Adenosylhomocysteinase (S-adenosyl-L-homocysteine hydrolase, EC 3.3.1.1 ) (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine. This enzyme is ubiquitous, highly conserved, and may play a key role in the regulation of the intracellular concentration of adenosylhomocysteine. AdoHcyase requires NAD + as a cofactor and contains a central glycine-rich region which is thought to be involved in NAD-binding. Since AdoHyc is a potent inhibitor of S-adenosyl-L-methionine dependent methyltransferases, AdoHycase plays a critical role in the modulation of the activity of various methyltransferases. The enzyme forms homotetramers, with each monomer binding one molecule of NAD+ [ (PUBMED:9586999) (PUBMED:16061414) (PUBMED:11325033) (PUBMED:15165742) ].
This family also includes S-adenosylhomocysteine hydrolase-like 1 (Ahcyl1), also known as IRBIT, and S-adenosylhomocysteine hydrolase-like protein 2 (Ahcyl2). Ahcyl1/IRBIT was shown to interact with inositol 1,4,5-trisphosphate receptors (IP3Rs), which function as intracellular Ca(2+) channels, and suppresses IP3 binding of IP3R [ (PUBMED:16793548) (PUBMED:16527252) ]. By competing with IP3, it modulates the threshold IP3 concentration required for the activation of the receptor [ (PUBMED:16793548) ]. Further studies indicate that Ahcyl1/IRBIT is in fact a multifunctional protein that regulates several ion channels and ion transporters [ (PUBMED:24518248) (PUBMED:21152975) ]. Despite its homology to S-adenosylhomocysteine hydrolases, Ahcyl1 has neither enzyme activity nor any effects on the enzyme activity of S-adenosylhomocysteine hydrolase [ (PUBMED:12525476) ]. Ahcyl2 lacks binding activity to IP3R [ (PUBMED:19220705) ]. Ahcyl2 upregulates NBCe1-B, which plays an important role in intracellular pH regulation [ (PUBMED:27382360) ].
Family alignment:
There are 16360 AdoHcyase domains in 16358 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing AdoHcyase domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with AdoHcyase domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing AdoHcyase domain in the selected taxonomic class.
Mutational and nucleotide sequence analysis of S-adenosyl-L-homocysteinehydrolase from Rhodobacter capsulatus.
Proc Natl Acad Sci U S A. 1992; 89: 6328-32
Display abstract
The genetic locus ahcY, encoding the enzyme S-adenosyl-L-homocysteinehydrolase (EC 3.3.1.1) from the bacterium Rhodobacter capsulatus, has beenmapped by mutational analysis to within a cluster of genes involved inregulating the induction and maintenance of the bacterial photosyntheticapparatus. Sequence analysis demonstrates that ahcY encodes a 51-kDapolypeptide that displays 64% sequence identity to its human homolog.Insertion mutants in ahcY lack detectable S-adenosyl-L-homocysteinehydrolase activity and, as a consequence, S-adenosyl-L-homocysteineaccumulates in the cells, resulting in a 16-fold decrease in theintracellular ratio of S-adenosyl-L-methionine toS-adenosyl-L-homocysteine as compared to wild-type cells. The ahcYdisrupted strain fails to grow in minimal medium; however, growth isrestored in minimal medium supplemented with methionine or homocysteine orin a complex medium, thereby indicating that the hydrolysis ofS-adenosyl-L-homocysteine plays a key role in the metabolism ofsulfur-containing amino acids. The ahcY mutant, when grown in supplementedmedium, synthesizes significantly reduced levels of bacteriochlorophyll,indicating that modulation of the intracellular ratio ofS-adenosyl-L-methionine to S-adenosyl-L-homocysteine may be an importantfactor in regulating bacteriochlorophyll biosynthesis.