TMLH_HUMAN
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 03-AUG-2022, entry version 173.
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}.
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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; 82.
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; Q9NVH6; -.
DR PeptideAtlas; Q9NVH6; -.
DR PRIDE; 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 Antibodypedia; 45457; 203 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 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; 868657at2759; -.
DR PhylomeDB; Q9NVH6; -.
DR TreeFam; TF313805; -.
DR BioCyc; MetaCyc:HS08089-MON; -.
DR BRENDA; 1.14.11.8; 2681.
DR PathwayCommons; Q9NVH6; -.
DR Reactome; R-HSA-71262; Carnitine synthesis.
DR SignaLink; Q9NVH6; -.
DR UniPathway; UPA00118; -.
DR BioGRID-ORCS; 55217; 9 hits in 706 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 111 other tissues.
DR Genevisible; Q9NVH6; HS.
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 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 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; unknown pathological
FT significance; 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
