TFEB_HUMAN
ID TFEB_HUMAN Reviewed; 476 AA.
AC P19484; Q709B3; Q7Z6P9; Q9BRJ5; Q9UJD8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2001, sequence version 3.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Transcription factor EB {ECO:0000303|PubMed:2115126};
DE AltName: Full=Class E basic helix-loop-helix protein 35;
DE Short=bHLHe35;
GN Name=TFEB {ECO:0000303|PubMed:2115126, ECO:0000312|HGNC:HGNC:11753};
GN Synonyms=BHLHE35;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND FUNCTION.
RC TISSUE=B-cell;
RX PubMed=2115126; DOI=10.1128/mcb.10.8.4384-4388.1990;
RA Carr C.S., Sharp P.A.;
RT "A helix-loop-helix protein related to the immunoglobulin E box-binding
RT proteins.";
RL Mol. Cell. Biol. 10:4384-4388(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=15118077; DOI=10.1093/nar/gkh571;
RA Kuiper R.P., Schepens M., Thijssen J., Schoenmakers E.F.P.M.,
RA Geurts van Kessel A.;
RT "Regulation of the MiTF/TFE bHLH-LZ transcription factors through
RT restricted spatial expression and alternative splicing of functional
RT domains.";
RL Nucleic Acids Res. 32:2315-2322(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 58-476 (ISOFORM 2).
RC TISSUE=Brain, and Lung;
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 [5]
RP DNA-BINDING, FUNCTION, INTERACTION WITH TFE3, AND DOMAIN.
RX PubMed=1748288; DOI=10.1101/gad.5.12a.2342;
RA Fisher D.E., Carr C.S., Parent L.A., Sharp P.A.;
RT "TFEB has DNA-binding and oligomerization properties of a unique helix-
RT loop-helix/leucine-zipper family.";
RL Genes Dev. 5:2342-2352(1991).
RN [6]
RP SUMOYLATION, AND INTERACTION WITH MITF.
RX PubMed=15507434; DOI=10.1074/jbc.m411757200;
RA Miller A.J., Levy C., Davis I.J., Razin E., Fisher D.E.;
RT "Sumoylation of MITF and its related family members TFE3 and TFEB.";
RL J. Biol. Chem. 280:146-155(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138 AND SER-142, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-467, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=19556463; DOI=10.1126/science.1174447;
RA Sardiello M., Palmieri M., di Ronza A., Medina D.L., Valenza M.,
RA Gennarino V.A., Di Malta C., Donaudy F., Embrione V., Polishchuk R.S.,
RA Banfi S., Parenti G., Cattaneo E., Ballabio A.;
RT "A gene network regulating lysosomal biogenesis and function.";
RL Science 325:473-477(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-138; SER-142;
RP THR-183 AND SER-441, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-142; SER-332 AND
RP SER-423, AND MUTAGENESIS OF SER-142; SER-332 AND SER-423.
RX PubMed=21617040; DOI=10.1126/science.1204592;
RA Settembre C., Di Malta C., Polito V.A., Garcia Arencibia M., Vetrini F.,
RA Erdin S., Erdin S.U., Huynh T., Medina D., Colella P., Sardiello M.,
RA Rubinsztein D.C., Ballabio A.;
RT "TFEB links autophagy to lysosomal biogenesis.";
RL Science 332:1429-1433(2011).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-211, AND MUTAGENESIS
RP OF SER-209; SER-210; SER-211 AND 331-THR-SER-332.
RX PubMed=22576015; DOI=10.4161/auto.19653;
RA Martina J.A., Chen Y., Gucek M., Puertollano R.;
RT "MTORC1 functions as a transcriptional regulator of autophagy by preventing
RT nuclear transport of TFEB.";
RL Autophagy 8:903-914(2012).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-142, AND MUTAGENESIS
RP OF SER-142.
RX PubMed=22343943; DOI=10.1038/emboj.2012.32;
RA Settembre C., Zoncu R., Medina D.L., Vetrini F., Erdin S., Erdin S.,
RA Huynh T., Ferron M., Karsenty G., Vellard M.C., Facchinetti V.,
RA Sabatini D.M., Ballabio A.;
RT "A lysosome-to-nucleus signalling mechanism senses and regulates the
RT lysosome via mTOR and TFEB.";
RL EMBO J. 31:1095-1108(2012).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-211, AND MUTAGENESIS
RP OF SER-211.
RX PubMed=22692423; DOI=10.1126/scisignal.2002790;
RA Roczniak-Ferguson A., Petit C.S., Froehlich F., Qian S., Ky J.,
RA Angarola B., Walther T.C., Ferguson S.M.;
RT "The transcription factor TFEB links mTORC1 signaling to transcriptional
RT control of lysosome homeostasis.";
RL Sci. Signal. 5:RA42-RA42(2012).
RN [15]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-211.
RX PubMed=24081491; DOI=10.1083/jcb.201307084;
RA Petit C.S., Roczniak-Ferguson A., Ferguson S.M.;
RT "Recruitment of folliculin to lysosomes supports the amino acid-dependent
RT activation of Rag GTPases.";
RL J. Cell Biol. 202:1107-1122(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-423 AND SER-467, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23434374; DOI=10.1016/j.molcel.2013.01.024;
RA Chauhan S., Goodwin J.G., Chauhan S., Manyam G., Wang J., Kamat A.M.,
RA Boyd D.D.;
RT "ZKSCAN3 is a master transcriptional repressor of autophagy.";
RL Mol. Cell 50:16-28(2013).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=27184844; DOI=10.1016/j.celrep.2016.04.052;
RA Najibi M., Labed S.A., Visvikis O., Irazoqui J.E.;
RT "An evolutionarily conserved PLC-PKD-TFEB pathway for host defense.";
RL Cell Rep. 15:1728-1742(2016).
RN [19]
RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF SER-142.
RX PubMed=27278822; DOI=10.1038/ncomms11803;
RA Bento C.F., Ashkenazi A., Jimenez-Sanchez M., Rubinsztein D.C.;
RT "The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate
RT autophagy via a common pathway.";
RL Nat. Commun. 7:11803-11803(2016).
RN [20]
RP FUNCTION.
RX PubMed=29146937; DOI=10.1038/s41467-017-01871-z;
RA Willett R., Martina J.A., Zewe J.P., Wills R., Hammond G.R.V.,
RA Puertollano R.;
RT "TFEB regulates lysosomal positioning by modulating TMEM55B expression and
RT JIP4 recruitment to lysosomes.";
RL Nat. Commun. 8:1580-1580(2017).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, PHOSPHORYLATION AT
RP SER-138; SER-142 AND SER-211, AND MUTAGENESIS OF SER-138; SER-142;
RP 144-MET--ILE-149 AND SER-211.
RX PubMed=30120233; DOI=10.1038/s41467-018-05862-6;
RA Napolitano G., Esposito A., Choi H., Matarese M., Benedetti V.,
RA Di Malta C., Monfregola J., Medina D.L., Lippincott-Schwartz J.,
RA Ballabio A.;
RT "mTOR-dependent phosphorylation controls TFEB nuclear export.";
RL Nat. Commun. 9:3312-3312(2018).
RN [22]
RP FUNCTION.
RX PubMed=31672913; DOI=10.1126/science.aax0364;
RA Lawrence R.E., Fromm S.A., Fu Y., Yokom A.L., Kim D.J., Thelen A.M.,
RA Young L.N., Lim C.Y., Samelson A.J., Hurley J.H., Zoncu R.;
RT "Structural mechanism of a Rag GTPase activation checkpoint by the
RT lysosomal folliculin complex.";
RL Science 366:971-977(2019).
RN [23]
RP SUBCELLULAR LOCATION, SUBCELLULAR LOCATION (MICROBIAL INFECTION),
RP PHOSPHORYLATION AT SER-211, PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), AND
RP MUTAGENESIS OF 60-GLN-SER-61.
RX PubMed=33691586; DOI=10.1080/15548627.2021.1896925;
RA Mohamud Y., Tang H., Xue Y.C., Liu H., Ng C.S., Bahreyni A., Luo H.;
RT "Coxsackievirus B3 targets TFEB to disrupt lysosomal function.";
RL Autophagy 10:1-15(2021).
CC -!- FUNCTION: Transcription factor that acts as a master regulator of
CC lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid
CC catabolism, energy metabolism and immune response (PubMed:21617040,
CC PubMed:22576015, PubMed:22343943, PubMed:22692423, PubMed:30120233,
CC PubMed:31672913). Specifically recognizes and binds E-box sequences
CC (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself
CC or with another MiT/TFE family member such as TFE3 or MITF
CC (PubMed:1748288, PubMed:19556463, PubMed:29146937). Involved in the
CC cellular response to amino acid availability by acting downstream of
CC MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR
CC promotes its cytosolic retention and subsequent inactivation
CC (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423).
CC Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB
CC dephosphorylation, resulting in nuclear localization and transcription
CC factor activity (PubMed:22576015, PubMed:22343943, PubMed:22692423).
CC Specifically recognizes and binds the CLEAR-box sequence (5'-
CC GTCACGTGAC-3') present in the regulatory region of many lysosomal
CC genes, leading to activate their expression, thereby playing a central
CC role in expression of lysosomal genes (PubMed:19556463,
CC PubMed:22692423). Regulates lysosomal positioning in response to
CC nutrient deprivation by promoting the expression of PIP4P1
CC (PubMed:29146937). Acts as a positive regulator of autophagy by
CC promoting expression of genes involved in autophagy (PubMed:21617040,
CC PubMed:22576015, PubMed:23434374, PubMed:27278822). In association with
CC TFE3, activates the expression of CD40L in T-cells, thereby playing a
CC role in T-cell-dependent antibody responses in activated CD4(+) T-cells
CC and thymus-dependent humoral immunity (By similarity). Specifically
CC recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-
CC chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the
CC signal transduction processes required for normal vascularization of
CC the placenta (By similarity). Involved in the immune response to
CC infection by the bacteria S.aureus or S.enterica, acting downstream of
CC protein kinase D (PKD), probably by regulating cytokine and chemokine
CC expression (By similarity). {ECO:0000250|UniProtKB:Q9R210,
CC ECO:0000269|PubMed:1748288, ECO:0000269|PubMed:19556463,
CC ECO:0000269|PubMed:2115126, ECO:0000269|PubMed:21617040,
CC ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015,
CC ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374,
CC ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:29146937,
CC ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:31672913}.
CC -!- SUBUNIT: Homodimer and heterodimer; with TFE3 or MITF.
CC {ECO:0000269|PubMed:15507434, ECO:0000269|PubMed:1748288}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21617040,
CC ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:23434374,
CC ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27278822,
CC ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:33691586}. Lysosome
CC membrane {ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22692423}.
CC Nucleus {ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943,
CC ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423,
CC ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:24081491,
CC ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27278822,
CC ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:33691586}. Note=Mainly
CC present in the cytoplasm (PubMed:23434374, PubMed:33691586). Under
CC aberrant lysosomal storage conditions, it translocates from the
CC cytoplasm to the nucleus (PubMed:21617040, PubMed:22576015,
CC PubMed:23434374). The translocation to the nucleus is regulated by
CC ATP13A2 (PubMed:23434374, PubMed:27278822). Colocalizes with mTORC1 on
CC the lysosomal membrane: when nutrients are present, phosphorylation by
CC MTOR prevents nuclear translocation and activity (PubMed:22343943,
CC PubMed:22692423). Conversely, inhibition of mTORC1, starvation and
CC lysosomal disruption, promotes dephosphorylation and translocation to
CC the nucleus (PubMed:22343943, PubMed:22692423). Exported from the
CC nucleus in response to nutrient availability (PubMed:30120233). In
CC macrophages, translocates into the nucleus upon live S.enterica
CC infection (PubMed:27184844). {ECO:0000269|PubMed:21617040,
CC ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015,
CC ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374,
CC ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27278822,
CC ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:33691586}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:33691586}.
CC Note=(Microbial infection) Following Coxsackievirus B3 infection, full
CC length TFEB and viral protease 3C-mediated cleavage product are
CC translocated from the cytoplasm to the nucleus.
CC {ECO:0000269|PubMed:33691586}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P19484-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P19484-2; Sequence=VSP_002159;
CC -!- DOMAIN: The leucin zipper region is essential for homo- or
CC heterodimerization and high-affinity DNA binding. DNA binding is
CC mediated by the basic region. {ECO:0000269|PubMed:1748288}.
CC -!- PTM: Phosphorylation by MTOR regulates its subcellular location and
CC activity (PubMed:21617040, PubMed:22576015, PubMed:22343943,
CC PubMed:22692423, PubMed:24081491, PubMed:30120233). When nutrients are
CC present, phosphorylation by MTOR promotes association with 14-3-3/YWHA
CC adapters and retention in the cytosol (PubMed:22576015,
CC PubMed:22343943, PubMed:22692423). Inhibition of mTORC1, starvation and
CC lysosomal disruption, promotes dephosphorylation and translocation to
CC the nucleus (PubMed:22576015, PubMed:22343943, PubMed:22692423).
CC Exported from the nucleus in a mTORC1-dependent manner in response to
CC nutrient availability (PubMed:30120233). Dephosphorylated by
CC phosphatase PPP3CA following Coxsackievirus B3 infection, leading to
CC nuclear translocation (PubMed:33691586). {ECO:0000269|PubMed:21617040,
CC ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015,
CC ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:24081491,
CC ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:33691586}.
CC -!- PTM: Sumoylated; does not affect dimerization with MITF.
CC {ECO:0000269|PubMed:15507434}.
CC -!- PTM: (Microbial infection) Cleavage by Coxsackievirus B3 protease 3C
CC after site Gln-60. This non-phosphorylated cleavage product retains its
CC ability to interact with TFEB, TFE3 or MITF and presents impaired
CC transcriptional activity, resulting in disruption of lysosomal
CC functions and increased viral infection. {ECO:0000269|PubMed:33691586}.
CC -!- SIMILARITY: Belongs to the MiT/TFE family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36730.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAE77681.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TFEBID531.html";
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DR EMBL; M33782; AAA36730.1; ALT_INIT; mRNA.
DR EMBL; AJ608786; CAE77681.1; ALT_INIT; mRNA.
DR EMBL; AL035588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006225; AAH06225.2; -; mRNA.
DR EMBL; BC032448; AAH32448.1; -; mRNA.
DR CCDS; CCDS4858.1; -. [P19484-1]
DR CCDS; CCDS64424.1; -. [P19484-2]
DR PIR; A35658; A35658.
DR RefSeq; NP_001161299.2; NM_001167827.2.
DR RefSeq; NP_001258872.1; NM_001271943.1. [P19484-2]
DR RefSeq; NP_001258873.1; NM_001271944.1. [P19484-1]
DR RefSeq; NP_001258874.1; NM_001271945.1. [P19484-1]
DR RefSeq; NP_009093.1; NM_007162.2. [P19484-1]
DR RefSeq; XP_005249468.1; XM_005249411.1. [P19484-1]
DR RefSeq; XP_005249469.1; XM_005249412.1. [P19484-1]
DR RefSeq; XP_006715275.1; XM_006715212.3. [P19484-1]
DR RefSeq; XP_006715276.1; XM_006715213.2.
DR RefSeq; XP_011513217.1; XM_011514915.1. [P19484-1]
DR RefSeq; XP_011513218.1; XM_011514916.2. [P19484-1]
DR AlphaFoldDB; P19484; -.
DR SMR; P19484; -.
DR BioGRID; 113668; 37.
DR DIP; DIP-61625N; -.
DR IntAct; P19484; 24.
DR STRING; 9606.ENSP00000351742; -.
DR GlyGen; P19484; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P19484; -.
DR PhosphoSitePlus; P19484; -.
DR BioMuta; TFEB; -.
DR DMDM; 19856774; -.
DR EPD; P19484; -.
DR jPOST; P19484; -.
DR MassIVE; P19484; -.
DR MaxQB; P19484; -.
DR PaxDb; P19484; -.
DR PeptideAtlas; P19484; -.
DR PRIDE; P19484; -.
DR ProteomicsDB; 53668; -. [P19484-1]
DR ProteomicsDB; 53669; -. [P19484-2]
DR Antibodypedia; 15889; 621 antibodies from 44 providers.
DR DNASU; 7942; -.
DR Ensembl; ENST00000230323.8; ENSP00000230323.4; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000343317.11; ENSP00000343948.7; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000373033.6; ENSP00000362124.1; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000403298.9; ENSP00000384203.4; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000406563.7; ENSP00000383998.3; ENSG00000112561.19. [P19484-2]
DR Ensembl; ENST00000416140.6; ENSP00000406491.2; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000419396.6; ENSP00000410391.2; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000419574.6; ENSP00000400276.2; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000420312.6; ENSP00000412551.2; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000424495.2; ENSP00000396168.2; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000445214.2; ENSP00000393874.2; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000677531.1; ENSP00000502927.1; ENSG00000112561.19. [P19484-1]
DR Ensembl; ENST00000678831.1; ENSP00000503069.1; ENSG00000112561.19. [P19484-1]
DR GeneID; 7942; -.
DR KEGG; hsa:7942; -.
DR MANE-Select; ENST00000373033.6; ENSP00000362124.1; NM_001271944.2; NP_001258873.1.
DR UCSC; uc003oqr.3; human. [P19484-1]
DR CTD; 7942; -.
DR DisGeNET; 7942; -.
DR GeneCards; TFEB; -.
DR HGNC; HGNC:11753; TFEB.
DR HPA; ENSG00000112561; Tissue enhanced (skeletal).
DR MalaCards; TFEB; -.
DR MIM; 600744; gene.
DR neXtProt; NX_P19484; -.
DR OpenTargets; ENSG00000112561; -.
DR Orphanet; 319308; MiT family translocation renal cell carcinoma.
DR PharmGKB; PA36468; -.
DR VEuPathDB; HostDB:ENSG00000112561; -.
DR eggNOG; KOG1318; Eukaryota.
DR GeneTree; ENSGT00940000159691; -.
DR HOGENOM; CLU_031638_3_1_1; -.
DR InParanoid; P19484; -.
DR OMA; VHYQSPP; -.
DR OrthoDB; 1211990at2759; -.
DR PhylomeDB; P19484; -.
DR TreeFam; TF317174; -.
DR PathwayCommons; P19484; -.
DR SignaLink; P19484; -.
DR SIGNOR; P19484; -.
DR BioGRID-ORCS; 7942; 11 hits in 1094 CRISPR screens.
DR ChiTaRS; TFEB; human.
DR GeneWiki; TFEB; -.
DR GenomeRNAi; 7942; -.
DR Pharos; P19484; Tbio.
DR PRO; PR:P19484; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P19484; protein.
DR Bgee; ENSG00000112561; Expressed in hindlimb stylopod muscle and 200 other tissues.
DR ExpressionAtlas; P19484; baseline and differential.
DR Genevisible; P19484; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IDA:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
DR GO; GO:0001892; P:embryonic placenta development; ISS:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; ISS:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IMP:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR021802; MiT/TFE_C.
DR InterPro; IPR031867; MiT/TFE_N.
DR InterPro; IPR024098; TFEB.
DR PANTHER; PTHR45776:SF5; PTHR45776:SF5; 1.
DR Pfam; PF11851; DUF3371; 1.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF15951; MITF_TFEB_C_3_N; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Adaptive immunity; Alternative splicing; Autophagy; Cytoplasm;
KW DNA-binding; Immunity; Lysosome; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..476
FT /note="Transcription factor EB"
FT /id="PRO_0000127473"
FT DOMAIN 235..288
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 107..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 156..165
FT /note="Strong transcription activation domain"
FT /evidence="ECO:0000255"
FT REGION 298..319
FT /note="Leucine-zipper"
FT REGION 349..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 447..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 136..153
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:30120233"
FT COMPBIAS 22..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..389
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 60..61
FT /note="(Microbial infection) Cleavage; by Coxsackievirus B3
FT protease 3C"
FT /evidence="ECO:0000269|PubMed:23434374"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R210"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R210"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:30120233,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"
FT MOD_RES 142
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000269|PubMed:21617040,
FT ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:30120233,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"
FT MOD_RES 183
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 211
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000269|PubMed:22576015,
FT ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:24081491,
FT ECO:0000269|PubMed:30120233"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21617040"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21617040,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R210"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R210"
FT VAR_SEQ 72..156
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:2115126"
FT /id="VSP_002159"
FT MUTAGEN 60..61
FT /note="QS->LP: Impaired cleavage by Coxsackievirus B3
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:33691586"
FT MUTAGEN 138
FT /note="S->A: Impaired nuclear export in response to
FT nutrient availability."
FT /evidence="ECO:0000269|PubMed:30120233"
FT MUTAGEN 142
FT /note="S->A: Impaired phosphorylation by MTOR, leading to
FT constitutive nuclear localization and transcription factor
FT activity. Impaired nuclear export in response to nutrient
FT availability."
FT /evidence="ECO:0000269|PubMed:21617040,
FT ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:27278822,
FT ECO:0000269|PubMed:30120233"
FT MUTAGEN 142
FT /note="S->D: Mimics phosphorylation status; abolished
FT translocation to the nucleus in response to starvation."
FT /evidence="ECO:0000269|PubMed:21617040"
FT MUTAGEN 144..149
FT /note="MAMLHI->AAMAHA: Abolished nuclear export in response
FT to nutrient availability."
FT /evidence="ECO:0000269|PubMed:30120233"
FT MUTAGEN 209
FT /note="S->A: Does not affect interaction with 14-3-3/YWHA
FT and subcellular localization."
FT /evidence="ECO:0000269|PubMed:22576015"
FT MUTAGEN 210
FT /note="S->A: Does not affect interaction with 14-3-3/YWHA
FT and subcellular localization."
FT /evidence="ECO:0000269|PubMed:22576015"
FT MUTAGEN 211
FT /note="S->A: Impaired phosphorylation by MTOR, leading to
FT reduced interaction with 14-3-3/YWHA and constitutive
FT nuclear localization. Does not affect nuclear export in
FT response to nutrient availability."
FT /evidence="ECO:0000269|PubMed:22576015,
FT ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:30120233"
FT MUTAGEN 331..332
FT /note="TS->AA: Does not affect interaction with 14-3-3/YWHA
FT and subcellular localization."
FT /evidence="ECO:0000269|PubMed:22576015"
FT MUTAGEN 332
FT /note="S->A: Does not affect nuclear localization."
FT /evidence="ECO:0000269|PubMed:21617040"
FT MUTAGEN 423
FT /note="S->A: Does not affect nuclear localization."
FT /evidence="ECO:0000269|PubMed:21617040"
FT CONFLICT 106
FT /note="A -> AA (in Ref. 1; AAA36730)"
FT /evidence="ECO:0000305"
FT CONFLICT 113..141
FT /note="GSPKPPPAASPGVRAGHVLSSSAGNSAPN -> ALRNPHQPPPQGCELDTCC
FT PPPLATVLPI (in Ref. 1; AAA36730)"
FT /evidence="ECO:0000305"
FT CONFLICT 168..170
FT /note="DDV -> TMS (in Ref. 1; AAA36730)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 52865 MW; 093AE3B79C760D99 CRC64;
MASRIGLRMQ LMREQAQQEE QRERMQQQAV MHYMQQQQQQ QQQQLGGPPT PAINTPVHFQ
SPPPVPGEVL KVQSYLENPT SYHLQQSQHQ KVREYLSETY GNKFAAHISP AQGSPKPPPA
ASPGVRAGHV LSSSAGNSAP NSPMAMLHIG SNPERELDDV IDNIMRLDDV LGYINPEMQM
PNTLPLSSSH LNVYSSDPQV TASLVGVTSS SCPADLTQKR ELTDAESRAL AKERQKKDNH
NLIERRRRFN INDRIKELGM LIPKANDLDV RWNKGTILKA SVDYIRRMQK DLQKSRELEN
HSRRLEMTNK QLWLRIQELE MQARVHGLPT TSPSGMNMAE LAQQVVKQEL PSEEGPGEAL
MLGAEVPDPE PLPALPPQAP LPLPTQPPSP FHHLDFSHSL SFGGREDEGP PGYPEPLAPG
HGSPFPSLSK KDLDLMLLDD SLLPLASDPL LSTMSPEASK ASSRRSSFSM EEGDVL
