TMLHE

TMLHE
Identifikatori
AliasiTMLHE
Vanjski ID-jeviOMIM: 300777 MGI: 2180203 HomoloGene: 21853 GeneCards: TMLHE
EC broj1.14.11.8
Lokacija gena (čovjek)
Hromosom X
Hrom.Hromosom X[1]
Hromosom X
Genomska lokacija za TMLHE
Genomska lokacija za TMLHE
BendXq28Početak155,489,011 bp[1]
Kraj155,719,098 bp[1]
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
VrsteČovjekMiš
Entrez

55217

192289

Ensembl

ENSG00000185973

ENSMUSG00000079834

UniProt

Q9NVH6

Q91ZE0

RefSeq (mRNK)

NM_001184797
NM_018196

NM_138758

RefSeq (bjelančevina)

NP_001171726
NP_060666

NP_620097

Lokacija (UCSC)Chr X: 155.49 – 155.72 Mbn/a
PubMed pretraga[2][3]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/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

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

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

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

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

Reference

  1. ^ a b c 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.
  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.
  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.
  6. ^ "Entrez Gene: TMLHE trimethyllysine hydroxylase, epsilon".
  7. ^ 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.
  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.
  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. ^ http://www.omim.org/entry/300872
  13. ^ "14 binary interactions found for search term TMLHE". IntAct Molecular Interaction Database. EMBL-EBI. Pristupljeno 25. 8. 2018.

Dopunska literatura

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