FMT_HUMAN
ID FMT_HUMAN Reviewed; 389 AA.
AC Q96DP5; B7Z734;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JAN-2003, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Methionyl-tRNA formyltransferase, mitochondrial;
DE Short=MtFMT;
DE EC=2.1.2.9 {ECO:0000269|PubMed:21907147, ECO:0000269|PubMed:25288793};
DE Flags: Precursor;
GN Name=MTFMT; Synonyms=FMT, FMT1;
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 [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 11-389 (ISOFORM 1).
RC TISSUE=Neuroblastoma, and Synovium;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, and Mammary gland;
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 [4]
RP VARIANTS COXPD15 LEU-125 AND LEU-209, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21907147; DOI=10.1016/j.cmet.2011.07.010;
RA Tucker E.J., Hershman S.G., Koehrer C., Belcher-Timme C.A., Patel J.,
RA Goldberger O.A., Christodoulou J., Silberstein J.M., McKenzie M.,
RA Ryan M.T., Compton A.G., Jaffe J.D., Carr S.A., Calvo S.E.,
RA RajBhandary U.L., Thorburn D.R., Mootha V.K.;
RT "Mutations in MTFMT underlie a human disorder of formylation causing
RT impaired mitochondrial translation.";
RL Cell Metab. 14:428-434(2011).
RN [5]
RP VARIANTS MC1DN27 LEU-209 AND 332-ARG--GLU-389 DEL.
RX PubMed=22499348; DOI=10.1136/jmedgenet-2012-100846;
RA Haack T.B., Haberberger B., Frisch E.M., Wieland T., Iuso A., Gorza M.,
RA Strecker V., Graf E., Mayr J.A., Herberg U., Hennermann J.B., Klopstock T.,
RA Kuhn K.A., Ahting U., Sperl W., Wilichowski E., Hoffmann G.F., Tesarova M.,
RA Hansikova H., Zeman J., Plecko B., Zeviani M., Wittig I., Strom T.M.,
RA Schuelke M., Freisinger P., Meitinger T., Prokisch H.;
RT "Molecular diagnosis in mitochondrial complex I deficiency using exome
RT sequencing.";
RL J. Med. Genet. 49:277-283(2012).
RN [6]
RP CHARACTERIZATION OF VARIANTS COXPD15 LEU-125 AND LEU-209, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=25288793; DOI=10.1074/jbc.m114.610626;
RA Sinha A., Koehrer C., Weber M.H., Masuda I., Mootha V.K., Hou Y.M.,
RA RajBhandary U.L.;
RT "Biochemical characterization of pathogenic mutations in human
RT mitochondrial methionyl-tRNA formyltransferase.";
RL J. Biol. Chem. 289:32729-32741(2014).
CC -!- FUNCTION: Methionyl-tRNA formyltransferase that formylates methionyl-
CC tRNA in mitochondria and is crucial for translation initiation.
CC {ECO:0000269|PubMed:21907147, ECO:0000269|PubMed:25288793}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-10-formyltetrahydrofolate + L-methionyl-tRNA(fMet) =
CC (6S)-5,6,7,8-tetrahydrofolate + H(+) + N-formyl-L-methionyl-
CC tRNA(fMet); Xref=Rhea:RHEA:24380, Rhea:RHEA-COMP:9952, Rhea:RHEA-
CC COMP:9953, ChEBI:CHEBI:15378, ChEBI:CHEBI:57453, ChEBI:CHEBI:57454,
CC ChEBI:CHEBI:78530, ChEBI:CHEBI:78844; EC=2.1.2.9;
CC Evidence={ECO:0000269|PubMed:25288793};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24381;
CC Evidence={ECO:0000269|PubMed:21907147};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:O77480}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96DP5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96DP5-2; Sequence=VSP_057059, VSP_057060;
CC -!- DOMAIN: Composed of an N- and a C-terminal domain. The N-terminal
CC domain carries the tetrahydrofolate (THF)-binding site and the C-
CC terminal domain is presumably involved in positioning the Met-tRNA
CC substrate for the formylation reaction.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 15 (COXPD15)
CC [MIM:614947]: An autosomal recessive, mitochondrial, neurologic
CC disorder characterized by features of Leigh syndrome and combined
CC oxidative phosphorylation deficiency. Clinical features include mild
CC global developmental delay, white matter abnormalities, ataxia,
CC incoordination, speech and reading difficulties, T2-weighted
CC hyperintensities in the basal ganglia, corpus callosum, and brainstem.
CC {ECO:0000269|PubMed:21907147, ECO:0000269|PubMed:25288793}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 27 (MC1DN27)
CC [MIM:618248]: A form of mitochondrial complex I deficiency, the most
CC common biochemical signature of mitochondrial disorders, a group of
CC highly heterogeneous conditions characterized by defective oxidative
CC phosphorylation, which collectively affects 1 in 5-10000 live births.
CC Clinical disorders have variable severity, ranging from lethal neonatal
CC disease to adult-onset neurodegenerative disorders. Phenotypes include
CC macrocephaly with progressive leukodystrophy, non-specific
CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh
CC syndrome, Leber hereditary optic neuropathy, and some forms of
CC Parkinson disease. MC1DN27 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:22499348}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the Fmt family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH16630.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH33687.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB70984.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK055688; BAB70984.1; ALT_INIT; mRNA.
DR EMBL; AK301390; BAH13470.1; -; mRNA.
DR EMBL; AC013553; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC103691; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016630; AAH16630.2; ALT_INIT; mRNA.
DR EMBL; BC033687; AAH33687.1; ALT_INIT; mRNA.
DR CCDS; CCDS45280.1; -. [Q96DP5-1]
DR RefSeq; NP_640335.2; NM_139242.3. [Q96DP5-1]
DR AlphaFoldDB; Q96DP5; -.
DR SMR; Q96DP5; -.
DR BioGRID; 125820; 94.
DR IntAct; Q96DP5; 5.
DR STRING; 9606.ENSP00000220058; -.
DR DrugBank; DB00116; Tetrahydrofolic acid.
DR iPTMnet; Q96DP5; -.
DR PhosphoSitePlus; Q96DP5; -.
DR BioMuta; MTFMT; -.
DR DMDM; 27923776; -.
DR EPD; Q96DP5; -.
DR jPOST; Q96DP5; -.
DR MassIVE; Q96DP5; -.
DR MaxQB; Q96DP5; -.
DR PaxDb; Q96DP5; -.
DR PeptideAtlas; Q96DP5; -.
DR PRIDE; Q96DP5; -.
DR ProteomicsDB; 6828; -.
DR ProteomicsDB; 76304; -. [Q96DP5-1]
DR Antibodypedia; 25895; 169 antibodies from 14 providers.
DR DNASU; 123263; -.
DR Ensembl; ENST00000220058.9; ENSP00000220058.4; ENSG00000103707.10. [Q96DP5-1]
DR Ensembl; ENST00000543678.1; ENSP00000443754.1; ENSG00000103707.10. [Q96DP5-2]
DR Ensembl; ENST00000558460.5; ENSP00000452646.1; ENSG00000103707.10. [Q96DP5-1]
DR GeneID; 123263; -.
DR KEGG; hsa:123263; -.
DR MANE-Select; ENST00000220058.9; ENSP00000220058.4; NM_139242.4; NP_640335.2.
DR UCSC; uc002aof.5; human. [Q96DP5-1]
DR CTD; 123263; -.
DR DisGeNET; 123263; -.
DR GeneCards; MTFMT; -.
DR GeneReviews; MTFMT; -.
DR HGNC; HGNC:29666; MTFMT.
DR HPA; ENSG00000103707; Low tissue specificity.
DR MalaCards; MTFMT; -.
DR MIM; 611766; gene.
DR MIM; 614947; phenotype.
DR MIM; 618248; phenotype.
DR neXtProt; NX_Q96DP5; -.
DR OpenTargets; ENSG00000103707; -.
DR Orphanet; 319524; Combined oxidative phosphorylation defect type 15.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA142671304; -.
DR VEuPathDB; HostDB:ENSG00000103707; -.
DR eggNOG; KOG3082; Eukaryota.
DR GeneTree; ENSGT00390000017828; -.
DR HOGENOM; CLU_033347_0_0_1; -.
DR InParanoid; Q96DP5; -.
DR OMA; FMPELHA; -.
DR OrthoDB; 963177at2759; -.
DR PhylomeDB; Q96DP5; -.
DR TreeFam; TF323405; -.
DR BRENDA; 2.1.2.9; 2681.
DR PathwayCommons; Q96DP5; -.
DR Reactome; R-HSA-5368286; Mitochondrial translation initiation.
DR SignaLink; Q96DP5; -.
DR BioGRID-ORCS; 123263; 141 hits in 1079 CRISPR screens.
DR ChiTaRS; MTFMT; human.
DR GeneWiki; MTFMT; -.
DR GenomeRNAi; 123263; -.
DR Pharos; Q96DP5; Tbio.
DR PRO; PR:Q96DP5; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96DP5; protein.
DR Bgee; ENSG00000103707; Expressed in left ventricle myocardium and 168 other tissues.
DR ExpressionAtlas; Q96DP5; baseline and differential.
DR Genevisible; Q96DP5; HS.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0004479; F:methionyl-tRNA formyltransferase activity; IDA:UniProtKB.
DR GO; GO:0071951; P:conversion of methionyl-tRNA to N-formyl-methionyl-tRNA; IDA:UniProtKB.
DR CDD; cd08646; FMT_core_Met-tRNA-FMT_N; 1.
DR InterPro; IPR005794; Fmt.
DR InterPro; IPR005793; Formyl_trans_C.
DR InterPro; IPR002376; Formyl_transf_N.
DR InterPro; IPR036477; Formyl_transf_N_sf.
DR InterPro; IPR011034; Formyl_transferase-like_C_sf.
DR InterPro; IPR041711; Met-tRNA-FMT_N.
DR Pfam; PF02911; Formyl_trans_C; 1.
DR Pfam; PF00551; Formyl_trans_N; 1.
DR SUPFAM; SSF50486; SSF50486; 1.
DR SUPFAM; SSF53328; SSF53328; 1.
DR TIGRFAMs; TIGR00460; fmt; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Mitochondrion;
KW Primary mitochondrial disease; Protein biosynthesis; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..389
FT /note="Methionyl-tRNA formyltransferase, mitochondrial"
FT /id="PRO_0000010093"
FT VAR_SEQ 141..144
FT /note="GILN -> SFQF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057059"
FT VAR_SEQ 145..389
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057060"
FT VARIANT 5
FT /note="V -> A (in dbSNP:rs2946655)"
FT /id="VAR_059289"
FT VARIANT 125
FT /note="S -> L (in COXPD15; loss of methionyl-tRNA
FT formyltransferase activity; dbSNP:rs397514614)"
FT /evidence="ECO:0000269|PubMed:21907147,
FT ECO:0000269|PubMed:25288793"
FT /id="VAR_069303"
FT VARIANT 209
FT /note="S -> L (in COXPD15 and MC1DN27; decreased methionyl-
FT tRNA formyltransferase activity; dbSNP:rs201431517)"
FT /evidence="ECO:0000269|PubMed:21907147,
FT ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:25288793"
FT /id="VAR_069304"
FT VARIANT 332..389
FT /note="Missing (in MC1DN27)"
FT /evidence="ECO:0000269|PubMed:22499348"
FT /id="VAR_081461"
SQ SEQUENCE 389 AA; 43832 MW; EBBE92142AB954E0 CRC64;
MRVLVRRCWG PPLAHGARRG RPSPQWRALA RLGWEDCRDS RVREKPPWRV LFFGTDQFAR
EALRALHAAR ENKEEELIDK LEVVTMPSPS PKGLPVKQYA VQSQLPVYEW PDVGSGEYDV
GVVASFGRLL NEALILKFPY GILNVHPSCL PRWRGPAPVI HTVLHGDTVT GVTIMQIRPK
RFDVGPILKQ ETVPVPPKST AKELEAVLSR LGANMLISVL KNLPESLSNG RQQPMEGATY
APKISAGTSC IKWEEQTSEQ IFRLYRAIGN IIPLQTLWMA NTIKLLDLVE VNSSVLADPK
LTGQALIPGS VIYHKQSQIL LVYCKDGWIG VRSVMLKKSL TATDFYNGYL HPWYQKNSQA
QPSQCRFQTL RLPTKKKQKK TVAMQQCIE
