UniProtKB - Q9R210 (TFEB_MOUSE)
Transcription factor EB
Tfeb
Functioni
Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:16936731, PubMed:22343943, PubMed:27278822).
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 TFE3 or MITF (PubMed:16936731, PubMed:27278822).
Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (By similarity).
Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (By similarity).
Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (By similarity).
Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937).
Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:27278822).
In association with TFE3, 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 gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (By similarity).
Plays a role in the signal transduction processes required for normal vascularization of the placenta (PubMed:9806910).
Involved in the immune response to infection by the bacteria S.aureus or S.enterica, acting downstream of protein kinase D (PKD), probably by regulating cytokine and chemokine expression (PubMed:24882217, PubMed:27184844).
By similarity7 PublicationsGO - Molecular functioni
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- enzyme binding Source: MGI
- protein heterodimerization activity Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: NTNU_SB
- sequence-specific double-stranded DNA binding Source: MGI
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- autophagy Source: UniProtKB-KW
- cellular response to amino acid starvation Source: UniProtKB
- cellular response to starvation Source: UniProtKB
- defense response to Gram-negative bacterium Source: UniProtKB
- embryonic placenta development Source: UniProtKB
- humoral immune response Source: UniProtKB
- lysosome localization Source: MGI
- lysosome organization Source: UniProtKB
- positive regulation of autophagy Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of gene expression Source: MGI
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Adaptive immunity, Autophagy, Immunity, Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Transcription factor EB1 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:103270, Tfeb |
VEuPathDBi | HostDB:ENSMUSG00000023990 |
Subcellular locationi
Lysosome
- Lysosome membrane By similarity
Cytoplasm and Cytosol
- cytosol 1 Publication
Nucleus
- Nucleus 1 Publication
Note: Mainly present in the cytoplasm (By similarity). Under aberrant lysosomal storage conditions, it translocates from the cytoplasm to the nucleus (By similarity). The translocation to the nucleus is regulated by ATP13A2 (PubMed:27278822). Colocalizes with mTORC1 on the lysosomal membrane: when nutrients are present, phosphorylation by MTOR prevents nuclear translocation and activity (By similarity). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (By similarity). Exported from the nucleus in response to nutrient availability (By similarity). In macrophages, translocates into the nucleus upon live S.enterica infection (By similarity).By similarity1 Publication
Cytosol
- cytosol Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- transcription regulator complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, Lysosome, Membrane, NucleusPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127474 | 1 – 475 | Transcription factor EBAdd BLAST | 475 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 108 | PhosphoserineCombined sources | 1 | |
Modified residuei | 113 | PhosphoserineCombined sources | 1 | |
Modified residuei | 121 | PhosphoserineCombined sources | 1 | |
Modified residuei | 137 | PhosphoserineCombined sources | 1 | |
Modified residuei | 141 | Phosphoserine; by MTORCombined sources | 1 | |
Modified residuei | 182 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 210 | Phosphoserine; by MTORBy similarity | 1 | |
Modified residuei | 331 | PhosphoserineBy similarity | 1 | |
Modified residuei | 422 | PhosphoserineBy similarity | 1 | |
Modified residuei | 440 | PhosphoserineBy similarity | 1 | |
Modified residuei | 465 | PhosphoserineCombined sources | 1 | |
Modified residuei | 466 | PhosphoserineCombined sources | 1 | |
Modified residuei | 468 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q9R210 |
jPOSTi | Q9R210 |
MaxQBi | Q9R210 |
PaxDbi | Q9R210 |
PRIDEi | Q9R210 |
ProteomicsDBi | 258862 |
PTM databases
iPTMneti | Q9R210 |
PhosphoSitePlusi | Q9R210 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000023990, Expressed in hindlimb stylopod muscle and 248 other tissues |
ExpressionAtlasi | Q9R210, baseline and differential |
Genevisiblei | Q9R210, MM |
Interactioni
Subunit structurei
Homodimer and heterodimer; with TFE3 or MITF.
By similarityGO - Molecular functioni
- enzyme binding Source: MGI
- protein heterodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 204016, 15 interactors |
IntActi | Q9R210, 1 interactor |
STRINGi | 10090.ENSMUSP00000024786 |
Miscellaneous databases
RNActi | Q9R210, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 234 – 287 | bHLHPROSITE-ProRule annotationAdd BLAST | 54 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 52 | DisorderedSequence analysisAdd BLAST | 52 | |
Regioni | 155 – 164 | Strong transcription activation domainSequence analysis | 10 | |
Regioni | 297 – 318 | Leucine-zipperAdd BLAST | 22 | |
Regioni | 351 – 429 | DisorderedSequence analysisAdd BLAST | 79 | |
Regioni | 445 – 475 | DisorderedSequence analysisAdd BLAST | 31 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 135 – 152 | Nuclear export signalBy similarityAdd BLAST | 18 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 22 – 49 | Polar residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 368 – 383 | Pro residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 451 – 468 | Polar residuesSequence analysisAdd BLAST | 18 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1318, Eukaryota |
GeneTreei | ENSGT00940000159691 |
HOGENOMi | CLU_031638_3_1_1 |
InParanoidi | Q9R210 |
OrthoDBi | 1211990at2759 |
PhylomeDBi | Q9R210 |
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 IPR024098, TFEB |
PANTHERi | PTHR45776:SF5, PTHR45776:SF5, 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 |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 9 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MASRIGLRMQ LMREQAQQEE QRERMQQQAV MHYMQQQQQQ QQQLGGPPTP
60 70 80 90 100
AINTPVHFQS PPPVPGEVLK VQSYLENPTS YHLQQSQHQK VREYLSETYG
110 120 130 140 150
NKFAAHVSPA QGSPKPAPAA SPGVRAGHVL STSAGNSAPN SPMAMLHISS
160 170 180 190 200
NPEKEFDDVI DNIMRLDSVL GYINPEMQMP NTLPLSSSHL NVYSGDPQVT
210 220 230 240 250
ASMVGVTSSS CPADLTQKRE LTDAESRALA KERQKKDNHN LIERRRRFNI
260 270 280 290 300
NDRIKELGML IPKANDLDVR WNKGTILKAS VDYIRRMQKD LQKSRELENH
310 320 330 340 350
SRRLEMTNKQ LWLRIQELEM QARVHGLPTT SPSGVNMAEL AQQVVKQELP
360 370 380 390 400
SEDGPGEALM LGPEVPEPEQ MPALPPQAPL PSAAQPQSPF HHLDFSHGLS
410 420 430 440 450
FGGGGDEGPT GYPDTLGTEH GSPFPNLSKK DLDLMLLDDS LLPLASDPLF
460 470
STMSPEASKA SSRRSSFSME EGDVL
Computationally mapped potential isoform sequencesi
There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ3UKG7 | Q3UKG7_MOUSE | Transcription factor EB | Tfeb Tcfeb | 534 | Annotation score: | ||
F6W7D6 | F6W7D6_MOUSE | Transcription factor EB | Tfeb | 334 | Annotation score: | ||
D3Z1X9 | D3Z1X9_MOUSE | Transcription factor EB | Tfeb | 105 | Annotation score: | ||
D3Z6Q7 | D3Z6Q7_MOUSE | Transcription factor EB | Tfeb | 267 | Annotation score: | ||
D3YZM7 | D3YZM7_MOUSE | Transcription factor EB | Tfeb | 103 | Annotation score: | ||
D3Z782 | D3Z782_MOUSE | Transcription factor EB | Tfeb | 76 | Annotation score: | ||
E9PWJ9 | E9PWJ9_MOUSE | Transcription factor EB | Tfeb | 77 | Annotation score: | ||
E9PXZ1 | E9PXZ1_MOUSE | Transcription factor EB | Tfeb | 78 | Annotation score: | ||
D3Z219 | D3Z219_MOUSE | Transcription factor EB | Tfeb | 32 | Annotation score: |
Sequence cautioni
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF079095 mRNA Translation: AAD20979.1 Different initiation. |
CCDSi | CCDS50133.1 |
RefSeqi | NP_001155194.1, NM_001161722.1 NP_001155195.1, NM_001161723.1 NP_035679.3, NM_011549.3 XP_006524066.2, XM_006524003.3 XP_006524069.1, XM_006524006.3 XP_006524070.1, XM_006524007.3 |
Genome annotation databases
Ensembli | ENSMUST00000086932; ENSMUSP00000084151; ENSMUSG00000023990 ENSMUST00000113288; ENSMUSP00000108913; ENSMUSG00000023990 |
GeneIDi | 21425 |
KEGGi | mmu:21425 |
UCSCi | uc008cwc.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF079095 mRNA Translation: AAD20979.1 Different initiation. |
CCDSi | CCDS50133.1 |
RefSeqi | NP_001155194.1, NM_001161722.1 NP_001155195.1, NM_001161723.1 NP_035679.3, NM_011549.3 XP_006524066.2, XM_006524003.3 XP_006524069.1, XM_006524006.3 XP_006524070.1, XM_006524007.3 |
3D structure databases
SMRi | Q9R210 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 204016, 15 interactors |
IntActi | Q9R210, 1 interactor |
STRINGi | 10090.ENSMUSP00000024786 |
PTM databases
iPTMneti | Q9R210 |
PhosphoSitePlusi | Q9R210 |
Proteomic databases
EPDi | Q9R210 |
jPOSTi | Q9R210 |
MaxQBi | Q9R210 |
PaxDbi | Q9R210 |
PRIDEi | Q9R210 |
ProteomicsDBi | 258862 |
Protocols and materials databases
Antibodypediai | 15889, 609 antibodies from 44 providers |
DNASUi | 21425 |
Genome annotation databases
Ensembli | ENSMUST00000086932; ENSMUSP00000084151; ENSMUSG00000023990 ENSMUST00000113288; ENSMUSP00000108913; ENSMUSG00000023990 |
GeneIDi | 21425 |
KEGGi | mmu:21425 |
UCSCi | uc008cwc.2, mouse |
Organism-specific databases
CTDi | 7942 |
MGIi | MGI:103270, Tfeb |
VEuPathDBi | HostDB:ENSMUSG00000023990 |
Phylogenomic databases
eggNOGi | KOG1318, Eukaryota |
GeneTreei | ENSGT00940000159691 |
HOGENOMi | CLU_031638_3_1_1 |
InParanoidi | Q9R210 |
OrthoDBi | 1211990at2759 |
PhylomeDBi | Q9R210 |
Miscellaneous databases
BioGRID-ORCSi | 21425, 3 hits in 65 CRISPR screens |
ChiTaRSi | Tfeb, mouse |
PROi | PR:Q9R210 |
RNActi | Q9R210, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000023990, Expressed in hindlimb stylopod muscle and 248 other tissues |
ExpressionAtlasi | Q9R210, baseline and differential |
Genevisiblei | Q9R210, 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 IPR024098, TFEB |
PANTHERi | PTHR45776:SF5, PTHR45776:SF5, 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 | TFEB_MOUSE | |
Accessioni | Q9R210Primary (citable) accession number: Q9R210 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 29, 2001 |
Last sequence update: | August 29, 2001 | |
Last modified: | February 23, 2022 | |
This is version 154 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