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    TFEB transcription factor EB [ Homo sapiens (human) ]

    Gene ID: 7942, updated on 16-Apr-2024

    Summary

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    Official Symbol
    TFEBprovided by HGNC
    Official Full Name
    transcription factor EBprovided by HGNC
    Primary source
    HGNC:HGNC:11753
    See related
    Ensembl:ENSG00000112561 MIM:600744; AllianceGenome:HGNC:11753
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TCFEB; BHLHE35; ALPHATFEB
    Summary
    Enables DNA-binding transcription factor activity; enzyme binding activity; and transcription cis-regulatory region binding activity. Involved in several processes, including cellular response to amino acid starvation; lysosome localization; and positive regulation of autophagy. Located in cytosol; lysosomal membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in spleen (RPKM 9.7), lymph node (RPKM 8.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TFEB in Genome Data Viewer
    Location:
    6p21.1
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (41683978..41736223, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (41512540..41564779, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (41651716..41703961, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41608279-41608859 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:41612529-41613514 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41614501-41615485 Neighboring gene MyoD family inhibitor Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41625153-41625767 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41641529-41642028 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41642607-41643108 Neighboring gene nucleophosmin 1 pseudogene 51 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41644810-41645324 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41645325-41645838 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:41649993-41650819 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:41650820-41651645 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:41655149-41656015 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41658364-41658864 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41673380-41673880 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41673881-41674381 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24519 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41680541-41681266 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41681267-41681990 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24520 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24521 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24522 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:41690842-41691384 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24523 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24524 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24525 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41700542-41701238 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17188 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17189 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17190 Neighboring gene microRNA 10398 Neighboring gene progastricsin Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:41735161-41736013 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17191 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17192 Neighboring gene fibroblast growth factor receptor substrate 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. TFEB-dependent lysosome biogenesis is required for senescence. Curnock R, et al. EMBO J, 2023 May 2. PMID 36970883, Free PMC Article
    2. Transcription factor EB regulates phosphatidylinositol-3-phosphate levels that control lysosome positioning in the bladder cancer model. Mathur P, et al. Commun Biol, 2023 Jan 28. PMID 36709383, Free PMC Article
    3. p38 MAPK-dependent phosphorylation of TFEB promotes monocyte-to-macrophage differentiation. Martina JA, et al. EMBO Rep, 2023 Feb 6. PMID 36507874, Free PMC Article
    4. Loss of transcription factor EB dysregulates the G1/S transition and DNA replication in mammary epithelial cells. Slade L, et al. J Biol Chem, 2022 Dec. PMID 36372230, Free PMC Article
    5. TFEB in Alzheimer's disease: From molecular mechanisms to therapeutic implications. Gu Z, et al. Neurobiol Dis, 2022 Oct 15. PMID 36031168

    See all (193) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Altered TFEB subcellular localization in nigral neurons of subjects with incidental, sporadic and GBA-related Lewy body diseases.
      Title: Altered TFEB subcellular localization in nigral neurons of subjects with incidental, sporadic and GBA-related Lewy body diseases.
    2. Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs.
      Title: Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs.
    3. ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis.
      Title: ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis.
    4. A SPLICS reporter reveals [Formula: see text]-synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation.
      Title: A SPLICS reporter reveals [Formula: see text]-synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation.
    5. TFEB regulates the odontoblastic differentiation of dental pulp stem cells by promoting a positive feedback loop between mitophagy and glycolysis.
      Title: TFEB regulates the odontoblastic differentiation of dental pulp stem cells by promoting a positive feedback loop between mitophagy and glycolysis.
    6. LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma.
      Title: LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma.
    7. A candidate prognostic biomarker: TFEB inhibits tumor progression via elevating CDKN1A in bladder cancer.
      Title: A candidate prognostic biomarker: TFEB inhibits tumor progression via elevating CDKN1A in bladder cancer.
    8. FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB.
      Title: FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB.
    9. Dissecting the multifaced function of transcription factor EB (TFEB) in human diseases: From molecular mechanism to pharmacological modulation.
      Title: Dissecting the multifaced function of transcription factor EB (TFEB) in human diseases: From molecular mechanism to pharmacological modulation.
    10. Transcription factor EB: A potential integrated network regulator in metabolic-associated cardiac injury.
      Title: Transcription factor EB: A potential integrated network regulator in metabolic-associated cardiac injury.
    Submit: New GeneRIF Correction See all GeneRIFs (173)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 activates (and dephosphorylates) TFEB in human macrophages at 24 hours post-treatment with purified HIV-1 virions PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef HIV-1 Nef inhibits TFEB nuclear localization and autophagic flux; HIV-1 Nef is required for anti-autophagy during permissive (ongoing) HIV infection PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein dimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription cis-regulatory region binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in antibacterial innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in autophagy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to amino acid starvation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to starvation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in embryonic placenta development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in humoral immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in lysosome localization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in lysosome organization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in lysosome organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of autophagy IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of autophagy IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of DNA-templated transcription NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    transcription factor EB
    Names
    T-cell transcription factor EB
    class E basic helix-loop-helix protein 35

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001167827.3 → NP_001161299.2  transcription factor EB isoform 2

      See identical proteins and their annotated locations for NP_001161299.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2, also known as TFEB-A) encodes the longest isoform (2).
      Source sequence(s)
      AJ608786, BC032448
      Consensus CDS
      CCDS64425.1
      UniProtKB/TrEMBL
      B0QYS6, B4DPL3
      Related
      ENSP00000351742.2, ENST00000358871.6
      Conserved Domains (3) summary
      cd00083
      Location:247 → 307
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:335 → 471
      DUF3371; Domain of unknown function (DUF3371)
      pfam15951
      Location:18 → 175
      MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus

    2. NM_001271943.2 → NP_001258872.1  transcription factor EB isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) contains an alternate 5' exon, which results in a downstream AUG start codon, and also lacks an in-frame coding exon, compared to variant 2. The resulting isoform (3) has a shorter N-terminus and lacks an internal segment, compared to isoform 2.
      Source sequence(s)
      AL365205, AW294760, BC032448, CT000098
      Consensus CDS
      CCDS64424.1
      UniProtKB/TrEMBL
      B1AKB5
      Related
      ENSP00000383998.3, ENST00000406563.7
      Conserved Domains (3) summary
      cd00083
      Location:148 → 208
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam11851
      Location:236 → 372
      DUF3371; Domain of unknown function (DUF3371)
      pfam15951
      Location:4 → 71
      MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus

    3. NM_001271944.2 → NP_001258873.1  transcription factor EB isoform 1

      See identical proteins and their annotated locations for NP_001258873.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) contains an alternate 5' exon, which results in a downstream AUG start codon, compared to variant 2. The resulting isoform (1) has a shorter N-terminus, compared to isoform 2. Variants 1, 3 and 4 encode the same isoform 1.
      Source sequence(s)
      AL365205, AW294760, BC032448
      Consensus CDS
      CCDS4858.1
      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8
      UniProtKB/TrEMBL
      B4DPL3
      Related
      ENSP00000362124.1, ENST00000373033.6
      Conserved Domains (2) summary
      cd00083
      Location:233 → 293
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam15951
      Location:4 → 161
      MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus

    4. NM_001271945.2 → NP_001258874.1  transcription factor EB isoform 1

      See identical proteins and their annotated locations for NP_001258874.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) contains an alternate 5' exon, which results in a downstream AUG start codon, compared to variant 2. The resulting isoform (1) has a shorter N-terminus, compared to isoform 2. Variants 1, 3 and 4 encode the same isoform 1.
      Source sequence(s)
      BC032448, BU527754
      Consensus CDS
      CCDS4858.1
      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8
      UniProtKB/TrEMBL
      B4DPL3
      Related
      ENSP00000384203.4, ENST00000403298.9
      Conserved Domains (2) summary
      cd00083
      Location:233 → 293
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam15951
      Location:4 → 161
      MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus

    5. NM_007162.3 → NP_009093.1  transcription factor EB isoform 1

      See identical proteins and their annotated locations for NP_009093.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) contains an alternate 5' sequence, which results in a downstream AUG start codon, compared to variant 2. The resulting isoform (1) has a shorter N-terminus, compared to isoform 2. Variants 1, 3 and 4 encode the same isoform 1.
      Source sequence(s)
      BC032448
      Consensus CDS
      CCDS4858.1
      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8
      UniProtKB/TrEMBL
      B4DPL3
      Related
      ENSP00000230323.4, ENST00000230323.8
      Conserved Domains (2) summary
      cd00083
      Location:233 → 293
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam15951
      Location:4 → 161
      MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      41683978..41736223 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005249411.2 → XP_005249468.1  transcription factor EB isoform X1

      See identical proteins and their annotated locations for XP_005249468.1

      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8
      UniProtKB/TrEMBL
      B4DPL3
      Related
      ENSP00000503069.1, ENST00000678831.1
      Conserved Domains (2) summary
      cd00083
      Location:233 → 293
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam15951
      Location:4 → 161
      MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus

    2. XM_047419361.1 → XP_047275317.1  transcription factor EB isoform X1

      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8

    3. XM_006715212.5 → XP_006715275.1  transcription factor EB isoform X1

      See identical proteins and their annotated locations for XP_006715275.1

      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8
      UniProtKB/TrEMBL
      B4DPL3
      Related
      ENSP00000400276.2, ENST00000419574.6
      Conserved Domains (2) summary
      cd00083
      Location:233 → 293
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      pfam15951
      Location:4 → 161
      MITF_TFEB_C_3_N; MITF/TFEB/TFEC/TFE3 N-terminus

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      41512540..41564779 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356422.1 → XP_054212397.1  transcription factor EB isoform X1

      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8

    2. XM_054356421.1 → XP_054212396.1  transcription factor EB isoform X1

      UniProtKB/Swiss-Prot
      P19484, Q709B3, Q7Z6P9, Q9BRJ5, Q9UJD8
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P19484.3 GenPept UniProtKB/Swiss-Prot:P19484

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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