TMLHE

TMLHE
Identifikatori
Aliasi	TMLHE
Vanjski ID-jevi	OMIM: 300777 MGI: 2180203 HomoloGene: 21853 GeneCards: TMLHE
Lokacija gena (čovjek)
Hrom.	Hromosom X
Kraj	155,719,098 bp
Ontologija gena
Molekularna funkcija	• iron ion binding; • oxidoreductase activity; • oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; • vezivanje iona metala; • dioxygenase activity; • trimethyllysine dioxygenase activity; • GO:0001948, GO:0016582 vezivanje za proteine;
Ćelijska komponenta	• mitochondrial matrix; • mitohondrija;
Biološki proces	• GO:2001216 negative regulation of oxidoreductase activity; • carnitine biosynthetic process;
	Izvori:Amigo / QuickGO
Ortolozi
	55217
	192289
	ENSG00000185973
	ENSMUSG00000079834
	Q9NVH6
	Q91ZE0
	NM_001184797; NM_018196
	NM_138758
	NP_001171726; NP_060666
	NP_620097
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Mitohondrijska trimetillizin-hidrolsilaza epsilon jest enzim koji je kood ljudi kodiran genom TMLHE.^[4]^[5]^[6] Mutacije u genu TMLHE koje rezultiraju poremećajem biosinteze karnitina povezane su sa simptomima autizma.^[7]

Struktura uredi

Gen TMHLE nalazi se na samom kraju regije Xq28, sa velikom genomskom nestabilnošću,^[8] a kodira protein trimetillizin-dioksigenazu, a, Fe2 + i 2-oksoglitarat ovisnu nehem-gvožđevu hidrolazu, lokaliziranu u mitohondrijama.^[9]

Funkcija uredi

Enzim trimetillizin-dioksigenaza katalizira prvi korak na putu biosinteze karnitina, koji je dio biosinteze amina. Karnitin je molekula koja ima bitnu ulogu u transportu aktiviranih masnih kiselina kroz unutrašnju mitohondrijsku membranu, gdje metaboliziraju. Kodirani protein pretvara trimetillizin u hidroksitrimetillizin, reakcijom (EC 1.14.11.8):

N₆,N₆,N(6)-trimetil-L-lizin + 2-oksoglutarat + O₂ = 3-hidroksi-N₆,N₆,N(6)-trimetil-L-lizin + sukcinat + CO₂.

I odgovarajući gvožđev i L-askorbat kao kofaktori.

Klinički značaj uredi

Mutacije u genu THLHE uzrokuju nedostatak epsilon-trimetillizin hidroksilaze (TMLHED),^[10]^[11] urođene greške metabolizma u biosintezi karnitina, što može povećati rizik od razvoja poremećaja neurorazvojnog procesa, ponašanja povezanih s autizmom i poremećaja iz spektra autizma.^[7]^[12]

Interakcije uredi

Pokazalo se da THLHE ima 14 binarnih interakcija protein-protein, uključujući 12 interakcija kompleksa. Čini se da THLHE komunicira sa SUGCT.^[13]

Reference uredi

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000185973 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Rogner UC, Heiss NS, Kioschis P, Wiemann S, Korn B, Poustka A (oktobar 1996). "Transcriptional analysis of the candidate region for incontinentia pigmenti (IP2) in Xq28". Genome Research. 6 (10): 922–34. doi:10.1101/gr.6.10.922. PMID 8908511.
^ Vaz FM, Ofman R, Westinga K, Back JW, Wanders RJ (septembar 2001). "Molecular and Biochemical Characterization of Rat epsilon -N-Trimethyllysine Hydroxylase, the First Enzyme of Carnitine Biosynthesis". The Journal of Biological Chemistry. 276 (36): 33512–7. doi:10.1074/jbc.M105929200. PMID 11431483.
^ "Entrez Gene: TMLHE trimethyllysine hydroxylase, epsilon".
^ ^a ^b Ziats MN, Comeaux MS, Yang Y, Scaglia F, Elsea SH, Sun Q, Beaudet AL, Schaaf CP (septembar 2015). "Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation". American Journal of Medical Genetics. Part A. 167A (9): 2162–7. doi:10.1002/ajmg.a.37144. PMID 25943046.
^ Monfregola J, Napolitano G, Conte I, Cevenini A, Migliaccio C, D'Urso M, Ursini MV (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. doi:10.1016/j.gene.2007.02.012. PMID 17408883.
^ Monfregola J, Cevenini A, Terracciano A, van Vlies N, Arbucci S, Wanders RJ, D'Urso M, Vaz FM, Ursini MV (2005). "Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting". J. Cell. Physiol. 204 (3): 839–47. doi:10.1002/jcp.20332. PMID 15754339.
^ Celestino-Soper PB, Shaw CA, Sanders SJ, Li J, Murtha MT, Ercan-Sencicek AG, Davis L, Thomson S, Gambin T, Chinault AC, Ou Z, German JR, Milosavljevic A, Sutcliffe JS, Cook EH, Stankiewicz P, State MW, Beaudet 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. doi:10.1093/hmg/ddr363. PMC 3196886. PMID 21865298.
^ Nava C, Lamari F, Héron D, Mignot C, Rastetter A, Keren B, Cohen D, Faudet A, Bouteiller D, Gilleron M, Jacquette A, Whalen S, Afenjar A, Périsse D, Laurent C, Dupuits C, Gautier C, Gérard M, Huguet G, Caillet S, Leheup B, Leboyer M, Gillberg C, Delorme R, Bourgeron T, Brice A, Depienne C (2012). "Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE". Transl Psychiatry. 2: e179. doi:10.1038/tp.2012.102. PMC 3565810. PMID 23092983.
^ http://www.omim.org/entry/300872
^ "14 binary interactions found for search term TMLHE". IntAct Molecular Interaction Database. EMBL-EBI. Pristupljeno 25. 8. 2018.

Dopunska literatura uredi

Hartley JL, Temple GF, Brasch MA (novembar 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (septembar 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (oktobar 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
Monfregola J, Cevenini A, Terracciano A, van Vlies N, Arbucci S, Wanders RJ, D'Urso M, Vaz FM, Ursini MV (septembar 2005). "Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting". Journal of Cellular Physiology. 204 (3): 839–47. doi:10.1002/jcp.20332. PMID 15754339.
Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (januar 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
Monfregola J, Napolitano G, Conte I, Cevenini A, Migliaccio C, D'Urso M, Ursini MV (juni 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. doi:10.1016/j.gene.2007.02.012. PMID 17408883.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000185973 - Ensembl, maj 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8908511-4] Rogner UC, Heiss NS, Kioschis P, Wiemann S, Korn B, Poustka A (oktobar 1996). "Transcriptional analysis of the candidate region for incontinentia pigmenti (IP2) in Xq28". Genome Research. 6 (10): 922–34. doi:10.1101/gr.6.10.922. PMID 8908511.

[pmid11431483-5] Vaz FM, Ofman R, Westinga K, Back JW, Wanders RJ (septembar 2001). "Molecular and Biochemical Characterization of Rat epsilon -N-Trimethyllysine Hydroxylase, the First Enzyme of Carnitine Biosynthesis". The Journal of Biological Chemistry. 276 (36): 33512–7. doi:10.1074/jbc.M105929200. PMID 11431483.

[entrez-6] "Entrez Gene: TMLHE trimethyllysine hydroxylase, epsilon".

[:0-7] Ziats MN, Comeaux MS, Yang Y, Scaglia F, Elsea SH, Sun Q, Beaudet AL, Schaaf CP (septembar 2015). "Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation". American Journal of Medical Genetics. Part A. 167A (9): 2162–7. doi:10.1002/ajmg.a.37144. PMID 25943046.

[8] Monfregola J, Napolitano G, Conte I, Cevenini A, Migliaccio C, D'Urso M, Ursini MV (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. doi:10.1016/j.gene.2007.02.012. PMID 17408883.

[ReferenceA-9] Monfregola J, Cevenini A, Terracciano A, van Vlies N, Arbucci S, Wanders RJ, D'Urso M, Vaz FM, Ursini MV (2005). "Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting". J. Cell. Physiol. 204 (3): 839–47. doi:10.1002/jcp.20332. PMID 15754339.

[10] Celestino-Soper PB, Shaw CA, Sanders SJ, Li J, Murtha MT, Ercan-Sencicek AG, Davis L, Thomson S, Gambin T, Chinault AC, Ou Z, German JR, Milosavljevic A, Sutcliffe JS, Cook EH, Stankiewicz P, State MW, Beaudet 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. doi:10.1093/hmg/ddr363. PMC 3196886. PMID 21865298.

[11] Nava C, Lamari F, Héron D, Mignot C, Rastetter A, Keren B, Cohen D, Faudet A, Bouteiller D, Gilleron M, Jacquette A, Whalen S, Afenjar A, Périsse D, Laurent C, Dupuits C, Gautier C, Gérard M, Huguet G, Caillet S, Leheup B, Leboyer M, Gillberg C, Delorme R, Bourgeron T, Brice A, Depienne C (2012). "Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE". Transl Psychiatry. 2: e179. doi:10.1038/tp.2012.102. PMC 3565810. PMID 23092983.

[12] ttp://www.omim.org/entry/300872

[13] "14 binary interactions found for search term TMLHE". IntAct Molecular Interaction Database. EMBL-EBI. Pristupljeno 25. 8. 2018.

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