Reviewed, UniProtKB/Swiss-Prot Q9NVH6 (TMLH_HUMAN)

Names and origin

Protein names

Recommended name:
    Trimethyllysine dioxygenase, mitochondrial
    EC=1.14.11.8
Alternative name(s):
    Epsilon-trimethyllysine 2-oxoglutarate dioxygenase
    TML-alpha-ketoglutarate dioxygenase
      Short name=TML dioxygenase
      Short name=TMLD
    TML hydroxylase

Gene names

Name:	TMLHE
Synonyms:	TMLH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	421 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML).
Catalytic activity	N6,N6,N(6)-trimethyl-L-lysine + 2-oxoglutarate + O2 = 3-hydroxy-N6,N6,N(6)-trimethyl-L-lysine + succinate + CO2.
Cofactor	Iron. Ascorbate.
Pathway	Amine and polyamine biosynthesis; carnitine biosynthesis.
Subunit structure	Homodimer By similarity.
Subcellular location	Mitochondrion matrix By similarity.
Sequence similarities	Belongs to the gamma-BBH/TMLD family.

Ontologies

Keywords
Biological process	Carnitine biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	Iron
Molecular function	Dioxygenase Oxidoreductase
Gene Ontology (GO)
Biological process	carnitine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	L-ascorbic acid binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW trimethyllysine dioxygenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: 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.

Isoform 2 (identifier: Q9NVH6-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 421		Trimethyllysine dioxygenase, mitochondrial		PRO_0000002795
Natural variations
	Alternative sequence	333 – 421	89	YNNYD…LGLQA → LFKEKQNTVNRQWNSSLQCD IPERILTYRHFVSGTSIEHR GSLI in isoform 2.		VSP_021579
Experimental info
	Sequence conflict	66	1	N → D in CAG33546. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 4E55DF349B866B43	FASTA	421	49,518
	10 20 30 40 50 60 MWYHRLSHLH SRLQDLLKGG VIYPALPQPN FKSLLPLAVH WHHTASKSLT CAWQQHEDHF 70 80 90 100 110 120 ELKYANTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV DLCIKPKTIR LDETTLFFTW 130 140 150 160 170 180 PDGHVTKYDL NWLVKNSYEG QKQKVIQPRI LWNAEIYQQA QVPSVDCQSF LETNEGLKKF 190 200 210 220 230 240 LQNFLLYGIA FVENVPPTQE HTEKLAERIS LIRETIYGRM WYFTSDFSRG DTAYTKLALD 250 260 270 280 290 300 RHTDTTYFQE PCGIQVFHCL KHEGTGGRTL LVDGFYAAEQ VLQKAPEEFE LLSKVPLKHE 310 320 330 340 350 360 YIEDVGECHN HMIGIGPVLN IYPWNKELYL IRYNNYDRAV INTVPYDVVH RWYTAHRTLT 370 380 390 400 410 420 IELRRPENEF WVKLKPGRVL FIDNWRVLHG RECFTGYRQL CGCYLTRDDV LNTARLLGLQ A
	Isoform 2. Checksum: AB6D7A1DC57D6FCF	FASTA	376	44,049
	10 20 30 40 50 60 MWYHRLSHLH SRLQDLLKGG VIYPALPQPN FKSLLPLAVH WHHTASKSLT CAWQQHEDHF 70 80 90 100 110 120 ELKYANTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV DLCIKPKTIR LDETTLFFTW 130 140 150 160 170 180 PDGHVTKYDL NWLVKNSYEG QKQKVIQPRI LWNAEIYQQA QVPSVDCQSF LETNEGLKKF 190 200 210 220 230 240 LQNFLLYGIA FVENVPPTQE HTEKLAERIS LIRETIYGRM WYFTSDFSRG DTAYTKLALD 250 260 270 280 290 300 RHTDTTYFQE PCGIQVFHCL KHEGTGGRTL LVDGFYAAEQ VLQKAPEEFE LLSKVPLKHE 310 320 330 340 350 360 YIEDVGECHN HMIGIGPVLN IYPWNKELYL IRLFKEKQNT VNRQWNSSLQ CDIPERILTY 370 RHFVSGTSIE HRGSLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular and biochemical characterization of rat epsilon-N-trimethyllysine hydroxylase, the first enzyme of carnitine biosynthesis." Vaz F.M., Ofman R., Westinga K., Back J.W., Wanders R.J.A. J. Biol. Chem. 276:33512-33517(2001) [PubMed: 11431483] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	Bechtel S., Schupp I., Duda A., Wellenreuther R., Mehrle A., Ruschke V., Poustka A., Wiemann S. Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Pancreas.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF373407 mRNA. Translation: AAL01871.1. AK001589 mRNA. Translation: BAA91775.1. 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.
IPI	IPI00301224. IPI00382858.
RefSeq	NP_060666.1.
UniGene	Hs.133321
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	Q9NVH6.
Genome annotation databases
Ensembl	ENSG00000185973. Homo sapiens. [Contig view]
GeneID	55217.
KEGG	hsa:55217.
Organism-specific databases
GeneCards	GC0XM154372. GC0XM154373.
H-InvDB	HIX0017170.
HGNC	HGNC:18308. TMLHE.
PharmGKB	PA38311.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9NVH6.
HOVERGEN	Q9NVH6.
OMA	Q9NVH6. CLIFDNW.
Enzyme and pathway databases
Reactome	REACT_13. Metabolism of amino acids.
Gene expression databases
ArrayExpress	Q9NVH6.
Bgee	Q9NVH6.
CleanEx	HS_TMLHE.
GermOnline	ENSG00000185973. Homo sapiens.
Family and domain databases
InterPro	IPR003819. Taurine_dOase. IPR012776. Trimethyllysine_dOase. [Graphical view]
PANTHER	PTHR10696:SF2. tMLys_dOase. 1 hit.
Pfam	PF02668. TauD. 1 hit. [Graphical view]
TIGRFAMs	TIGR02410. carnitine_TMLD. 1 hit.
ProtoNet	Search...
Other Resources
DrugBank	DB00139. Succinic acid. DB00126. Vitamin C.
NextBio	59184.

Entry information

Entry name

TMLH_HUMAN

Accession

Primary (citable) accession number: Q9NVH6
Secondary accession number(s): Q5TZB5, Q6IA90, Q8TBT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	October 1, 2000
Last modified:	June 16, 2009
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)