Poly(A) polymerase alpha

Known also as: Polynucleotide adenylyltransferase alpha
Known abbreviations: PAPOLA, PAP, PAP-alpha

Yeast homolog: Pla1

Protein

745

PAP_central

PAP_RNA-bind

Models
Domains

Secondary structure

Disorder

This protein is highly disordered (40 % of residues are predicted to be disordered)

Top 3 models:


Template: 2q66, chain A Method: mgenthreader Fragment: 17-509	Template: 3dxj, chain N Method: compass Fragment: 370-732	Template: 1gt8, chain A Method: compass Fragment: 432-732

This protein has alternative isoforms:
Isoform 1:

Sequence length:	745 aa
Molecular weight:	82.843 kDa
Isoelectric point:	7.14

Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MPFPVTTQGSQQTQPPQKHYGITSPISLAAPKETDCVLTQKLIETLKPFGVFEEEEELQRRILILGKLNNLVKEWIREISESKNLPQSVIENVGGKIFTFGSYRLGVHTKGADIDALCVAPRHVDRSDFF
TSFYDKLKLQEEVKDLRAVEEAFVPVIKLCFDGIEIDILFARLALQTIPEDLDLRDDSLLKNLDIRCIRSLNGCRVTDEILHLVPNIDNFRLTLRAIKLWAKRHNIYSNILGFLGGVSWAMLVARTCQLY
PNAIASTLVHKFFLVFSKWEWPNPVLLKQPEECNLNLPVWDPRVNPSDRYHLMPIITPAYPQQNSTYNVSVSTRMVMVEEFKQGLAITDEILLSKAEWSKLFEAPNFFQKYKHYIVLLASAPTEKQRLEW
VGLVESKIRILVGSLEKNEFITLAHVNPQSFPAPKENPDKEEFRTMWVIGLVFKKTENSENLSVDLTYDIQSFTDTVYRQAINSKMFEVDMKIAAMHVKRKQLHQLLPNHVLQKKKKHSTEGVKLTALND
SSLDLSMDSDNSMSVPSPTSATKTSPLNSSGSSQGRNSPAPAVTAASVTNIQATEVSVPQVNSSESSGGTSSESIPQTATQPAISPPPKPTVSRVVSSTRLVNPPPRSSGNAATSGNAATKIPTPIVGVK
RTSSPHKEESPKKTKTEEDETSEDANCLALSGHDKTEAKEQLDTETSTTQSETIQTAASLLASQKTSSTDLSDIPALPANPIPVIKNSIKLRLNR

Isoform 2:

Sequence length:	285 aa
Molecular weight:	32.626 kDa
Isoelectric point:	7.61

Summary
Polymerase that creates the 3'-poly(A) tail of mRNA's. Also required for the endoribonucleolytic cleavage reaction at some polyadenylation sites. May acquire specificity through interaction with a cleavage and polyadenylation specificity factor (CPSF) at its C-terminus.

Found in a complex with CPSF1 and FIP1L1. Interacts with FIP1L1

Polysumoylated. Varying sumolyation depending on tissue- and cell-type. Highly sumoylated in bladder and NIH 3T3 cells. Sumoylation is required for nuclear localization and enhances PAP stability. Desumoylated by SENP1. Inhibits polymerase activity.
Hyperphosphorylation on multiple CDK2 consensus and non-consensus sites in the C-terminal Ser/Thr-rich region represses PAP activity in late M-phase. Phosphorylation/dephosphorylation may regulate the interaction between PAP and CPSF.
Acetylated in the C-terminus. Acetylation decreases interaction with NUDT21 and KPNB1, and inhibits nuclear localization through inhibiting binding to the importin alpha/beta complex.

See this protein in other databases:

Literature:

Mellman DL, Gonzales ML, Song C et al. A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs. Nature 2008 451(7181):1013-7, doi: 10.1038/nature06666, PMID: 18288197.
Raabe T, Bollum FJ, Manley JL et al. Primary structure and expression of bovine poly(A) polymerase. Nature 1991 353(6341):229-34, doi: 10.1038/353229a0, PMID: 1896071.
Rapti A, Trangas T, Samiotaki M et al. The structure of the 5"-untranslated region of mammalian poly(A) polymerase-alpha mRNA suggests a mechanism of translational regulation. Mol Cell Biochem 2010 340(1-2):91-6, doi: 10.1007/s11010-010-0405-x, PMID: 20174964.
Thuresson AC, Astrom J, Astrom A et al. Multiple forms of poly(A) polymerases in human cells. Proc Natl Acad Sci U S A 1994 91(3):979-83, doi: , PMID: 8302877.

Additional computationally mapped references ...

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Poly(A) polymerase beta