SUMOylation
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "SUMOylation".

Small Ubiquitin-like Modifier or SUMO proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle [1].

SUMO proteins are similar to ubiquitin, and SUMOylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. In contrast to ubiquitin, SUMO is not used to tag proteins for degradation. Mature SUMO is produced when the last four amino acids of the C-terminus have been cleaved off to allow for formation of an isopeptide bond between the C-terminal glycine residue of SUMO and an acceptor lysine on the target protein.

SUMO family members often have dissimilar names; the SUMO homologue in yeast, for example, is called SMT3 (suppressor of mif two 3). Several pseudogenes have been reported for this gene.

Structure schematic of human SUMO1 protein made with iMol and based on PDB file 1A5R, an NMR structure; the backbone of the protein is represented as a ribbon, highlighting secondary structure; N-terminus in blue, C-terminus in red
Structure schematic of human SUMO1 protein made with iMol and based on PDB file 1A5R, an NMR structure; the backbone of the protein is represented as a ribbon, highlighting secondary structure; N-terminus in blue, C-terminus in red
The same structure represented with atoms represented as spheres to show the shape of the protein; human SUMO1, PDB file 1A5R
The same structure represented with atoms represented as spheres to show the shape of the protein; human SUMO1, PDB file 1A5R
content

Contents

Function

SUMO modification of proteins has many functions. Among the most frequent and best studied are protein stability, nuclear-cytosolic transport, and transcriptional regulation. Typically, only a small fraction of a given protein is SUMOylated and this modification is rapidly reversed by the action of deSUMOylating enzymes. SUMOylation of target proteins has been shown to cause a number of different outcomes including altered localisation and binding partners. For example, the SUMO modification of hNinein leads to its movement from the centrosome to the nucleus [2]. In many cases SUMO modification of transcriptional regulators correlates with inhibition of transcription [3]. Refer to the GeneRIFs of the Sumo proteins, e.g. human SUMO1 [4], to find out more.

There are 3 confirmed SUMO isoforms in humans; SUMO-1, SUMO-2 and SUMO-3. SUMO-2/3 show high a high degree of similarity to each other and are distinct from SUMO-1. SUMO-4 shows similarity to -2/3 but it is as yet unclear whether it is a pseudogene or merely restricted in its expression pattern.

SUMO-2/3 modifications seem to be involved specifically in the stress response. SUMO-1 and SUMO-2/3 can form mixed chains, however, because SUMO-1 does not contain the internal SUMO consensus sites found in SUMO-2/3, it terminates these poly-SUMO chains [5].

Structure

SUMO proteins are small; most are around 100 amino acids in length and 12 kDa in mass. The exact length and mass varies between SUMO family members and depends on which organism the protein comes from. Although SUMO has very little homology with Ubiquitin at the amino acid level, it has a nearly identical structural fold.

The structure of human SUMO1 is depicted on the right. It shows SUMO1 as a globular protein with both ends of the amino acid chain (shown in red and blue) sticking out of the protein's centre. The spherical core consists of an alpha helix and a beta sheet. The diagrams shown are based on an NMR analysis of the protein in solution.

Prediction of SUMO attachment

Most SUMO-modified proteins contain the tetrapeptide consensus motif Ψ-K-x-D/E where Ψ is a hydrophobic residue, K is the lysine conjugated to SUMO, x is any amino acid (aa), D or E is an acidic residue. Substrate specificity appears to be derived directly from Ubc9 and the respective substrate motif. SUMOplot is an online free access software developed to predict the probability for the SUMO consensus sequence (SUMO-CS) to be engaged in SUMO attachment.[6] The SUMOplot score system is based on two criteria: 1) direct amino acid match to the SUMO-CS observed and shown to bind Ubc9, and 2) substitution of the consensus amino acid residues with amino acid residues exhibiting similar hydrophobicity. SUMOplot has been used in the past to predict Ubc9 dependent sites. Seventeen (17) articles have been published so far for the complete list click here.[7] Alternative prediction engines such as SUMOsp are also available [8].

SUMO Conjugation

SUMO conjugation to its target is analogous to that of Ubiquitin (as it is for the other Ubiquitin-like proteins such as NEDD 8). A C-terminal peptide is cleaved from SUMO by a protease (in human these are the SENP proteases or Ulp1 in yeast) using ATP to reveal a di-glycine motif. SUMO then becomes bound to an E1 enzyme (SUMO Activating Enzyme (SAE)) which is a heterodimer. It is then passed to an E2 which is a conjugating enzyme (Ubc9). Finally, one of a small number of E3 ligating proteins attaches it to the protein. In yeast, there are four SUMO E3 proteins, Cst9[9], Mms21, Siz1 and Siz2. While in ubiquitination an E3 is essential to add ubiquitin to its target, evidence suggests that the E2 is sufficient in Sumoylation as long as the consensus sequence is present. It is thought that the E3 ligase promotes the efficiency of sumoylation and in some cases has been shown to direct SUMO conjugation onto non-consensus motifs. E3 enzymes can be largely classed into PIAS proteins, such as Mms21 (a member of the Smc5/6 complex) and Pias-gamma and HECT proteins. Some E3's such as RanBP2 however are neither [10]. Recent evidence has shown that PIAS-gamma is required for the sumoylation of the transcription factor yy1 but it is independent of the zinc-RING finger (identified as the functional domain of the E3 ligases). SUMOylation is reversible and is removed from targets by specific SUMO proteases in an ATP dependent manner. In budding yeast, the Ulp1 SUMO protease is found bound at the nuclear pore, whereas Ulp2 is nucleoplasmic. The distinct subnuclear localisation of deSUMOylating enzymes is conserved in higher eukaryotes[11]

References

  1. ^ http://www.molecule.org/content/article/abstract?uid=PIIS1097276505011822
  2. ^ SUMO-1 modification of centrosomal protein hNinein...[Life Sci. 2006] - PubMed Result
  3. ^ [Curr Opin Genet Dev. 2005] - PubMed Result
  4. ^ Gene Result
  5. ^ In vivo identification of human small ubiquitin-li...[Mol Cell Proteomics. 2008] - PubMed Result
  6. ^ Gramatikoff K. et al. In Frontiers of Biotechnology and Pharmaceuticals, Science Press (2004) 4: pp.181-210.
  7. ^ SUMOplot usage - list of 17 articles
  8. ^ bioinformatics.lcd-ustc.org/sumosp/
  9. ^ http://www.genesdev.org/cgi/content/full/20/15/2067
  10. ^ http://www.nature.com/nsmb/journal/v11/n10/abs/nsmb834.html;jsessionid=AD17A0BE7A40B2E08091663D0C2BC720
  11. ^ http://www.ncbi.nlm.nih.gov/pubmed/17499995?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

External links

v • d • e
Protein primary structure and posttranslational modifications
General
N terminus
C terminus
Lysine
Cysteine
Serine/Threonine
Tyrosine
Asparagine
Aspartate
Glutamine
Glutamate
Arginine
Proline
© jGames.co.uk 2007 (some content from Wikipedia under GDL ) !-- ValueClick Media 468x60 and 728x90 Banner CODE for jgames.co.uk -->
Your Ad Here