LOCUS       NM_018196               3952 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens trimethyllysine hydroxylase, epsilon (TMLHE),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_018196 XM_938703
VERSION     NM_018196.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3952)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   2  (bases 1 to 3952)
  AUTHORS   Wang,Y., Reddy,Y.V., Al Temimi,A.H.K., Venselaar,H.,
            Nelissen,F.H.T., Lenstra,D.C. and Mecinovic,J.
  TITLE     Investigating the active site of human trimethyllysine hydroxylase
  JOURNAL   Biochem J 476 (7), 1109-1119 (2019)
   PUBMED   30898847
  REMARK    GeneRIF: This work demonstrates the importance of the recognition
            sites that contribute to the enzymatic activity of TMLH: the
            Fe(II)-binding H242-D244-H389 residues, R391-R398 involved in 2OG
            binding and several residues (D231, N334 and the aromatic cage
            comprised of W221, Y217 and Y234) associated with binding of (2S)-N
            (epsilon)-trimethyllysine.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3952)
  AUTHORS   Chen,C., Xie,X., Wu,X., Lu,Y., Wang,X., Wu,W., Hu,Y. and Ding,Q.
  TITLE     Complex recombination with deletion in the F8 and duplication in
            the TMLHE mediated by int22h copies during early embryogenesis
  JOURNAL   Thromb Haemost 117 (8), 1478-1485 (2017)
   PUBMED   28492696
  REMARK    GeneRIF: Case Report: complex recombination with deletion in the F8
            and duplication in the TMLHE mediated by int22h copies during early
            embryogenesis in proband's mother.
REFERENCE   4  (bases 1 to 3952)
  AUTHORS   Floyd,B.J., Wilkerson,E.M., Veling,M.T., Minogue,C.E., Xia,C.,
            Beebe,E.T., Wrobel,R.L., Cho,H., Kremer,L.S., Alston,C.L.,
            Gromek,K.A., Dolan,B.K., Ulbrich,A., Stefely,J.A., Bohl,S.L.,
            Werner,K.M., Jochem,A., Westphall,M.S., Rensvold,J.W., Taylor,R.W.,
            Prokisch,H., Kim,J.P., Coon,J.J. and Pagliarini,D.J.
  TITLE     Mitochondrial Protein Interaction Mapping Identifies Regulators of
            Respiratory Chain Function
  JOURNAL   Mol Cell 63 (4), 621-632 (2016)
   PUBMED   27499296
REFERENCE   5  (bases 1 to 3952)
  AUTHORS   Nava,C., Lamari,F., Heron,D., Mignot,C., Rastetter,A., Keren,B.,
            Cohen,D., Faudet,A., Bouteiller,D., Gilleron,M., Jacquette,A.,
            Whalen,S., Afenjar,A., Perisse,D., Laurent,C., Dupuits,C.,
            Gautier,C., Gerard,M., Huguet,G., Caillet,S., Leheup,B.,
            Leboyer,M., Gillberg,C., Delorme,R., Bourgeron,T., Brice,A. and
            Depienne,C.
  TITLE     Analysis of the chromosome X exome in patients with autism spectrum
            disorders identified novel candidate genes, including TMLHE
  JOURNAL   Transl Psychiatry 2 (10), e179 (2012)
   PUBMED   23092983
  REMARK    GeneRIF: Study found 3 mutations in TMLHE to be associated with
            autism spectrum disorder, c.229C>T/p.Arg77X, c.730G>C/p.Asp244His,
            and c.1107G>T/p.Glu369Asp.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3952)
  AUTHORS   Celestino-Soper,P.B., Shaw,C.A., Sanders,S.J., Li,J., Murtha,M.T.,
            Ercan-Sencicek,A.G., Davis,L., Thomson,S., Gambin,T.,
            Chinault,A.C., Ou,Z., German,J.R., Milosavljevic,A.,
            Sutcliffe,J.S., Cook,E.H. Jr., Stankiewicz,P., State,M.W. and
            Beaudet,A.L.
  TITLE     Use of array CGH to detect exonic copy number variants throughout
            the genome in autism families detects a novel deletion in TMLHE
  JOURNAL   Hum Mol Genet 20 (22), 4360-4370 (2011)
   PUBMED   21865298
  REMARK    GeneRIF: Use of array CGH to detect exonic copy number variants
            throughout the genome in autism families detects a novel deletion
            in TMLHE.
REFERENCE   7  (bases 1 to 3952)
  AUTHORS   Monfregola,J., Napolitano,G., Conte,I., Cevenini,A., Migliaccio,C.,
            D'Urso,M. and Ursini,M.V.
  TITLE     Functional characterization of the TMLH gene: promoter analysis, in
            situ hybridization, identification and mapping of alternative
            splicing variants
  JOURNAL   Gene 395 (1-2), 86-97 (2007)
   PUBMED   17408883
  REMARK    GeneRIF: By 5' and 3' RACE, we identified and mapped two
            alternative 5' TMLH first exons and seven alternative 3'-splice
            variants.
REFERENCE   8  (bases 1 to 3952)
  AUTHORS   Monfregola,J., Cevenini,A., Terracciano,A., van Vlies,N.,
            Arbucci,S., Wanders,R.J., D'Urso,M., Vaz,F.M. and Ursini,M.V.
  TITLE     Functional analysis of TMLH variants and definition of domains
            required for catalytic activity and mitochondrial targeting
  JOURNAL   J Cell Physiol 204 (3), 839-847 (2005)
   PUBMED   15754339
  REMARK    GeneRIF: C-terminal region of trimethyllysine hydroxylase, epsilon
            contains the main determinants for its enzymatic activity including
            a key H389 residue
REFERENCE   9  (bases 1 to 3952)
  AUTHORS   Vaz,F.M., Ofman,R., Westinga,K., Back,J.W. and Wanders,R.J.
  TITLE     Molecular and Biochemical Characterization of Rat epsilon
            -N-Trimethyllysine Hydroxylase, the First Enzyme of Carnitine
            Biosynthesis
  JOURNAL   J Biol Chem 276 (36), 33512-33517 (2001)
   PUBMED   11431483
REFERENCE   10 (bases 1 to 3952)
  AUTHORS   Rogner,U.C., Heiss,N.S., Kioschis,P., Wiemann,S., Korn,B. and
            Poustka,A.
  TITLE     Transcriptional analysis of the candidate region for incontinentia
            pigmenti (IP2) in Xq28
  JOURNAL   Genome Res 6 (10), 922-934 (1996)
   PUBMED   8908511
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB174485.1, AK001589.1 and
            BX571846.3.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_018196.3.
            
            Summary: This gene encodes the protein trimethyllysine dioxygenase
            which is the first enzyme in the carnitine biosynthesis pathway.
            Carnitine play an essential role in the transport of activated
            fatty acids across the inner mitochondrial membrane. The encoded
            protein converts trimethyllysine into hydroxytrimethyllysine. A
            pseudogene of this gene is found on chromosome X. Alternate
            splicing results in multiple transcript variants.[provided by
            RefSeq, May 2010].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803617.2538.1, SRR1803611.712.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: inferred from homology
            MANE Ensembl match                 :: ENST00000334398.8/
                                                  ENSP00000335261.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-16                DB174485.1         10-25
            17-1670             AK001589.1         1-1654
            1671-3952           BX571846.3         87099-89380         c
FEATURES             Location/Qualifiers
     source          1..3952
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xq28"
     gene            1..3952
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /note="trimethyllysine hydroxylase, epsilon"
                     /db_xref="GeneID:55217"
                     /db_xref="HGNC:HGNC:18308"
                     /db_xref="MIM:300777"
     exon            1..161
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     exon            162..343
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     CDS             163..1428
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /EC_number="1.14.11.8"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; butyrobetaine (gamma), 2-oxoglutarate
                     dioxygenase (gamma-butyrobetaine hydroxylase) 2;
                     trimethyllysine dioxygenase, mitochondrial; TML
                     hydroxylase; TML-alpha-ketoglutarate dioxygenase;
                     epsilon-trimethyllysine 2-oxoglutarate dioxygenase;
                     epsilon-trimethyllysine hydroxylase"
                     /codon_start=1
                     /product="trimethyllysine dioxygenase, mitochondrial
                     isoform 1 precursor"
                     /protein_id="NP_060666.1"
                     /db_xref="CCDS:CCDS14768.1"
                     /db_xref="GeneID:55217"
                     /db_xref="HGNC:HGNC:18308"
                     /db_xref="MIM:300777"
                     /translation="MWYHRLSHLHSRLQDLLKGGVIYPALPQPNFKSLLPLAVHWHHT
                     ASKSLTCAWQQHEDHFELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDL
                     CIKPKTIRLDETTLFFTWPDGHVTKYDLNWLVKNSYEGQKQKVIQPRILWNAEIYQQA
                     QVPSVDCQSFLETNEGLKKFLQNFLLYGIAFVENVPPTQEHTEKLAERISLIRETIYG
                     RMWYFTSDFSRGDTAYTKLALDRHTDTTYFQEPCGIQVFHCLKHEGTGGRTLLVDGFY
                     AAEQVLQKAPEEFELLSKVPLKHEYIEDVGECHNHMIGIGPVLNIYPWNKELYLIRYN
                     NYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRE
                     CFTGYRQLCGCYLTRDDVLNTARLLGLQA"
     exon            344..520
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     exon            521..800
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     exon            801..920
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     exon            921..1157
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     exon            1158..1296
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     exon            1297..3952
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3928..3933
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /note="hexamer: AATGAA"
     polyA_site      3952
                     /gene="TMLHE"
                     /gene_synonym="AUTSX6; BBOX2; TMLD; TMLH; TMLHED; XAP130"
                     /note="major polyA site"
ORIGIN      
        1 aggctctccg ctgggcccga gcgggctggg ggaggggagc gtggggccga cagttttggg
       61 ggtgaaaagg caaaaggcgg gtgaaaggct gcctcccgag actctccttg cttggaattc
      121 tgcccactct gcggagttag cagtcacgac ctccagcaca ggatgtggta ccacagattg
      181 tcccacctac acagcaggct tcaggacttg ctgaagggag gagtcatata tccggccctt
      241 ccacagccca acttcaaaag cttacttcct ttagctgtcc attggcacca tacagcctcc
      301 aagtctctga cttgtgcttg gcagcaacat gaagatcatt ttgagctgaa atatgctaat
      361 accgtgatgc gctttgatta cgtctggctt cgagaccact gccgctcagc atcgtgctac
      421 aactctaaga ctcaccagcg cagcctggat actgccagtg tggatttatg tatcaagcca
      481 aagaccattc gtctggatga gaccacactc tttttcactt ggccagatgg tcatgtgact
      541 aaatatgatt tgaattggct ggtgaaaaac agctatgaag ggcagaaaca aaaagtcatc
      601 cagcctagaa tactatggaa tgctgaaatc taccagcaag cccaagttcc atcggtagat
      661 tgccagagct tcttagaaac caacgaggga ctgaagaagt ttctgcaaaa ctttctgctc
      721 tatggaattg cattcgtaga aaatgtccct cccactcaag agcacacaga gaagttggca
      781 gaaaggatca gcttaatcag agaaaccatt tatgggagga tgtggtattt cacttcagac
      841 ttctccagag gtgacactgc gtacaccaag ctagctctgg atcggcacac tgacactacc
      901 tattttcaag agccctgtgg cattcaagtg tttcattgtc ttaaacatga aggaactggt
      961 ggcaggacac tgctagtaga tggattctat gcagcagaac aggtacttca aaaggcacct
     1021 gaggaatttg aactcctcag taaagtgcca ttgaagcatg aatatattga agatgttgga
     1081 gaatgtcaca accacatgat tgggattggg ccagtcttaa atatctaccc atggaataaa
     1141 gagctgtatt tgatcaggta caacaactat gaccgggctg tcatcaatac cgttccttat
     1201 gatgtcgtcc atcgctggta tacagcacac cggactctaa cgatagagtt gaggagacct
     1261 gagaatgagt tttgggtcaa actaaagcct ggcagggtcc tatttataga caactggcgt
     1321 gtcctacatg gcagggaatg cttcactggc taccgccaac tgtgtggctg ctatttaaca
     1381 agagatgatg tattaaacac tgctcgcctc ttggggcttc aggcttaaaa ttgacagcat
     1441 ctggattatg aatacacctg gcaccctggc taccagaatt tcatatgggc agaataatat
     1501 tgtgtcaaac tctacttcag attgtctcct tatcccatcc cacaaaacag aatctgtccg
     1561 tttctctagt aagggagact tgttggagag gcgggactct gagttatcta atgtcagaca
     1621 tctagtgggg cagctctctt cctcatgtta taacatggat ccacttgttt gatttaaacc
     1681 ttttaatata attttggtca gtctccttca gaaatataat ctccatattg ataggaaagc
     1741 aataattgcc atgaggtaac gatttttttc ccaagtagat cagttagaaa gaaatgcatt
     1801 ctagaaataa caaaaatcct gataaagcaa caatttgcaa aatgtttggt cttaggacac
     1861 cttaacactc ttaaaagtta ttgaaggccc caaggagttc ttgggtgtgg gttctatcta
     1921 ttgatactaa ttattttagg tattaagact gagaaatatt taaagctcaa gaagaacaca
     1981 gaagcacaca tccctcagct atgagagaga tgacataacc atatgtcatg tagcctctgg
     2041 aaaagtcctc tgtatcctca tgagataacg agagggggaa aaaaagctac tactgccttt
     2101 gtaacttcca cttagcctac tacagggcta tgcacatctt agtttccaaa agtctgctta
     2161 atttcaaaag aaaaatgcct aattgaatgt aactcatctt ggtgttatta tacaaaataa
     2221 tttttaatct gcagacccac gaaaagggtc tcagggactc ctccaggggt cttcagacca
     2281 tactttgaga acccatgggc tagcgactac cttgagacag tcctttacct aggcctgtgg
     2341 attaaagggt ttagctgaaa ccctagattc ttctctgtag tctaatagaa ctccaaacat
     2401 tgtaagaatt gcttggtagc ataagctcag ggataaggtg ggaattgagt tcaaatatag
     2461 tgttttatct tccacacaaa tcatctctat aggagttaaa ttaggaagtc acaacagcgc
     2521 ctgttgaaca aactcatcag tgtggtaatc ctatgaggga taattgcaga aaggttttag
     2581 agacttgtga ggttccatat gataattctt tacacctccc cccccaagag aaagtacaca
     2641 gggctattct gtaatattgt tcagggaaat cagcatgata gatgctgtgc ctccagagag
     2701 ttctctggag attactaccc aaatgtgtat tttggcaatt tggtggtatt taggatgtaa
     2761 tatgttttcc tccatttctg ctaattttct ctctctctct ctcataacat actatacatg
     2821 ctaattgcca agatttgaat gagtcaaatt tagtagcttg ctgcttttat tttttaaatg
     2881 gcttctttta cgtattggcg ggggcgggtg gggggcaggg tatgaggctt cttttccctc
     2941 agctttcatt gaaagtgaag ctgtacaata accacattga ccactgtaga atgatgaaag
     3001 agaatatagg ctaggatgca cacaagaggg gggaaaaggc attattagtg aagataggag
     3061 ttacaaagca aagcaaagtc agtattcaga tagagaatag agcctaatct gatgtttgca
     3121 gggagttcct agatcacatt tggcaattta cacattattt tattgaccta tccagtgctc
     3181 caaaatgtgt tccaaaatat tttggcattt tatttgtact acataggaat ctttagggga
     3241 gtccctgaaa tttgttttcc tcttaggtca aaggactgat aattaacttt ggttcttaag
     3301 gagtatgccc tttagcaata agaacagcaa taacatttta ccctgcagtt ttttctctat
     3361 acctactatt atgcactcct aaaatatgtc atcattagtc ttcatgagga tgtttaccat
     3421 ttctgaagtt ttgcgtaaat tagccttgaa gattacacta taactgaggt catcagcatt
     3481 gacttatggc cagcaaagga catgctcatg gccctggaga gatgaggaca caaaacaaat
     3541 caatttcccc acttactgaa ggactcccct taccttctgt ctctcctgag accttgactc
     3601 attaattatt ttactctcct ttttggaaat ttgcaaccgg tccttctcaa caatgtgctc
     3661 cctttagtac actgaagaaa aagagaaggg gattatttga gtcctgatca cgatgcattg
     3721 aaaacttcct atgtgagatg tttctgtttt tatatctctt ccaggtgtcc ctgagtatat
     3781 aagcatgggt ctatgtctac caagctcact gtagagtcac ttttaccttt tgctatggtg
     3841 gaatgggatc tgtagggtca ggaacacagc acctaacaca gtgccttatg gatagtagtt
     3901 ttataataca gatgtgttgg aagaataaat gaatgggtcc ttttcaaaca aa
//
