{PDOC51201}
{PS51201; RCK_N}
{PS51202; RCK_C}
{BEGIN}
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* RCK N-terminal and C-terminal domain profiles *
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Regulators  of  K+  conductance  (RCK) domain is found in many ligand-gated K+
channels,  most  often  attached  to  the  intracellular carboxy terminus. The
domain  is  prevalent  among  prokaryotic  K+  channels,  and  also  found  in
eukaryotic,   high-conductance   Ca2+-activated  K+  channels  (BK  channels).
[1,4,5].  Largely  involved  in redox-linked regulation of potassium channels,
the  N-terminal  part  of  the  RCK  domain  is  predicted  to  be  an  active
dehydrogenase at least in some cases [1]. Some have a conserved sequence motif
(G-x-G-x-x-G-x(n)-[DE])  for  NAD+  binding [2], but others do not, reflecting
the  diversity  of  ligands  for  RCK  domains.  The  C-terminal  part is less
conserved,  being  absent  in  some channels, such as the kefC antiporter from
Escherichia coli. It is predicted to bind unidentified ligands and to regulate
sulfate, sodium and other transporters.

The  X-ray  structure  of several RCK domains has been solved (see for example
<PDB:1LNQ>)  [3,4,5].  It  reveals an alpha-beta fold similar to dehydrogenase
enzymes. The domain forms a homodimer, producing a cleft between two lobes. It
has  a  composite  structure,  with  an  N-terminal  (RCK-N), and a C-terminal
(RCK-C)  subdomains.  The RCK-N subdomain forms a Rossmann fold with two alpha
helices  (alpha  A  and  alpha  B) on one side of a six stranded parallel beta
sheet  (beta  A to beta F) and three alpha helices (alpha C, alpha D and alpha
E) on the other side. The RCK-C subdomain is an all-beta-strand fold. It forms
an  extention  of the dimer interface and further stabilizes the RCK homodimer
[3,4,5].  Ca2+ is a ligand that opens the channel in a concentration-dependent
manner.  Two  Ca2+  ions  are  located  at the base of a cleft between two RCK
domains,  coordinated by the carboxylate groups of two glutamate residues, and
by an aspartate residue [3,4,5].

RCK  domains  occur  in  at  least five different contexts:

 - As a single domain on the C terminus of some K+ channels (for example, many
   prokaryotic K+ channels).
 - As  two tandem RCK domains on the C terminus of some transporters that form
   gating  rings (for example, eukaryotic BK channels). The gating ring has an
   arrangement  of  eight  identical  RCK  domains,  one from each of the four
   pore-forming subunits and four from the intracellular solution.
 - As  two  domains,  one  at  the N terminus and another at the C terminus of
   transporter  (for  example,  the  prokaryotic  trk  system potassium uptake
   protein A).
 - As  a  soluble protein (not part of a K+ channel)  consisting of two tandem
   RCK domains.
 - As a soluble protein consisting of a single RCK domain.

We  developed two profiles for this domain, one that spans the RCK-N subdomain
and the other which covers the RCK-C subdomain.

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

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

-Note: The RCK domain is also named as trkA or KTN.

-Last update: June 2006 / Profile revised.

[ 1] Anantharaman V., Koonin E.V., Aravind L.
     "Regulatory potential, phyletic distribution and evolution of ancient,
     intracellular small-molecule-binding domains."
     J. Mol. Biol. 307:1271-1292(2001).
     PubMed=11292341; DOI=10.1006/jmbi.2001.4508
[ 2] Schlosser A., Hamann A., Bossemeyer D., Schneider E., Bakker E.P.
     "NAD+ binding to the Escherichia coli K(+)-uptake protein TrkA and
     sequence similarity between TrkA and domains of a family of
     dehydrogenases suggest a role for NAD+ in bacterial transport."
     Mol. Microbiol. 9:533-543(1993).
     PubMed=8412700
[ 3] Dong J., Shi N., Berke I., Chen L., Jiang Y.
     "Structures of the MthK RCK domain and the effect of Ca2+ on gating
     ring stability."
     J. Biol. Chem. 280:41716-41724(2005).
     PubMed=16227203; DOI=10.1074/jbc.M508144200
[ 4] Jiang Y., Pico A., Cadene M., Chait B.T., MacKinnon R.
     "Structure of the RCK domain from the E. coli K+ channel and
     demonstration of its presence in the human BK channel."
     Neuron 29:593-601(2001).
     PubMed=11301020
[ 5] Jiang Y., Lee A., Chen J., Cadene M., Chait B.T., MacKinnon R.
     "Crystal structure and mechanism of a calcium-gated potassium
     channel."
     Nature 417:515-522(2002).
     PubMed=12037559; DOI=10.1038/417515a

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