TMLH_MOUSE
ID TMLH_MOUSE Reviewed; 421 AA.
AC Q91ZE0; Q3TSX6; Q3UMX1; Q91XH1;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Trimethyllysine dioxygenase, mitochondrial;
DE EC=1.14.11.8 {ECO:0000250|UniProtKB:Q9NVH6};
DE AltName: Full=Epsilon-trimethyllysine 2-oxoglutarate dioxygenase;
DE AltName: Full=TML hydroxylase;
DE AltName: Full=TML-alpha-ketoglutarate dioxygenase;
DE Short=TML dioxygenase;
DE Short=TMLD;
DE Flags: Precursor;
GN Name=Tmlhe; Synonyms=Tmlh;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung, 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-421.
RC STRAIN=FVB/N;
RX PubMed=11431483; DOI=10.1074/jbc.m105929200;
RA Vaz F.M., Ofman R., Westinga K., Back J.W., Wanders R.J.A.;
RT "Molecular and biochemical characterization of rat epsilon-N-
RT trimethyllysine hydroxylase, the first enzyme of carnitine biosynthesis.";
RL J. Biol. Chem. 276:33512-33517(2001).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=17408883; DOI=10.1016/j.gene.2007.02.012;
RA Monfregola J., Napolitano G., Conte I., Cevenini A., Migliaccio C.,
RA D'Urso M., Ursini M.V.;
RT "Functional characterization of the TMLH gene: promoter analysis, in situ
RT hybridization, identification and mapping of alternative splicing
RT variants.";
RL Gene 395:86-97(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Pancreas, and Testis;
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Converts trimethyllysine (TML) into hydroxytrimethyllysine
CC (HTML). {ECO:0000250|UniProtKB:Q9NVH6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysine + O2 =
CC (3S)-3-hydroxy-N(6),N(6),N(6)-trimethyl-L-lysine + CO2 + succinate;
CC Xref=Rhea:RHEA:14181, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:58100,
CC ChEBI:CHEBI:141499; EC=1.14.11.8;
CC Evidence={ECO:0000250|UniProtKB:Q9NVH6};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q91ZW6}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q9NVH6}.
CC -!- DEVELOPMENTAL STAGE: Present already at 9.0 dpc. At 10.5 dpc, expressed
CC throughout the embryo. At 12.5 dpc, higher levels in the developing
CC lung, liver and brain compared to other tissues. In the postnatal day 7
CC brain, high levels in the Purkinje cell layer of the cerebellum and in
CC the hippocampal areas of the dentate gyrus and CA1, CA2 and CA3
CC pyramidal cells. {ECO:0000269|PubMed:17408883}.
CC -!- SIMILARITY: Belongs to the gamma-BBH/TMLD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK54387.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK144627; BAE25977.1; -; mRNA.
DR EMBL; AK161724; BAE36549.1; -; mRNA.
DR EMBL; CAAA01137825; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01183048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01120074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01019119; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466822; EDL07804.1; -; Genomic_DNA.
DR EMBL; BC010495; AAH10495.1; -; mRNA.
DR EMBL; BC115365; AAI15366.1; -; mRNA.
DR EMBL; AY033513; AAK54387.1; ALT_INIT; mRNA.
DR RefSeq; NP_620097.1; NM_138758.1.
DR AlphaFoldDB; Q91ZE0; -.
DR SMR; Q91ZE0; -.
DR BioGRID; 228687; 3.
DR STRING; 10090.ENSMUSP00000111624; -.
DR iPTMnet; Q91ZE0; -.
DR PhosphoSitePlus; Q91ZE0; -.
DR SwissPalm; Q91ZE0; -.
DR EPD; Q91ZE0; -.
DR MaxQB; Q91ZE0; -.
DR PaxDb; Q91ZE0; -.
DR PeptideAtlas; Q91ZE0; -.
DR PRIDE; Q91ZE0; -.
DR ProteomicsDB; 259579; -.
DR GeneID; 192289; -.
DR KEGG; mmu:192289; -.
DR UCSC; uc009uyo.1; mouse.
DR CTD; 55217; -.
DR MGI; MGI:2180203; Tmlhe.
DR VEuPathDB; HostDB:ENSMUSG00000079834; -.
DR eggNOG; KOG3889; Eukaryota.
DR HOGENOM; CLU_021859_2_0_1; -.
DR InParanoid; Q91ZE0; -.
DR OrthoDB; 868657at2759; -.
DR PhylomeDB; Q91ZE0; -.
DR TreeFam; TF313805; -.
DR BRENDA; 1.14.11.8; 3474.
DR UniPathway; UPA00118; -.
DR BioGRID-ORCS; 192289; 1 hit in 14 CRISPR screens.
DR PRO; PR:Q91ZE0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q91ZE0; protein.
DR Genevisible; Q91ZE0; MM.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IDA:MGI.
DR GO; GO:0050353; F:trimethyllysine dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0045329; P:carnitine biosynthetic process; IDA:MGI.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; ISO:MGI.
DR Gene3D; 3.30.2020.30; -; 1.
DR Gene3D; 3.60.130.10; -; 1.
DR InterPro; IPR010376; GBBH-like_N.
DR InterPro; IPR038492; GBBH-like_N_sf.
DR InterPro; IPR042098; TauD-like_sf.
DR InterPro; IPR003819; TauD/TfdA-like.
DR InterPro; IPR012776; Trimethyllysine_dOase.
DR Pfam; PF06155; GBBH-like_N; 1.
DR Pfam; PF02668; TauD; 1.
DR TIGRFAMs; TIGR02410; carnitine_TMLD; 1.
PE 1: Evidence at protein level;
KW Acetylation; Carnitine biosynthesis; Dioxygenase; Iron; Metal-binding;
KW Mitochondrion; Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..15
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 16..421
FT /note="Trimethyllysine dioxygenase, mitochondrial"
FT /id="PRO_0000002796"
FT BINDING 242
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 244
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 389
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT MOD_RES 179
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 236
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH6"
FT CONFLICT 8
FT /note="H -> Q (in Ref. 1; BAE36549)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="G -> K (in Ref. 1; BAE36549)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 49610 MW; 1474AD5742E88F43 CRC64;
MWYHKLLHQQ SRLRNLMKRG NIAQGLHLSN FKSLFSSSIH WCHTTSKSVN CTWHQHEDHL
ELQYAGTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV DLCIKPKTVH LDETMLFFTW
PDGHVTRYDL DWLVKNSYEG QKQKVIQPRI LWNSKLYQQA QVPSVDFQCF LETNEGLKKF
LQNFLLYGIA FVENVPPTEE HTEKLAERIS LIRETIYGRM WYFTSDFSRG DTAYTKLALD
RHTDTTYFQE PCGIQVFHCL KHEGTGGRTL LVDGFYAAQQ VLQKAPEEFE LLSKVPLKHE
YIENVGQCHN HMIGVGPILN IYPWNKELYL IRYNNYDRAV INTVPYDVVH RWYTAHRTLT
TELRRPENEL WVKLKPGKVL FIDNWRVLHG RESFTGYRQL CGCYLTRDDV LNTARLLGLH
A
