TFAM_HUMAN
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 03-AUG-2022, entry version 200.
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.
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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 SMR; Q00059; -.
DR BioGRID; 112877; 371.
DR ComplexPortal; CPX-7241; Mitochondrial transcription initiation complex.
DR IntAct; Q00059; 129.
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; Q00059; -.
DR PeptideAtlas; Q00059; -.
DR PRIDE; Q00059; -.
DR ProteomicsDB; 1958; -.
DR ProteomicsDB; 57840; -. [Q00059-1]
DR TopDownProteomics; Q00059-1; -. [Q00059-1]
DR Antibodypedia; 14209; 562 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 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; ISVQAKM; -.
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; 495 hits in 1098 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 206 other tissues.
DR ExpressionAtlas; Q00059; baseline and differential.
DR Genevisible; Q00059; HS.
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:0008301; F:DNA binding, bending; IBA:GO_Central.
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 transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006391; P:transcription initiation from mitochondrial promoter; IDA:UniProtKB.
DR Gene3D; 1.10.30.10; -; 2.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF09011; HMG_box_2; 1.
DR SMART; SM00398; HMG; 2.
DR SUPFAM; SSF47095; SSF47095; 2.
DR PROSITE; PS50118; HMG_BOX_2; 2.
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
