{PDOC51371}
{PS51371; CBS}
{BEGIN}
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* CBS domain profile *
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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 beta-alpha-beta-beta-alpha
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 beta-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)  gamma-subunit. AMPK is a
   heterotrimer  of  three  different  subunits  (alpha, beta, and gamma) with
   alpha  being  the  catalytic  subunit  and beta and gamma 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  betaine/carnitine/choline  transport  ATP-binding  protein. an ABC
   transporter     involved     in     a    high    affinity    multicomponent
   binding-protein-dependent  transport  system for glycine betaine, carnitine
   and  choline;  probably  responsible  for  energy coupling to the transport
   system.

The profile we developed covers the entire CBS domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

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

-Last update: February 2008 / First entry.

[ 1] Bateman A.
     "The structure of a domain common to archaebacteria and the
     homocystinuria disease protein."
     Trends Biochem. Sci. 22:12-13(1997).
     PubMed=9020585
[ 2] Ignoul S., Eggermont J.
     "CBS domains: structure, function, and pathology in human proteins."
     Am. J. Physiol. 289:C1369-C1378(2005).
     PubMed=16275737; DOI=10.1152/ajpcell.00282.2005
[ 3] Scott J.W., Hawley S.A., Green K.A., Anis M., Stewart G.,
     Scullion G.A., Norman D.G., Hardie D.G.
     "CBS domains form energy-sensing modules whose binding of adenosine
     ligands is disrupted by disease mutations."
     J. Clin. Invest. 113:274-284(2004).
     PubMed=14722619; DOI=10.1172/JCI200419874
[ 4] Kemp B.E.
     "Bateman domains and adenosine derivatives form a binding contract."
     J. Clin. Invest. 113:182-184(2004).
     PubMed=14722609; DOI=10.1172/JCI200420846
[ 5] Zhang R., Evans G., Rotella F.J., Westbrook E.M., Beno D.,
     Huberman E., Joachimiak A., Collart F.R.
     "Characteristics and crystal structure of bacterial
     inosine-5'-monophosphate dehydrogenase."
     Biochemistry 38:4691-4700(1999).
     PubMed=10200156; DOI=10.1021/bi982858v
[ 6] Xiao 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.
     "Structural basis for AMP binding to mammalian AMP-activated protein
     kinase."
     Nature 449:496-500(2007).
     PubMed=17851531; DOI=10.1038/nature06161

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