SUMO-Protein

• UniProt: P63165.1

The SUMO protein (. Engl of small ubiquitin -related modifier, small ubiquitin - related modifier ') is a post-translational modification, which - similar to ubiquitin or Urm1 - marks proteins for degradation in the proteasome. The operation of the marker with the SUMO protein is referred to as sumoylation (English SUMOylation ).

Properties

The SUMOylation plays in various cellular processes play a role, eg in the nuclear transport in apoptosis in the regulation of transcription by induction of degradation of histones in the protein degradation ( autophagy ) as an antiviral mechanism in stress responses, in chromosome segregation in mitosis and in the initiation of the next phase in the cell cycle. SUMO proteins here serve as a regulatory protein in the organism.

In protein misfolding diseases, such as Huntington's disease, Alzheimer's disease, Parkinson 's disease and spinocerebellar ataxia 1, the inclusion bodies are indeed sumoylated, but not eliminated. In various diseases an erroneous SUMOylation has been observed, for example, in cancer, in amyotrophic lateral sclerosis, as well as in infections with adenoviruses and herpesviruses. These viruses use the SUMOylation for the transport of viral proteins.

Mechanism

SUMO proteins consist of about 100 amino acids (12 kilodaltons ) and be Sentrin - specific proteases ( SENPs ) into its active form. SUMO -1, is thereby reduced at the C -terminus by four amino acids, SUMO -2 and SUMO to eleven amino -3 by two amino acids. The SUMOylation, as the ubiquitination by three enzymes catalyzing enzymes E1 ( SUMO -activating enzyme), E2 enzymes ( SUMO - conjugating enzyme ) and E3 enzymes ( SUMO ligase ).

Through a thioester bond to a cysteine ​​residue of the heterodimeric enzyme E1 SAE1 SUMO - SAE2 the protein is activated, and then also transferred via a thioester bond to a cysteine ​​of the E2 enzyme Ubc9. The terminal C-terminal carboxyl group of the glycine of the SUMO - proteins, in the third sub-step by the E3 enzyme SUMO ligase to the lysine in the recognition sequence of the degraded proteins ψ - KXD / E ( a hydrophobic amino acid, lysine, any amino acid and an acidic amino acid such as aspartic acid or glutamic acid) linked via an isopeptide bond to the ε - amine. SUMO ligase ( an E3 enzyme, eg RanBP2 ) binds to the Ubc9 ( an E2 enzyme ) and the degraded protein. The release of the SUMO proteins for reuse done by the SENPs.

The E3 enzymes may be due to their homologies in three groups, the RanBP2 - type, the HECT - type and RING - type (eg yeasts Siz1, Siz2, Mms21, Cst9 and Zip3 and human PIAS1, PIAS3, PIASxα, PIASxβ and PIASy ). In Saccharomyces cerevisiae is called the SUMO protein SMT3 (English suppressor of mif two 3), the E1 enzyme AOS1 - UBA2. There are yeasts as SUMO protease Ulp1 at nuclear pores and Ulp2 in the nucleus.