ID   TMLH_RAT                Reviewed;         421 AA.
AC   Q91ZW6; Q5U2P7;
DT   20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2006, sequence version 2.
DT   03-AUG-2022, entry version 139.
DE   RecName: Full=Trimethyllysine dioxygenase, mitochondrial;
DE            EC=1.14.11.8 {ECO:0000269|PubMed:11431483};
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Kidney;
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 17-421 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE,
RP   FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND SUBCELLULAR LOCATION.
RC   STRAIN=Wistar;
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).
CC   -!- FUNCTION: Converts trimethyllysine (TML) into hydroxytrimethyllysine
CC       (HTML) (PubMed:11431483). {ECO:0000269|PubMed:11431483}.
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:0000269|PubMed:11431483};
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:0000269|PubMed:11431483}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000269|PubMed:11431483}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q91ZW6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q91ZW6-2; Sequence=VSP_021580;
CC   -!- SIMILARITY: Belongs to the gamma-BBH/TMLD family. {ECO:0000305}.
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DR   EMBL; BC085923; AAH85923.1; -; mRNA.
DR   EMBL; AF374406; AAL01252.1; -; mRNA.
DR   RefSeq; NP_596878.2; NM_133387.2. [Q91ZW6-2]
DR   RefSeq; XP_006255917.1; XM_006255855.1. [Q91ZW6-1]
DR   AlphaFoldDB; Q91ZW6; -.
DR   SMR; Q91ZW6; -.
DR   IntAct; Q91ZW6; 1.
DR   STRING; 10116.ENSRNOP00000068031; -.
DR   iPTMnet; Q91ZW6; -.
DR   PhosphoSitePlus; Q91ZW6; -.
DR   jPOST; Q91ZW6; -.
DR   PaxDb; Q91ZW6; -.
DR   PRIDE; Q91ZW6; -.
DR   Ensembl; ENSRNOT00000076655; ENSRNOP00000068322; ENSRNOG00000000729. [Q91ZW6-1]
DR   Ensembl; ENSRNOT00000076901; ENSRNOP00000068031; ENSRNOG00000000729. [Q91ZW6-2]
DR   GeneID; 170898; -.
DR   KEGG; rno:170898; -.
DR   UCSC; RGD:620629; rat. [Q91ZW6-1]
DR   CTD; 55217; -.
DR   RGD; 620629; Tmlhe.
DR   eggNOG; KOG3889; Eukaryota.
DR   GeneTree; ENSGT00530000063582; -.
DR   HOGENOM; CLU_021859_2_0_1; -.
DR   InParanoid; Q91ZW6; -.
DR   OMA; EEKVCIQ; -.
DR   OrthoDB; 868657at2759; -.
DR   PhylomeDB; Q91ZW6; -.
DR   TreeFam; TF313805; -.
DR   BioCyc; MetaCyc:MON-14429; -.
DR   BRENDA; 1.14.11.8; 5301.
DR   Reactome; R-RNO-71262; Carnitine synthesis.
DR   UniPathway; UPA00118; -.
DR   PRO; PR:Q91ZW6; -.
DR   Proteomes; UP000002494; Chromosome 20.
DR   Bgee; ENSRNOG00000000729; Expressed in kidney and 19 other tissues.
DR   Genevisible; Q91ZW6; RN.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IDA:RGD.
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; ISO:RGD.
DR   GO; GO:0050353; F:trimethyllysine dioxygenase activity; IDA:RGD.
DR   GO; GO:0045329; P:carnitine biosynthetic process; ISS:UniProtKB.
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; Alternative splicing; Carnitine biosynthesis; Dioxygenase;
KW   Direct protein sequencing; Iron; Metal-binding; Mitochondrion;
KW   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_0000002797"
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:0000250|UniProtKB:Q91ZE0"
FT   MOD_RES         236
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NVH6"
FT   VAR_SEQ         62
FT                   /note="L -> LGTKPRALRLLEL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_021580"
SQ   SEQUENCE   421 AA;  49568 MW;  487AB5FCA0D02D25 CRC64;
     MWYHKLLHQQ SRLQNLMKRG DIAHGLRLSG FKSLFPFSLH WCHTASKSVN CTWHQHEDHL
     ELQYASTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV DLCIKPKTIR LDESTLFFTW
     PDGHVTRYDL DWLVKNSYEG QKQEVIQPRV LWNAKLYQDA QLPSVDFQGF LETKEGLKKF
     LQNFLLYGIA FVENVPPTQE HTEKLARRVS LIRETIYGRM WYFTSDFSRG DTAYTKLALD
     RHTDTTYFQE PCGIQVFHCL KHEGTGGRTL LVDGFYAAQQ VLQRAPEEFD LLSQVPLKHE
     YIENVGQCHN HMIGVGPILN IYPWNKELYL IRYNNYDRAV INTVPYDVVR RWYAAHRTLT
     TELRRPENEL WVKLKPGKVL FIDNWRVLHG RESFTGYRQL CGCYLTRDDV LNTARILGLH
     A