{PDOC51701}
{PS51701; 6_CYS}
{BEGIN}
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* 6-Cysteine (6-Cys) domain profile *
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The 6-Cysteine  (6-Cys)  domain  is  found  in  Plasmodium  proteins  that are
expressed in  all stages of the parasite life cycle in both the vertebrate and
mosquito hosts.  The  domain  is  of  roughly 120 amino acids and contains six
positionally conserved  cysteines.  It might occur in 1-14 copies per protein,
either as  the  sole  globular domain or in combination wih beta-helix-forming
hexapeptide repeats  as  is  the  case of sequestrin. It is generally found in
tandem pairs of A-type and B-type domains. Previously believed to be exclusive
to Plasmodium,  the  6-Cys domain also exists in proteins found in all members
of the  aconoidasidan  (hematozoan)  clade  of  Apicomplexa,  which unites the
haemosporidians (Plasmodium) and piroplasms) [1,2,3,4,5].

The 6-cys  domain  is  a  beta-sandwich formed by two sheets with a mixture of
parallel and  antiparallel strands (see <PDB:2LOE>). Three disulfide bonds are
present in  the  6_Cys domain with C1-C2, C3-C6, and C4-C5 connectivity. C1-C2
and C3-C6  pin  together  the  two  sheets of the beta-sandwich, whereas C4-C5
links an ancyllary loop to the core domain [4,5].

Some Plasmodium proteins known to contain a 6-Cys domain are listed below:

 - Pfs48/45,  involved in male/female gamete fusion in the mosquito midgut. It
   is predicted  to  be  glycosylphosphatidylinositol  (GPI)-anchored  to  the
   gamete surface.
 - Pfs230, involved in male/female gamete fusion in the mosquito midgut. It is
   a soluble  protein  that  associates with the gamete membrane by binding to
   Pfs48/45.
 - Pfs47,  involved in male/female gamete fusion in the mosquito midgut. It is
   found on female gametes.
 - P52,  expressed  in  the  sporozoite.  May  be  required  for  invasion  of
   hepatocytes and to promote normal development in the liver.
 - P36,  expressed  in  the  sporozoite.  May  be  required  for  invasion  of
   hepatocytes and to promote normal development in the liver.
 - Pf41, located on the surface of merozoites and has a signal sequence.
 - Pf38, located on the surface of merozoites. It has a signal sequence and is
   GPI-anchored to the merozoite surface.
 - Pf12, located on the surface of merozoites. It has a signal sequence and is
   GPI-anchored to the merozoite surface.
 - Pf92, located on the surface of merozoites. It has a signal sequence and is
   GPI-anchored to the merozoite surface.

The profile we developed covers the entire 6-Cys domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2014 / First entry.

[ 1] van Dijk M.R., Janse C.J., Thompson J., Waters A.P., Braks J.A.M.,
     Dodemont H.J., Stunnenberg H.G., van Gemert G.J., Sauerwein R.W.,
     Eling W.
     "A central role for P48/45 in malaria parasite male gamete
     fertility."
     Cell 104:153-164(2001).
     PubMed=11163248
[ 2] Gerloff D.L., Creasey A., Maslau S., Carter R.
     "Structural models for the protein family characterized by gamete
     surface protein  Pfs230 of Plasmodium falciparum."
     Proc. Natl. Acad. Sci. U.S.A. 102:13598-13603(2005).
     PubMed=16155126; DOI=10.1073/pnas.0502378102
[ 3] van Dijk M.R., van Schaijk B.C.L., Khan S.M., van Dooren M.W.,
     Ramesar J., Kaczanowski S., van Gemert G.-J., Kroeze H.,
     Stunnenberg H.G., Eling W.M., Sauerwein R.W., Waters A.P.,
     Janse C.J.
     "Three members of the 6-cys protein family of Plasmodium play a role
     in gamete fertility."
     PLoS Pathog. 6:E1000853-E1000853(2010).
     PubMed=20386715; DOI=10.1371/journal.ppat.1000853
[ 4] Arredondo S.A., Cai M., Takayama Y., MacDonald N.J., Anderson D.E.,
     Aravind L., Clore G.M., Miller L.H.
     "Structure of the Plasmodium 6-cysteine s48/45 domain."
     Proc. Natl. Acad. Sci. U.S.A. 109:6692-6697(2012).
     PubMed=22493233; DOI=10.1073/pnas.1204363109
[ 5] Tonkin M.L., Arredondo S.A., Loveless B.C., Serpa J.J.,
     Makepeace K.A., Sundar N., Petrotchenko E.V., Miller L.H., Grigg M.E.,
     Boulanger M.J.
     "Structural and biochemical characterization of Plasmodium falciparum
     12 (Pf12) reveals a unique interdomain organization and the potential
     for an antiparallel arrangement with Pf41."
     J. Biol. Chem. 288:12805-12817(2013).
     PubMed=23511632; DOI=10.1074/jbc.M113.455667

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