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PROSITE documentation PDOC51796 [for PROSITE entry PS51796]

MSS4 domain profile


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 β 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 β sheet (βG-βK) flanked by a β hairpin (βB-βC) 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 βB-βC and βI-βJ loops, appears to play an important structural role by reinforcing the hydrophobic core formed by the βB-βC hairpin, the βG-βH loop, and the central β sheet [2,3,4].

The profile we developed covers the entire MSS4 domain.

Last update:

April 2016 / First entry.


Technical section

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

MSS4, PS51796; MSS4 domain profile  (MATRIX)


1AuthorsWalter B.M. Nordhoff C. Varga G. Goncharenko G. Schneider S.W. Ludwig S. Wixler V.
TitleMss4 protein is a regulator of stress response and apoptosis.
SourceCell Death Dis. 3:E297-E297(2012).
PubMed ID22495352

2AuthorsYu H. Schreiber S.L.
TitleStructure of guanine-nucleotide-exchange factor human Mss4 and identification of its Rab-interacting surface.
SourceNature 376:788-791(1995).
PubMed ID7651540

3AuthorsZhu Z. Dumas J.J. Lietzke S.E. Lambright D.G.
TitleA helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release.
SourceBiochemistry 40:3027-3036(2001).
PubMed ID11258916

4AuthorsItzen A. Pylypenko O. Goody R.S. Alexandrov K. Rak A.
TitleNucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4.
SourceEMBO J. 25:1445-1455(2006).
PubMed ID16541104

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