PROSITE documentation PDOC51796
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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