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Protein

Transcription factor EB

Gene

TFEB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • autophagy Source: UniProtKB-KW
  • embryonic placenta development Source: UniProtKB
  • humoral immune response Source: UniProtKB
  • lysosome organization Source: UniProtKB
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • 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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000112561-MONOMER.
SIGNORiP19484.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:11753. TFEB.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi7942.
MalaCardsiTFEB.
OpenTargetsiENSG00000112561.
Orphaneti319308. Translocation renal cell carcinoma.
PharmGKBiPA36468.

Polymorphism and mutation databases

BioMutaiTFEB.
DMDMi19856774.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274731 – 476Transcription factor EBAdd BLAST476

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei109PhosphoserineBy similarity1
Modified residuei114PhosphoserineBy similarity1
Modified residuei122PhosphoserineCombined sources1
Modified residuei138PhosphoserineCombined sources1
Modified residuei142PhosphoserineCombined sources1
Modified residuei183PhosphothreonineCombined sources1
Modified residuei423PhosphoserineCombined sources1
Modified residuei441PhosphoserineCombined sources1
Modified residuei466PhosphoserineBy similarity1
Modified residuei467PhosphoserineCombined sources1
Modified residuei469PhosphoserineBy similarity1

Post-translational modificationi

Sumoylated; does not affect dimerization with MITF.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP19484.
PaxDbiP19484.
PeptideAtlasiP19484.
PRIDEiP19484.

PTM databases

iPTMnetiP19484.
PhosphoSitePlusiP19484.

Expressioni

Gene expression databases

BgeeiENSG00000112561.
CleanExiHS_TFEB.
ExpressionAtlasiP19484. baseline and differential.
GenevisibleiP19484. HS.

Organism-specific databases

HPAiCAB070416.

Interactioni

Subunit structurei

Homodimer and heterodimer; with TFE3 or MITF.

Protein-protein interaction databases

BioGridi113668. 23 interactors.
DIPiDIP-61625N.
IntActiP19484. 15 interactors.
STRINGi9606.ENSP00000230323.

Structurei

3D structure databases

ProteinModelPortaliP19484.
SMRiP19484.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini235 – 288bHLHPROSITE-ProRule annotationAdd BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni156 – 165Strong transcription activation domainSequence analysis10
Regioni298 – 319Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi10 – 44Gln-richAdd BLAST35
Compositional biasi35 – 44Poly-Gln10
Compositional biasi366 – 414Pro-richAdd BLAST49

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

eggNOGiKOG1318. Eukaryota.
ENOG4110SME. LUCA.
GeneTreeiENSGT00390000004402.
HOGENOMiHOG000231368.
HOVERGENiHBG006768.
InParanoidiP19484.
KOiK15590.
PhylomeDBiP19484.
TreeFamiTF317174.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR021802. MiT/TFE_C.
IPR031867. MiT/TFE_N.
IPR024098. TFEB.
[Graphical view]
PANTHERiPTHR12565:SF133. PTHR12565:SF133. 2 hits.
PfamiPF11851. DUF3371. 1 hit.
PF00010. HLH. 1 hit.
PF15951. MITF_TFEB_C_3_N. 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. AlignAdd to basket

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106A → AA in AAA36730 (PubMed:2115126).Curated1
Sequence conflicti113 – 141GSPKP…NSAPN → ALRNPHQPPPQGCELDTCCP PPLATVLPI in AAA36730 (PubMed:2115126).CuratedAdd BLAST29
Sequence conflicti168 – 170DDV → TMS in AAA36730 (PubMed:2115126).Curated3

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00215972 – 156Missing in isoform 2. 2 PublicationsAdd BLAST85

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006715212.3. [P19484-1]
XP_006715276.1. XM_006715213.2. [P19484-1]
XP_011513217.1. XM_011514915.1. [P19484-1]
XP_011513218.1. XM_011514916.2. [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.3. human. [P19484-1]

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:
EMBLi
GenBanki
DDBJi
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_006715212.3. [P19484-1]
XP_006715276.1. XM_006715213.2. [P19484-1]
XP_011513217.1. XM_011514915.1. [P19484-1]
XP_011513218.1. XM_011514916.2. [P19484-1]
UniGeneiHs.485360.

3D structure databases

ProteinModelPortaliP19484.
SMRiP19484.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113668. 23 interactors.
DIPiDIP-61625N.
IntActiP19484. 15 interactors.
STRINGi9606.ENSP00000230323.

PTM databases

iPTMnetiP19484.
PhosphoSitePlusiP19484.

Polymorphism and mutation databases

BioMutaiTFEB.
DMDMi19856774.

Proteomic databases

MaxQBiP19484.
PaxDbiP19484.
PeptideAtlasiP19484.
PRIDEiP19484.

Protocols and materials databases

DNASUi7942.
Structural Biology KnowledgebaseSearch...

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.3. human. [P19484-1]

Organism-specific databases

CTDi7942.
DisGeNETi7942.
GeneCardsiTFEB.
HGNCiHGNC:11753. TFEB.
HPAiCAB070416.
MalaCardsiTFEB.
MIMi600744. gene.
neXtProtiNX_P19484.
OpenTargetsiENSG00000112561.
Orphaneti319308. Translocation renal cell carcinoma.
PharmGKBiPA36468.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1318. Eukaryota.
ENOG4110SME. LUCA.
GeneTreeiENSGT00390000004402.
HOGENOMiHOG000231368.
HOVERGENiHBG006768.
InParanoidiP19484.
KOiK15590.
PhylomeDBiP19484.
TreeFamiTF317174.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000112561-MONOMER.
SIGNORiP19484.

Miscellaneous databases

ChiTaRSiTFEB. human.
GeneWikiiTFEB.
GenomeRNAii7942.
PROiP19484.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112561.
CleanExiHS_TFEB.
ExpressionAtlasiP19484. baseline and differential.
GenevisibleiP19484. HS.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR021802. MiT/TFE_C.
IPR031867. MiT/TFE_N.
IPR024098. TFEB.
[Graphical view]
PANTHERiPTHR12565:SF133. PTHR12565:SF133. 2 hits.
PfamiPF11851. DUF3371. 1 hit.
PF00010. HLH. 1 hit.
PF15951. MITF_TFEB_C_3_N. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 168 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.