PAN2
Domain
Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex.
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3.
Function
Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenylation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. Also acts as an important regulator of the HIF1A-mediated hypoxic response. Required for HIF1A mRNA stability independent of poly(A) tail length regulation.
Sequence Similarities
Belongs to the peptidase C19 family. PAN2 subfamily.
Cellular localization
- Cytoplasm
- Cytoplasm
- P-body
- Nucleus
- Shuttles between nucleus and cytoplasm.
Alternative names
KIAA0710, USP52, PAN2, PAN2-PAN3 deadenylation complex catalytic subunit PAN2, Inactive ubiquitin carboxyl-terminal hydrolase 52, PAB1P-dependent poly(A)-specific ribonuclease, Poly(A)-nuclease deadenylation complex subunit 2, PAN deadenylation complex subunit 2