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P19484

- TFEB_HUMAN

UniProt

P19484 - TFEB_HUMAN

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Protein

Transcription factor EB

Gene

TFEB

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  2. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. autophagy Source: UniProtKB-KW
  2. embryonic placenta development Source: UniProtKB
  3. humoral immune response Source: UniProtKB
  4. lysosome organization Source: UniProtKB
  5. positive regulation of autophagy Source: UniProtKB
  6. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  7. regulation of transcription, DNA-templated Source: UniProtKB
  8. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Adaptive immunity, Autophagy, Immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor EB
Alternative name(s):
Class E basic helix-loop-helix protein 35
Short name:
bHLHe35
Gene namesi
Name:TFEB
Synonyms:BHLHE35
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:11753. TFEB.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

Orphaneti319308. Translocation renal cell carcinoma.
PharmGKBiPA36468.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 476476Transcription factor EBPRO_0000127473Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei122 – 1221Phosphoserine1 Publication
Modified residuei138 – 1381Phosphoserine2 Publications
Modified residuei142 – 1421Phosphoserine2 Publications
Modified residuei183 – 1831Phosphothreonine1 Publication
Modified residuei441 – 4411Phosphoserine1 Publication
Modified residuei467 – 4671Phosphoserine1 Publication

Post-translational modificationi

Sumoylated; does not affect dimerization with MITF.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP19484.
PaxDbiP19484.
PRIDEiP19484.

PTM databases

PhosphoSiteiP19484.

Expressioni

Gene expression databases

BgeeiP19484.
CleanExiHS_TFEB.
ExpressionAtlasiP19484. baseline and differential.
GenevestigatoriP19484.

Organism-specific databases

HPAiHPA049532.

Interactioni

Subunit structurei

Homodimer and heterodimer; with TFE3 or MITF.

Protein-protein interaction databases

BioGridi113668. 2 interactions.
IntActiP19484. 2 interactions.
STRINGi9606.ENSP00000230323.

Structurei

3D structure databases

ProteinModelPortaliP19484.
SMRiP19484. Positions 236-326.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini235 – 28854bHLHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni156 – 16510Strong transcription activation domainSequence Analysis
Regioni298 – 31922Leucine-zipperAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi10 – 4435Gln-richAdd
BLAST
Compositional biasi35 – 4410Poly-Gln
Compositional biasi366 – 41449Pro-richAdd
BLAST

Domaini

The leucin zipper region is essential for homo- or heterodimerization and high-affinity DNA binding. DNA binding is mediated by the basic region.1 Publication

Sequence similaritiesi

Belongs to the MiT/TFE family.Curated
Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG251286.
GeneTreeiENSGT00390000004402.
HOGENOMiHOG000231368.
HOVERGENiHBG006768.
InParanoidiP19484.
KOiK15590.
PhylomeDBiP19484.
TreeFamiTF317174.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR021802. bHLH_ZIP_TF_MiT/TFE.
IPR024098. TFEB.
[Graphical view]
PANTHERiPTHR10014:SF9. PTHR10014:SF9. 1 hit.
PfamiPF11851. DUF3371. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P19484-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MASRIGLRMQ LMREQAQQEE QRERMQQQAV MHYMQQQQQQ QQQQLGGPPT
60 70 80 90 100
PAINTPVHFQ SPPPVPGEVL KVQSYLENPT SYHLQQSQHQ KVREYLSETY
110 120 130 140 150
GNKFAAHISP AQGSPKPPPA ASPGVRAGHV LSSSAGNSAP NSPMAMLHIG
160 170 180 190 200
SNPERELDDV IDNIMRLDDV LGYINPEMQM PNTLPLSSSH LNVYSSDPQV
210 220 230 240 250
TASLVGVTSS SCPADLTQKR ELTDAESRAL AKERQKKDNH NLIERRRRFN
260 270 280 290 300
INDRIKELGM LIPKANDLDV RWNKGTILKA SVDYIRRMQK DLQKSRELEN
310 320 330 340 350
HSRRLEMTNK QLWLRIQELE MQARVHGLPT TSPSGMNMAE LAQQVVKQEL
360 370 380 390 400
PSEEGPGEAL MLGAEVPDPE PLPALPPQAP LPLPTQPPSP FHHLDFSHSL
410 420 430 440 450
SFGGREDEGP PGYPEPLAPG HGSPFPSLSK KDLDLMLLDD SLLPLASDPL
460 470
LSTMSPEASK ASSRRSSFSM EEGDVL
Length:476
Mass (Da):52,865
Last modified:August 29, 2001 - v3
Checksum:i093AE3B79C760D99
GO
Isoform 2 (identifier: P19484-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:391
Mass (Da):43,803
Checksum:i9B43BAA84C5517B2
GO

Sequence cautioni

The sequence AAA36730.1 differs from that shown. Reason: Erroneous initiation.
The sequence CAE77681.1 differs from that shown. Reason: Erroneous initiation.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti106 – 1061A → AA in AAA36730. (PubMed:2115126)Curated
Sequence conflicti113 – 14129GSPKP…NSAPN → ALRNPHQPPPQGCELDTCCP PPLATVLPI in AAA36730. (PubMed:2115126)CuratedAdd
BLAST
Sequence conflicti168 – 1703DDV → TMS in AAA36730. (PubMed:2115126)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei72 – 15685Missing in isoform 2. 2 PublicationsVSP_002159Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS4858.1. [P19484-1]
CCDS64424.1. [P19484-2]
PIRiA35658.
RefSeqiNP_001161299.2. NM_001167827.2.
NP_001258872.1. NM_001271943.1. [P19484-2]
NP_001258873.1. NM_001271944.1. [P19484-1]
NP_001258874.1. NM_001271945.1. [P19484-1]
NP_009093.1. NM_007162.2. [P19484-1]
XP_005249468.1. XM_005249411.1. [P19484-1]
XP_005249469.1. XM_005249412.1. [P19484-1]
XP_006715275.1. XM_006715212.1. [P19484-1]
XP_006715276.1. XM_006715213.1. [P19484-1]
UniGeneiHs.485360.

Genome annotation databases

EnsembliENST00000230323; ENSP00000230323; ENSG00000112561. [P19484-1]
ENST00000373033; ENSP00000362124; ENSG00000112561. [P19484-1]
ENST00000403298; ENSP00000384203; ENSG00000112561. [P19484-1]
ENST00000420312; ENSP00000412551; ENSG00000112561. [P19484-2]
GeneIDi7942.
KEGGihsa:7942.
UCSCiuc003oqr.2. human. [P19484-2]
uc003oqs.1. human. [P19484-1]

Polymorphism databases

DMDMi19856774.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS4858.1. [P19484-1 ]
CCDS64424.1. [P19484-2 ]
PIRi A35658.
RefSeqi NP_001161299.2. NM_001167827.2.
NP_001258872.1. NM_001271943.1. [P19484-2 ]
NP_001258873.1. NM_001271944.1. [P19484-1 ]
NP_001258874.1. NM_001271945.1. [P19484-1 ]
NP_009093.1. NM_007162.2. [P19484-1 ]
XP_005249468.1. XM_005249411.1. [P19484-1 ]
XP_005249469.1. XM_005249412.1. [P19484-1 ]
XP_006715275.1. XM_006715212.1. [P19484-1 ]
XP_006715276.1. XM_006715213.1. [P19484-1 ]
UniGenei Hs.485360.

3D structure databases

ProteinModelPortali P19484.
SMRi P19484. Positions 236-326.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113668. 2 interactions.
IntActi P19484. 2 interactions.
STRINGi 9606.ENSP00000230323.

PTM databases

PhosphoSitei P19484.

Polymorphism databases

DMDMi 19856774.

Proteomic databases

MaxQBi P19484.
PaxDbi P19484.
PRIDEi P19484.

Protocols and materials databases

DNASUi 7942.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000230323 ; ENSP00000230323 ; ENSG00000112561 . [P19484-1 ]
ENST00000373033 ; ENSP00000362124 ; ENSG00000112561 . [P19484-1 ]
ENST00000403298 ; ENSP00000384203 ; ENSG00000112561 . [P19484-1 ]
ENST00000420312 ; ENSP00000412551 ; ENSG00000112561 . [P19484-2 ]
GeneIDi 7942.
KEGGi hsa:7942.
UCSCi uc003oqr.2. human. [P19484-2 ]
uc003oqs.1. human. [P19484-1 ]

Organism-specific databases

CTDi 7942.
GeneCardsi GC06M041651.
HGNCi HGNC:11753. TFEB.
HPAi HPA049532.
MIMi 600744. gene.
neXtProti NX_P19484.
Orphaneti 319308. Translocation renal cell carcinoma.
PharmGKBi PA36468.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG251286.
GeneTreei ENSGT00390000004402.
HOGENOMi HOG000231368.
HOVERGENi HBG006768.
InParanoidi P19484.
KOi K15590.
PhylomeDBi P19484.
TreeFami TF317174.

Miscellaneous databases

ChiTaRSi TFEB. human.
GeneWikii TFEB.
GenomeRNAii 7942.
NextBioi 30462.
PROi P19484.
SOURCEi Search...

Gene expression databases

Bgeei P19484.
CleanExi HS_TFEB.
ExpressionAtlasi P19484. baseline and differential.
Genevestigatori P19484.

Family and domain databases

Gene3Di 4.10.280.10. 1 hit.
InterProi IPR011598. bHLH_dom.
IPR021802. bHLH_ZIP_TF_MiT/TFE.
IPR024098. TFEB.
[Graphical view ]
PANTHERi PTHR10014:SF9. PTHR10014:SF9. 1 hit.
Pfami PF11851. DUF3371. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view ]
SMARTi SM00353. HLH. 1 hit.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
PROSITEi PS50888. BHLH. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.

Entry informationi

Entry nameiTFEB_HUMAN
AccessioniPrimary (citable) accession number: P19484
Secondary accession number(s): Q709B3
, Q7Z6P9, Q9BRJ5, Q9UJD8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: August 29, 2001
Last modified: October 29, 2014
This is version 149 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3