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Protein

Transcription factor EB

Gene

Tfeb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

  • DNA binding Source: MGI
  • DNA binding transcription factor activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • autophagy Source: UniProtKB-KW
  • defense response to Gram-negative bacterium Source: UniProtKB
  • embryonic placenta development Source: UniProtKB
  • humoral immune response Source: UniProtKB
  • lysosome organization Source: UniProtKB
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • regulation of defense response to bacterium, incompatible interaction Source: UniProtKB

Keywordsi

Molecular functionActivator, DNA-binding
Biological processAdaptive immunity, Autophagy, Immunity, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor EB
Gene namesi
Name:Tfeb
Synonyms:Tcfeb
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:103270 Tfeb

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Death between 9.5 and 10.5 days in embryonic development. Embryos display severe defects in placental vascularization. The embryonic vasculature forms normally but few vessels are seen entering the placenta and those that do enter fail to thrive and branch normally.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274741 – 475Transcription factor EBAdd BLAST475

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei108PhosphoserineCombined sources1
Modified residuei113PhosphoserineCombined sources1
Modified residuei121PhosphoserineCombined sources1
Modified residuei137PhosphoserineCombined sources1
Modified residuei141PhosphoserineCombined sources1
Modified residuei182PhosphothreonineBy similarity1
Modified residuei422PhosphoserineBy similarity1
Modified residuei440PhosphoserineBy similarity1
Modified residuei465PhosphoserineCombined sources1
Modified residuei466PhosphoserineCombined sources1
Modified residuei468PhosphoserineCombined sources1

Post-translational modificationi

Sumoylated; does not affect dimerization with MITF.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9R210
MaxQBiQ9R210
PaxDbiQ9R210
PRIDEiQ9R210

PTM databases

iPTMnetiQ9R210
PhosphoSitePlusiQ9R210

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Developmental stagei

Expressed at low levels in the embryo but at high levels in the labyrinthine trophoblast cells of the placenta.1 Publication

Gene expression databases

BgeeiENSMUSG00000023990
CleanExiMM_TCFEB
ExpressionAtlasiQ9R210 baseline and differential
GenevisibleiQ9R210 MM

Interactioni

Subunit structurei

Homodimer and heterodimer; with TFE3 or MITF.By similarity

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi204016, 1 interactor
IntActiQ9R210, 2 interactors
MINTiQ9R210
STRINGi10090.ENSMUSP00000024786

Structurei

3D structure databases

ProteinModelPortaliQ9R210
SMRiQ9R210
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini234 – 287bHLHPROSITE-ProRule annotationAdd BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni155 – 164Strong transcription activation domainSequence analysis10
Regioni297 – 318Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi10 – 43Gln-richAdd BLAST34
Compositional biasi35 – 43Poly-Gln9
Compositional biasi363 – 413Pro-richAdd BLAST51

Domaini

The leucin zipper region is essential for homo- or heterodimerization and high-affinity DNA binding. DNA binding is mediated by the basic region (By similarity).By similarity

Sequence similaritiesi

Belongs to the MiT/TFE family.Curated

Phylogenomic databases

eggNOGiKOG1318 Eukaryota
ENOG4110SME LUCA
GeneTreeiENSGT00390000004402
HOGENOMiHOG000231368
HOVERGENiHBG006768
InParanoidiQ9R210
KOiK15590
PhylomeDBiQ9R210

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR021802 MiT/TFE_C
IPR031867 MiT/TFE_N
IPR024098 TFEB
PANTHERiPTHR12565:SF133 PTHR12565:SF133, 1 hit
PfamiView protein in Pfam
PF11851 DUF3371, 1 hit
PF00010 HLH, 1 hit
PF15951 MITF_TFEB_C_3_N, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequencei

Sequence statusi: Complete.

Q9R210-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASRIGLRMQ LMREQAQQEE QRERMQQQAV MHYMQQQQQQ QQQLGGPPTP
60 70 80 90 100
AINTPVHFQS PPPVPGEVLK VQSYLENPTS YHLQQSQHQK VREYLSETYG
110 120 130 140 150
NKFAAHVSPA QGSPKPAPAA SPGVRAGHVL STSAGNSAPN SPMAMLHISS
160 170 180 190 200
NPEKEFDDVI DNIMRLDSVL GYINPEMQMP NTLPLSSSHL NVYSGDPQVT
210 220 230 240 250
ASMVGVTSSS CPADLTQKRE LTDAESRALA KERQKKDNHN LIERRRRFNI
260 270 280 290 300
NDRIKELGML IPKANDLDVR WNKGTILKAS VDYIRRMQKD LQKSRELENH
310 320 330 340 350
SRRLEMTNKQ LWLRIQELEM QARVHGLPTT SPSGVNMAEL AQQVVKQELP
360 370 380 390 400
SEDGPGEALM LGPEVPEPEQ MPALPPQAPL PSAAQPQSPF HHLDFSHGLS
410 420 430 440 450
FGGGGDEGPT GYPDTLGTEH GSPFPNLSKK DLDLMLLDDS LLPLASDPLF
460 470
STMSPEASKA SSRRSSFSME EGDVL
Length:475
Mass (Da):52,614
Last modified:August 29, 2001 - v2
Checksum:i4249C6F501968326
GO

Sequence cautioni

The sequence AAD20979 differs from that shown. Reason: Erroneous initiation.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079095 mRNA Translation: AAD20979.1 Different initiation.
CCDSiCCDS50133.1
RefSeqiNP_001155194.1, NM_001161722.1
NP_001155195.1, NM_001161723.1
NP_035679.3, NM_011549.3
XP_006524066.2, XM_006524003.3
XP_006524069.1, XM_006524006.3
XP_006524070.1, XM_006524007.3
UniGeneiMm.2305

Genome annotation databases

EnsembliENSMUST00000086932; ENSMUSP00000084151; ENSMUSG00000023990
ENSMUST00000113288; ENSMUSP00000108913; ENSMUSG00000023990
GeneIDi21425
KEGGimmu:21425
UCSCiuc008cwc.2 mouse

Similar proteinsi

Entry informationi

Entry nameiTFEB_MOUSE
AccessioniPrimary (citable) accession number: Q9R210
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: August 29, 2001
Last modified: March 28, 2018
This is version 132 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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