Adenosylhomocysteinase-like (IPR000043)

Short name: Adenosylhomocysteinase-like

Overlapping homologous superfamilies

Family relationships


Adenosylhomocysteinase (S-adenosyl-L-homocysteine hydrolase, EC: (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+ [PMID: 9586999,PMID: 16061414,PMID: 11325033,PMID: 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 [PMID: 16793548, PMID: 16527252]. By competing with IP3, it modulates the threshold IP3 concentration required for the activation of the receptor [PMID: 16793548]. Further studies indicate that Ahcyl1/IRBIT is in fact a multifunctional protein that regulates several ion channels and ion transporters [PMID: 24518248, PMID: 21152975]. Despite its homology to S-adenosylhomocysteine hydrolases, Ahcyl1 has neither enzyme activity nor any effects on the enzyme activity of S-adenosylhomocysteine hydrolase [PMID: 12525476]. Ahcyl2 lacks binding activity to IP3R [PMID: 19220705]. Ahcyl2 upregulates NBCe1-B, which plays an important role in intracellular pH regulation [PMID: 27382360].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.