ID TFAM_HUMAN Reviewed; 246 AA. AC Q00059; A8MRB2; A9QXC6; B5BU05; Q5U0C6; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1993, sequence version 1. DT 27-MAR-2024, entry version 209. DE RecName: Full=Transcription factor A, mitochondrial {ECO:0000305}; DE Short=mtTFA; DE AltName: Full=Mitochondrial transcription factor 1; DE Short=MtTF1; DE AltName: Full=Transcription factor 6; DE Short=TCF-6; DE AltName: Full=Transcription factor 6-like 2; DE Flags: Precursor; GN Name=TFAM {ECO:0000312|HGNC:HGNC:11741}; Synonyms=TCF6, TCF6L2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 1-21. RX PubMed=2035027; DOI=10.1126/science.2035027; RA Parisi M.A., Clayton D.A.; RT "Similarity of human mitochondrial transcription factor 1 to high mobility RT group proteins."; RL Science 252:965-969(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hepatoma; RA Li K.N., Zhang Y.Q., Yang S.J.; RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-12. RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., RA Nomura N.; RT "Human protein factory for converting the transcriptome into an in vitro- RT expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-34, AND VARIANT THR-12. RC TISSUE=Lymphocyte; RX PubMed=1610904; DOI=10.1016/0167-4781(92)90082-b; RA Tominaga K., Akiyama S., Kagawa Y., Ohta S.; RT "Upstream region of a genomic gene for human mitochondrial transcription RT factor 1."; RL Biochim. Biophys. Acta 1131:217-219(1992). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=1737790; DOI=10.1016/s0021-9258(19)50739-6; RA Fisher R.P., Lisowsky T., Parisi M.A., Clayton D.A.; RT "DNA wrapping and bending by a mitochondrial high mobility group-like RT transcriptional activator protein."; RL J. Biol. Chem. 267:3358-3367(1992). RN [10] RP INTERACTION WITH TFB1M AND TFB2M. RX PubMed=12897151; DOI=10.1128/mcb.23.16.5816-5824.2003; RA McCulloch V., Shadel G.S.; RT "Human mitochondrial transcription factor B1 interacts with the C-terminal RT activation region of h-mtTFA and stimulates transcription independently of RT its RNA methyltransferase activity."; RL Mol. Cell. Biol. 23:5816-5824(2003). RN [11] RP SUBCELLULAR LOCATION, ASSOCIATION WITH MITOCHONDRIAL DNA, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=18063578; DOI=10.1074/jbc.m708444200; RA Bogenhagen D.F., Rousseau D., Burke S.; RT "The layered structure of human mitochondrial DNA nucleoids."; RL J. Biol. Chem. 283:3665-3675(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP FUNCTION. RX PubMed=20410300; DOI=10.1074/jbc.c110.128918; RA Litonin D., Sologub M., Shi Y., Savkina M., Anikin M., Falkenberg M., RA Gustafsson C.M., Temiakov D.; RT "Human mitochondrial transcription revisited: only TFAM and TFB2M are RT required for transcription of the mitochondrial genes in vitro."; RL J. Biol. Chem. 285:18129-18133(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CLPX. RX PubMed=22841477; DOI=10.1016/j.yexcr.2012.07.012; RA Kasashima K., Sumitani M., Endo H.; RT "Maintenance of mitochondrial genome distribution by mitochondrial AAA+ RT protein ClpX."; RL Exp. Cell Res. 318:2335-2343(2012). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-122; SER-193 AND SER-195, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP PHOSPHORYLATION AT SER-55; SER-56; SER-61 AND SER-160. RX PubMed=23201127; DOI=10.1016/j.molcel.2012.10.023; RA Lu B., Lee J., Nie X., Li M., Morozov Y.I., Venkatesh S., Bogenhagen D.F., RA Temiakov D., Suzuki C.K.; RT "Phosphorylation of human TFAM in mitochondria impairs DNA binding and RT promotes degradation by the AAA+ Lon protease."; RL Mol. Cell 49:121-132(2013). RN [19] RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER PHE-42, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [20] RP INVOLVEMENT IN MTDPS15, AND VARIANT MTDPS15 LEU-178. RX PubMed=27448789; DOI=10.1016/j.ymgme.2016.07.001; RA Stiles A.R., Simon M.T., Stover A., Eftekharian S., Khanlou N., Wang H.L., RA Magaki S., Lee H., Partynski K., Dorrani N., Chang R., RA Martinez-Agosto J.A., Abdenur J.E.; RT "Mutations in TFAM, encoding mitochondrial transcription factor A, cause RT neonatal liver failure associated with mtDNA depletion."; RL Mol. Genet. Metab. 119:91-99(2016). RN [21] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FOXO3; SIRT3 AND POLRMT, AND RP SUBCELLULAR LOCATION. RX PubMed=29445193; DOI=10.1038/s41419-018-0336-0; RA Celestini V., Tezil T., Russo L., Fasano C., Sanese P., Forte G., RA Peserico A., Lepore Signorile M., Longo G., De Rasmo D., Signorile A., RA Gadaleta R.M., Scialpi N., Terao M., Garattini E., Cocco T., Villani G., RA Moschetta A., Grossi V., Simone C.; RT "Uncoupling FoxO3A mitochondrial and nuclear functions in cancer cells RT undergoing metabolic stress and chemotherapy."; RL Cell Death Dis. 9:231-231(2018). RN [22] RP FUNCTION. RX PubMed=32183942; DOI=10.1016/j.molcel.2020.02.018; RA Hao Z., Wu T., Cui X., Zhu P., Tan C., Dou X., Hsu K.W., Lin Y.T., RA Peng P.H., Zhang L.S., Gao Y., Hu L., Sun H.L., Zhu A., Liu J., Wu K.J., RA He C.; RT "N6-deoxyadenosine methylation in mammalian mitochondrial DNA."; RL Mol. Cell 0:0-0(2020). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 153-218, FUNCTION, AND SUBUNIT. RX PubMed=19304746; DOI=10.1093/nar/gkp157; RA Gangelhoff T.A., Mungalachetty P.S., Nix J.C., Churchill M.E.; RT "Structural analysis and DNA binding of the HMG domains of the human RT mitochondrial transcription factor A."; RL Nucleic Acids Res. 37:3153-3164(2009). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 43-246 IN COMPLEX WITH DNA, RP DNA-BINDING, DOMAIN, SUBUNIT, SITE, AND FUNCTION. RX PubMed=22037172; DOI=10.1038/nsmb.2160; RA Rubio-Cosials A., Sidow J.F., Jimenez-Menendez N., Fernandez-Millan P., RA Montoya J., Jacobs H.T., Coll M., Bernado P., Sola M.; RT "Human mitochondrial transcription factor A induces a U-turn structure in RT the light strand promoter."; RL Nat. Struct. Mol. Biol. 18:1281-1289(2011). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 43-246 IN COMPLEX WITH DNA, RP FUNCTION, DNA-BINDING, DOMAIN, SUBUNIT, AND MUTAGENESIS OF THR-77 AND RP TYR-162. RX PubMed=22037171; DOI=10.1038/nsmb.2159; RA Ngo H.B., Kaiser J.T., Chan D.C.; RT "The mitochondrial transcription and packaging factor Tfam imposes a U-turn RT on mitochondrial DNA."; RL Nat. Struct. Mol. Biol. 18:1290-1296(2011). RN [26] {ECO:0007744|PDB:6ERP, ECO:0007744|PDB:6ERQ} RP X-RAY CRYSTALLOGRAPHY (4.50 ANGSTROMS) OF 43-245 IN COMPLEX WITH POLRMT; RP TFB2M AND DNA, AND SUBUNIT. RX PubMed=29149603; DOI=10.1016/j.cell.2017.10.036; RA Hillen H.S., Morozov Y.I., Sarfallah A., Temiakov D., Cramer P.; RT "Structural Basis of Mitochondrial Transcription Initiation."; RL Cell 171:1072-1081.e10(2017). RN [27] RP VARIANT THR-12. RX PubMed=19096125; DOI=10.1155/2008/575323; RA Alonso-Montes C., Castro M.G., Reguero J.R., Perrot A., Ozcelik C., RA Geier C., Posch M.G., Moris C., Alvarez V., Ruiz-Ortega M., Coto E.; RT "Mitochondrial transcription factors TFA, TFB1 and TFB2: a search for DNA RT variants/haplotypes and the risk of cardiac hypertrophy."; RL Dis. Markers 25:131-139(2008). CC -!- FUNCTION: Binds to the mitochondrial light strand promoter and CC functions in mitochondrial transcription regulation (PubMed:29445193, CC PubMed:32183942). Component of the mitochondrial transcription CC initiation complex, composed at least of TFB2M, TFAM and POLRMT that is CC required for basal transcription of mitochondrial DNA CC (PubMed:29149603). In this complex, TFAM recruits POLRMT to a specific CC promoter whereas TFB2M induces structural changes in POLRMT to enable CC promoter opening and trapping of the DNA non-template strand CC (PubMed:20410300). Required for accurate and efficient promoter CC recognition by the mitochondrial RNA polymerase (PubMed:22037172). CC Promotes transcription initiation from the HSP1 and the light strand CC promoter by binding immediately upstream of transcriptional start sites CC (PubMed:22037172). Is able to unwind DNA (PubMed:22037172). Bends the CC mitochondrial light strand promoter DNA into a U-turn shape via its HMG CC boxes (PubMed:1737790). Required for maintenance of normal levels of CC mitochondrial DNA (PubMed:22841477, PubMed:19304746). May play a role CC in organizing and compacting mitochondrial DNA (PubMed:22037171). CC {ECO:0000269|PubMed:1737790, ECO:0000269|PubMed:19304746, CC ECO:0000269|PubMed:20410300, ECO:0000269|PubMed:22037171, CC ECO:0000269|PubMed:22037172, ECO:0000269|PubMed:22841477, CC ECO:0000269|PubMed:29149603, ECO:0000269|PubMed:29445193, CC ECO:0000269|PubMed:32183942}. CC -!- SUBUNIT: Monomer; binds DNA as a monomer (PubMed:19304746, CC PubMed:22037171, PubMed:22037172). Homodimer (PubMed:29149603). CC Component of the mitochondrial transcription initiation complex, CC composed at least of TFB2M, TFAM and POLRMT (PubMed:29149603). In this CC complex TFAM recruits POLRMT to the promoter whereas TFB2M induces CC structural changes in POLRMT to enable promoter opening and trapping of CC the DNA non-template strand (PubMed:29149603). Upon metabolic stress, CC forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT CC (PubMed:29445193, PubMed:12897151). Interacts with TFB1M and TFB2M CC (PubMed:12897151). Interacts with CLPX; this enhances DNA-binding CC (PubMed:22841477). {ECO:0000269|PubMed:12897151, CC ECO:0000269|PubMed:19304746, ECO:0000269|PubMed:22037171, CC ECO:0000269|PubMed:22037172, ECO:0000269|PubMed:22841477, CC ECO:0000269|PubMed:29149603, ECO:0000269|PubMed:29445193}. CC -!- INTERACTION: CC Q00059; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-1049924, EBI-741181; CC Q00059; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-1049924, EBI-11522760; CC Q00059; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-1049924, EBI-714543; CC Q00059; Q4VAQ0: COL8A2; NbExp=3; IntAct=EBI-1049924, EBI-10241815; CC Q00059; O14880: MGST3; NbExp=4; IntAct=EBI-1049924, EBI-724754; CC Q00059; P02808: STATH; NbExp=3; IntAct=EBI-1049924, EBI-738687; CC Q00059; Q9NZ01: TECR; NbExp=3; IntAct=EBI-1049924, EBI-2877718; CC Q00059; Q8WVM0: TFB1M; NbExp=2; IntAct=EBI-1049924, EBI-2615570; CC Q00059; O60635: TSPAN1; NbExp=3; IntAct=EBI-1049924, EBI-3914312; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:1737790, CC ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:22841477, CC ECO:0000269|PubMed:29445193}. Mitochondrion matrix, mitochondrion CC nucleoid {ECO:0000269|PubMed:18063578}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q00059-1; Sequence=Displayed; CC Name=2; CC IsoId=Q00059-2; Sequence=VSP_047019; CC -!- DOMAIN: Binds DNA via its HMG boxes. When bound to the mitochondrial CC light strand promoter, bends DNA into a U-turn shape, each HMG box CC bending the DNA by 90 degrees. {ECO:0000269|PubMed:22037171, CC ECO:0000269|PubMed:22037172}. CC -!- PTM: Phosphorylation by PKA within the HMG box 1 impairs DNA binding CC and promotes degradation by the AAA+ Lon protease. CC {ECO:0000269|PubMed:23201127}. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 15, hepatocerebral type CC (MTDPS15) [MIM:617156]: An autosomal recessive mitochondrial disorder CC characterized by severe intrauterine growth restriction, neonatal-onset CC hypoglycemia and liver dysfunction, mitochondrial DNA depletion in CC liver and skeletal muscle, and abnormal mitochondrial morphology CC observed in skeletal muscle. Hepatic pathology includes cirrhosis, CC steatosis and cholestasis. Progression to liver failure and death is CC rapid with no evidence of neurological impairment or other organ CC involvement. {ECO:0000269|PubMed:27448789}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M62810; AAA59849.1; -; mRNA. DR EMBL; EU279428; ABX72056.1; -; mRNA. DR EMBL; BT019658; AAV38464.1; -; mRNA. DR EMBL; BT019659; AAV38465.1; -; mRNA. DR EMBL; AK312558; BAG35455.1; -; mRNA. DR EMBL; AB451241; BAG70055.1; -; mRNA. DR EMBL; AB451366; BAG70180.1; -; mRNA. DR EMBL; AC023170; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC126366; AAI26367.1; -; mRNA. DR EMBL; X64269; CAA45562.1; -; Genomic_DNA. DR CCDS; CCDS59217.1; -. [Q00059-2] DR CCDS; CCDS7253.1; -. [Q00059-1] DR PIR; JC1496; JC1496. DR RefSeq; NP_001257711.1; NM_001270782.1. [Q00059-2] DR RefSeq; NP_003192.1; NM_003201.2. [Q00059-1] DR PDB; 3FGH; X-ray; 1.35 A; A=153-218. DR PDB; 3TMM; X-ray; 2.50 A; A=43-246. DR PDB; 3TQ6; X-ray; 2.45 A; A/B=43-246. DR PDB; 4NNU; X-ray; 2.81 A; A/B=43-237. DR PDB; 4NOD; X-ray; 2.90 A; A/B/G/H=43-237. DR PDB; 6ERP; X-ray; 4.50 A; C/G=43-245. DR PDB; 6ERQ; X-ray; 4.50 A; C/G=43-245. DR PDB; 6HB4; X-ray; 3.05 A; A/D/G/J=42-246. DR PDB; 6HC3; X-ray; 3.10 A; A/D/G/J=34-246. DR PDB; 7LBW; X-ray; 2.84 A; A/B=43-246. DR PDB; 7LBX; X-ray; 2.70 A; A/B=43-246. DR PDBsum; 3FGH; -. DR PDBsum; 3TMM; -. DR PDBsum; 3TQ6; -. DR PDBsum; 4NNU; -. DR PDBsum; 4NOD; -. DR PDBsum; 6ERP; -. DR PDBsum; 6ERQ; -. DR PDBsum; 6HB4; -. DR PDBsum; 6HC3; -. DR PDBsum; 7LBW; -. DR PDBsum; 7LBX; -. DR AlphaFoldDB; Q00059; -. DR EMDB; EMD-2529; -. DR SMR; Q00059; -. DR BioGRID; 112877; 407. DR ComplexPortal; CPX-7241; Mitochondrial transcription initiation complex. DR IntAct; Q00059; 142. DR MINT; Q00059; -. DR STRING; 9606.ENSP00000420588; -. DR GlyGen; Q00059; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q00059; -. DR MetOSite; Q00059; -. DR PhosphoSitePlus; Q00059; -. DR SwissPalm; Q00059; -. DR BioMuta; TFAM; -. DR DMDM; 417324; -. DR EPD; Q00059; -. DR jPOST; Q00059; -. DR MassIVE; Q00059; -. DR MaxQB; Q00059; -. DR PaxDb; 9606-ENSP00000420588; -. DR PeptideAtlas; Q00059; -. DR ProteomicsDB; 1958; -. DR ProteomicsDB; 57840; -. [Q00059-1] DR Pumba; Q00059; -. DR TopDownProteomics; Q00059-1; -. [Q00059-1] DR Antibodypedia; 14209; 625 antibodies from 41 providers. DR DNASU; 7019; -. DR Ensembl; ENST00000373895.7; ENSP00000363002.3; ENSG00000108064.11. [Q00059-2] DR Ensembl; ENST00000487519.6; ENSP00000420588.1; ENSG00000108064.11. [Q00059-1] DR GeneID; 7019; -. DR KEGG; hsa:7019; -. DR MANE-Select; ENST00000487519.6; ENSP00000420588.1; NM_003201.3; NP_003192.1. DR UCSC; uc001jkf.5; human. [Q00059-1] DR AGR; HGNC:11741; -. DR CTD; 7019; -. DR DisGeNET; 7019; -. DR GeneCards; TFAM; -. DR HGNC; HGNC:11741; TFAM. DR HPA; ENSG00000108064; Low tissue specificity. DR MalaCards; TFAM; -. DR MIM; 600438; gene. DR MIM; 617156; phenotype. DR neXtProt; NX_Q00059; -. DR OpenTargets; ENSG00000108064; -. DR PharmGKB; PA36458; -. DR VEuPathDB; HostDB:ENSG00000108064; -. DR eggNOG; KOG0381; Eukaryota. DR GeneTree; ENSGT00440000039001; -. DR HOGENOM; CLU_083132_0_0_1; -. DR InParanoid; Q00059; -. DR OMA; YMQLAED; -. DR OrthoDB; 5472820at2759; -. DR PhylomeDB; Q00059; -. DR TreeFam; TF318343; -. DR PathwayCommons; Q00059; -. DR Reactome; R-HSA-163282; Mitochondrial transcription initiation. DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis. DR SignaLink; Q00059; -. DR SIGNOR; Q00059; -. DR BioGRID-ORCS; 7019; 524 hits in 1188 CRISPR screens. DR ChiTaRS; TFAM; human. DR EvolutionaryTrace; Q00059; -. DR GeneWiki; TFAM; -. DR GenomeRNAi; 7019; -. DR Pharos; Q00059; Tbio. DR PRO; PR:Q00059; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q00059; Protein. DR Bgee; ENSG00000108064; Expressed in right testis and 208 other cell types or tissues. DR ExpressionAtlas; Q00059; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0031072; F:heat shock protein binding; IEA:Ensembl. DR GO; GO:0001018; F:mitochondrial promoter sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0034246; F:mitochondrial transcription factor activity; IMP:GO_Central. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central. DR GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl. DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; IEA:Ensembl. DR GO; GO:0006390; P:mitochondrial transcription; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0006391; P:transcription initiation at mitochondrial promoter; IDA:UniProtKB. DR CDD; cd21986; HMG-box_TFAM_rpt1; 1. DR CDD; cd21987; HMG-box_TFAM_rpt2; 1. DR Gene3D; 1.10.30.10; High mobility group box domain; 2. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR036910; HMG_box_dom_sf. DR PANTHER; PTHR48112; HIGH MOBILITY GROUP PROTEIN DSP1; 1. DR PANTHER; PTHR48112:SF38; TRANSCRIPTION FACTOR A, MITOCHONDRIAL; 1. DR Pfam; PF00505; HMG_box; 1. DR Pfam; PF09011; HMG_box_2; 1. DR SMART; SM00398; HMG; 2. DR SUPFAM; SSF47095; HMG-box; 2. DR PROSITE; PS50118; HMG_BOX_2; 2. DR Genevisible; Q00059; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing; KW Disease variant; DNA-binding; Mitochondrion; Mitochondrion nucleoid; KW Phosphoprotein; Primary mitochondrial disease; Reference proteome; Repeat; KW Transcription; Transcription regulation; Transit peptide. FT TRANSIT 1..42 FT /note="Mitochondrion" FT /evidence="ECO:0000255, ECO:0007744|PubMed:25944712" FT CHAIN 43..246 FT /note="Transcription factor A, mitochondrial" FT /id="PRO_0000013470" FT DNA_BIND 50..118 FT /note="HMG box 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267" FT DNA_BIND 155..219 FT /note="HMG box 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267" FT SITE 58 FT /note="Intercalates between bases and promotes DNA bending" FT SITE 182 FT /note="Intercalates between bases and promotes DNA bending" FT MOD_RES 55 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:23201127" FT MOD_RES 56 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:23201127" FT MOD_RES 61 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:23201127" FT MOD_RES 122 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 160 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:23201127" FT MOD_RES 193 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 195 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 148..179 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_047019" FT VARIANT 12 FT /note="S -> T (in dbSNP:rs1937)" FT /evidence="ECO:0000269|PubMed:1610904, FT ECO:0000269|PubMed:19054851, ECO:0000269|PubMed:19096125" FT /id="VAR_016124" FT VARIANT 178 FT /note="P -> L (in MTDPS15; dbSNP:rs757075712)" FT /evidence="ECO:0000269|PubMed:27448789" FT /id="VAR_077842" FT MUTAGEN 77 FT /note="T->A: Moderate reduction in DNA bending." FT /evidence="ECO:0000269|PubMed:22037171" FT MUTAGEN 162 FT /note="Y->A: Moderate reduction in DNA bending." FT /evidence="ECO:0000269|PubMed:22037171" FT CONFLICT 34 FT /note="S -> R (in Ref. 8; CAA45562)" FT /evidence="ECO:0000305" FT HELIX 45..48 FT /evidence="ECO:0007829|PDB:3TQ6" FT HELIX 56..71 FT /evidence="ECO:0007829|PDB:3TQ6" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:7LBW" FT HELIX 77..90 FT /evidence="ECO:0007829|PDB:3TQ6" FT HELIX 93..120 FT /evidence="ECO:0007829|PDB:3TQ6" FT HELIX 123..151 FT /evidence="ECO:0007829|PDB:3TQ6" FT HELIX 161..173 FT /evidence="ECO:0007829|PDB:3FGH" FT STRAND 175..177 FT /evidence="ECO:0007829|PDB:3FGH" FT HELIX 178..190 FT /evidence="ECO:0007829|PDB:3FGH" FT HELIX 194..217 FT /evidence="ECO:0007829|PDB:3FGH" FT HELIX 228..230 FT /evidence="ECO:0007829|PDB:3TQ6" SQ SEQUENCE 246 AA; 29097 MW; 81F00CFA12DA4924 CRC64; MAFLRSMWGV LSALGRSGAE LCTGCGSRLR SPFSFVYLPR WFSSVLASCP KKPVSSYLRF SKEQLPIFKA QNPDAKTTEL IRRIAQRWRE LPDSKKKIYQ DAYRAEWQVY KEEISRFKEQ LTPSQIMSLE KEIMDKHLKR KAMTKKKELT LLGKPKRPRS AYNVYVAERF QEAKGDSPQE KLKTVKENWK NLSDSEKELY IQHAKEDETR YHNEMKSWEE QMIEVGRKDL LRRTIKKQRK YGAEEC //