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PROSITE documentation PDOC51371 [for PROSITE entry PS51371]

CBS domain profile





Description

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.

Note:

Each pair of CBS motifs is also known as a Bateman domain [4].

Last update:

February 2008 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

CBS, PS51371; CBS domain profile  (MATRIX)


References

1AuthorsBateman A.
TitleThe structure of a domain common to archaebacteria and the homocystinuria disease protein.
SourceTrends Biochem. Sci. 22:12-13(1997).
PubMed ID9020585

2AuthorsIgnoul S., Eggermont J.
TitleCBS domains: structure, function, and pathology in human proteins.
SourceAm. J. Physiol. 289:C1369-C1378(2005).
PubMed ID16275737
DOI10.1152/ajpcell.00282.2005

3AuthorsScott J.W., Hawley S.A., Green K.A., Anis M., Stewart G., Scullion G.A., Norman D.G., Hardie D.G.
TitleCBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.
SourceJ. Clin. Invest. 113:274-284(2004).
PubMed ID14722619
DOI10.1172/JCI200419874

4AuthorsKemp B.E.
TitleBateman domains and adenosine derivatives form a binding contract.
SourceJ. Clin. Invest. 113:182-184(2004).
PubMed ID14722609
DOI10.1172/JCI200420846

5AuthorsZhang R., Evans G., Rotella F.J., Westbrook E.M., Beno D., Huberman E., Joachimiak A., Collart F.R.
TitleCharacteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase.
SourceBiochemistry 38:4691-4700(1999).
PubMed ID10200156
DOI10.1021/bi982858v

6AuthorsXiao B., Heath R., Saiu P., Leiper F.C., Leone P., Jing C., Walker P.A., Haire L., Eccleston J.F., Davis C.T., Martin S.R., Carling D., Gamblin S.J.
TitleStructural basis for AMP binding to mammalian AMP-activated protein kinase.
SourceNature 449:496-500(2007).
PubMed ID17851531
DOI10.1038/nature06161



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