UniProt ID: E7EXP6 |
FUNCTION: Regulatory 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 deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. PAN3 acts as a positive regulator for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its interaction with RNA and PABP, and to miRNA targets via its interaction with GW182 family proteins. {ECO:0000256|HAMAP-Rule:MF_03181}. SUBUNIT: Homodimer. Forms a heterotrimer with a catalytic subunit PAN2 to form the poly(A)-nuclease (PAN) deadenylation complex. Interacts (via PAM-2 motif) with poly(A)-binding protein PABPC1 (via PABC domain), conferring substrate specificity of the enzyme complex. Interacts with the GW182 family proteins TNRC6A, TNRC6B and TNRC6C. {ECO:0000256|HAMAP-Rule:MF_03181}. SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000256|HAMAP- Rule:MF_03181}. DOMAIN: Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs. {ECO:0000256|HAMAP- Rule:MF_03181}. DOMAIN: The N-terminal zinc finger binds to poly(A) RNA. {ECO:0000256|HAMAP-Rule:MF_03181}. DOMAIN: The pseudokinase domain, the coiled-coil (CC), and C-terminal knob domain (CK) form a structural unit (PKC) that forms an extensive high-affinity interaction surface for PAN2. {ECO:0000256|HAMAP- Rule:MF_03181}. SIMILARITY: Belongs to the protein kinase superfamily. PAN3 family. {ECO:0000256|HAMAP-Rule:MF_03181}. CAUTION: Lacks conserved residue(s) required for the propagation of feature annotation. {ECO:0000256|HAMAP-Rule:MF_03181}. |
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