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P40630

- TFAM_MOUSE

UniProt

P40630 - TFAM_MOUSE

Protein

Transcription factor A, mitochondrial

Gene

Tfam

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 2 (30 Aug 2002)
      Previous versions | rss
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    Functioni

    Isoform Mitochondrial binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation. Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase. Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites. Is able to unwind DNA. Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes. Required for maintenance of normal levels of mitochondrial DNA. May play a role in organizing and compacting mitochondrial DNA. Isoform Nuclear may also function as a transcriptional activator or may have a structural role in the compaction of nuclear DNA during spermatogenesis.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei57 – 571Intercalates between bases and promotes DNA bendingBy similarity
    Sitei181 – 1811Intercalates between bases and promotes DNA bendingBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi49 – 11769HMG box 1PROSITE-ProRule annotationAdd
    BLAST
    DNA bindingi154 – 21865HMG box 2PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: UniProtKB
    2. DNA binding, bending Source: UniProtKB
    3. mitochondrial light strand promoter sense binding Source: UniProtKB
    4. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. mitochondrial respiratory chain complex assembly Source: MGI
    2. positive regulation of transcription, DNA-templated Source: UniProtKB
    3. transcription from mitochondrial promoter Source: UniProtKB
    4. transcription initiation from mitochondrial promoter Source: UniProtKB

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_205251. Transcriptional activation of mitochondrial biogenesis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcription factor A, mitochondrial
    Short name:
    mtTFA
    Alternative name(s):
    Testis-specific high mobility group protein
    Short name:
    TS-HMG
    Gene namesi
    Name:Tfam
    Synonyms:Hmgts
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:107810. Tfam.

    Subcellular locationi

    GO - Cellular componenti

    1. mitochondrial nucleoid Source: UniProtKB
    2. mitochondrion Source: MGI
    3. nucleus Source: UniProtKB-SubCell
    4. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Mitochondrion, Mitochondrion nucleoid, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Embryonic lethal, due to absence of mitochondrial DNA. Mutant embryos die before 10.5 dpc.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 4242MitochondrionSequence AnalysisAdd
    BLAST
    Chaini43 – 243201Transcription factor A, mitochondrialPRO_0000013471Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei54 – 541Phosphoserine; by PKABy similarity
    Modified residuei55 – 551Phosphoserine; by PKABy similarity
    Modified residuei60 – 601Phosphoserine; by PKABy similarity
    Modified residuei66 – 661N6-succinyllysine1 Publication
    Modified residuei159 – 1591Phosphoserine; by PKABy similarity
    Modified residuei192 – 1921PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylation by PKA within the HMG box 1 impairs DNA binding and promotes degradation by the AAA+ Lon protease.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP40630.
    PaxDbiP40630.
    PRIDEiP40630.

    PTM databases

    PhosphoSiteiP40630.

    Expressioni

    Tissue specificityi

    The mitochondrial isoform is widely expressed while the nuclear isoform is testis-specific.

    Gene expression databases

    ArrayExpressiP40630.
    BgeeiP40630.
    CleanExiMM_TFAM.
    GenevestigatoriP40630.

    Interactioni

    Subunit structurei

    Monomer; binds DNA as a monomer. Interacts with TFB1M and TFB2M. Interacts with CLPX; this enhances DNA-binding By similarity.By similarity

    Protein-protein interaction databases

    BioGridi204137. 2 interactions.
    IntActiP40630. 4 interactions.
    MINTiMINT-1861500.

    Structurei

    3D structure databases

    ProteinModelPortaliP40630.
    SMRiP40630. Positions 43-232.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domaini

    Binds DNA via its HMG boxes. When bound to the mitochondrial light strand promoter, bends DNA into a U-turn shape, each HMG box bending the DNA by 90 degrees By similarity.By similarity

    Sequence similaritiesi

    Contains 2 HMG box DNA-binding domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Transit peptide

    Phylogenomic databases

    eggNOGiNOG297801.
    GeneTreeiENSGT00440000039001.
    HOGENOMiHOG000139423.
    HOVERGENiHBG106674.
    InParanoidiP40630.
    KOiK11830.
    OMAiDDKIRYE.
    OrthoDBiEOG7CG724.
    PhylomeDBiP40630.
    TreeFamiTF318343.

    Family and domain databases

    Gene3Di1.10.30.10. 2 hits.
    InterProiIPR009071. HMG_box_dom.
    [Graphical view]
    PfamiPF00505. HMG_box. 1 hit.
    PF09011. HMG_box_2. 1 hit.
    [Graphical view]
    SMARTiSM00398. HMG. 2 hits.
    [Graphical view]
    SUPFAMiSSF47095. SSF47095. 2 hits.
    PROSITEiPS50118. HMG_BOX_2. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Mitochondrial (identifier: P40630-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MALFRGMWSV LKALGRTGVE MCAGCGGRIP SSISLVCIPK CFSSMGSYPK    50
    KPMSSYLRFS TEQLPKFKAK HPDAKLSELV RKIAALWREL PEAEKKVYEA 100
    DFKAEWKAYK EAVSKYKEQL TPSQLMGMEK EARQRRLKKK ALVKRRELIL 150
    LGKPKRPRSA YNIYVSESFQ EAKDDSAQGK LKLVNEAWKN LSPEEKQAYI 200
    QLAKDDRIRY DNEMKSWEEQ MAEVGRSDLI RRSVKRSGDI SEH 243
    Length:243
    Mass (Da):27,988
    Last modified:August 30, 2002 - v2
    Checksum:i3477F6EEAD9A3EBF
    GO
    Isoform Nuclear (identifier: P40630-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-28: Missing.
         29-34: IPSSIS → MAGAWG

    Show »
    Length:215
    Mass (Da):25,036
    Checksum:iB728ED1DF9053452
    GO

    Sequence cautioni

    The sequence AK004857 differs from that shown. Reason: Frameshift at position 195.
    The sequence AAA02579.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti34 – 341S → R in AAA02579. (PubMed:8321234)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2828Missing in isoform Nuclear. 1 PublicationVSP_002185Add
    BLAST
    Alternative sequencei29 – 346IPSSIS → MAGAWG in isoform Nuclear. 1 PublicationVSP_002186

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U57939 mRNA. Translation: AAC52815.1.
    U63858 mRNA. Translation: AAC52816.1.
    BC001987 mRNA. Translation: AAH01987.1.
    BC083084 mRNA. Translation: AAH83084.1.
    AK004857 mRNA. No translation available.
    AK050446 mRNA. Translation: BAC34258.1.
    AK167348 mRNA. Translation: BAE39447.1.
    AK167777 mRNA. Translation: BAE39809.1.
    AK169808 mRNA. Translation: BAE41382.1.
    U63712 mRNA. Translation: AAB06395.1.
    L07107 mRNA. Translation: AAA02579.1. Different initiation.
    CCDSiCCDS23916.1. [P40630-1]
    PIRiI49745.
    RefSeqiNP_033386.1. NM_009360.4. [P40630-1]
    UniGeneiMm.229292.

    Genome annotation databases

    EnsembliENSMUST00000092430; ENSMUSP00000090086; ENSMUSG00000003923. [P40630-1]
    ENSMUST00000105432; ENSMUSP00000101072; ENSMUSG00000003923. [P40630-2]
    ENSMUST00000121685; ENSMUSP00000113581; ENSMUSG00000003923.
    GeneIDi21780.
    KEGGimmu:21780.
    UCSCiuc007fol.1. mouse. [P40630-2]
    uc007fom.1. mouse. [P40630-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U57939 mRNA. Translation: AAC52815.1 .
    U63858 mRNA. Translation: AAC52816.1 .
    BC001987 mRNA. Translation: AAH01987.1 .
    BC083084 mRNA. Translation: AAH83084.1 .
    AK004857 mRNA. No translation available.
    AK050446 mRNA. Translation: BAC34258.1 .
    AK167348 mRNA. Translation: BAE39447.1 .
    AK167777 mRNA. Translation: BAE39809.1 .
    AK169808 mRNA. Translation: BAE41382.1 .
    U63712 mRNA. Translation: AAB06395.1 .
    L07107 mRNA. Translation: AAA02579.1 . Different initiation.
    CCDSi CCDS23916.1. [P40630-1 ]
    PIRi I49745.
    RefSeqi NP_033386.1. NM_009360.4. [P40630-1 ]
    UniGenei Mm.229292.

    3D structure databases

    ProteinModelPortali P40630.
    SMRi P40630. Positions 43-232.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204137. 2 interactions.
    IntActi P40630. 4 interactions.
    MINTi MINT-1861500.

    PTM databases

    PhosphoSitei P40630.

    Proteomic databases

    MaxQBi P40630.
    PaxDbi P40630.
    PRIDEi P40630.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000092430 ; ENSMUSP00000090086 ; ENSMUSG00000003923 . [P40630-1 ]
    ENSMUST00000105432 ; ENSMUSP00000101072 ; ENSMUSG00000003923 . [P40630-2 ]
    ENSMUST00000121685 ; ENSMUSP00000113581 ; ENSMUSG00000003923 .
    GeneIDi 21780.
    KEGGi mmu:21780.
    UCSCi uc007fol.1. mouse. [P40630-2 ]
    uc007fom.1. mouse. [P40630-1 ]

    Organism-specific databases

    CTDi 7019.
    MGIi MGI:107810. Tfam.

    Phylogenomic databases

    eggNOGi NOG297801.
    GeneTreei ENSGT00440000039001.
    HOGENOMi HOG000139423.
    HOVERGENi HBG106674.
    InParanoidi P40630.
    KOi K11830.
    OMAi DDKIRYE.
    OrthoDBi EOG7CG724.
    PhylomeDBi P40630.
    TreeFami TF318343.

    Enzyme and pathway databases

    Reactomei REACT_205251. Transcriptional activation of mitochondrial biogenesis.

    Miscellaneous databases

    ChiTaRSi TFAM. mouse.
    NextBioi 301118.
    PROi P40630.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P40630.
    Bgeei P40630.
    CleanExi MM_TFAM.
    Genevestigatori P40630.

    Family and domain databases

    Gene3Di 1.10.30.10. 2 hits.
    InterProi IPR009071. HMG_box_dom.
    [Graphical view ]
    Pfami PF00505. HMG_box. 1 hit.
    PF09011. HMG_box_2. 1 hit.
    [Graphical view ]
    SMARTi SM00398. HMG. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47095. SSF47095. 2 hits.
    PROSITEi PS50118. HMG_BOX_2. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A single mouse gene encodes the mitochondrial transcription factor A and a testis-specific nuclear HMG-box protein."
      Larsson N.G., Garman J.D., Oldfors A., Barsh G.S., Clayton D.A.
      Nat. Genet. 13:296-302(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MITOCHONDRIAL AND NUCLEAR), FUNCTION, ALTERNATIVE SPLICING.
      Tissue: Lymphocyte and Testis.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
      Strain: C57BL/6J, DBA/2 and NOD.
      Tissue: Liver and Thymus.
    4. Cermakian N., Cedergren R.
      Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-48 (ISOFORM MITOCHONDRIAL).
      Strain: CD-1.
      Tissue: Testis.
    5. "A testis-specific gene encoding a nuclear high-mobility-group box protein located in elongating spermatids."
      Boissonneault G., Lau Y.-F.C.
      Mol. Cell. Biol. 13:4323-4330(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 34-243 (ISOFORM MITOCHONDRIAL).
      Strain: BALB/c.
      Tissue: Testis.
    6. "Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice."
      Larsson N.G., Wang J., Wilhelmsson H., Oldfors A., Rustin P., Lewandoski M., Barsh G.S., Clayton D.A.
      Nat. Genet. 18:231-236(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    7. "The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures."
      Kaufman B.A., Durisic N., Mativetsky J.M., Costantino S., Hancock M.A., Grutter P., Shoubridge E.A.
      Mol. Biol. Cell 18:3225-3236(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    8. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-66, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.

    Entry informationi

    Entry nameiTFAM_MOUSE
    AccessioniPrimary (citable) accession number: P40630
    Secondary accession number(s): P97894
    , P97906, Q543I8, Q9DBM9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: August 30, 2002
    Last modified: October 1, 2014
    This is version 127 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3