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

More general terms

• poly[A]polymerase

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10914
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10914
• OMIM: https://mirror.omim.org/entry/605553
• UniProt: http://www.uniprot.org/uniprot/P51003.html