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P19484 (TFEB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor EB
Alternative name(s):
Class E basic helix-loop-helix protein 35
Short name=bHLHe35
Gene names
Name:TFEB
Synonyms:BHLHE35
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length476 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor that 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. 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. 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. It thereby plays a central role in expression of lysosomal genes. Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy. Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer. Plays a role in the signal transduction processes required for normal vascularization of the placenta. Ref.9 Ref.11

Subunit structure

Homodimer and heterodimer; with TFE3 or MITF.

Subcellular location

Cytoplasm. Nucleus. Note: Mainly present in the cytoplasm. Under aberrant lysosomal storage conditions, it translocates from the cytoplasm to the nucleus.

Domain

The leucin zipper region is essential for homo- or heterodimerization and high-affinity DNA binding. DNA binding is mediated by the basic region. Ref.5

Post-translational modification

Sumoylated; does not affect dimerization with MITF. Ref.6

Sequence similarities

Belongs to the MiT/TFE family.

Contains 1 bHLH (basic helix-loop-helix) domain.

Sequence caution

The sequence AAA36730.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAE77681.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processAdaptive immunity
Autophagy
Immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processautophagy

Inferred from electronic annotation. Source: UniProtKB-KW

embryonic placenta development

Inferred from sequence or structural similarity. Source: UniProtKB

humoral immune response

Inferred from sequence or structural similarity. Source: UniProtKB

lysosome organization

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of autophagy

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.9. Source: UniProtKB

regulation of transcription, DNA-templated

Non-traceable author statement Ref.1. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

nucleus

Inferred from direct assay Ref.9. Source: UniProtKB

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionsequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.9. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from direct assay Ref.9. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P19484-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P19484-2)

The sequence of this isoform differs from the canonical sequence as follows:
     72-156: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 476476Transcription factor EB
PRO_0000127473

Regions

Domain235 – 28854bHLH
Region156 – 16510Strong transcription activation domain Potential
Region298 – 31922Leucine-zipper
Compositional bias10 – 4435Gln-rich
Compositional bias35 – 4410Poly-Gln
Compositional bias366 – 41449Pro-rich

Amino acid modifications

Modified residue1221Phosphoserine Ref.10
Modified residue1381Phosphoserine Ref.7 Ref.10
Modified residue1421Phosphoserine Ref.7 Ref.10
Modified residue1831Phosphothreonine Ref.10
Modified residue4411Phosphoserine Ref.10
Modified residue4671Phosphoserine Ref.8

Natural variations

Alternative sequence72 – 15685Missing in isoform 2.
VSP_002159

Experimental info

Sequence conflict1061A → AA in AAA36730. Ref.1
Sequence conflict113 – 14129GSPKP…NSAPN → ALRNPHQPPPQGCELDTCCP PPLATVLPI in AAA36730. Ref.1
Sequence conflict168 – 1703DDV → TMS in AAA36730. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 29, 2001. Version 3.
Checksum: 093AE3B79C760D99

FASTA47652,865
        10         20         30         40         50         60 
MASRIGLRMQ LMREQAQQEE QRERMQQQAV MHYMQQQQQQ QQQQLGGPPT PAINTPVHFQ 

        70         80         90        100        110        120 
SPPPVPGEVL KVQSYLENPT SYHLQQSQHQ KVREYLSETY GNKFAAHISP AQGSPKPPPA 

       130        140        150        160        170        180 
ASPGVRAGHV LSSSAGNSAP NSPMAMLHIG SNPERELDDV IDNIMRLDDV LGYINPEMQM 

       190        200        210        220        230        240 
PNTLPLSSSH LNVYSSDPQV TASLVGVTSS SCPADLTQKR ELTDAESRAL AKERQKKDNH 

       250        260        270        280        290        300 
NLIERRRRFN INDRIKELGM LIPKANDLDV RWNKGTILKA SVDYIRRMQK DLQKSRELEN 

       310        320        330        340        350        360 
HSRRLEMTNK QLWLRIQELE MQARVHGLPT TSPSGMNMAE LAQQVVKQEL PSEEGPGEAL 

       370        380        390        400        410        420 
MLGAEVPDPE PLPALPPQAP LPLPTQPPSP FHHLDFSHSL SFGGREDEGP PGYPEPLAPG 

       430        440        450        460        470 
HGSPFPSLSK KDLDLMLLDD SLLPLASDPL LSTMSPEASK ASSRRSSFSM EEGDVL 

« Hide

Isoform 2 [UniParc].

Checksum: 9B43BAA84C5517B2
Show »

FASTA39143,803

References

« Hide 'large scale' references
[1]"A helix-loop-helix protein related to the immunoglobulin E box-binding proteins."
Carr C.S., Sharp P.A.
Mol. Cell. Biol. 10:4384-4388(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: B-cell.
[2]"Regulation of the MiTF/TFE bHLH-LZ transcription factors through restricted spatial expression and alternative splicing of functional domains."
Kuiper R.P., Schepens M., Thijssen J., Schoenmakers E.F.P.M., Geurts van Kessel A.
Nucleic Acids Res. 32:2315-2322(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-476 (ISOFORM 2).
Tissue: Brain and Lung.
[5]"TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family."
Fisher D.E., Carr C.S., Parent L.A., Sharp P.A.
Genes Dev. 5:2342-2352(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, INTERACTION WITH TFE3, DOMAIN.
[6]"Sumoylation of MITF and its related family members TFE3 and TFEB."
Miller A.J., Levy C., Davis I.J., Razin E., Fisher D.E.
J. Biol. Chem. 280:146-155(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION, INTERACTION WITH MITF.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138 AND SER-142, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-467, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[9]"A gene network regulating lysosomal biogenesis and function."
Sardiello M., Palmieri M., di Ronza A., Medina D.L., Valenza M., Gennarino V.A., Di Malta C., Donaudy F., Embrione V., Polishchuk R.S., Banfi S., Parenti G., Cattaneo E., Ballabio A.
Science 325:473-477(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-138; SER-142; THR-183 AND SER-441, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"ZKSCAN3 is a master transcriptional repressor of autophagy."
Chauhan S., Goodwin J.G., Chauhan S., Manyam G., Wang J., Kamat A.M., Boyd D.D.
Mol. Cell 50:16-28(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M33782 mRNA. Translation: AAA36730.1. Different initiation.
AJ608786 mRNA. Translation: CAE77681.1. Different initiation.
AL035588 Genomic DNA. Translation: CAD92604.1.
BC006225 mRNA. Translation: AAH06225.2.
BC032448 mRNA. Translation: AAH32448.1.
PIRA35658.
RefSeqNP_001161299.2. NM_001167827.2.
NP_001258872.1. NM_001271943.1.
NP_001258873.1. NM_001271944.1.
NP_001258874.1. NM_001271945.1.
NP_009093.1. NM_007162.2.
XP_005249468.1. XM_005249411.1.
XP_005249469.1. XM_005249412.1.
UniGeneHs.485360.

3D structure databases

ProteinModelPortalP19484.
SMRP19484. Positions 236-326.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113668. 2 interactions.
IntActP19484. 2 interactions.
STRING9606.ENSP00000230323.

PTM databases

PhosphoSiteP19484.

Polymorphism databases

DMDM19856774.

Proteomic databases

PaxDbP19484.
PRIDEP19484.

Protocols and materials databases

DNASU7942.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000230323; ENSP00000230323; ENSG00000112561. [P19484-1]
ENST00000373033; ENSP00000362124; ENSG00000112561. [P19484-1]
ENST00000403298; ENSP00000384203; ENSG00000112561. [P19484-1]
ENST00000420312; ENSP00000412551; ENSG00000112561. [P19484-2]
GeneID7942.
KEGGhsa:7942.
UCSCuc003oqr.2. human. [P19484-2]
uc003oqs.1. human. [P19484-1]

Organism-specific databases

CTD7942.
GeneCardsGC06M041651.
HGNCHGNC:11753. TFEB.
HPAHPA049532.
MIM600744. gene.
neXtProtNX_P19484.
Orphanet319308. Translocation renal cell carcinoma.
PharmGKBPA36468.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG251286.
HOGENOMHOG000231368.
HOVERGENHBG006768.
InParanoidP19484.
KOK15590.
PhylomeDBP19484.
TreeFamTF317174.

Gene expression databases

ArrayExpressP19484.
BgeeP19484.
CleanExHS_TFEB.
GenevestigatorP19484.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR024097. bHLH_ZIP_TF.
IPR021802. bHLH_ZIP_TF_MiT/TFE.
IPR024098. TFEB.
[Graphical view]
PANTHERPTHR10014. PTHR10014. 1 hit.
PTHR10014:SF9. PTHR10014:SF9. 1 hit.
PfamPF11851. DUF3371. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTFEB. human.
GeneWikiTFEB.
GenomeRNAi7942.
NextBio30462.
PROP19484.
SOURCESearch...

Entry information

Entry nameTFEB_HUMAN
AccessionPrimary (citable) accession number: P19484
Secondary accession number(s): Q709B3 expand/collapse secondary AC list , Q7Z6P9, Q9BRJ5, Q9UJD8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: August 29, 2001
Last modified: April 16, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM