Ubiquitin protein ligases

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Schematic representation of ubiquitination

Ubiquitin protein ligases , synonymous with ubiquitin ligases , are enzymes from the group of ligases .

properties

Ubiquitin protein ligases catalyze the transfer of the protein ubiquitin to another protein . The resulting ubiquitin-coupled (fachsprachlich ubiquitinylated or ubiquitinated ) protein is among others by the ubiquitin-proteasome system bound and degraded or - depending on behängtem protein, and depending on the number of the attached ubiquitin - regulates a cellular process such as endocytosis , the transcription , the Protein transport in peroxisomes or the cell cycle .

The ubiquitin protein ligases occur in all cells ( ubiquitous ) and couple ubiquitin to a protein in a three-step process with three different ubiquitin protein ligases. In the first step E1, a ubiquitin protein ligase catalyses the hydrolysis of adenosine triphosphate (ATP) binding of the carboxy group (COOH group) of the C -terminal glycine of ubiquitin to a thiol group (SH group) of a particular cysteine on the surface of E1 ubiquitin protein ligase. The E1 ubiquitin protein ligase then transfers the ubiquitin to the thiol group of a certain cysteine ​​of the E2 ubiquitin protein ligase. In the first two steps of the enzymatic transfer of ubiquitin is performed on the enzymes themselves, while in the third step an E3 ubiquitin protein ligase, the transfer of ubiquitin from the E2 ubiquitin-protein ligase to the ε- amino group of a specific lysine to catalyzes the surface of the protein to be labeled.

Examples

Ubiquitin-protein ligases, for example, E3A , mdm2 , anaphase-promoting complex (APC), UBR5 (EDD1), SOCS , LNXp80 , CBX4 , CBLL1 , HACE1 , HECTD1 , HECTD2 , HECTD3 , HECTD4 , HECW1 , HECW2 , HERC1 , HERC2 , HERC3 , HERC4 , HERC5 , HERC6 , HUWE1 , ITCH , NEDD4 , NEDD4L , PPIL2 , PRPF19 , PIAS1 , PIAS2 , PIAS3 , PIAS4 , RanBP2 , RNF4 , RBX1 , SMURF1 , Smurf2 , STUB1 , TOPORS , TRIP12 , UBE3A , UBE3B , UBE3C , UBE3D , UBE4A , UBE4B , UBOX5 , UBR1 , UBR5, WWP1 , WWP2 and Parkin .

Individual evidence

  1. ↑ a b c d e Werner Müller-Esterl: Biochemistry. Springer-Verlag, 2017, ISBN 978-3-662-54851-6 , p. 252.
  2. ^ A b Peter C. Heinrich: Löffler / Petrides Biochemistry and Pathobiochemistry. Springer-Verlag, 2014, ISBN 978-3-642-17972-3 , pp. 624, 625.
  3. ↑ Leonardo K. Teixeira, Steven I. Reed: Ubiquitin ligases and cell cycle control . In: Annual Review of Biochemistry . tape 82 , 2013, ISSN  1545-4509 , p. 387-414 , doi : 10.1146 / annurev-biochem-060410-105307 , PMID 23495935 .
  4. ↑ A. Hershko, A. Ciechanover: The ubiquitin system . In: Annual Review of Biochemistry . tape 67 , 1998, ISSN  0066-4154 , pp. 425-479 , doi : 10.1146 / annurev.biochem.67.1.425 , PMID 9759494 .