MTTF_DROME
ID MTTF_DROME Reviewed; 410 AA.
AC Q9V3F3; Q86LS0;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Transcription termination factor, mitochondrial {ECO:0000305};
DE AltName: Full=Mitochondrial transcription termination factor {ECO:0000303|PubMed:12626700};
DE Short=mTTF {ECO:0000303|PubMed:12626700};
DE Flags: Precursor;
GN Name=mTTF {ECO:0000303|PubMed:12626700, ECO:0000312|FlyBase:FBgn0028530};
GN ORFNames=CG18124 {ECO:0000312|FlyBase:FBgn0028530};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|EMBL:AAO38861.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=12626700; DOI=10.1093/nar/gkg272;
RA Roberti M., Loguercio Polosa P., Bruni F., Musicco C., Gadaleta M.N.,
RA Cantatore P.;
RT "DmTTF, a novel mitochondrial transcription termination factor that
RT recognises two sequences of Drosophila melanogaster mitochondrial DNA.";
RL Nucleic Acids Res. 31:1597-1604(2003).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4] {ECO:0000312|EMBL:AAL68092.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL68092.1};
RC TISSUE=Testis {ECO:0000312|EMBL:AAL68092.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=15845400; DOI=10.1016/j.bbrc.2005.03.173;
RA Roberti M., Fernandez-Silva P., Polosa P.L., Fernandez-Vizarra E.,
RA Bruni F., Deceglie S., Montoya J., Gadaleta M.N., Cantatore P.;
RT "In vitro transcription termination activity of the Drosophila
RT mitochondrial DNA-binding protein DmTTF.";
RL Biochem. Biophys. Res. Commun. 331:357-362(2005).
RN [6] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16648357; DOI=10.1093/nar/gkl181;
RA Roberti M., Bruni F., Polosa P.L., Gadaleta M.N., Cantatore P.;
RT "The Drosophila termination factor DmTTF regulates in vivo mitochondrial
RT transcription.";
RL Nucleic Acids Res. 34:2109-2116(2006).
RN [7] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=19032147; DOI=10.1042/bj20081174;
RA Fernandez-Moreno M.A., Bruni F., Adan C., Sierra R.H., Polosa P.L.,
RA Cantatore P., Garesse R., Roberti M.;
RT "The Drosophila nuclear factor DREF positively regulates the expression of
RT the mitochondrial transcription termination factor DmTTF.";
RL Biochem. J. 418:453-462(2009).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=22784680; DOI=10.1016/j.mito.2012.06.010;
RA Bruni F., Manzari C., Filice M., Loguercio Polosa P., Colella M.,
RA Carmone C., Hambardjieva E., Garcia-Diaz M., Cantatore P., Roberti M.;
RT "D-MTERF5 is a novel factor modulating transcription in Drosophila
RT mitochondria.";
RL Mitochondrion 12:492-499(2012).
RN [9] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=24068965; DOI=10.1371/journal.pgen.1003800;
RA Joers P., Lewis S.C., Fukuoh A., Parhiala M., Ellilae S., Holt I.J.,
RA Jacobs H.T.;
RT "Mitochondrial transcription terminator family members mTTF and mTerf5 have
RT opposing roles in coordination of mtDNA synthesis.";
RL PLoS Genet. 9:E1003800-E1003800(2013).
CC -!- FUNCTION: Transcription termination factor (PubMed:12626700,
CC PubMed:15845400, PubMed:16648357). Binds promoter DNA and regulates
CC mitochondrial replication and transcription (PubMed:12626700,
CC PubMed:15845400, PubMed:16648357, PubMed:24068965). Transcription
CC termination activity may be polarized with highest termination activity
CC occurring when its DNA-binding site is positioned in the reverse
CC orientation with respect to the incoming RNA polymerase
CC (PubMed:15845400). Required for normal topology and maintenance of
CC mitochondrial DNA (mtDNA) levels (PubMed:24068965). Regulates mtDNA
CC replication by promoting replication pausing, possibly by acting as a
CC natural barrier to replication fork progression (PubMed:24068965). Its
CC function in replication pausing prevents unregulated replication that
CC may occur for example by collisions between the machineries of DNA
CC replication and transcription during mtDNA synthesis (PubMed:24068965).
CC This ensures the incorporation of RNA transcripts into replication
CC intermediates at the replication fork and allow for proper fork
CC progression (PubMed:24068965). Shares mtDNA binding sites with the
CC mitochondrial termination factor mTerf5 and thereby may antagonize
CC mTerf5 function during replication to regulate pausing
CC (PubMed:22784680, PubMed:24068965). Likely to function downstream of
CC Dref which activates genes involved in mtDNA replication and
CC maintenance (PubMed:19032147, PubMed:24068965).
CC {ECO:0000269|PubMed:12626700, ECO:0000269|PubMed:15845400,
CC ECO:0000269|PubMed:16648357, ECO:0000269|PubMed:19032147,
CC ECO:0000269|PubMed:22784680, ECO:0000269|PubMed:24068965}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16648357,
CC ECO:0000269|PubMed:24068965}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis.
CC {ECO:0000269|PubMed:19032147}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is lethal. Most mutants
CC fail to develop past the L3 larval stage, and the few pupal escapers do
CC not develop to the late pupal stages. Mitochondrial DNA (mtDNA) copy
CC number fails to increase during larval development and instead steadily
CC decreases. Increase in broken mTDNA replication intermediates.
CC {ECO:0000269|PubMed:24068965}.
CC -!- SIMILARITY: Belongs to the mTERF family. {ECO:0000305}.
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DR EMBL; AY196479; AAO38861.1; -; mRNA.
DR EMBL; AE014134; AAF53386.1; -; Genomic_DNA.
DR EMBL; AY075225; AAL68092.1; -; mRNA.
DR RefSeq; NP_609709.1; NM_135865.4.
DR AlphaFoldDB; Q9V3F3; -.
DR IntAct; Q9V3F3; 2.
DR STRING; 7227.FBpp0080213; -.
DR PaxDb; Q9V3F3; -.
DR PRIDE; Q9V3F3; -.
DR DNASU; 34837; -.
DR EnsemblMetazoa; FBtr0080641; FBpp0080213; FBgn0028530.
DR GeneID; 34837; -.
DR KEGG; dme:Dmel_CG18124; -.
DR UCSC; CG18124-RA; d. melanogaster.
DR CTD; 34837; -.
DR FlyBase; FBgn0028530; mTTF.
DR VEuPathDB; VectorBase:FBgn0028530; -.
DR eggNOG; ENOG502S44V; Eukaryota.
DR GeneTree; ENSGT00530000063817; -.
DR HOGENOM; CLU_664440_0_0_1; -.
DR InParanoid; Q9V3F3; -.
DR OMA; FRYTPKS; -.
DR OrthoDB; 1181628at2759; -.
DR PhylomeDB; Q9V3F3; -.
DR Reactome; R-DME-163316; Mitochondrial transcription termination.
DR BioGRID-ORCS; 34837; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 34837; -.
DR PRO; PR:Q9V3F3; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0028530; Expressed in spermathecum and 21 other tissues.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0003677; F:DNA binding; IDA:FlyBase.
DR GO; GO:0003690; F:double-stranded DNA binding; IEA:InterPro.
DR GO; GO:0003676; F:nucleic acid binding; IBA:GO_Central.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0006393; P:termination of mitochondrial transcription; IDA:FlyBase.
DR Gene3D; 1.25.70.10; -; 1.
DR InterPro; IPR003690; MTERF.
DR InterPro; IPR038538; MTERF_sf.
DR PANTHER; PTHR15437; PTHR15437; 1.
DR Pfam; PF02536; mTERF; 1.
DR SMART; SM00733; Mterf; 3.
PE 2: Evidence at transcript level;
KW DNA replication; Mitochondrion; Reference proteome; Transcription;
KW Transcription regulation; Transit peptide.
FT TRANSIT 1..44
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 45..410
FT /note="Transcription termination factor, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000438974"
FT CONFLICT 46
FT /note="S -> P (in Ref. 1; AAO38861)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="T -> A (in Ref. 1; AAO38861)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="V -> I (in Ref. 1; AAO38861)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="N -> T (in Ref. 1; AAO38861)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 410 AA; 48281 MW; D8BDA9134A44D598 CRC64;
MIRSLLRSFE TALKLHAGLN MHPMHCSRRL LFSQYENRAS PSRLTSSGTL GSNEAENDYV
PYRQDRETGT KTRVLLEALR ERFRFTDAEL QKIISDELVH RCYRGRSLTL VMDTLQLEGV
SRRSFVEYPW LLSLDNKRLE LKMQLLKSMD FKDINHFVPF LRLTVPRLRK LVGALNSERD
AMPQRNRVYY ISEKLDVSPD IVSKYLSKRL FILEMPFEMF EKNLQHMIDY NVSPINVLKD
LWAFRYTPKS VQLRLERAKR AKKDKIMPWM VRCPEPILQR SLKLSLDELK VLGEFSSVVE
YLAHRLGFST SEAKAIMDKH PQVHTVRVTK IKEVLDYLLD EAQFTRFEVA QNPRILCHSL
KTTKERMEEL KSHGCRPSSL VILCRSRREY DKFLQNWISH ERNPQSVSEG
