Q9NVH6 · TMLH_HUMAN

  • Protein
    Trimethyllysine dioxygenase, mitochondrial
  • Gene
    TMLHE
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) (PubMed:11431483, PubMed:23092983).

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
Fe2+ (UniProtKB | Rhea| CHEBI:29033 )

Note: Binds 1 Fe2+ ion per subunit.
L-ascorbate (UniProtKB | Rhea| CHEBI:38290 )

Pathway

Amine and polyamine biosynthesis; carnitine biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site242Fe cation (UniProtKB | ChEBI); catalytic
Binding site244Fe cation (UniProtKB | ChEBI); catalytic
Binding site389Fe cation (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Cellular Componentmitochondrial matrix
Cellular Componentmitochondrion
Molecular Functioniron ion binding
Molecular Functiontrimethyllysine dioxygenase activity
Biological Processcarnitine biosynthetic process
Biological Processnegative regulation of oxidoreductase activity

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Trimethyllysine dioxygenase, mitochondrial
  • EC number
  • Alternative names
    • Epsilon-trimethyllysine 2-oxoglutarate dioxygenase
    • Epsilon-trimethyllysine hydroxylase
    • TML hydroxylase
    • TML-alpha-ketoglutarate dioxygenase (TML dioxygenase; TMLD)

Gene names

    • Name
      TMLHE
    • Synonyms
      TMLH

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q9NVH6
  • Secondary accessions
    • A8K6M9
    • B4E3R3
    • Q5TZB5
    • Q6IA90
    • Q8TBT0

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Involvement in disease

Autism, X-linked 6 (AUTSX6)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A form of autism, a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability. AUTSX6 patients may respond favorably to carnitine supplementation.
  • See also
    MIM:300872
Natural variants in AUTSX6
Variant IDPosition(s)ChangeDescription
VAR_076251244D>Hin AUTSX6; loss of function; dbSNP:rs869320708
VAR_076252369E>Din AUTSX6; uncertain significance; dbSNP:rs782001959

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_076251244in AUTSX6; loss of function; dbSNP:rs869320708
Natural variantVAR_076252369in AUTSX6; uncertain significance; dbSNP:rs782001959
Mutagenesis389No catalytic activity.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 321 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for transit peptide, chain, modified residue.

TypeIDPosition(s)Description
Transit peptide1-15Mitochondrion
ChainPRO_000000279516-421Trimethyllysine dioxygenase, mitochondrial
Modified residue179N6-acetyllysine
Modified residue236N6-acetyllysine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

All isoforms, but isoform 8, are widely expressed in adult and fetal tissues. Isoform 8 is restricted to heart and skeletal muscle.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Homodimer.

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Sequence similarities

Belongs to the gamma-BBH/TMLD family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (8)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 8 isoforms produced by Alternative promoter usage & Alternative splicing.

Q9NVH6-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    TMLHa, TMLH1a
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    421
  • Mass (Da)
    49,518
  • Last updated
    2000-10-01 v1
  • Checksum
    4E55DF349B866B43
MWYHRLSHLHSRLQDLLKGGVIYPALPQPNFKSLLPLAVHWHHTASKSLTCAWQQHEDHFELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDLCIKPKTIRLDETTLFFTWPDGHVTKYDLNWLVKNSYEGQKQKVIQPRILWNAEIYQQAQVPSVDCQSFLETNEGLKKFLQNFLLYGIAFVENVPPTQEHTEKLAERISLIRETIYGRMWYFTSDFSRGDTAYTKLALDRHTDTTYFQEPCGIQVFHCLKHEGTGGRTLLVDGFYAAEQVLQKAPEEFELLSKVPLKHEYIEDVGECHNHMIGIGPVLNIYPWNKELYLIRYNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA

Q9NVH6-3

  • Name
    2
  • Synonyms
    TMLHb
  • Note
    Produced by alternative splicing. Lacks enzymatic activity.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 333-421: YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA → VLRSWCSTRTIEATSKEIKLYIVCRYSYFGETLFPRSKETVTSLPHMCAYKAAATNRPWLSGVFYTI

Q9NVH6-4

  • Name
    3
  • Synonyms
    TMLHc
  • Note
    Produced by alternative splicing. Lacks enzymatic activity.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q9NVH6-2

  • Name
    4
  • Synonyms
    TMLHd
  • Note
    Produced by alternative splicing. Lacks enzymatic activity.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 333-421: YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA → LFKEKQNTVNRQWNSSLQCDIPERILTYRHFVSGTSIEHRGSLI

Q9NVH6-5

  • Name
    5
  • Synonyms
    TMLHe
  • Note
    Produced by alternative splicing. Lacks enzymatic activity.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q9NVH6-6

  • Name
    6
  • Synonyms
    TMLHf
  • Note
    Produced by alternative splicing. Lacks the mitochondrial transit signal.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 61-120: ELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDLCIKPKTIRLDETTLFFTW → G

Q9NVH6-7

  • Name
    7
  • Synonyms
    TMLHg
  • Note
    Produced by alternative splicing.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q9NVH6-8

  • Name
    8
  • Synonyms
    TMLH1b
  • Note
    Produced by alternative promoter usage. Although the expression of the alternative 5' exon has been detected by PCR in heart and skeletal muscle, the identification of the alternative promoter leading to this form remains elusive (PubMed:17408883).
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-1: M → MKIDSFLPILRM

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0422761in isoform 8
Alternative sequenceVSP_0422751-68in isoform 7
Alternative sequenceVSP_04227761-120in isoform 6
Sequence conflict66in Ref. 3; CAG33546
Sequence conflict170in Ref. 2; BAF84383
Alternative sequenceVSP_042278333-421in isoform 2
Alternative sequenceVSP_042279333-421in isoform 3
Alternative sequenceVSP_021579333-421in isoform 4
Alternative sequenceVSP_042280380-383in isoform 5
Alternative sequenceVSP_042281384-421in isoform 5

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF373407
EMBL· GenBank· DDBJ
AAL01871.1
EMBL· GenBank· DDBJ
mRNA
AK001589
EMBL· GenBank· DDBJ
BAA91775.1
EMBL· GenBank· DDBJ
mRNA
AK291694
EMBL· GenBank· DDBJ
BAF84383.1
EMBL· GenBank· DDBJ
mRNA
AK304830
EMBL· GenBank· DDBJ
BAG65575.1
EMBL· GenBank· DDBJ
mRNA
AK310667
EMBL· GenBank· DDBJ
-mRNA No translation available.
CR457265
EMBL· GenBank· DDBJ
CAG33546.1
EMBL· GenBank· DDBJ
mRNA
AM393196
EMBL· GenBank· DDBJ
CAL38074.1
EMBL· GenBank· DDBJ
mRNA
BX276110
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC025269
EMBL· GenBank· DDBJ
AAH25269.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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