{PDOC51796}
{PS51796; MSS4}
{BEGIN}
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* MSS4 domain profile *
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MSS4 (mammalian  suppressor  of  Sec4)  is  an evolutionarily highly conserved
protein, which  is  expressed  in all mammalian tissues. Although it was first
proposed to  function  as  a guanine exchange factor (GEF) for Rab GTPases, it
was soon  described  as  a  quite  inefficient  GEF  and was thus suggested to
function rather   as   a  chaperone,  protecting  nucleotide  free  Rabs  from
degradation, than as a GEF [1].

The structure  of  MSS4 revealed a mostly beta fold stabilized by a Zn(2+) ion
coordinated by  cysteine  residues  from two CxxC motifs. The fold of the MSS4
domain consists  of  a  central  beta  sheet  (betaG-betaK)  flanked by a beta
hairpin (betaB-betaC) on one side and a small variable sheet on the other (see
<PDB:1HXR>). A  single Zn(2+) ion, coordinated by the thiol groups of cysteine
residues from  two  CxxC  motifs  located  in  the betaB-betaC and betaI-betaJ
loops, appears  to  play  an  important  structural  role  by  reinforcing the
hydrophobic core  formed by the betaB-betaC hairpin, the betaG-betaH loop, and
the central beta sheet [2,3,4].

The profile we developed covers the entire MSS4 domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2016 / First entry.

[ 1] Walter B.M., Nordhoff C., Varga G., Goncharenko G., Schneider S.W.,
     Ludwig S., Wixler V.
     "Mss4 protein is a regulator of stress response and apoptosis."
     Cell Death Dis. 3:E297-E297(2012).
     PubMed=22495352; DOI=10.1038/cddis.2012.37
[ 2] Yu H., Schreiber S.L.
     "Structure of guanine-nucleotide-exchange factor human Mss4 and
     identification of  its Rab-interacting surface."
     Nature 376:788-791(1995).
     PubMed=7651540; DOI=10.1038/376788a0
[ 3] Zhu Z., Dumas J.J., Lietzke S.E., Lambright D.G.
     "A helical turn motif in Mss4 is a critical determinant of Rab binding
     and nucleotide release."
     Biochemistry 40:3027-3036(2001).
     PubMed=11258916
[ 4] Itzen A., Pylypenko O., Goody R.S., Alexandrov K., Rak A.
     "Nucleotide exchange via local protein unfolding--structure of Rab8 in
     complex with MSS4."
     EMBO J. 25:1445-1455(2006).
     PubMed=16541104; DOI=10.1038/sj.emboj.7601044

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