poly(A) polymerase alpha; PAP-alpha polynucleotide adenylyltransferase alpha (PAPOLA, PAP)

Function: - synthesis of 3' poly(A) tail of mRNA - endodeoxyribonuclease cleavage reaction at some polyadenylylation sites - may acquire specificity through interaction with a cleavage & polyadenylation specificity factor (CPSF) at its C-terminus - polysumoylated - varying sumolyation depending on tissue- & cell-type - highly sumoylated in bladder & NIH 3T3 cells - sumoylation is required for nuclear localization & enhances PAPOLA stability - desumoylated by SENP1 inhibits polymerase activity - hyperphosphorylation on multiple CDK2 consensus & non- consensus sites in the C-terminal Ser/Thr-rich region represses PAPOLA activity in late M-phase - phosphorylation/dephosphorylation may regulate interaction between PAPOLA & CPSF - acetylated in the C-terminus - acetylation decreases interaction with NUDT21 & KPNB1 - inhibits nuclear localization through inhibiting binding to the importin alpha/beta complex (putative) - found in a complex with CPSF1, FIP1L1 & PAPOLA - interacts with FIP1L1 (putative) - interacts with NUDT21; - interaction is diminished by acetylation - interacts with KPNB1 - interaction promotes PAPOLA nuclear import - interaction is inhibited by acetylation of PAP (putative) Cofactor: - binds 2 Mg⁺² - also active with Mn+2 Structure: - monomer - belongs to the poly(A) polymerase family Compartment: - cytoplasm, nucleus - the 90 kD form is nuclear - the 100 kD & the 106 kD forms are both nuclear & cytoplasmic Alternative splicing: named isoforms=2

Properties

SIZE: entity length = 745 aa MW = 83 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S24} glutamate-rich region {53-57} MOTIF: glutamate residue (SEVERAL) ATP-binding site NAME: ATP-binding site SITE: 100-102 ATP-binding site NAME: ATP-binding site SITE: 109-109 ATP-binding site NAME: ATP-binding site SITE: 113-115 MOTIF: Mg+2-binding site SITE: 113-113 Mg+2-binding site SITE: 115-115 phenylalanine residue {153} lysine residue {158} Mg+2-binding site SITE: 167-167 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 167-167 ATP-binding site NAME: ATP-binding site SITE: 228-228 ATP-binding site NAME: ATP-binding site SITE: 237-237 ATP-binding site NAME: ATP-binding site SITE: 246-247 asparagine residue {328} arginine residue {399} nuclear translocation signal {490-507} MOTIF: lysine-rich region {504-507} MOTIF: lysine residue (SEVERAL) Ser/Thr-rich {508-643} MOTIF: aspartate residue {524} Ser phosphorylation site {S534} Ser phosphorylation site {S537} Ser phosphorylation site {S553} nuclear translocation signal {650-665} NUDT21 interaction {677-745}

Database Correlations

OMIM 605553 UniProt P51003 PFAM correlations Entrez Gene 10914 Kegg hsa:10914 ENZYME 2.7.7.19

References

UniProt :accession P51003