TFAM

Mitochondrial transcription factor A, abbreviated as TFAM or mtTFA, is a protein that in humans is encoded by the TFAM gene.[5][6]

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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)[1] Band 10q21.1 Start 58,385,345 bp[1] End 58,399,220 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 B5.3|10 36.83 cM Start 71,225,464 bp[2] End 71,238,280 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0070361, GO:0070364, GO:0070363, GO:0070362 mitochondrial promoter sequence-specific DNA binding • heat shock protein binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • chromatin binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001948 protein binding • transcription coactivator binding • DNA binding, bending • RNA binding • sequence-specific DNA binding Cellular component • cytosol • mitochondrial matrix • mitochondrion • mitochondrial nucleoid • cell nucleus • macromolecular complex Biological process • DNA-dependent DNA replication • regulation of transcription, DNA-templated • regulation of transcription from RNA polymerase I promoter • 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 from RNA polymerase II promoter • transcription from RNA polymerase II promoter • transcription from mitochondrial promoter 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: 71.23 – 71.24 Mb
PubMed search	[3]	[4]
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.[6]

TFAM is a double box High-mobility group DNA-binding and bending protein.[7] 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. [8]

Interactions

TFAM has been shown to interact with TFB1M and[9] TFB2M.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000108064 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000003923 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Tiranti V, Rossi E, Ruiz-Carrillo A, Rossi G, Rocchi M, DiDonato S, Zuffardi O, Zeviani M (Jul 1995). "Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involved in mitochondrial biogenesis". Genomics. 25 (2): 559–64. doi:10.1016/0888-7543(95)80058-T. PMID 7789991.
6. "Entrez Gene: TFAM transcription factor A, mitochondrial".
7. Murugesapillai D, McCauley MJ, Maher LJ, Williams MC (15 November 2016). "Single-molecule studies of high-mobility group B architectural DNA bending proteins". Biophysical Reviews. 9 (1): 17–40. doi:10.1007/s12551-016-0236-4. PMC 5331113. PMID 28303166.
8. Ngo, HB; Kaiser, JT; Chan, DC (30 October 2011). "The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA". Nature Structural & Molecular Biology. 18 (11): 1290–6. doi:10.1038/nsmb.2159. PMC 3210390. PMID 22037171.
9. McCulloch V, Shadel GS (Aug 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.
10. Hillen, HS; Morozov, YI; Sarfallah, A; Temiakov, D; Cramer, P (16 November 2017). "Structural Basis of Mitochondrial Transcription Initiation". Cell. 171 (5): 1072–1081.e10. doi:10.1016/j.cell.2017.10.036. PMC 6590061. PMID 29149603.

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. 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.
• 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.
• 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.
• 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.
• 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.