TFAM_MOUSE
ID TFAM_MOUSE Reviewed; 243 AA.
AC P40630; P97894; P97906; Q543I8; Q9DBM9;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2002, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Transcription factor A, mitochondrial {ECO:0000305};
DE Short=mtTFA;
DE AltName: Full=Testis-specific high mobility group protein;
DE Short=TS-HMG;
DE Flags: Precursor;
GN Name=Tfam {ECO:0000312|MGI:MGI:107810}; Synonyms=Hmgts;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MITOCHONDRIAL AND NUCLEAR), FUNCTION,
RP ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RC TISSUE=Lymphocyte, and Testis;
RX PubMed=8673128; DOI=10.1038/ng0796-296;
RA Larsson N.G., Garman J.D., Oldfors A., Barsh G.S., Clayton D.A.;
RT "A single mouse gene encodes the mitochondrial transcription factor A and a
RT testis-specific nuclear HMG-box protein.";
RL Nat. Genet. 13:296-302(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
RC STRAIN=C57BL/6J, DBA/2J, and NOD; TISSUE=Liver, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-48 (ISOFORM MITOCHONDRIAL).
RC STRAIN=CD-1; TISSUE=Testis;
RA Cermakian N., Cedergren R.;
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-243 (ISOFORM MITOCHONDRIAL).
RC STRAIN=BALB/cJ; TISSUE=Testis;
RX PubMed=8321234; DOI=10.1128/mcb.13.7.4323-4330.1993;
RA Boissonneault G., Lau Y.-F.C.;
RT "A testis-specific gene encoding a nuclear high-mobility-group box protein
RT located in elongating spermatids.";
RL Mol. Cell. Biol. 13:4323-4330(1993).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9500544; DOI=10.1038/ng0398-231;
RA Larsson N.G., Wang J., Wilhelmsson H., Oldfors A., Rustin P.,
RA Lewandoski M., Barsh G.S., Clayton D.A.;
RT "Mitochondrial transcription factor A is necessary for mtDNA maintenance
RT and embryogenesis in mice.";
RL Nat. Genet. 18:231-236(1998).
RN [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=17581862; DOI=10.1091/mbc.e07-05-0404;
RA Kaufman B.A., Durisic N., Mativetsky J.M., Costantino S., Hancock M.A.,
RA Grutter P., Shoubridge E.A.;
RT "The mitochondrial transcription factor TFAM coordinates the assembly of
RT multiple DNA molecules into nucleoid-like structures.";
RL Mol. Biol. Cell 18:3225-3236(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-66, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: [Isoform Mitochondrial]: Binds to the mitochondrial light
CC strand promoter and functions in mitochondrial transcription regulation
CC (By similarity). 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 (By similarity).
CC In this complex, TFAM recruits POLRMT to a specific promoter whereas
CC TFB2M induces structural changes in POLRMT to enable promoter opening
CC and trapping of the DNA non-template strand (By similarity). Required
CC for accurate and efficient promoter recognition by the mitochondrial
CC RNA polymerase (By similarity). Promotes transcription initiation from
CC the HSP1 and the light strand promoter by binding immediately upstream
CC of transcriptional start sites (By similarity). Is able to unwind DNA
CC (By similarity). Bends the mitochondrial light strand promoter DNA into
CC a U-turn shape via its HMG boxes (By similarity). Required for
CC maintenance of normal levels of mitochondrial DNA (PubMed:9500544). May
CC play a role in organizing and compacting mitochondrial DNA
CC (PubMed:17581862). {ECO:0000250|UniProtKB:Q00059,
CC ECO:0000269|PubMed:17581862, ECO:0000269|PubMed:9500544}.
CC -!- FUNCTION: [Isoform Nuclear]: May also function as a transcriptional
CC activator or may have a structural role in the compaction of nuclear
CC DNA during spermatogenesis. {ECO:0000269|PubMed:8673128}.
CC -!- SUBUNIT: Monomer; binds DNA as a monomer. Homodimer. Component of the
CC mitochondrial transcription initiation complex, composed at least of
CC TFB2M, TFAM and POLRMT. In this complex TFAM recruits POLRMT to the
CC promoter whereas TFB2M induces structural changes in POLRMT to enable
CC promoter opening and trapping of the DNA non-template strand. Upon
CC metabolic stress, forms a complex composed of FOXO3, SIRT3, TFAM and
CC POLRMT. Interacts with TFB1M and TFB2M. Interacts with CLPX; this
CC enhances DNA-binding. {ECO:0000250|UniProtKB:Q00059}.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC {ECO:0000250|UniProtKB:Q00059}. Mitochondrion matrix, mitochondrion
CC nucleoid {ECO:0000250|UniProtKB:Q00059}.
CC -!- SUBCELLULAR LOCATION: [Isoform Nuclear]: Nucleus
CC {ECO:0000269|PubMed:8673128}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=P40630-1; Sequence=Displayed;
CC Name=Nuclear;
CC IsoId=P40630-2; Sequence=VSP_002185, VSP_002186;
CC -!- TISSUE SPECIFICITY: The mitochondrial isoform is widely expressed while
CC the nuclear isoform is testis-specific.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation by PKA within the HMG box 1 impairs DNA binding
CC and promotes degradation by the AAA+ Lon protease. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal, due to absence of mitochondrial
CC DNA. Mutant embryos die before 10.5 dpc. {ECO:0000269|PubMed:9500544}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA02579.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AK004857; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U57939; AAC52815.1; -; mRNA.
DR EMBL; U63858; AAC52816.1; -; mRNA.
DR EMBL; BC001987; AAH01987.1; -; mRNA.
DR EMBL; BC083084; AAH83084.1; -; mRNA.
DR EMBL; AK004857; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK050446; BAC34258.1; -; mRNA.
DR EMBL; AK167348; BAE39447.1; -; mRNA.
DR EMBL; AK167777; BAE39809.1; -; mRNA.
DR EMBL; AK169808; BAE41382.1; -; mRNA.
DR EMBL; U63712; AAB06395.1; -; mRNA.
DR EMBL; L07107; AAA02579.1; ALT_INIT; mRNA.
DR CCDS; CCDS23916.1; -. [P40630-1]
DR PIR; I49745; I49745.
DR RefSeq; NP_033386.1; NM_009360.4. [P40630-1]
DR AlphaFoldDB; P40630; -.
DR SMR; P40630; -.
DR BioGRID; 204137; 9.
DR IntAct; P40630; 2.
DR STRING; 10090.ENSMUSP00000090086; -.
DR iPTMnet; P40630; -.
DR PhosphoSitePlus; P40630; -.
DR EPD; P40630; -.
DR MaxQB; P40630; -.
DR PaxDb; P40630; -.
DR PeptideAtlas; P40630; -.
DR PRIDE; P40630; -.
DR ProteomicsDB; 262881; -. [P40630-1]
DR ProteomicsDB; 262882; -. [P40630-2]
DR Antibodypedia; 14209; 562 antibodies from 41 providers.
DR DNASU; 21780; -.
DR Ensembl; ENSMUST00000092430; ENSMUSP00000090086; ENSMUSG00000003923. [P40630-1]
DR Ensembl; ENSMUST00000105432; ENSMUSP00000101072; ENSMUSG00000003923. [P40630-2]
DR GeneID; 21780; -.
DR KEGG; mmu:21780; -.
DR UCSC; uc007fol.1; mouse. [P40630-2]
DR UCSC; uc007fom.1; mouse. [P40630-1]
DR CTD; 7019; -.
DR MGI; MGI:107810; Tfam.
DR VEuPathDB; HostDB:ENSMUSG00000003923; -.
DR eggNOG; KOG0381; Eukaryota.
DR GeneTree; ENSGT00440000039001; -.
DR InParanoid; P40630; -.
DR OMA; ISVQAKM; -.
DR OrthoDB; 1641977at2759; -.
DR PhylomeDB; P40630; -.
DR TreeFam; TF318343; -.
DR Reactome; R-MMU-163282; Mitochondrial transcription initiation.
DR BioGRID-ORCS; 21780; 18 hits in 77 CRISPR screens.
DR ChiTaRS; Tfam; mouse.
DR PRO; PR:P40630; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P40630; protein.
DR Bgee; ENSMUSG00000003923; Expressed in ventricular zone and 254 other tissues.
DR ExpressionAtlas; P40630; baseline and differential.
DR Genevisible; P40630; MM.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0008301; F:DNA binding, bending; IBA:GO_Central.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0001018; F:mitochondrial promoter sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0034246; F:mitochondrial transcription factor activity; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI.
DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; IMP:MGI.
DR GO; GO:0006390; P:mitochondrial transcription; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006391; P:transcription initiation from mitochondrial promoter; ISS: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 Activator; Alternative splicing; DNA-binding; Mitochondrion;
KW Mitochondrion nucleoid; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 43..243
FT /note="Transcription factor A, mitochondrial"
FT /id="PRO_0000013471"
FT DNA_BIND 49..117
FT /note="HMG box 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT DNA_BIND 154..218
FT /note="HMG box 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT SITE 57
FT /note="Intercalates between bases and promotes DNA bending"
FT /evidence="ECO:0000250"
FT SITE 181
FT /note="Intercalates between bases and promotes DNA bending"
FT /evidence="ECO:0000250"
FT MOD_RES 54
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q00059"
FT MOD_RES 55
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q00059"
FT MOD_RES 60
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q00059"
FT MOD_RES 66
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 121
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q00059"
FT MOD_RES 159
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q00059"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00059"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform Nuclear)"
FT /evidence="ECO:0000303|PubMed:8673128"
FT /id="VSP_002185"
FT VAR_SEQ 29..34
FT /note="IPSSIS -> MAGAWG (in isoform Nuclear)"
FT /evidence="ECO:0000303|PubMed:8673128"
FT /id="VSP_002186"
FT CONFLICT 34
FT /note="S -> R (in Ref. 5; AAA02579)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 243 AA; 27988 MW; 3477F6EEAD9A3EBF CRC64;
MALFRGMWSV LKALGRTGVE MCAGCGGRIP SSISLVCIPK CFSSMGSYPK KPMSSYLRFS
TEQLPKFKAK HPDAKLSELV RKIAALWREL PEAEKKVYEA DFKAEWKAYK EAVSKYKEQL
TPSQLMGMEK EARQRRLKKK ALVKRRELIL LGKPKRPRSA YNIYVSESFQ EAKDDSAQGK
LKLVNEAWKN LSPEEKQAYI QLAKDDRIRY DNEMKSWEEQ MAEVGRSDLI RRSVKRSGDI
SEH
