Summary
Basic Information
Immunogen
Monoclonal antibody is produced by immunizing animals with a synthetic phospho-peptide corresponding to residues surrounding Ser211 of human TFEB protein.
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Buffer
100 µg/ml BSA, 50% glycerol
Preservative
0.02% sodium azide
Purity
> 95% Purity determined by SDS-PAGE.
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.
Target
Full Name
TFEB Gene(Protein Coding) Transcription Factor EB
Introduction
TFEB (Transcription Factor EB) is a Protein Coding gene. Diseases associated with TFEB include Renal Cell Carcinoma, Xp11-Associated and Microphthalmia. Among its related pathways are Mitophagy - animal and PI3K-AKT-mTOR signaling pathway and therapeutic opportunities. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and protein dimerization activity. An important paralog of this gene is MITF.
Alternative Names
Transcription Factor EB; Class E Basic Helix-Loop-Helix Protein 35; BHLHE35; T-Cell Transcription Factor EB; ALPHATFEB; TCFEB;
Function
Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423, PubMed:30120233, PubMed:31672913).
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:1748288, PubMed:19556463, PubMed:29146937).
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 (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423).
Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22576015, PubMed:22343943, PubMed:22692423).
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 (PubMed:19556463, PubMed:22692423).
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:21617040, PubMed:22576015, PubMed:23434374, 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 (By similarity).
Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126).
Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity).
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 (By similarity).
Biological Process
Adaptive immune responseIEA:UniProtKB-KW
AutophagyIEA:UniProtKB-KW
Cellular response to amino acid starvationManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to starvationManual Assertion Based On ExperimentIDA:UniProtKB
Embryonic placenta developmentISS:UniProtKB
Humoral immune responseISS:UniProtKB
Lysosome localizationManual Assertion Based On ExperimentIMP:UniProtKB
Lysosome organizationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of autophagyManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of gene expressionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Regulation of transcription, DNA-templated1 PublicationNAS:UniProtKB
Cellular Location
Cytoplasm, cytosol
Lysosome membrane
Nucleus
Mainly present in the cytoplasm (PubMed:23434374, PubMed:33691586).
Under aberrant lysosomal storage conditions, it translocates from the cytoplasm to the nucleus (PubMed:21617040, PubMed:22576015, PubMed:23434374).
The translocation to the nucleus is regulated by ATP13A2 (PubMed:23434374, PubMed:27278822).
Colocalizes with mTORC1 on the lysosomal membrane: when nutrients are present, phosphorylation by MTOR prevents nuclear translocation and activity (PubMed:22343943, PubMed:22692423).
Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:22343943, PubMed:22692423).
Exported from the nucleus in response to nutrient availability (PubMed:30120233).
In macrophages, translocates into the nucleus upon live S.enterica infection (PubMed:27184844).
Nucleus
(Microbial infection) Following Coxsackievirus B3 infection, full length TFEB and viral protease 3C-mediated cleavage product are translocated from the cytoplasm to the nucleus.
PTM
Phosphorylation by MTOR regulates its subcellular location and activity (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423, PubMed:24081491, PubMed:30120233).
When nutrients are present, phosphorylation by MTOR promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:22576015, PubMed:22343943, PubMed:22692423).
Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:22576015, PubMed:22343943, PubMed:22692423).
Exported from the nucleus in a mTORC1-dependent manner in response to nutrient availability (PubMed:30120233).
Dephosphorylated by phosphatase PPP3CA following Coxsackievirus B3 infection, leading to nuclear translocation (PubMed:33691586).
Sumoylated; does not affect dimerization with MITF.
(Microbial infection) Cleavage by Coxsackievirus B3 protease 3C after site Gln-60. This non-phosphorylated cleavage product retains its ability to interact with TFEB, TFE3 or MITF and presents impaired transcriptional activity, resulting in disruption of lysosomal functions and increased viral infection.