SOON AVAILABLE:
Recombinant TRIM21(V287-L465), PRYSPRY domain, Tripartite motif-containing 21 protein, E3 Ligase

Our recombinant GSG_TRIM21(V287-L465) protein contains the C-terminal PRY-SPRY domain of TRIM21, which spans residues V287 - L465. The construct also contains an N-terminal GSG linker, which serves to optimize tag cleavage by a TEV Protease.

Protein Construct: GSG_TRIM21(V287-L465)
Source: Human
Expression Host: Escherichia coli
Molecular weight [kDa]: 20.5
pI: 5.9
Extinction Coefficient [M^-1cm^-1]: 43430
Tag: none

Amino acid sequence:

Structure and function

The tripartite motif (TRIM) protein family includes around 70 proteins involved in a wide range of cellular functions such as cell growth, differentiation, and programmed cell death. The multidomain TRIM21 protein consists of an N-terminal RING finger domain with E3 ligase activity, a coiled-coil domain mediating oligomerization after ubiquitination of substrates targeted for degradation as well as a C-terminal PRYSPRY domain. The latter adopts a distorted beta-sandwich fold and features a canonical binding interface for the Fc region of immunoglobulins which coat pathogens that can be marked for proteasomal degradation.

TRIM21 as an important drug target

A key element of TRIM21’s activity is the PRYSPRY domain, as it enables binding to the Fc regions of immunoglobulins and subsequent ubiquitination and degradation of antibody-bound pathogens. The PRYSPRY domain remains a central target for therapeutic intervention, as it contains, in addition to two antibody-binding pockets, other smaller ligand binding pockets (Kim et al., 2025). The capacity of the TRIM21-PRYSPRY domain to break down pathogenic cargo bound to endogenous antibodies has been utilized in the so-called TRIM-AWAY technique. In this approach, introducing an antibody that targets a specific protein into cells triggers its degradation through TRIM21.
The development of bivalent molecules has also been successful in the field of anticancer therapeutics, where so-called “TRIMTACs”, direct TRIM21 to nuclear pore proteins, disrupting nuclear transport and leading to rapid cancer cell death (Scemama de Gialluly et al., 2025). It has also been discovered that TRIM21 preferentially ubiquitinates large, multimeric complexes in vivo, which makes it a potentially interesting E3 ligase for the development of PROTACs against protein aggregates.
Additionally, mutations in the PRYSPRY domain have been linked to autoimmune diseases like rheumatoid arthritis or systemic lupus erythematosus, making it an important target for autoimmune therapeutics.