PROSITE documentation PDOC51371

CBS domain profile

CBS domains contain about 60 amino acid residues and occur as tandem pairs in a variety of proteins in bacteria, archaea, and eukaryotes [1,2]. They are mainly found in proteins that are regulated by adenosyl metabolites. Depending on the protein in which they occur, CBS domains have been proposed to affect multimerization and sorting of proteins, channel gating, and ligand binding. However, recent experiments revealing that CBS domains can bind adenosine-containing ligands such ATP, AMP, or S-adenosylmethionine have led to the hypothesis that CBS domains function as sensors of intracellular metabolites [3,4].

Crystallographic studies of CBS domains have shown that pairs of CBS sequences form a globular domain where each CBS unit adopts a β-α-β-β-α pattern (see <PDB:1ZFJ>) [5]. Crystal structure of the CBS domains of the AMP-activated protein kinase in complexes with AMP and ATP shows that the phosphate groups of AMP/ATP lie in a surface pocket at the interface of two CBS domains, which is lined with basic residues, many of which are associated with disease-causing mutations [6].

Some proteins known to contain a CBS domain:

• Cystathione β-synthase (CBS) protein. CBS performs a crucial step in the biosynthetic pathway of cysteine by providing a regulatory control point for S-adenosylmethionine.
• Mammalian AMP-activated protein kinase (AMPK) γ-subunit. AMPK is a heterotrimer of three different subunits (α, β, and γ) with α being the catalytic subunit and β and γ having regulatory roles. AMPK is a serine/threonine protein kinase that has a central role in controlling whole-body metabolism in response to nutrients and hormonal signals.
• Inosine-5'-monophosphate dehydrogenase (IMPDH) protein. This enzyme catalyzes the first committed step in the purine nucleoside-synthesis pathway for the generation of GMP.
• CLC Chloride Channel family. These channels are voltage gated chloride channels that sustain a wide variety of cellular functions, including membrane excitability, synaptic communication, transepithelial transport, cell volume regulation, cell proliferation, and acidification of endosomes and lysosomes.
• Glycine βine/carnitine/choline transport ATP-binding protein. an ABC transporter involved in a high affinity multicomponent binding-protein-dependent transport system for glycine βine, carnitine and choline; probably responsible for energy coupling to the transport system.

The profile we developed covers the entire CBS domain.