ID TMLH_HUMAN Reviewed; 421 AA. AC Q9NVH6; A8K6M9; B4E3R3; Q5TZB5; Q6IA90; Q8TBT0; DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 29-MAY-2024, entry version 182. DE RecName: Full=Trimethyllysine dioxygenase, mitochondrial; DE EC=1.14.11.8 {ECO:0000269|PubMed:27965989, ECO:0000269|PubMed:28045275}; DE AltName: Full=Epsilon-trimethyllysine 2-oxoglutarate dioxygenase; DE AltName: Full=Epsilon-trimethyllysine hydroxylase; 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 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 [MRNA] (ISOFORM 1), AND FUNCTION. 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 7), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 66-332 (ISOFORM 3). RC TISSUE=Placenta, Teratocarcinoma, Thymus, and Uterus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RA Bechtel S., Schupp I., Duda A., Wellenreuther R., Mehrle A., Ruschke V., RA Poustka A., Wiemann S.; RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Pancreas; 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 [7] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, TRANSIT PEPTIDE CLEAVAGE SITE, RP MUTAGENESIS OF HIS-389, AND ALTERNATIVE SPLICING (ISOFORMS 1 AND 2). RX PubMed=15754339; DOI=10.1002/jcp.20332; RA Monfregola J., Cevenini A., Terracciano A., van Vlies N., Arbucci S., RA Wanders R.J., D'Urso M., Vaz F.M., Ursini M.V.; RT "Functional analysis of TMLH variants and definition of domains required RT for catalytic activity and mitochondrial targeting."; RL J. Cell. Physiol. 204:839-847(2005). RN [8] RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. 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 [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-236, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP INVOLVEMENT IN AUTSX6. RX PubMed=21865298; DOI=10.1093/hmg/ddr363; RA Celestino-Soper P.B., Shaw C.A., Sanders S.J., Li J., Murtha M.T., RA Ercan-Sencicek A.G., Davis L., Thomson S., Gambin T., Chinault A.C., Ou Z., RA German J.R., Milosavljevic A., Sutcliffe J.S., Cook E.H. Jr., RA Stankiewicz P., State M.W., Beaudet A.L.; RT "Use of array CGH to detect exonic copy number variants throughout the RT genome in autism families detects a novel deletion in TMLHE."; RL Hum. Mol. Genet. 20:4360-4370(2011). RN [11] RP CATALYTIC ACTIVITY. RX PubMed=27965989; DOI=10.1039/c6cc08381a; RA Lesniak R.K., Markolovic S., Tars K., Schofield C.J.; RT "Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nepsilon- RT trimethyllysine."; RL Chem. Commun. (Camb.) 53:440-442(2016). RN [12] RP CATALYTIC ACTIVITY. RX PubMed=28045275; DOI=10.1021/acs.orglett.6b03608; RA Reddy Y.V., Al Temimi A.H., White P.B., Mecinovic J.; RT "Evidence that trimethyllysine hydroxylase catalyzes the formation of RT (2S,3S)-3-hydroxy-Nepsilon-trimethyllysine."; RL Org. Lett. 19:400-403(2017). RN [13] RP VARIANTS AUTSX6 HIS-244 AND ASP-369, CHARACTERIZATION OF VARIANTS AUTSX6 RP HIS-244 AND ASP-369, AND FUNCTION. RX PubMed=23092983; DOI=10.1038/tp.2012.102; RA Nava C., Lamari F., Heron D., Mignot C., Rastetter A., Keren B., Cohen D., RA Faudet A., Bouteiller D., Gilleron M., Jacquette A., Whalen S., Afenjar A., RA Perisse D., Laurent C., Dupuits C., Gautier C., Gerard M., Huguet G., RA Caillet S., Leheup B., Leboyer M., Gillberg C., Delorme R., Bourgeron T., RA Brice A., Depienne C.; RT "Analysis of the chromosome X exome in patients with autism spectrum RT disorders identified novel candidate genes, including TMLHE."; RL Transl. Psychiatry 2:E179-E179(2012). CC -!- FUNCTION: Converts trimethyllysine (TML) into hydroxytrimethyllysine CC (HTML) (PubMed:11431483, PubMed:23092983). CC {ECO:0000269|PubMed:11431483, ECO:0000269|PubMed:23092983}. 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:27965989, ECO:0000269|PubMed:28045275}; 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:0000269|PubMed:15754339}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=8; CC Name=1; Synonyms=TMLHa, TMLH1a; CC IsoId=Q9NVH6-1; Sequence=Displayed; CC Name=2; Synonyms=TMLHb; CC IsoId=Q9NVH6-3; Sequence=VSP_042278; CC Name=3; Synonyms=TMLHc; CC IsoId=Q9NVH6-4; Sequence=VSP_042279; CC Name=4; Synonyms=TMLHd; CC IsoId=Q9NVH6-2; Sequence=VSP_021579; CC Name=5; Synonyms=TMLHe; CC IsoId=Q9NVH6-5; Sequence=VSP_042280, VSP_042281; CC Name=6; Synonyms=TMLHf; CC IsoId=Q9NVH6-6; Sequence=VSP_042277; CC Name=7; Synonyms=TMLHg; CC IsoId=Q9NVH6-7; Sequence=VSP_042275; CC Name=8; Synonyms=TMLH1b; CC IsoId=Q9NVH6-8; Sequence=VSP_042276; CC -!- TISSUE SPECIFICITY: All isoforms, but isoform 8, are widely expressed CC in adult and fetal tissues. Isoform 8 is restricted to heart and CC skeletal muscle. {ECO:0000269|PubMed:15754339, CC ECO:0000269|PubMed:17408883}. CC -!- DISEASE: Autism, X-linked 6 (AUTSX6) [MIM:300872]: A form of autism, a CC complex multifactorial, pervasive developmental disorder characterized CC by impairments in reciprocal social interaction and communication, CC restricted and stereotyped patterns of interests and activities, and CC the presence of developmental abnormalities by 3 years of age. Most CC individuals with autism also manifest moderate intellectual disability. CC AUTSX6 patients may respond favorably to carnitine supplementation. CC {ECO:0000269|PubMed:21865298, ECO:0000269|PubMed:23092983}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing. Lacks CC enzymatic activity. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing. Lacks CC enzymatic activity. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing. Lacks CC enzymatic activity. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative splicing. Lacks CC enzymatic activity. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative splicing. Lacks the CC mitochondrial transit signal. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 7]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 8]: Produced by alternative promoter usage. CC Although the expression of the alternative 5' exon has been detected by CC PCR in heart and skeletal muscle, the identification of the alternative CC promoter leading to this form remains elusive (PubMed:17408883). CC {ECO:0000305|PubMed:17408883}. CC -!- SIMILARITY: Belongs to the gamma-BBH/TMLD family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF373407; AAL01871.1; -; mRNA. DR EMBL; AK001589; BAA91775.1; -; mRNA. DR EMBL; AK291694; BAF84383.1; -; mRNA. DR EMBL; AK304830; BAG65575.1; -; mRNA. DR EMBL; AK310667; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; CR457265; CAG33546.1; -; mRNA. DR EMBL; AM393196; CAL38074.1; -; mRNA. DR EMBL; BX276110; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC025269; AAH25269.1; -; mRNA. DR CCDS; CCDS14768.1; -. [Q9NVH6-1] DR CCDS; CCDS55547.1; -. [Q9NVH6-2] DR RefSeq; NP_001171726.1; NM_001184797.1. [Q9NVH6-2] DR RefSeq; NP_060666.1; NM_018196.3. [Q9NVH6-1] DR AlphaFoldDB; Q9NVH6; -. DR SMR; Q9NVH6; -. DR BioGRID; 120513; 85. DR IntAct; Q9NVH6; 13. DR MINT; Q9NVH6; -. DR STRING; 9606.ENSP00000335261; -. DR DrugBank; DB00126; Ascorbic acid. DR iPTMnet; Q9NVH6; -. DR PhosphoSitePlus; Q9NVH6; -. DR BioMuta; TMLHE; -. DR DMDM; 21542295; -. DR EPD; Q9NVH6; -. DR jPOST; Q9NVH6; -. DR MassIVE; Q9NVH6; -. DR MaxQB; Q9NVH6; -. DR PaxDb; 9606-ENSP00000335261; -. DR PeptideAtlas; Q9NVH6; -. DR ProteomicsDB; 82803; -. [Q9NVH6-1] DR ProteomicsDB; 82804; -. [Q9NVH6-2] DR ProteomicsDB; 82805; -. [Q9NVH6-3] DR ProteomicsDB; 82806; -. [Q9NVH6-4] DR ProteomicsDB; 82807; -. [Q9NVH6-5] DR ProteomicsDB; 82808; -. [Q9NVH6-6] DR ProteomicsDB; 82809; -. [Q9NVH6-7] DR ProteomicsDB; 82810; -. [Q9NVH6-8] DR Pumba; Q9NVH6; -. DR Antibodypedia; 45457; 213 antibodies from 24 providers. DR DNASU; 55217; -. DR Ensembl; ENST00000334398.8; ENSP00000335261.3; ENSG00000185973.12. [Q9NVH6-1] DR Ensembl; ENST00000369439.4; ENSP00000358447.4; ENSG00000185973.12. [Q9NVH6-2] DR Ensembl; ENST00000675642.1; ENSP00000502604.1; ENSG00000185973.12. [Q9NVH6-8] DR GeneID; 55217; -. DR KEGG; hsa:55217; -. DR MANE-Select; ENST00000334398.8; ENSP00000335261.3; NM_018196.4; NP_060666.1. DR UCSC; uc004fnn.5; human. [Q9NVH6-1] DR AGR; HGNC:18308; -. DR CTD; 55217; -. DR DisGeNET; 55217; -. DR GeneCards; TMLHE; -. DR HGNC; HGNC:18308; TMLHE. DR HPA; ENSG00000185973; Low tissue specificity. DR MalaCards; TMLHE; -. DR MIM; 300777; gene. DR MIM; 300872; phenotype. DR neXtProt; NX_Q9NVH6; -. DR OpenTargets; ENSG00000185973; -. DR PharmGKB; PA38311; -. DR VEuPathDB; HostDB:ENSG00000185973; -. DR eggNOG; KOG3889; Eukaryota. DR GeneTree; ENSGT00530000063582; -. DR HOGENOM; CLU_021859_2_0_1; -. DR InParanoid; Q9NVH6; -. DR OMA; EEKVCIQ; -. DR OrthoDB; 5485575at2759; -. DR PhylomeDB; Q9NVH6; -. DR TreeFam; TF313805; -. DR BioCyc; MetaCyc:HS08089-MONOMER; -. DR BRENDA; 1.14.11.8; 2681. DR PathwayCommons; Q9NVH6; -. DR Reactome; R-HSA-71262; Carnitine synthesis. DR SignaLink; Q9NVH6; -. DR SIGNOR; Q9NVH6; -. DR UniPathway; UPA00118; -. DR BioGRID-ORCS; 55217; 9 hits in 781 CRISPR screens. DR ChiTaRS; TMLHE; human. DR GeneWiki; TMLHE; -. DR GenomeRNAi; 55217; -. DR Pharos; Q9NVH6; Tbio. DR PRO; PR:Q9NVH6; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q9NVH6; Protein. DR Bgee; ENSG00000185973; Expressed in skeletal muscle tissue and 112 other cell types or tissues. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0050353; F:trimethyllysine dioxygenase activity; IDA:BHF-UCL. DR GO; GO:0045329; P:carnitine biosynthetic process; IDA:BHF-UCL. DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; IDA:BHF-UCL. DR CDD; cd00250; CAS_like; 1. DR Gene3D; 3.30.2020.30; -; 1. DR Gene3D; 3.60.130.10; Clavaminate synthase-like; 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 NCBIfam; TIGR02410; carnitine_TMLD; 1. DR PANTHER; PTHR10696; GAMMA-BUTYROBETAINE HYDROXYLASE-RELATED; 1. DR PANTHER; PTHR10696:SF51; TRIMETHYLLYSINE DIOXYGENASE, MITOCHONDRIAL; 1. DR Pfam; PF06155; GBBH-like_N; 1. DR Pfam; PF02668; TauD; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative promoter usage; Alternative splicing; Autism; KW Autism spectrum disorder; Carnitine biosynthesis; Dioxygenase; KW Disease variant; Iron; Metal-binding; Mitochondrion; Oxidoreductase; KW Reference proteome; Transit peptide. FT TRANSIT 1..15 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:15754339" FT CHAIN 16..421 FT /note="Trimethyllysine dioxygenase, mitochondrial" FT /id="PRO_0000002795" 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:0007744|PubMed:19608861" FT VAR_SEQ 1..68 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042275" FT VAR_SEQ 1 FT /note="M -> MKIDSFLPILRM (in isoform 8)" FT /evidence="ECO:0000305" FT /id="VSP_042276" FT VAR_SEQ 61..120 FT /note="ELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDLCIKPKTIRLD FT ETTLFFTW -> G (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_042277" FT VAR_SEQ 333..421 FT /note="YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDN FT WRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA -> VLRSWCSTRTIEATSKEI FT KLYIVCRYSYFGETLFPRSKETVTSLPHMCAYKAAATNRPWLSGVFYTI (in FT isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_042278" FT VAR_SEQ 333..421 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042279" FT VAR_SEQ 333..421 FT /note="YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDN FT WRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA -> LFKEKQNTVNRQWNSSLQ FT CDIPERILTYRHFVSGTSIEHRGSLI (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4" FT /id="VSP_021579" FT VAR_SEQ 380..383 FT /note="LFID -> GPN (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_042280" FT VAR_SEQ 384..421 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_042281" FT VARIANT 244 FT /note="D -> H (in AUTSX6; loss of function; FT dbSNP:rs869320708)" FT /evidence="ECO:0000269|PubMed:23092983" FT /id="VAR_076251" FT VARIANT 369 FT /note="E -> D (in AUTSX6; uncertain significance; FT dbSNP:rs782001959)" FT /evidence="ECO:0000269|PubMed:23092983" FT /id="VAR_076252" FT MUTAGEN 389 FT /note="H->L: No catalytic activity." FT /evidence="ECO:0000269|PubMed:15754339" FT CONFLICT 66 FT /note="N -> D (in Ref. 3; CAG33546)" FT /evidence="ECO:0000305" FT CONFLICT 170 FT /note="F -> S (in Ref. 2; BAF84383)" FT /evidence="ECO:0000305" SQ SEQUENCE 421 AA; 49518 MW; 4E55DF349B866B43 CRC64; MWYHRLSHLH SRLQDLLKGG VIYPALPQPN FKSLLPLAVH WHHTASKSLT CAWQQHEDHF ELKYANTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV DLCIKPKTIR LDETTLFFTW PDGHVTKYDL NWLVKNSYEG QKQKVIQPRI LWNAEIYQQA QVPSVDCQSF LETNEGLKKF LQNFLLYGIA FVENVPPTQE HTEKLAERIS LIRETIYGRM WYFTSDFSRG DTAYTKLALD RHTDTTYFQE PCGIQVFHCL KHEGTGGRTL LVDGFYAAEQ VLQKAPEEFE LLSKVPLKHE YIEDVGECHN HMIGIGPVLN IYPWNKELYL IRYNNYDRAV INTVPYDVVH RWYTAHRTLT IELRRPENEF WVKLKPGRVL FIDNWRVLHG RECFTGYRQL CGCYLTRDDV LNTARLLGLQ A //