TFE3_HUMAN
ID TFE3_HUMAN Reviewed; 575 AA.
AC P19532; A8MZL6; Q5JU74; Q92757; Q92758; Q99964;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 4.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Transcription factor E3 {ECO:0000303|PubMed:9393982};
DE AltName: Full=Class E basic helix-loop-helix protein 33;
DE Short=bHLHe33;
GN Name=TFE3 {ECO:0000303|PubMed:9393982, ECO:0000312|HGNC:HGNC:11752};
GN Synonyms=BHLHE33 {ECO:0000312|HGNC:HGNC:11752};
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] (ISOFORM 1), AND CHROMOSOMAL TRANSLOCATION WITH
RP PSF AND NONO.
RX PubMed=9393982; DOI=10.1038/sj.onc.1201394;
RA Clark J., Lu Y.-J., Sidhar S.K., Parker C., Gill S., Smedley D.,
RA Hamoudi R., Linehan W.M., Shipley J., Cooper C.S.;
RT "Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in
RT papillary renal cell carcinoma.";
RL Oncogene 15:2233-2239(1997).
RN [2]
RP SEQUENCE REVISION.
RA Clark J.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-219, CHROMOSOMAL TRANSLOCATION WITH
RP PRCC, AND TISSUE SPECIFICITY.
RX PubMed=8986805; DOI=10.1073/pnas.93.26.15294;
RA Weterman M.A.J., Wilbrink M., Geurts van Kessel A.;
RT "Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in
RT t(X;1)(p11;q21)-positive papillary renal cell carcinomas.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:15294-15298(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 149-575, AND CHROMOSOMAL TRANSLOCATION
RP WITH PRCC.
RC TISSUE=Monocyte;
RX PubMed=8872474; DOI=10.1093/hmg/5.9.1333;
RA Sidhar S.K., Clark J., Gill S., Hamoudi R., Crew A.J., Gwilliam R.,
RA Ross M., Linehan W.M., Birdsall S., Shipley J., Cooper C.S.;
RT "The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma
RT fuses a novel gene PRCC to the TFE3 transcription factor gene.";
RL Hum. Mol. Genet. 5:1333-1338(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 212-575 (ISOFORM 1), AND FUNCTION.
RC TISSUE=Leukemia;
RX PubMed=2338243; DOI=10.1101/gad.4.2.167;
RA Beckmann H., Su L.-K., Kadesch T.;
RT "TFE3: a helix-loop-helix protein that activates transcription through the
RT immunoglobulin enhancer muE3 motif.";
RL Genes Dev. 4:167-179(1990).
RN [8]
RP INTERACTION WITH TFEB.
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 [9]
RP CHROMOSOMAL TRANSLOCATION WITH ASPSCR1.
RX PubMed=11358836;
RA Heimann P., El Housni H., Ogur G., Weterman M.A.J., Petty E.M., Vassart G.;
RT "Fusion of a novel gene, RCC17, to the TFE3 gene in t(X;17)(p11.2;q25.3)-
RT bearing papillary renal cell carcinomas.";
RL Cancer Res. 61:4130-4135(2001).
RN [10]
RP CHROMOSOMAL TRANSLOCATION WITH ASPSCR1, AND INVOLVEMENT IN ASPS.
RX PubMed=11244503; DOI=10.1038/sj.onc.1204074;
RA Ladanyi M., Lui M.Y., Antonescu C.R., Krause-Boehm A., Meindl A.,
RA Argani P., Healey J.H., Ueda T., Yoshikawa H., Meloni-Ehrig A.,
RA Sorensen P.H.B., Mertens F., Mandahl N., van den Berghe H., Sciot R.,
RA Dal Cin P., Bridge J.;
RT "The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the
RT TFE3 transcription factor gene to ASPL, a novel gene at 17q25.";
RL Oncogene 20:48-57(2001).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-560, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=21209915; DOI=10.1371/journal.pone.0015793;
RA Hong S.B., Oh H., Valera V.A., Baba M., Schmidt L.S., Linehan W.M.;
RT "Inactivation of the FLCN tumor suppressor gene induces TFE3
RT transcriptional activity by increasing its nuclear localization.";
RL PLoS ONE 5:E15793-E15793(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548; SER-556 AND SER-560, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-556 AND SER-568, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP SUBCELLULAR LOCATION.
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548; SER-556 AND SER-560, 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-542 AND SER-548, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=30733432; DOI=10.1038/s41467-018-08020-0;
RA Mathieu J., Detraux D., Kuppers D., Wang Y., Cavanaugh C., Sidhu S.,
RA Levy S., Robitaille A.M., Ferreccio A., Bottorff T., McAlister A.,
RA Somasundaram L., Artoni F., Battle S., Hawkins R.D., Moon R.T., Ware C.B.,
RA Paddison P.J., Ruohola-Baker H.;
RT "Folliculin regulates mTORC1/2 and WNT pathways in early human
RT pluripotency.";
RL Nat. Commun. 10:632-632(2019).
RN [23]
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 [24]
RP VARIANTS MRXSPF PRO-119; LEU-186; ARG-187; MET-187 AND PRO-201, AND
RP INVOLVEMENT IN MRXSPF.
RX PubMed=30595499; DOI=10.1016/j.stem.2018.11.021;
RA Villegas F., Lehalle D., Mayer D., Rittirsch M., Stadler M.B., Zinner M.,
RA Olivieri D., Vabres P., Duplomb-Jego L., De Bont E.S.J.M., Duffourd Y.,
RA Duijkers F., Avila M., Genevieve D., Houcinat N., Jouan T., Kuentz P.,
RA Lichtenbelt K.D., Thauvin-Robinet C., St-Onge J., Thevenon J.,
RA van Gassen K.L.I., van Haelst M., van Koningsbruggen S., Hess D.,
RA Smallwood S.A., Riviere J.B., Faivre L., Betschinger J.;
RT "Lysosomal signaling licenses embryonic stem cell differentiation via
RT inactivation of Tfe3.";
RL Cell Stem Cell 24:257-270(2019).
RN [25]
RP VARIANT MRXSPF GLN-117, AND INVOLVEMENT IN MRXSPF.
RX PubMed=31833172; DOI=10.1002/ajmg.a.61437;
RA Diaz J., Berger S., Leon E.;
RT "TFE3-associated neurodevelopmental disorder: A distinct recognizable
RT syndrome.";
RL Am. J. Med. Genet. A 182:584-590(2020).
RN [26]
RP VARIANTS MRXSPF GLN-117; GLY-184; LYS-187; MET-187; PRO-187; CYS-189;
RP GLN-190 AND PRO-191.
RX PubMed=32409512; DOI=10.1136/jmedgenet-2019-106508;
RA Lehalle D., Vabres P., Sorlin A., Bierhals T., Avila M., Carmignac V.,
RA Chevarin M., Torti E., Abe Y., Bartolomaeus T., Clayton-Smith J., Cogne B.,
RA Cusco I., Duplomb L., De Bont E., Duffourd Y., Duijkers F., Elpeleg O.,
RA Fattal A., Genevieve D., Guillen Sacoto M.J., Guimier A., Harris D.J.,
RA Hempel M., Isidor B., Jouan T., Kuentz P., Koshimizu E., Lichtenbelt K.,
RA Loik Ramey V., Maik M., Miyakate S., Murakami Y., Pasquier L., Pedro H.,
RA Simone L., Sondergaard-Schatz K., St-Onge J., Thevenon J., Valenzuela I.,
RA Abou Jamra R., van Gassen K., van Haelst M.M., van Koningsbruggen S.,
RA Verdura E., Whelan Habela C., Zacher P., Riviere J.B., Thauvin-Robinet C.,
RA Betschinger J., Faivre L.;
RT "De novo mutations in the X-linked TFE3 gene cause intellectual disability
RT with pigmentary mosaicism and storage disorder-like features.";
RL J. Med. Genet. 57:808-819(2020).
CC -!- FUNCTION: Transcription factor that acts as a master regulator of
CC lysosomal biogenesis and immune response (PubMed:2338243,
CC PubMed:29146937, PubMed:30733432, PubMed:31672913). Specifically
CC recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-
CC binding requires dimerization with itself or with another MiT/TFE
CC family member such as TFEB or MITF (By similarity). Involved in the
CC cellular response to amino acid availability by acting downstream of
CC MTOR: in the presence of nutrients, TFE3 phosphorylation by MTOR
CC promotes its cytosolic retention and subsequent inactivation
CC (PubMed:31672913). Upon starvation or lysosomal stress, inhibition of
CC MTOR induces TFE3 dephosphorylation, resulting in nuclear localization
CC and transcription factor activity (PubMed:31672913). Maintains the
CC pluripotent state of embryonic stem cells by promoting the expression
CC of genes such as ESRRB; mTOR-dependent TFE3 cytosolic retention and
CC inactivation promotes exit from pluripotency (By similarity). Required
CC to maintain the naive pluripotent state of hematopoietic stem cell;
CC mTOR-dependent cytoplasmic retention of TFE3 promotes the exit of
CC hematopoietic stem cell from pluripotency (PubMed:30733432). TFE3
CC activity is also involved in the inhibition of neuronal progenitor
CC differentiation (By similarity). Acts as a positive regulator of
CC browning of adipose tissue by promoting expression of target genes;
CC mTOR-dependent phosphorylation promotes cytoplasmic retention of TFE3
CC and inhibits browning of adipose tissue (By similarity). In association
CC with TFEB, activates the expression of CD40L in T-cells, thereby
CC playing a role in T-cell-dependent antibody responses in activated
CC CD4(+) T-cells and thymus-dependent humoral immunity (By similarity).
CC Specifically recognizes the MUE3 box, a subset of E-boxes, present in
CC the immunoglobulin enhancer (PubMed:2338243). It also binds very well
CC to a USF/MLTF site (PubMed:2338243). May regulate lysosomal positioning
CC in response to nutrient deprivation by promoting the expression of
CC PIP4P1 (PubMed:29146937). {ECO:0000250|UniProtKB:Q64092,
CC ECO:0000269|PubMed:2338243, ECO:0000269|PubMed:29146937,
CC ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:31672913}.
CC -!- SUBUNIT: Homodimer and heterodimer; with TFEB or MITF. Interacts with
CC RRAGC/RagC GDP-bound and RRAGD/RagD GDP-bound (By similarity).
CC {ECO:0000250|UniProtKB:Q64092, ECO:0000269|PubMed:15507434,
CC ECO:0000269|PubMed:1748288}.
CC -!- INTERACTION:
CC P19532; O15397: IPO8; NbExp=2; IntAct=EBI-1048957, EBI-358808;
CC P19532; Q9UHA4: LAMTOR3; NbExp=3; IntAct=EBI-1048957, EBI-1038192;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21209915,
CC ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:30733432}. Nucleus
CC {ECO:0000269|PubMed:21209915, ECO:0000269|PubMed:22692423,
CC ECO:0000269|PubMed:30733432}. Note=When nutrients are present,
CC phosphorylation by MTOR prevents nuclear translocation and activity
CC (PubMed:22692423, PubMed:30733432). Conversely, inhibition of mTORC1,
CC starvation and lysosomal disruption, promotes dephosphorylation and
CC translocation to the nucleus (PubMed:22692423, PubMed:30733432).
CC {ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:30733432}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P19532-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P19532-2; Sequence=VSP_056882, VSP_056883;
CC -!- TISSUE SPECIFICITY: Ubiquitous in fetal and adult tissues.
CC {ECO:0000269|PubMed:8986805}.
CC -!- PTM: Sumoylated; does not affect dimerization with MITF.
CC {ECO:0000269|PubMed:15507434}.
CC -!- PTM: Phosphorylation by MTOR regulates its subcellular location and
CC activity (PubMed:21209915, PubMed:30733432). When nutrients are
CC present, phosphorylation by MTOR promotes retention in the cytosol
CC (PubMed:30733432). Inhibition of mTORC1, starvation and lysosomal
CC disruption, promotes dephosphorylation and translocation to the nucleus
CC (PubMed:30733432). {ECO:0000269|PubMed:21209915,
CC ECO:0000269|PubMed:30733432}.
CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic, with
CC pigmentary mosaicism and coarse facies (MRXSPF) [MIM:301066]: A
CC disorder characterized by severe developmental delay with impaired
CC intellectual development and poor speech, coarse facial dysmorphisms,
CC and Blaschkoid pigmentary mosaicism. Additional clinical features may
CC include epilepsy, orthopedic abnormalities, hypotonia, and growth
CC abnormalities. The disorder affects both males and females.
CC {ECO:0000269|PubMed:30595499, ECO:0000269|PubMed:31833172,
CC ECO:0000269|PubMed:32409512}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=A chromosomal aberration involving TFE3 is found in
CC patients with alveolar soft part sarcoma. Translocation
CC t(X;17)(p11;q25) with ASPSCR1 forms a ASPSCR1-TFE3 fusion protein.
CC {ECO:0000269|PubMed:11358836}.
CC -!- DISEASE: Note=Chromosomal aberrations involving TFE3 are found in
CC patients with papillary renal cell carcinoma. Translocation
CC t(X;1)(p11.2;q21.2) with PRCC; translocation t(X;1)(p11.2;p34) with
CC PSF; inversion inv(X)(p11.2;q12) that fuses NONO to TFE3.
CC {ECO:0000269|PubMed:8872474, ECO:0000269|PubMed:8986805}.
CC -!- SIMILARITY: Belongs to the MiT/TFE family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA35714.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA65800.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TFE3ID86.html";
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DR EMBL; X96717; CAA65478.1; -; mRNA.
DR EMBL; AL161985; CAI46207.1; -; mRNA.
DR EMBL; AC146820; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF196779; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX572102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X99721; CAA68061.1; -; Genomic_DNA.
DR EMBL; X97160; CAA65800.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X97161; CAA65800.1; JOINED; Genomic_DNA.
DR EMBL; X97162; CAA65800.1; JOINED; Genomic_DNA.
DR EMBL; X51330; CAA35714.1; ALT_SEQ; mRNA.
DR CCDS; CCDS14315.3; -. [P19532-1]
DR PIR; A34596; A34596.
DR RefSeq; NP_001269071.1; NM_001282142.1.
DR RefSeq; NP_006512.2; NM_006521.5. [P19532-1]
DR PDB; 7F09; X-ray; 2.60 A; A/B/C/D=360-430.
DR PDBsum; 7F09; -.
DR AlphaFoldDB; P19532; -.
DR SMR; P19532; -.
DR BioGRID; 112888; 46.
DR DIP; DIP-50187N; -.
DR IntAct; P19532; 21.
DR STRING; 9606.ENSP00000314129; -.
DR ChEMBL; CHEMBL4295726; -.
DR GlyGen; P19532; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P19532; -.
DR PhosphoSitePlus; P19532; -.
DR BioMuta; TFE3; -.
DR DMDM; 160113240; -.
DR EPD; P19532; -.
DR jPOST; P19532; -.
DR MassIVE; P19532; -.
DR MaxQB; P19532; -.
DR PaxDb; P19532; -.
DR PeptideAtlas; P19532; -.
DR PRIDE; P19532; -.
DR ProteomicsDB; 53672; -. [P19532-1]
DR Antibodypedia; 11943; 429 antibodies from 40 providers.
DR DNASU; 7030; -.
DR Ensembl; ENST00000315869.8; ENSP00000314129.7; ENSG00000068323.17. [P19532-1]
DR Ensembl; ENST00000493583.5; ENSP00000476976.1; ENSG00000068323.17. [P19532-2]
DR GeneID; 7030; -.
DR KEGG; hsa:7030; -.
DR MANE-Select; ENST00000315869.8; ENSP00000314129.7; NM_006521.6; NP_006512.2.
DR UCSC; uc004dmb.5; human. [P19532-1]
DR CTD; 7030; -.
DR DisGeNET; 7030; -.
DR GeneCards; TFE3; -.
DR HGNC; HGNC:11752; TFE3.
DR HPA; ENSG00000068323; Low tissue specificity.
DR MalaCards; TFE3; -.
DR MIM; 301066; phenotype.
DR MIM; 314310; gene.
DR neXtProt; NX_P19532; -.
DR OpenTargets; ENSG00000068323; -.
DR Orphanet; 163699; Alveolar soft tissue sarcoma.
DR Orphanet; 157791; Epithelioid hemangioendothelioma.
DR Orphanet; 319308; MiT family translocation renal cell carcinoma.
DR PharmGKB; PA36467; -.
DR VEuPathDB; HostDB:ENSG00000068323; -.
DR eggNOG; KOG1318; Eukaryota.
DR GeneTree; ENSGT00940000157503; -.
DR HOGENOM; CLU_2196061_0_0_1; -.
DR InParanoid; P19532; -.
DR OMA; DEMRWNK; -.
DR PhylomeDB; P19532; -.
DR TreeFam; TF317174; -.
DR PathwayCommons; P19532; -.
DR SignaLink; P19532; -.
DR SIGNOR; P19532; -.
DR BioGRID-ORCS; 7030; 13 hits in 726 CRISPR screens.
DR ChiTaRS; TFE3; human.
DR GeneWiki; TFE3; -.
DR GenomeRNAi; 7030; -.
DR Pharos; P19532; Tbio.
DR PRO; PR:P19532; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P19532; protein.
DR Bgee; ENSG00000068323; Expressed in inferior olivary complex and 204 other tissues.
DR ExpressionAtlas; P19532; baseline and differential.
DR Genevisible; P19532; 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:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
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; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006959; P:humoral immune response; ISS:UniProtKB.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IEA:InterPro.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; IPR024100; TFE3.
DR PANTHER; PTHR45776:SF3; PTHR45776:SF3; 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 3D-structure; Activator; Adaptive immunity; Alternative splicing;
KW Chromosomal rearrangement; Cytoplasm; Disease variant; DNA-binding;
KW Immunity; Intellectual disability; Isopeptide bond; Methylation; Nucleus;
KW Phosphoprotein; Proto-oncogene; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..575
FT /note="Transcription factor E3"
FT /id="PRO_0000127471"
FT DOMAIN 346..399
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 90..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..271
FT /note="Strong transcription activation domain"
FT /evidence="ECO:0000255"
FT REGION 409..430
FT /note="Leucine-zipper"
FT REGION 473..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 178..179
FT /note="Breakpoint for translocation to form PRCC-TFE3
FT oncogene"
FT SITE 260..261
FT /note="Breakpoint for translocation to form ASPSCR1-TFE3
FT oncogene"
FT SITE 295..296
FT /note="Breakpoint for translocation to form NONO-TFE3, PSF-
FT TFE3 and ASPSCR1-TFE3 oncogenes"
FT MOD_RES 188
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q64092"
FT MOD_RES 321
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000250|UniProtKB:Q64092"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64092"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT CROSSLNK 339
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 77..109
FT /note="SLPISLQATPATPATLSASSSAGGSRTPAMSSS -> RGLQDPCHVVIFFIE
FT GLAAAAANAGPGAGAGEA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_056882"
FT VAR_SEQ 110..575
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_056883"
FT VARIANT 96
FT /note="S -> C (in dbSNP:rs5953258)"
FT /id="VAR_027501"
FT VARIANT 117
FT /note="R -> Q (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:31833172,
FT ECO:0000269|PubMed:32409512"
FT /id="VAR_086338"
FT VARIANT 119
FT /note="Q -> P (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:30595499"
FT /id="VAR_086339"
FT VARIANT 184
FT /note="E -> G (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:32409512"
FT /id="VAR_086340"
FT VARIANT 186
FT /note="P -> L (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:30595499"
FT /id="VAR_086341"
FT VARIANT 187
FT /note="T -> K (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:32409512"
FT /id="VAR_086342"
FT VARIANT 187
FT /note="T -> M (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:30595499,
FT ECO:0000269|PubMed:32409512"
FT /id="VAR_086343"
FT VARIANT 187
FT /note="T -> P (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:32409512"
FT /id="VAR_086344"
FT VARIANT 187
FT /note="T -> R (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:30595499"
FT /id="VAR_086345"
FT VARIANT 189
FT /note="Y -> C (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:32409512"
FT /id="VAR_086346"
FT VARIANT 190
FT /note="H -> Q (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:32409512"
FT /id="VAR_086347"
FT VARIANT 191
FT /note="L -> P (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:32409512"
FT /id="VAR_086348"
FT VARIANT 201
FT /note="Q -> P (in MRXSPF)"
FT /evidence="ECO:0000269|PubMed:30595499"
FT /id="VAR_086349"
FT VARIANT 313
FT /note="T -> A (in dbSNP:rs3027470)"
FT /id="VAR_027502"
FT CONFLICT 172
FT /note="V -> M (in Ref. 6; CAA65800)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="P -> S (in Ref. 6; CAA65800)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="P -> K (in Ref. 7; CAA35714)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="P -> L (in Ref. 6; CAA65800)"
FT /evidence="ECO:0000305"
FT CONFLICT 443
FT /note="P -> G (in Ref. 7; CAA35714)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="A -> T (in Ref. 6; CAA65800 and 7; CAA35714)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="A -> R (in Ref. 7; CAA35714)"
FT /evidence="ECO:0000305"
FT CONFLICT 575
FT /note="S -> M (in Ref. 6; CAA65800)"
FT /evidence="ECO:0000305"
FT HELIX 361..372
FT /evidence="ECO:0007829|PDB:7F09"
FT HELIX 385..429
FT /evidence="ECO:0007829|PDB:7F09"
SQ SEQUENCE 575 AA; 61521 MW; EF1F11AB624C6BE1 CRC64;
MSHAAEPARD GVEASAEGPR AVFVLLEERR PADSAQLLSL NSLLPESGIV ADIELENVLD
PDSFYELKSQ PLPLRSSLPI SLQATPATPA TLSASSSAGG SRTPAMSSSS SSRVLLRQQL
MRAQAQEQER RERREQAAAA PFPSPAPASP AISVVGVSAG GHTLSRPPPA QVPREVLKVQ
THLENPTRYH LQQARRQQVK QYLSTTLGPK LASQALTPPP GPASAQPLPA PEAAHTTGPT
GSAPNSPMAL LTIGSSSEKE IDDVIDEIIS LESSYNDEML SYLPGGTTGL QLPSTLPVSG
NLLDVYSSQG VATPAITVSN SCPAELPNIK REISETEAKA LLKERQKKDN HNLIERRRRF
NINDRIKELG TLIPKSSDPE MRWNKGTILK ASVDYIRKLQ KEQQRSKDLE SRQRSLEQAN
RSLQLRIQEL ELQAQIHGLP VPPTPGLLSL ATTSASDSLK PEQLDIEEEG RPGAATFHVG
GGPAQNAPHQ QPPAPPSDAL LDLHFPSDHL GDLGDPFHLG LEDILMEEEE GVVGGLSGGA
LSPLRAASDP LLSSVSPAVS KASSRRSSFS MEEES
