipose tissue (PubMed:27913603).
Maintains the pluripotent state of embryonic stem cells by promoting the expression of genes such as ESRRB; mTOR-dependent nuclear exclusion promotes exit from pluripotency (PubMed:23582324).
Required to maintain the naive pluripotent state of hematopoietic stem cell; mTOR-dependent cytoplasmic retention of TFE3 promotes the exit of hematopoietic stem cell from pluripotency (By similarity).
By similarity4 PublicationsGO - Molecular functioni
- DNA binding Source: MGI
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- protein heterodimerization activity Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific double-stranded DNA binding Source: MGI
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- humoral immune response Source: UniProtKB
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- positive regulation of brown fat cell differentiation Source: UniProtKB
- positive regulation of cell adhesion Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of osteoclast differentiation Source: MGI
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Adaptive immunity, Immunity, Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Transcription factor E31 PublicationShort name: mTFE31 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:98511, Tfe3 |
VEuPathDBi | HostDB:ENSMUSG00000000134 |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol 1 Publication2 Publications
Nucleus
- Nucleus 3 Publications
Note: When nutrients are present, phosphorylation by MTOR prevents nuclear translocation and activity (PubMed:23582324, PubMed:27913603). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:23582324, PubMed:27913603).2 Publications
Cytosol
- cytosol Source: UniProtKB
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- transcription regulator complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 320 | S → A: Impaired phosphorylation by MTOR, leading to constitutive nuclear localization. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127472 | 1 – 572 | Transcription factor E3Add BLAST | 572 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 187 | Asymmetric dimethylarginineCombined sources | 1 | |
Modified residuei | 320 | Phosphoserine; by MTOR1 Publication | 1 | |
Cross-linki | 338 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 539 | PhosphoserineBy similarity | 1 | |
Modified residuei | 545 | PhosphoserineCombined sources | 1 | |
Modified residuei | 551 | PhosphoserineCombined sources | 1 | |
Modified residuei | 553 | PhosphoserineCombined sources | 1 | |
Modified residuei | 557 | PhosphoserineCombined sources | 1 | |
Modified residuei | 565 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | Q64092 |
MaxQBi | Q64092 |
PaxDbi | Q64092 |
PRIDEi | Q64092 |
ProteomicsDBi | 263164 [Q64092-1] 263165 [Q64092-2] 263166 [Q64092-3] 263167 [Q64092-4] |
PTM databases
iPTMneti | Q64092 |
PhosphoSitePlusi | Q64092 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000000134, Expressed in secondary oocyte and 282 other tissues |
ExpressionAtlasi | Q64092, baseline and differential |
Genevisiblei | Q64092, MM |
Interactioni
Subunit structurei
Homodimer and heterodimer; with TFEB or MITF.
By similarityGO - Molecular functioni
- protein heterodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 229078, 324 interactors |
IntActi | Q64092, 1 interactor |
STRINGi | 10090.ENSMUSP00000076864 |
Miscellaneous databases
RNActi | Q64092, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 345 – 398 | bHLHPROSITE-ProRule annotationAdd BLAST | 54 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 87 – 152 | DisorderedSequence analysisAdd BLAST | 66 | |
Regioni | 210 – 248 | DisorderedSequence analysisAdd BLAST | 39 | |
Regioni | 259 – 270 | Strong transcription activation domainSequence analysisAdd BLAST | 12 | |
Regioni | 408 – 429 | Leucine-zipperAdd BLAST | 22 | |
Regioni | 439 – 495 | DisorderedSequence analysisAdd BLAST | 57 | |
Regioni | 530 – 572 | DisorderedSequence analysisAdd BLAST | 43 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 87 – 122 | Polar residuesSequence analysisAdd BLAST | 36 | |
Compositional biasi | 445 – 459 | Polar residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1318, Eukaryota |
GeneTreei | ENSGT00940000157503 |
HOGENOMi | CLU_031638_3_2_1 |
InParanoidi | Q64092 |
OMAi | DEMRWNK |
OrthoDBi | 1211990at2759 |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR021802, MiT/TFE_C IPR031867, MiT/TFE_N IPR024100, TFE3 |
PANTHERi | PTHR45776:SF3, PTHR45776:SF3, 1 hit |
Pfami | View protein in Pfam PF11851, DUF3371, 1 hit PF00010, HLH, 1 hit PF15951, MITF_TFEB_C_3_N, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSHAAEPARD AVEASAEGPR AVFLLLEERR PAESAQLLSL NSLLPESGIV
60 70 80 90 100
ADIELENILD PDSFYELKSQ PLFLRSSLPI SLQATPTTPA TLSASSSAGG
110 120 130 140 150
SRTPAMSSSS SRVLLRQQLM RAQAQEQERR ERREQAAAAP FPSPAPASPA
160 170 180 190 200
ISVIGVSAGG HTLSRPPPAQ VPREVLKVQT HLENPTRYHL QQARRQQVKQ
210 220 230 240 250
YLSTTLGPKL ASQALTPPPG PSSAQPLPAP ETAHATGPTG SAPNSPMALL
260 270 280 290 300
TIGSSSEKEI DDVIDEIISL ESSYNDEMLS YLPGGTAGLQ LPSTLPVSGN
310 320 330 340 350
LLDVYSSQGV ATPAITVSNS CPAELPNIKR EISETEAKAL LKERQKKDNH
360 370 380 390 400
NLIERRRRFN INDRIKELGT LIPKSNDPEM RWNKGTILKA SVDYIRKLQK
410 420 430 440 450
EQQRSKDLES RQRSLEQANR SLQLRIQELE LQAQIHGLPV PPNPGLLSLT
460 470 480 490 500
TSSVSDSLKP EQLDIEEEGR PSTTFHVSGG PAQNAPPQQP PAPPSDALLD
510 520 530 540 550
LHFPSDHLGD LGDPFHLGLE DILMEEEGMV GGLSGGALSP LRAASDPLLS
560 570
SVSPAVSKAS SRRSSFSMEE ES
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA2AEW1 | A2AEW1_MOUSE | Transcription factor E3 | Tfe3 | 572 | Annotation score: | ||
A2AEW0 | A2AEW0_MOUSE | Transcription factor E3 | Tfe3 | 537 | Annotation score: | ||
A2AEW2 | A2AEW2_MOUSE | Transcription factor E3 | Tfe3 | 136 | Annotation score: | ||
Z4YLF7 | Z4YLF7_MOUSE | Transcription factor E3 | Tfe3 | 108 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 73 | F → S in BAE24128 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 73 | F → S in BAE25994 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 127 – 131 | QERRE → TSGTR in AAB21130 (PubMed:1732746).Curated | 5 | |
Sequence conflicti | 143 | S → G in BAE25994 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 558 | K → N in AAB21130 (PubMed:1732746).Curated | 1 | |
Sequence conflicti | 568 | M → I in AAB21130 (PubMed:1732746).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_022143 | 1 – 105 | Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST | 105 | |
Alternative sequenceiVSP_022144 | 260 – 294 | Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST | 35 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK089762 mRNA Translation: BAC40955.1 AK139756 mRNA Translation: BAE24128.1 AK144657 mRNA Translation: BAE25994.1 AK152221 mRNA Translation: BAE31048.1 AL671995 Genomic DNA No translation available. BC056358 mRNA Translation: AAH56358.1 BC063047 mRNA Translation: AAH63047.1 S76673 mRNA Translation: AAB21130.1 |
CCDSi | CCDS52984.1 [Q64092-1] CCDS52985.1 [Q64092-4] CCDS72332.1 [Q64092-2] CCDS72333.1 [Q64092-3] |
PIRi | A42029 |
RefSeqi | NP_001098666.1, NM_001105196.1 NP_001098667.1, NM_001105197.1 [Q64092-2] NP_001258418.1, NM_001271489.1 [Q64092-2] NP_001258419.1, NM_001271490.1 [Q64092-2] NP_001258420.1, NM_001271491.1 [Q64092-3] NP_766060.2, NM_172472.3 XP_006527641.1, XM_006527578.2 [Q64092-2] XP_017173942.1, XM_017318453.1 [Q64092-2] XP_017173943.1, XM_017318454.1 [Q64092-3] |
Genome annotation databases
Ensembli | ENSMUST00000101695; ENSMUSP00000099219; ENSMUSG00000000134 [Q64092-2] ENSMUST00000115677; ENSMUSP00000111341; ENSMUSG00000000134 [Q64092-2] ENSMUST00000115678; ENSMUSP00000111342; ENSMUSG00000000134 [Q64092-3] ENSMUST00000115679; ENSMUSP00000111343; ENSMUSG00000000134 [Q64092-2] ENSMUST00000137467; ENSMUSP00000134125; ENSMUSG00000000134 [Q64092-2] |
GeneIDi | 209446 |
KEGGi | mmu:209446 |
UCSCi | uc009smg.2, mouse [Q64092-1] uc009smk.2, mouse [Q64092-3] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK089762 mRNA Translation: BAC40955.1 AK139756 mRNA Translation: BAE24128.1 AK144657 mRNA Translation: BAE25994.1 AK152221 mRNA Translation: BAE31048.1 AL671995 Genomic DNA No translation available. BC056358 mRNA Translation: AAH56358.1 BC063047 mRNA Translation: AAH63047.1 S76673 mRNA Translation: AAB21130.1 |
CCDSi | CCDS52984.1 [Q64092-1] CCDS52985.1 [Q64092-4] CCDS72332.1 [Q64092-2] CCDS72333.1 [Q64092-3] |
PIRi | A42029 |
RefSeqi | NP_001098666.1, NM_001105196.1 NP_001098667.1, NM_001105197.1 [Q64092-2] NP_001258418.1, NM_001271489.1 [Q64092-2] NP_001258419.1, NM_001271490.1 [Q64092-2] NP_001258420.1, NM_001271491.1 [Q64092-3] NP_766060.2, NM_172472.3 XP_006527641.1, XM_006527578.2 [Q64092-2] XP_017173942.1, XM_017318453.1 [Q64092-2] XP_017173943.1, XM_017318454.1 [Q64092-3] |
3D structure databases
SMRi | Q64092 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 229078, 324 interactors |
IntActi | Q64092, 1 interactor |
STRINGi | 10090.ENSMUSP00000076864 |
PTM databases
iPTMneti | Q64092 |
PhosphoSitePlusi | Q64092 |
Proteomic databases
jPOSTi | Q64092 |
MaxQBi | Q64092 |
PaxDbi | Q64092 |
PRIDEi | Q64092 |
ProteomicsDBi | 263164 [Q64092-1] 263165 [Q64092-2] 263166 [Q64092-3] 263167 [Q64092-4] |
Protocols and materials databases
Antibodypediai | 11943, 424 antibodies from 40 providers |
DNASUi | 209446 |
Genome annotation databases
Ensembli | ENSMUST00000101695; ENSMUSP00000099219; ENSMUSG00000000134 [Q64092-2] ENSMUST00000115677; ENSMUSP00000111341; ENSMUSG00000000134 [Q64092-2] ENSMUST00000115678; ENSMUSP00000111342; ENSMUSG00000000134 [Q64092-3] ENSMUST00000115679; ENSMUSP00000111343; ENSMUSG00000000134 [Q64092-2] ENSMUST00000137467; ENSMUSP00000134125; ENSMUSG00000000134 [Q64092-2] |
GeneIDi | 209446 |
KEGGi | mmu:209446 |
UCSCi | uc009smg.2, mouse [Q64092-1] uc009smk.2, mouse [Q64092-3] |
Organism-specific databases
CTDi | 7030 |
MGIi | MGI:98511, Tfe3 |
VEuPathDBi | HostDB:ENSMUSG00000000134 |
Phylogenomic databases
eggNOGi | KOG1318, Eukaryota |
GeneTreei | ENSGT00940000157503 |
HOGENOMi | CLU_031638_3_2_1 |
InParanoidi | Q64092 |
OMAi | DEMRWNK |
OrthoDBi | 1211990at2759 |
Miscellaneous databases
BioGRID-ORCSi | 209446, 5 hits in 64 CRISPR screens |
PROi | PR:Q64092 |
RNActi | Q64092, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000000134, Expressed in secondary oocyte and 282 other tissues |
ExpressionAtlasi | Q64092, baseline and differential |
Genevisiblei | Q64092, MM |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR021802, MiT/TFE_C IPR031867, MiT/TFE_N IPR024100, TFE3 |
PANTHERi | PTHR45776:SF3, PTHR45776:SF3, 1 hit |
Pfami | View protein in Pfam PF11851, DUF3371, 1 hit PF00010, HLH, 1 hit PF15951, MITF_TFEB_C_3_N, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TFE3_MOUSE | |
Accessioni | Q64092Primary (citable) accession number: Q64092 Secondary accession number(s): A2AEW3 Q8BN29 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | January 9, 2007 | |
Last modified: | February 23, 2022 | |
This is version 149 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families