TFAM

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Mitochondrial transcription factor A, abbreviated as TFAM or mtTFA, is a protein that in humans is encoded by the TFAM gene.

TFAM
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3FGH, 3TMM, 3TQ6, 4NNU, 4NOD
Identifiers
Aliases	TFAM, MTTF1, MTTFA, TCF6, TCF6L1, TCF6L2, TCF6L3, transcription factor A, mitochondrial, MTDPS15
External IDs	OMIM: 600438 MGI: 107810 HomoloGene: 31139 GeneCards: TFAM
Gene location (Human) Chr. Chromosome 10 (human) Band 10q21.1 Start 58,385,345 bp End 58,399,220 bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10 B5.3|10 36.83 cM Start 71,061,294 bp End 71,074,110 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte Achilles tendon monocyte germinal epithelium ganglionic eminence internal globus pallidus lymph node rectum islet of Langerhans thymus Top expressed in endocardial cushion atrioventricular valve abdominal wall somite triceps brachii muscle primitive streak medial ganglionic eminence temporal muscle spermatid duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding mitochondrial promoter sequence-specific DNA binding heat shock protein binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific chromatin binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein binding transcription coactivator binding DNA binding, bending RNA binding sequence-specific DNA binding Cellular component cytosol mitochondrial matrix mitochondrion mitochondrial nucleoid nucleus protein-containing complex Biological process DNA-dependent DNA replication regulation of transcription, DNA-templated regulation of transcription by RNA polymerase I transcription initiation from mitochondrial promoter mitochondrion organization transcription, DNA-templated positive regulation of transcription, DNA-templated mitochondrial respiratory chain complex assembly positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II mitochondrial transcription Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7019 21780 Ensembl ENSG00000108064 ENSMUSG00000003923 UniProt Q00059 P40630 RefSeq (mRNA) NM_001270782 NM_003201 NM_012251 NM_009360 RefSeq (protein) NP_001257711 NP_003192 NP_033386 Location (UCSC) Chr 10: 58.39 – 58.4 Mb Chr 10: 71.06 – 71.07 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a mitochondrial transcription factor that is a key activator of mitochondrial transcription as well as a participant in mitochondrial genome replication. TFAM binds mitochondrial promoter DNA to aid transcription of the mitochondrial genome. Studies in mice have demonstrated that this gene product is required to regulate the mitochondrial genome copy number and is essential for embryonic development. A mouse model for Kearns–Sayre syndrome was produced when expression of this gene was eliminated by targeted disruption in heart and muscle cells.

TFAM is a double box High-mobility group DNA-binding and bending protein. This bending action is important for mitochondrial transcription initiation in mammals, but not in yeasts with the homolog Abf2. TFAM may also participate in the packaging of the mitochondrial genome, as its binding activity is non-sequence-specific.

Interactions

TFAM has been shown to interact with TFB1M and TFB2M.

Further reading

• Tominaga K, Akiyama S, Kagawa Y, Ohta S (1992). "Upstream region of a genomic gene for human mitochondrial transcription factor 1". Biochim. Biophys. Acta. 1131 (2): 217–9. doi:10.1016/0167-4781(92)90082-b. PMID 1610904.
• Fisher RP, Lisowsky T, Parisi MA, Clayton DA (1992). "DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein". J. Biol. Chem. 267 (5): 3358–67. doi:10.1016/S0021-9258(19)50739-6. PMID 1737790.
• Parisi MA, Clayton DA (1991). "Similarity of human mitochondrial transcription factor 1 to high mobility group proteins". Science. 252 (5008): 965–9. Bibcode:1991Sci...252..965P. doi:10.1126/science.2035027. PMID 2035027.
• Tominaga K, Hayashi J, Kagawa Y, Ohta S (1993). "Smaller isoform of human mitochondrial transcription factor 1: its wide distribution and production by alternative splicing". Biochem. Biophys. Res. Commun. 194 (1): 544–51. doi:10.1006/bbrc.1993.1854. PMID 8333869.
• Larsson NG, Oldfors A, Garman JD, Barsh GS, Clayton DA (1997). "Down-regulation of mitochondrial transcription factor A during spermatogenesis in humans". Hum. Mol. Genet. 6 (2): 185–91. doi:10.1093/hmg/6.2.185. PMID 9063738.
• Lezza AM, Pesce V, Cormio A, Fracasso F, Vecchiet J, Felzani G, Cantatore P, Gadaleta MN (2001). "Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects". FEBS Lett. 501 (1): 74–8. doi:10.1016/S0014-5793(01)02628-X. PMID 11457459. S2CID 45160010.
• Takamatsu C, Umeda S, Ohsato T, Ohno T, Abe Y, Fukuoh A, Shinagawa H, Hamasaki N, Kang D (2002). "Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein". EMBO Rep. 3 (5): 451–6. doi:10.1093/embo-reports/kvf099. PMC 1084112. PMID 11964388.
• Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM (2002). "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA". Nat. Genet. 31 (3): 289–94. doi:10.1038/ng909. PMID 12068295. S2CID 11164308.
• Reyes A, Mezzina M, Gadaleta G (2002). "Human mitochondrial transcription factor A (mtTFA): gene structure and characterization of related pseudogenes". Gene. 291 (1–2): 223–32. doi:10.1016/S0378-1119(02)00600-5. PMID 12095695.
• Yoshida Y, Izumi H, Ise T, Uramoto H, Torigoe T, Ishiguchi H, Murakami T, Tanabe M, Nakayama Y, Itoh H, Kasai H, Kohno K (2002). "Human mitochondrial transcription factor A binds preferentially to oxidatively damaged DNA". Biochem. Biophys. Res. Commun. 295 (4): 945–51. doi:10.1016/S0006-291X(02)00757-X. PMID 12127986.
• Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN (2003). "Composition and dynamics of human mitochondrial nucleoids". Mol. Biol. Cell. 14 (4): 1583–96. doi:10.1091/mbc.E02-07-0399. PMC 153124. PMID 12686611.
• Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Itoh H, Kang D, Kohno K (2003). "P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA". Cancer Res. 63 (13): 3729–34. PMID 12839966.
• McCulloch V, Shadel GS (2003). "Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity". Mol. Cell. Biol. 23 (16): 5816–24. doi:10.1128/MCB.23.16.5816-5824.2003. PMC 166325. PMID 12897151.
• Deschauer M, Kiefer R, Blakely EL, He L, Zierz S, Turnbull DM, Taylor RW (2003). "A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia". Neuromuscul. Disord. 13 (7–8): 568–72. doi:10.1016/S0960-8966(03)00071-3. PMID 12921794. S2CID 23020569.
• Günther C, von Hadeln K, Müller-Thomsen T, Alberici A, Binetti G, Hock C, Nitsch RM, Stoppe G, Reiss J, Gal A, Finckh U (2005). "Possible association of mitochondrial transcription factor A (TFAM) genotype with sporadic Alzheimer disease". Neurosci. Lett. 369 (3): 219–23. doi:10.1016/j.neulet.2004.07.070. PMID 15464268. S2CID 25710306.
• Kanki T, Ohgaki K, Gaspari M, Gustafsson CM, Fukuoh A, Sasaki N, Hamasaki N, Kang D (2004). "Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA". Mol. Cell. Biol. 24 (22): 9823–34. doi:10.1128/MCB.24.22.9823-9834.2004. PMC 525493. PMID 15509786.
• Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, Kluger Y, Dynlacht BD (2004). "A common set of gene regulatory networks links metabolism and growth inhibition". Mol. Cell. 16 (3): 399–411. doi:10.1016/j.molcel.2004.09.037. PMID 15525513.

External links

• Overview of all the structural information available in the PDB for UniProt: Q00059 (Transcription factor A, mitochondrial) at the PDBe-KB.