Pan3 is a regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of the two eukaryotic poly(A) nuclease complexes (Ccr4-Caf1 and Pan2-Pan3) involved in mRNA decay [, ]. It contains a PABP-interacting motif 2 (PAM2) that binds to the C-terminal domain of polyA binding proteins (PABPs) []. It recruits the Pan2-Pan3 complex to mRNA through the Pan3-PABP interaction [].Regulation of mRNA decay rates in eukaryotic cells affects gene expression []. The Pan2-Pan3 complex shortens cytoplasmic mRNA 3' polyA tails to regulate mRNA stability []. In the complex Pan2 provides the catalytic activity, whereas Pan3 mediates Pan2 recruitment to mRNA targets [].
This is a pseudokinase (PK) domain found in PAB-dependent poly(A)-specific ribonuclease subunit PAN3. PAN3 proteins contain three prominent regions: an unstructured N-terminal region (N-term), a central PK domain, and a highly conserved C-terminal domain (C-term). The PAN3 PK domain has retained its ATP binding capacity, and this function is required for mRNA degradation in vivo. Analysis of Pan3 amino acids sequences show that, despite of retaining the general structural characteristics of protein kinases, the PK domain has substitutions in all the conserved motifs that are critical for kinase activity, such as in the catalytic VAIK and HRD motifs and in the Mg2+ binding DFG motif. However, the PAN3 PK domain has been shown to bind ATP. Furthermore, similar to other kinases, the ATP-binding site is located in the cleft between the N- and C-lobes of the kinase fold, however, the ATP-binding pocket is wider than that of typical kinases [].
The poly(A)-specific nuclease (PAN) is a deadenylating enzyme involved in cytoplasmic mRNA turnover and consists of two subunits, PAN2 and PAN3, which form a conserved complex acting in the initial trimming of poly(A) tails, a process followed by the processive action of CCR4-NOT complex. PAN2 is the catalytic subunit and has two independent structural units, the N-terminal assembly unit which engages in a bipartite interaction with PAN3 dimers and the C-terminal catalytic unit [, , ]. The C-terminal unit contains the ubiquitin C-terminal hydrolase (UCH) domain, represented in this entry, and a RNase domain of the DEDD superfamily () [, ].
Pan2 is a catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of the two eukaryotic poly(A) nuclease complexes (Ccr4-Caf1 and Pan2-Pan3) involved in mRNA decay [, ]. Pan2 is involved in the initial stage of deadenylation of mRNA, which is required for poly(A) tail shortening []. Regulation of mRNA decay rates in eukaryotic cells affects gene expression []. The Pan2-Pan3 complex shortens cytoplasmic mRNA 3' polyA tails to regulate mRNA stability []. In the complex Pan2 provides the catalytic activity, whereas Pan3 mediates Pan2 recruitment tomRNA targets [].
