Q9NVH6 · TMLH_HUMAN
- ProteinTrimethyllysine dioxygenase, mitochondrial
- GeneTMLHE
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids421 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) (PubMed:11431483, PubMed:23092983).
Catalytic activity
- 2-oxoglutarate + N6,N6,N6-trimethyl-L-lysine + O2 = (3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + CO2 + succinate
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 Fe2+ ion per subunit.
Pathway
Amine and polyamine biosynthesis; carnitine biosynthesis.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | iron ion binding | |
Molecular Function | trimethyllysine dioxygenase activity | |
Biological Process | carnitine biosynthetic process | |
Biological Process | negative regulation of oxidoreductase activity |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTrimethyllysine dioxygenase, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NVH6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Autism, X-linked 6 (AUTSX6)
- Note
- DescriptionA 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 alsoMIM:300872
Natural variants in AUTSX6
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_076251 | 244 | D>H | in AUTSX6; loss of function; dbSNP:rs869320708 | |
VAR_076252 | 369 | E>D | in AUTSX6; uncertain significance; dbSNP:rs782001959 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_076251 | 244 | in AUTSX6; loss of function; dbSNP:rs869320708 | |||
Sequence: D → H | ||||||
Natural variant | VAR_076252 | 369 | in AUTSX6; uncertain significance; dbSNP:rs782001959 | |||
Sequence: E → D | ||||||
Mutagenesis | 389 | No catalytic activity. | ||||
Sequence: H → L |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-15 | Mitochondrion | ||||
Sequence: MWYHRLSHLHSRLQD | ||||||
Chain | PRO_0000002795 | 16-421 | Trimethyllysine dioxygenase, mitochondrial | |||
Sequence: LLKGGVIYPALPQPNFKSLLPLAVHWHHTASKSLTCAWQQHEDHFELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDLCIKPKTIRLDETTLFFTWPDGHVTKYDLNWLVKNSYEGQKQKVIQPRILWNAEIYQQAQVPSVDCQSFLETNEGLKKFLQNFLLYGIAFVENVPPTQEHTEKLAERISLIRETIYGRMWYFTSDFSRGDTAYTKLALDRHTDTTYFQEPCGIQVFHCLKHEGTGGRTLLVDGFYAAEQVLQKAPEEFELLSKVPLKHEYIEDVGECHNHMIGIGPVLNIYPWNKELYLIRYNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA | ||||||
Modified residue | 179 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 236 | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe 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.
- Name1
- SynonymsTMLHa, TMLH1a
- Length421
- Mass (Da)49,518
- Last updated2000-10-01 v1
- Checksum4E55DF349B866B43
Q9NVH6-3
- Name2
- SynonymsTMLHb
- NoteProduced by alternative splicing. Lacks enzymatic activity.
- Differences from canonical
- 333-421: YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA → VLRSWCSTRTIEATSKEIKLYIVCRYSYFGETLFPRSKETVTSLPHMCAYKAAATNRPWLSGVFYTI
Q9NVH6-4
- Name3
- SynonymsTMLHc
- NoteProduced by alternative splicing. Lacks enzymatic activity.
- Differences from canonical
- 333-421: Missing
Q9NVH6-2
- Name4
- SynonymsTMLHd
- NoteProduced by alternative splicing. Lacks enzymatic activity.
- Differences from canonical
- 333-421: YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA → LFKEKQNTVNRQWNSSLQCDIPERILTYRHFVSGTSIEHRGSLI
Q9NVH6-5
- Name5
- SynonymsTMLHe
- NoteProduced by alternative splicing. Lacks enzymatic activity.
Q9NVH6-6
- Name6
- SynonymsTMLHf
- NoteProduced by alternative splicing. Lacks the mitochondrial transit signal.
- Differences from canonical
- 61-120: ELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDLCIKPKTIRLDETTLFFTW → G
Q9NVH6-7
- Name7
- SynonymsTMLHg
- NoteProduced by alternative splicing.
- Differences from canonical
- 1-68: Missing
Q9NVH6-8
- Name8
- SynonymsTMLH1b
- NoteProduced 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).
- Differences from canonical
- 1-1: M → MKIDSFLPILRM
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_042276 | 1 | in isoform 8 | |||
Sequence: M → MKIDSFLPILRM | ||||||
Alternative sequence | VSP_042275 | 1-68 | in isoform 7 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_042277 | 61-120 | in isoform 6 | |||
Sequence: ELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDLCIKPKTIRLDETTLFFTW → G | ||||||
Sequence conflict | 66 | in Ref. 3; CAG33546 | ||||
Sequence: N → D | ||||||
Sequence conflict | 170 | in Ref. 2; BAF84383 | ||||
Sequence: F → S | ||||||
Alternative sequence | VSP_042278 | 333-421 | in isoform 2 | |||
Sequence: YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA → VLRSWCSTRTIEATSKEIKLYIVCRYSYFGETLFPRSKETVTSLPHMCAYKAAATNRPWLSGVFYTI | ||||||
Alternative sequence | VSP_042279 | 333-421 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_021579 | 333-421 | in isoform 4 | |||
Sequence: YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVKLKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTARLLGLQA → LFKEKQNTVNRQWNSSLQCDIPERILTYRHFVSGTSIEHRGSLI | ||||||
Alternative sequence | VSP_042280 | 380-383 | in isoform 5 | |||
Sequence: LFID → GPN | ||||||
Alternative sequence | VSP_042281 | 384-421 | in isoform 5 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |