Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Trimethyllysine dioxygenase, mitochondrial

Gene

TMLHE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) (PubMed:11431483, PubMed:23092983).2 Publications

Catalytic activityi

N6,N6,N(6)-trimethyl-L-lysine + 2-oxoglutarate + O2 = 3-hydroxy-N6,N6,N(6)-trimethyl-L-lysine + succinate + CO2.

Cofactori

Protein has several cofactor binding sites:
  • Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity
  • L-ascorbate

Pathwayi: carnitine biosynthesis

This protein is involved in the pathway carnitine biosynthesis, which is part of Amine and polyamine biosynthesis.
View all proteins of this organism that are known to be involved in the pathway carnitine biosynthesis and in Amine and polyamine biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi242Iron; catalyticBy similarity1
Metal bindingi244Iron; catalyticBy similarity1
Metal bindingi389Iron; catalyticBy similarity1

GO - Molecular functioni

GO - Biological processi

  • carnitine biosynthetic process Source: BHF-UCL
  • negative regulation of oxidoreductase activity Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Carnitine biosynthesis

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08089-MONOMER.
ZFISH:HS08089-MONOMER.
BRENDAi1.14.11.8. 2681.
ReactomeiR-HSA-71262. Carnitine synthesis.
UniPathwayiUPA00118.

Names & Taxonomyi

Protein namesi
Recommended name:
Trimethyllysine dioxygenase, mitochondrial (EC:1.14.11.8)
Alternative name(s):
Epsilon-trimethyllysine 2-oxoglutarate dioxygenase
Epsilon-trimethyllysine hydroxylase
TML hydroxylase
TML-alpha-ketoglutarate dioxygenase
Short name:
TML dioxygenase
Short name:
TMLD
Gene namesi
Name:TMLHE
Synonyms:TMLH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:18308. TMLHE.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Autism, X-linked 6 (AUTSX6)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 mental retardation. AUTSX6 patients may respond favorably to carnitine supplementation.
See also OMIM:300872
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076251244D → H in AUTSX6; loss of function. 1 Publication1
Natural variantiVAR_076252369E → D in AUTSX6; unknown pathological significance; no loss of function. 1 PublicationCorresponds to variant rs782001959dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi389H → L: No catalytic activity. 1 Publication1

Keywords - Diseasei

Autism, Autism spectrum disorder, Disease mutation

Organism-specific databases

DisGeNETi55217.
MalaCardsiTMLHE.
MIMi300872. phenotype.
OpenTargetsiENSG00000185973.
Orphaneti106. Autism.
PharmGKBiPA38311.

Chemistry databases

DrugBankiDB00139. Succinic acid.
DB00126. Vitamin C.

Polymorphism and mutation databases

BioMutaiTMLHE.
DMDMi21542295.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 15Mitochondrion1 PublicationAdd BLAST15
ChainiPRO_000000279516 – 421Trimethyllysine dioxygenase, mitochondrialAdd BLAST406

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei179N6-acetyllysineBy similarity1
Modified residuei236N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9NVH6.
MaxQBiQ9NVH6.
PaxDbiQ9NVH6.
PeptideAtlasiQ9NVH6.
PRIDEiQ9NVH6.

PTM databases

iPTMnetiQ9NVH6.
PhosphoSitePlusiQ9NVH6.

Expressioni

Tissue specificityi

All isoforms, but isoform 8, are widely expressed in adult and fetal tissues. Isoform 8 is restricted to heart and skeletal muscle.2 Publications

Gene expression databases

BgeeiENSG00000185973.
CleanExiHS_TMLHE.
GenevisibleiQ9NVH6. HS.

Organism-specific databases

HPAiHPA034589.
HPA040331.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi120513. 3 interactors.
IntActiQ9NVH6. 8 interactors.
MINTiMINT-3074990.
STRINGi9606.ENSP00000335261.

Structurei

3D structure databases

ProteinModelPortaliQ9NVH6.
SMRiQ9NVH6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the gamma-BBH/TMLD family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG3889. Eukaryota.
COG2175. LUCA.
GeneTreeiENSGT00530000063582.
HOGENOMiHOG000210004.
HOVERGENiHBG035650.
InParanoidiQ9NVH6.
KOiK00474.
OMAiIEINEFW.
OrthoDBiEOG091G062L.
PhylomeDBiQ9NVH6.
TreeFamiTF313805.

Family and domain databases

InterProiIPR010376. DUF971.
IPR003819. TauD/TfdA-like.
IPR012776. Trimethyllysine_dOase.
[Graphical view]
PfamiPF06155. DUF971. 1 hit.
PF02668. TauD. 1 hit.
[Graphical view]
TIGRFAMsiTIGR02410. carnitine_TMLD. 1 hit.

Sequences (8)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 8 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NVH6-1) [UniParc]FASTAAdd to basket
Also known as: TMLHa, TMLH1a

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.

« Hide

        10         20         30         40         50
MWYHRLSHLH SRLQDLLKGG VIYPALPQPN FKSLLPLAVH WHHTASKSLT
60 70 80 90 100
CAWQQHEDHF ELKYANTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV
110 120 130 140 150
DLCIKPKTIR LDETTLFFTW PDGHVTKYDL NWLVKNSYEG QKQKVIQPRI
160 170 180 190 200
LWNAEIYQQA QVPSVDCQSF LETNEGLKKF LQNFLLYGIA FVENVPPTQE
210 220 230 240 250
HTEKLAERIS LIRETIYGRM WYFTSDFSRG DTAYTKLALD RHTDTTYFQE
260 270 280 290 300
PCGIQVFHCL KHEGTGGRTL LVDGFYAAEQ VLQKAPEEFE LLSKVPLKHE
310 320 330 340 350
YIEDVGECHN HMIGIGPVLN IYPWNKELYL IRYNNYDRAV INTVPYDVVH
360 370 380 390 400
RWYTAHRTLT IELRRPENEF WVKLKPGRVL FIDNWRVLHG RECFTGYRQL
410 420
CGCYLTRDDV LNTARLLGLQ A
Length:421
Mass (Da):49,518
Last modified:October 1, 2000 - v1
Checksum:i4E55DF349B866B43
GO
Isoform 2 (identifier: Q9NVH6-3) [UniParc]FASTAAdd to basket
Also known as: TMLHb

The sequence of this isoform differs from the canonical sequence as follows:
     333-421: YNNYDRAVIN...NTARLLGLQA → VLRSWCSTRT...PWLSGVFYTI

Note: Produced by alternative splicing. Lacks enzymatic activity.
Show »
Length:399
Mass (Da):46,590
Checksum:i73A092B32CB15DF1
GO
Isoform 3 (identifier: Q9NVH6-4) [UniParc]FASTAAdd to basket
Also known as: TMLHc

The sequence of this isoform differs from the canonical sequence as follows:
     333-421: Missing.

Note: Produced by alternative splicing. Lacks enzymatic activity.
Show »
Length:332
Mass (Da):38,864
Checksum:i864FB6A12712C1D3
GO
Isoform 4 (identifier: Q9NVH6-2) [UniParc]FASTAAdd to basket
Also known as: TMLHd

The sequence of this isoform differs from the canonical sequence as follows:
     333-421: YNNYDRAVIN...NTARLLGLQA → LFKEKQNTVN...TSIEHRGSLI

Note: Produced by alternative splicing. Lacks enzymatic activity.
Show »
Length:376
Mass (Da):44,049
Checksum:iAB6D7A1DC57D6FCF
GO
Isoform 5 (identifier: Q9NVH6-5) [UniParc]FASTAAdd to basket
Also known as: TMLHe

The sequence of this isoform differs from the canonical sequence as follows:
     380-383: LFID → GPN
     384-421: Missing.

Note: Produced by alternative splicing. Lacks enzymatic activity.
Show »
Length:382
Mass (Da):44,902
Checksum:i634B62F65E00F528
GO
Isoform 6 (identifier: Q9NVH6-6) [UniParc]FASTAAdd to basket
Also known as: TMLHf

The sequence of this isoform differs from the canonical sequence as follows:
     61-120: ELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVDLCIKPKTIRLDETTLFFTW → G

Note: Produced by alternative splicing. Lacks the mitochondrial transit signal.
Show »
Length:362
Mass (Da):42,416
Checksum:i36F27DC4C85AC9B5
GO
Isoform 7 (identifier: Q9NVH6-7) [UniParc]FASTAAdd to basket
Also known as: TMLHg

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: Missing.

Note: Produced by alternative splicing.
Show »
Length:353
Mass (Da):41,537
Checksum:iE7CDDCCF3D91E4E9
GO
Isoform 8 (identifier: Q9NVH6-8) [UniParc]FASTAAdd to basket
Also known as: TMLH1b

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKIDSFLPILRM

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).1 Publication
Show »
Length:432
Mass (Da):50,832
Checksum:i47019D752A5E120A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66N → D in CAG33546 (Ref. 3) Curated1
Sequence conflicti170F → S in BAF84383 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076251244D → H in AUTSX6; loss of function. 1 Publication1
Natural variantiVAR_076252369E → D in AUTSX6; unknown pathological significance; no loss of function. 1 PublicationCorresponds to variant rs782001959dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0422751 – 68Missing in isoform 7. 1 PublicationAdd BLAST68
Alternative sequenceiVSP_0422761M → MKIDSFLPILRM in isoform 8. Curated1
Alternative sequenceiVSP_04227761 – 120ELKYA…LFFTW → G in isoform 6. CuratedAdd BLAST60
Alternative sequenceiVSP_042278333 – 421YNNYD…LGLQA → VLRSWCSTRTIEATSKEIKL YIVCRYSYFGETLFPRSKET VTSLPHMCAYKAAATNRPWL SGVFYTI in isoform 2. CuratedAdd BLAST89
Alternative sequenceiVSP_042279333 – 421Missing in isoform 3. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_021579333 – 421YNNYD…LGLQA → LFKEKQNTVNRQWNSSLQCD IPERILTYRHFVSGTSIEHR GSLI in isoform 4. 2 PublicationsAdd BLAST89
Alternative sequenceiVSP_042280380 – 383LFID → GPN in isoform 5. Curated4
Alternative sequenceiVSP_042281384 – 421Missing in isoform 5. CuratedAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF373407 mRNA. Translation: AAL01871.1.
AK001589 mRNA. Translation: BAA91775.1.
AK291694 mRNA. Translation: BAF84383.1.
AK304830 mRNA. Translation: BAG65575.1.
AK310667 mRNA. No translation available.
CR457265 mRNA. Translation: CAG33546.1.
AM393196 mRNA. Translation: CAL38074.1.
BX276110 Genomic DNA. Translation: CAH71441.1.
BX276110 Genomic DNA. Translation: CAH71442.1.
BC025269 mRNA. Translation: AAH25269.1.
CCDSiCCDS14768.1. [Q9NVH6-1]
CCDS55547.1. [Q9NVH6-2]
RefSeqiNP_001171726.1. NM_001184797.1. [Q9NVH6-2]
NP_060666.1. NM_018196.3. [Q9NVH6-1]
UniGeneiHs.133321.

Genome annotation databases

EnsembliENST00000334398; ENSP00000335261; ENSG00000185973. [Q9NVH6-1]
ENST00000369439; ENSP00000358447; ENSG00000185973. [Q9NVH6-2]
GeneIDi55217.
KEGGihsa:55217.
UCSCiuc004fnn.5. human. [Q9NVH6-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF373407 mRNA. Translation: AAL01871.1.
AK001589 mRNA. Translation: BAA91775.1.
AK291694 mRNA. Translation: BAF84383.1.
AK304830 mRNA. Translation: BAG65575.1.
AK310667 mRNA. No translation available.
CR457265 mRNA. Translation: CAG33546.1.
AM393196 mRNA. Translation: CAL38074.1.
BX276110 Genomic DNA. Translation: CAH71441.1.
BX276110 Genomic DNA. Translation: CAH71442.1.
BC025269 mRNA. Translation: AAH25269.1.
CCDSiCCDS14768.1. [Q9NVH6-1]
CCDS55547.1. [Q9NVH6-2]
RefSeqiNP_001171726.1. NM_001184797.1. [Q9NVH6-2]
NP_060666.1. NM_018196.3. [Q9NVH6-1]
UniGeneiHs.133321.

3D structure databases

ProteinModelPortaliQ9NVH6.
SMRiQ9NVH6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120513. 3 interactors.
IntActiQ9NVH6. 8 interactors.
MINTiMINT-3074990.
STRINGi9606.ENSP00000335261.

Chemistry databases

DrugBankiDB00139. Succinic acid.
DB00126. Vitamin C.

PTM databases

iPTMnetiQ9NVH6.
PhosphoSitePlusiQ9NVH6.

Polymorphism and mutation databases

BioMutaiTMLHE.
DMDMi21542295.

Proteomic databases

EPDiQ9NVH6.
MaxQBiQ9NVH6.
PaxDbiQ9NVH6.
PeptideAtlasiQ9NVH6.
PRIDEiQ9NVH6.

Protocols and materials databases

DNASUi55217.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000334398; ENSP00000335261; ENSG00000185973. [Q9NVH6-1]
ENST00000369439; ENSP00000358447; ENSG00000185973. [Q9NVH6-2]
GeneIDi55217.
KEGGihsa:55217.
UCSCiuc004fnn.5. human. [Q9NVH6-1]

Organism-specific databases

CTDi55217.
DisGeNETi55217.
GeneCardsiTMLHE.
HGNCiHGNC:18308. TMLHE.
HPAiHPA034589.
HPA040331.
MalaCardsiTMLHE.
MIMi300777. gene.
300872. phenotype.
neXtProtiNX_Q9NVH6.
OpenTargetsiENSG00000185973.
Orphaneti106. Autism.
PharmGKBiPA38311.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3889. Eukaryota.
COG2175. LUCA.
GeneTreeiENSGT00530000063582.
HOGENOMiHOG000210004.
HOVERGENiHBG035650.
InParanoidiQ9NVH6.
KOiK00474.
OMAiIEINEFW.
OrthoDBiEOG091G062L.
PhylomeDBiQ9NVH6.
TreeFamiTF313805.

Enzyme and pathway databases

UniPathwayiUPA00118.
BioCyciMetaCyc:HS08089-MONOMER.
ZFISH:HS08089-MONOMER.
BRENDAi1.14.11.8. 2681.
ReactomeiR-HSA-71262. Carnitine synthesis.

Miscellaneous databases

GeneWikiiTMLHE.
GenomeRNAii55217.
PROiQ9NVH6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185973.
CleanExiHS_TMLHE.
GenevisibleiQ9NVH6. HS.

Family and domain databases

InterProiIPR010376. DUF971.
IPR003819. TauD/TfdA-like.
IPR012776. Trimethyllysine_dOase.
[Graphical view]
PfamiPF06155. DUF971. 1 hit.
PF02668. TauD. 1 hit.
[Graphical view]
TIGRFAMsiTIGR02410. carnitine_TMLD. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTMLH_HUMAN
AccessioniPrimary (citable) accession number: Q9NVH6
Secondary accession number(s): A8K6M9
, B4E3R3, Q5TZB5, Q6IA90, Q8TBT0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.