Literature summary for 2.1.1.5 extracted from

Ou, X.; Yang, H.; Ramani, K.; Ara, A.I.; Chen, H.; Mato, J.M.; Lu, S.C.
Inhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine (2007), Biochem. J., 401, 87-96.

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Application

Application	Comment	Organism
molecular biology	S-adenosylmethionine and 5-methylthioadenosine down-regulate BHMT expression in HepG2 cells in part by inducing NF-kappaB, which acts as a repressor for the human BHMT gene. While S-adenosylmethionines mechanism is NF-kappaB-dependent, 5-methylthioadenosine has both NF-kappaB-dependent and -independent mechanisms	Homo sapiens
additional information	lower BHMT expression can impair homocysteine metabolism, which can induce endoplasmic reticulum stress	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
a 2.7 kb 5'-flanking region of the human BHMT gene cloned between MluI and SmaI sites of a promoterless pGL-3-basic vector creating the recombinant plasmid -2698/+33 BHMT-LUC, expression in HepG2 cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	deletion mutants ranging from -2698 to +33, construct -347/+33 has maximal promoter activity, inhibition in promoter activity by S-adenosylmethionine or 5'-methylthioadenosine most pronounced within this construct, cycloleucine treatment increases the reporter activity driven by the BHMT promoter construct -347/+33 but does not block the ability of 5'-methylthioadenosine to inhibit the BHMT promoter activity and blocks the conversion of 5'-methylthioadenosine into S-adenosylmethionine	Homo sapiens
additional information	S-adenosylmethionine and 5-methylthioadenosine treatment of HepG2 cells result in a dose- and time-dependent decrease in BHMT mRNA levels, which parallels their effects on the BHMT promoter activity. Maximal suppression is observed with BHMT promoter construct -347/+33, containing a number of NF-kappaB binding sites. S-adenosylmethionine and 5-methylthioadenosine treatment increases NF-kappaB nuclear binding and NF-kappaB-driven luciferasece activities, and increases nuclear binding activity of multiple histone deacetylase co-repressors to the NF-kappaB sites. Overexpression of p50 and p65 decreases BHMT promoter activity, while blocking NF-kappaB activation increases BHMT expression and promoter activity, and prevents S-adenosylmethionine but not 5-methylthioadenosines ability to inhibit BHMT expression	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
additional information	S-adenosylmethionine decreases BHMT mRNA levels in dose- and time-dependent manner, down-regulates BHMT expression in part by inducing nuclear factor kappaB, which acts as a repressor for the human BHMT gene, the inhibitor is nuclear factor kappaB dependent. 5'-methylthioadenosine decreases BHMT mRNA levels in dose- and time-dependent manner, down-regulates BHMT expression in part by inducing nuclear factor kappaB, which acts as a repressor for the human BHMT gene, the inhibitor has nuclear factor kappaB dependent and -independent mechanisms	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q6EI07	-	-
Homo sapiens	Q6EI07	fragment	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
Hep-G2 cell	-	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
betaine-homocysteine methyltransferase	-	Homo sapiens
betaine-homocysteine S-methyltransferase	-	Homo sapiens
BHMT	-	Homo sapiens

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Release 2023.1 (January 2023)