TMLHE
| TMLHE | |||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||
| Aliases | TMLHE, AUTSX6, BBOX2, TMLD, TMLH, TMLHED, XAP130, D430017M14Rik, trimethyllysine hydroxylase, epsilon | ||||||||||||||||||||||||
| External IDs | MGI: 2180203 HomoloGene: 21853 GeneCards: TMLHE | ||||||||||||||||||||||||
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| Orthologs | |||||||||||||||||||||||||
| Species | Human | Mouse | |||||||||||||||||||||||
| Entrez | |||||||||||||||||||||||||
| Ensembl | |||||||||||||||||||||||||
| UniProt | |||||||||||||||||||||||||
| RefSeq (mRNA) | |||||||||||||||||||||||||
| RefSeq (protein) | |||||||||||||||||||||||||
| Location (UCSC) | Chr X: 155.49 – 155.67 Mb | n/a | |||||||||||||||||||||||
| PubMed search | [2] | [3] | |||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||
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Trimethyllysine dioxygenase, mitochondrial is an enzyme that in humans is encoded by the TMLHE gene in chromosome X.[4][5][6]
Structure
The TMHLE gene is located at the extreme end of the Xq28 region with high genomic instability,[7] and encodes a protein trimethyllysine dioxygenase, a , Fe2+ and 2-oxoglytarate dependen non-heme-ferrous iron hydrolase localized to the mitochondrial matrix.[8]
Function
The trimethyllysine dioxygenase enzyme catalyzes the first step in the carnitine biosynthesis pathway,[8] which is part of amine biosynthesis. Carnitine is a molecule that play an essential role in the transport of activated fatty acids across the inner mitochondrial membrane where they are metabolized. The encoded protein converts trimethyllysine into hydroxytrimethyllysine with the reaction (EC 1.14.11.8):
N6,N6,N(6)-trimethyl-L-lysine + 2-oxoglutarate + O2 = 3-hydroxy-N6,N6,N(6)-trimethyl-L-lysine + succinate + CO2.
and requires iron and L-ascorbate as co-factors.
Clinical Significance
Mutations in the THLHE gene causes Epsilon-trimethyllysine hydroxylase deficiency (TMLHED),[9][10] an inborn error of metabolism in carnitine biosynthesis, which is increased with risks for developing autism-related behaviours and Autism spectrum disorders [11]
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000185973 - Ensembl, May 2017
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Rogner UC, Heiss NS, Kioschis P, Wiemann S, Korn B, Poustka A (Feb 1997). "Transcriptional analysis of the candidate region for incontinentia pigmenti (IP2) in Xq28". Genome Res. 6 (10): 922–34. PMID 8908511. doi:10.1101/gr.6.10.922.
- ↑ Vaz FM, Ofman R, Westinga K, Back JW, Wanders RJ (Sep 2001). "Molecular and Biochemical Characterization of Rat epsilon -N-Trimethyllysine Hydroxylase, the First Enzyme of Carnitine Biosynthesis". J Biol Chem. 276 (36): 33512–7. PMID 11431483. doi:10.1074/jbc.M105929200.
- ↑ "Entrez Gene: TMLHE trimethyllysine hydroxylase, epsilon".
- ↑ Monfregola J, Napolitano G, Conte I, Cevenini A, Migliaccio C, D'Urso M, et al. (2007). "Functional characterization of the TMLH gene: promoter analysis, in situ hybridization, identification and mapping of alternative splicing variants". Gene. 395 (1-2): 86–97. PMID 17408883. doi:10.1016/j.gene.2007.02.012.
- 1 2 Monfregola J, Cevenini A, Terracciano A, van Vlies N, Arbucci S, Wanders RJ, et al. (2005). "Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting". J. Cell. Physiol. 204 (3): 839–47. PMID 15754339. doi:10.1002/jcp.20332.
- ↑ Celestino-Soper PB, Shaw CA, Sanders SJ, Li J, Murtha MT, Ercan-Sencicek AG, et al. (2011). "Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE". Hum. Mol. Genet. 20 (22): 4360–70. PMC 3196886
. PMID 21865298. doi:10.1093/hmg/ddr363. - ↑ Nava C, Lamari F, Héron D, Mignot C, Rastetter A, Keren B, et al. (2012). "Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE". Transl Psychiatry. 2: e179. PMC 3565810 . PMID 23092983. doi:10.1038/tp.2012.102.
- ↑ http://www.omim.org/entry/300872
Further reading
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. PMC 310948 . PMID 11076863. doi:10.1101/gr.143000.
- Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.". EMBO Rep. 1 (3): 287–92. PMC 1083732 . PMID 11256614. doi:10.1093/embo-reports/kvd058.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. PMID 14702039. doi:10.1038/ng1285.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504.
- Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. PMC 528930 . PMID 15489336. doi:10.1101/gr.2576704.
- Monfregola J, Cevenini A, Terracciano A, et al. (2005). "Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting.". J. Cell. Physiol. 204 (3): 839–47. PMID 15754339. doi:10.1002/jcp.20332.
- Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the human X chromosome.". Nature. 434 (7031): 325–37. PMC 2665286 . PMID 15772651. doi:10.1038/nature03440.
- Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. PMC 1347501 . PMID 16381901. doi:10.1093/nar/gkj139.
- Monfregola J, Napolitano G, Conte I, et al. (2007). "Functional characterization of the TMLH gene: promoter analysis, in situ hybridization, identification and mapping of alternative splicing variants.". Gene. 395 (1–2): 86–97. PMID 17408883. doi:10.1016/j.gene.2007.02.012.