The following text describes a protein:
Function:
Decreases PAN2-mediated deadenylation, possibly by preventing progression into the second CCR4-NOT mediated stage of biphasic deadenylation. Has a significant effect on mRNA stability, generally stabilizing a subset of the transcriptome. Stabilizes mRNAs degraded by the AU-rich element (ARE)-mediated mRNA decay pathway but promotes degradation of mRNAs by the microRNA-mediated pathway. Its activity influences mRNP remodeling, specifically reducing formation of a subset of P-bodies containing GW220, an isoform of TNRC6A; Enhances PAN2 deadenylase activity and has an extensive effect on mRNA stability, generally enhancing mRNA decay across the transcriptome by multiple pathways, including the AU-rich element (ARE)-mediated pathway, microRNA-mediated pathway and the nonsense-mediated pathway (NMD). Its activity is required for efficient P-body formation. May be involved in regulating mRNAs of genes involved in cell cycle progression and cell proliferation; 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; 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 deadenylation-dependent mRNA decapping and subsequent 5'-3' exonucleolytic degradation by XRN1. PAN3 acts as a 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.
Subcellular Localization:
Cytoplasm, P-body. Nucleus.
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; The N-terminal zinc finger binds to poly(A) RNA; 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.
Sequence:
MNSGGLPPPASSSSSGAAALKLKFCRYYAKDKTCFYGEECQFLHEDPAAGPGLGLGLHGSGAAAVAGPPGSKKAELDGLRLTIPGVDGGALADSSLTDSYFSTSFIGVNGFGSPAEAKYPMMQRMTNSSSSPSLLNDSAKSYASHDPLSSPASSLFNDFGALSISQRRKPRKYRLGMLEERLVPVGSKTRKSKNPIGSLADRCKSGVPINMVWWNRVTENNLQTPNPTASEFIPKGGSTSRLSNVSQSNMSAFSQALFSHPSMGGPATAGLAPGMSLSAGSSPLHSPKITPHTSPAPRRRSHTPNPANYLVPSSASTPVNNPVTQAPSPGQVIQKETVGGTTYFYTDTTPAPVTGMVFPNYHIYPPTAPHVAYMQPKANAPSFFMADELRQELINRHLITMAQIDQADIPAVPAEVDSYHSLFPLEPLPPPNRIQKSSNFGYITSCYKAVNSKDDLPYCLRRIHGFRLVNTKCMVLVDMWKKIQHSNIVTLREVFTTKAFGEHSLVFAYDFHAGGETMMSRHFNDPSADAYFTKRKWGQHDGPLPRQHAGLLPESLIWAYIVQLSSALRTVHTAGLACRVMDPTKILVTGKTRLRVNCVGVFDVLTFDSSQNNPLALMAQFQQADLISLGKVVLALACNSLAGIQRENLQKAMELVTINYSSDLKNLILYLLTDQNRLRSVNDIMPMIGARFYTQLDAAQMRNDVIEEDLAKEVQNGRLFRLLAKLGTINERPEFQKDPTWSETGDRYLLKLFRDHLFHQVTEAGTPWIDLSHIISCLNKLDAGVPEKISLISRDEKSVLVVTYSDLKRCFENTFQELIAAANGQL