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FLASH GENE
Symbol TFAM contributors: mct/pgu/shn - updated : 24-06-2016
HGNC name transcription factor A, mitochondrial
HGNC id 11741
Location 10q21.1      Physical location : 60.145.175 - 60.155.896
Synonym name
  • transcription factor 6-like 2 (mitochondrial transcription factor)
  • mitochondrial transcription factor A
  • mitochondrial transcription factor 1
  • transcription factor 6
  • Synonym symbol(s) TCF6, MtTFA, MtTF1, TCF6L2, TCF6L1, TCF6L3
    DNA
    TYPE functioning gene
    STRUCTURE 10.72 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • promoter harbors a complex organization with at least six transcriptional regulatory elements
  • A and C elements are required in addition to the SBS1, SBS2, Sp1 and NRF-2 motifs for full activity of the promoter
  • two functional recognition sites SBS1 and SBS2 for transcription factor ZNF143
  • potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescent
  • MAPPING cloned Y linked N status confirmed
    Map cen - D10S1659 - D10S1756 - TFAM - D10S549 - D10S1244 - qter
    Physical map
    LOC389970 10 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) ZWINT 10q21-q22 ZW10 interactor MRPS35P3 10q21 mitochondrial ribosomal protein S35 pseudogene 3 IPMK MDS029 UBE2D1 10q11.2-q21 ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast) TFAM 10q21 transcription factor A, mitochondrial BICC1 10q21.3 bicaudal C homolog 1 (Drosophila) LOC389971 10 hypothetical gene supported by U78798; NM_004620 KIAA1796 10q11 KIAA1796 protein FAM13C1 10q21 family with sequence similarity 13, member C1 MRPL50P4 10q23.1 family with sequence similarity 13, member C1 C10orf36 D10S170 ANK3 10q21 ankyrin 3, node of Ranvier (ankyrin G) LOC387684 10 similar to ADP-ribosylation factor-like protein 4 CDC2 10q21.1 cell division cycle 2, G1 to S and G2 to M RHOBTB1 10q22.1 Rho-related BTB domain containing 1 MGC35010 10q21.3 hypothetical protein MGC35010 MGC44593 10q21.3 hypothetical protein MGC44593 MRF2 10q21.3 hypothetical protein MGC44593 RTKN2 10q21.3 rhotekin 2 ZNF365 10q21.2 zinc finger protein 365 LOC387685 10 LOC387685
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1936 - 246 - 2009 19735641
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Lymphoid/Immunethymus    
    Nervousbrain    
    Reproductivefemale systemovary   
    Respiratorylung    
    Urinarykidney    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal HMG domain
  • a basic linker region
  • a second HMG domain
  • a basic C terminal tail
  • two cross-species conserved binding sites for the transcription factor ZNF143
  • C-terminal domain essential for the formation of trimers that finally assemble into large EMILIN multimers
  • conjugated PhosphoP
    mono polymer homomer , monomer , dimer
    HOMOLOGY
    interspecies ortholog to Tfam, mus musculus
    ortholog to Tfam, Rattus norvegicus
    ortholog to tfam, Danio rerio
    ortholog to TFAM, Pan troglodytes
    Homologene
    FAMILY
  • HMG box protein family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,nucleus
    text in the mitochondrial matrix
    basic FUNCTION
  • transcription factor involved in strictly maternal transmission of mtDNA in the maintenance of mitochondrial genome
  • playing a role in direct regulation of mitochondrial DNA copy number
  • playing an essential role for transcription initiation and replication of mitochondrial DNA
  • crucial for mitochondrial biogenesis during development and differentiation
  • required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase
  • is able to unwind and bend DNA
  • essential for mtDNA transcription and for mtDNA packaging in mtDNA maintenance
  • essential for the maintenance of mtDNA
  • required for both transcription from and maintenance of mitochondrial genomes
  • functions in both nuclei and mitochondria to promote cell growth
  • may regulate nuclear gene expression and/or chromatin structure in addition to its mitochondrial role
  • is required for mitochondrial DNA (mtDNA) replication and transcription
  • abundant protein that binds and bends promoter DNA 15-40&
  • 8201;base pairs upstream of the transcription start site, and stimulates the recruitment of POLRMT and TFB2M to the promoter
  • organization of TFAM, POLRMT and TFB2M around thelight-strand promoter (LSP), represent the first structural characterization of the entire mitochondrial transcriptional initiation complex
  • TFAM first recruits POLRMT to the promoter, followed by TFB2M binding and induction of promoter melting
  • transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation of mitochondrial transcription
  • is a key regulator of mitochondria biogenesis
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • TFB2M along with two other proteins, POLRMT and TFAM, are key components of the core mitochondrial transcription apparatus
  • INTERACTION
    DNA
  • mitochondrial genome
  • RNA
    small molecule
    protein
  • mtTFB1
  • N-terminal transactivation domain and to the C-terminal regulatory domain of TP53
  • interacting with TFB1M and TFB2M
  • PHB
  • ERAL1
  • LONP1
  • although TFAM and TFB2M are recognized as mtDNA-specific transcription factors, they also regulate transcription of nuclear DNA, ATP2A2 gene
  • BIRC5 gene expression is transcriptionally regulated by TFAM in the nucleus
  • in cells with normal mtDNA levels, HMG1-phosphorylated TFAM is degraded by LONP1, but in cells with severe mtDNA deficits, nonphosphorylated TFAM is also degraded, as it is DNA free
  • IMMT interacts with mitochondrial transcription factors TFAM and TFB2M
  • POLRMT needs both TFB2M and TFAM to melt the promoter
  • JAG1 and NOTCH2 play a key role in kidney fibrosis development by regulating TFAM expression and metabolic reprogramming
  • down-regulation of TFAM increases the sensitivity of tumour cells to radiation via TP53/TIGAR signalling pathway
  • cell & other
    REGULATION
    Phosphorylated by phosphorylated within its HMG box 1 (HMG1) by cAMP-dependent protein kinase in mitochondria
    Other degradation of TFAM by LONP1 protease, facilitated by mtDNA depletion
    ASSOCIATED DISORDERS
    corresponding disease(s)
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in muscle from HD subjects (
    tumoral     --over  
    in cancer cells and be related to malignant progression and proliferative activity
    tumoral somatic mutation      
    truncating mutation of TFAM induces mitochondrial DNA depletion and apoptotic resistance in microsatellite-unstable colorectal cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativehuntington chorea
    activator PPARGC1A and TFAM may be a potential therapeutic strategy in Huntington disease
    ANIMAL & CELL MODELS
  • Heterozygous Tfam knockout mice exhibit reduced mtDNA copy number and respiratory chain deficiency in heart
  • Homozygous Tfam knockout embryos exhibit a severe mtDNA depletion with abolished oxidative phosphorylation
  • disrupted Tfam in mouse heart and muscle lead to a mosaic cardiac-specific progressive respiratory chain deficiency, dilated cardiomyopathy, atrioventricular heart conduction blocks and death at 2-4 weeks of age
  • reduced sarcoplasmic reticulum (SR) Ca2+ storage capacity in murine Tfam KO muscles due to a decreased expression of calsequestrin-1, resulting in decreased SR Ca2+ release during contraction and hence lower force production
  • mtTFA-null mice show an embryonic lethal phenotype and apoptosis in heart cells
  • reduced sarcoplasmic reticulum (SR) Ca(2+) storage capacity in Tfam KO muscles due to a decreased expression of calsequestrin-1
  • expression levels of TFAM is significantly decreased in both Alzheimer's disease hippocampal tissues and AD-causing amyloid precursor protein mutant cells