PAPOA_MOUSE
ID PAPOA_MOUSE Reviewed; 739 AA.
AC Q61183; Q61208; Q61209; Q8K4X2;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Poly(A) polymerase alpha;
DE Short=PAP-alpha;
DE EC=2.7.7.19 {ECO:0000269|PubMed:18084034};
DE AltName: Full=Polynucleotide adenylyltransferase;
GN Name=Papola; Synonyms=Pap, Plap;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Brain;
RX PubMed=8628305; DOI=10.1128/mcb.16.5.2378;
RA Zhao W., Manley J.L.;
RT "Complex alternative RNA processing generates an unexpected diversity of
RT poly(A) polymerase isoforms.";
RL Mol. Cell. Biol. 16:2378-2386(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC STRAIN=129/SvJ;
RX PubMed=12471261; DOI=10.1126/science.1074632;
RA Kashiwabara S., Noguchi J., Zhuang T., Ohmura K., Honda A., Sugiura S.,
RA Miyamoto K., Takahashi S., Inoue K., Ogura A., Baba T.;
RT "Regulation of spermatogenesis by testis-specific, cytoplasmic poly(A)
RT polymerase TPAP.";
RL Science 298:1999-2002(2002).
RN [3]
RP INTERACTION WITH NUDT21.
RX PubMed=11716503; DOI=10.1006/bbrc.2001.5992;
RA Kim H., Lee Y.;
RT "Interaction of poly(A) polymerase with the 25-kDa subunit of cleavage
RT factor I.";
RL Biochem. Biophys. Res. Commun. 289:513-518(2001).
RN [4]
RP SUMOYLATION AT LYS-444; LYS-445; LYS-506; LYS-507; LYS-730 AND LYS-734,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, AND MUTAGENESIS OF
RP 444-LYS-LYS-445; 506-LYS-LYS-507 AND 656-LYS-LYS-657.
RX PubMed=18281463; DOI=10.1101/gad.1628208;
RA Vethantham V., Rao N., Manley J.L.;
RT "Sumoylation regulates multiple aspects of mammalian poly(A) polymerase
RT function.";
RL Genes Dev. 22:499-511(2008).
RN [5]
RP PHOSPHORYLATION AT SER-537, FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND MUTAGENESIS OF SER-537.
RX PubMed=18084034; DOI=10.1093/nar/gkm1091;
RA Lee S.-H., Choi H.-S., Kim H., Lee Y.;
RT "ERK is a novel regulatory kinase for poly(A) polymerase.";
RL Nucleic Acids Res. 36:803-813(2008).
RN [6]
RP INTERACTION WITH FIP1L1.
RX PubMed=19224921; DOI=10.1074/jbc.m807136200;
RA Kiefer H., Mizutani A., Iemura S., Natsume T., Ando H., Kuroda Y.,
RA Mikoshiba K.;
RT "Inositol 1,4,5-triphosphate receptor-binding protein released with
RT inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA
RT 3' processing machinery in a phosphorylation-dependent manner and inhibits
RT polyadenylation.";
RL J. Biol. Chem. 284:10694-10705(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Polymerase that creates the 3'-poly(A) tail of mRNA's. Also
CC required for the endoribonucleolytic cleavage reaction at some
CC polyadenylation sites. May acquire specificity through interaction with
CC a cleavage and polyadenylation specificity factor (CPSF) at its C-
CC terminus. {ECO:0000250|UniProtKB:P51003, ECO:0000269|PubMed:18084034,
CC ECO:0000269|PubMed:18281463}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide;
CC Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395,
CC ChEBI:CHEBI:173115; EC=2.7.7.19;
CC Evidence={ECO:0000269|PubMed:18084034};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium ions. Also active with manganese. {ECO:0000250};
CC -!- SUBUNIT: Monomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA.
CC Interacts with AHCYL1 and FIP1L1; the interaction with AHCYL1 seems to
CC increase interaction with FIP1L1 (PubMed:19224921). Interacts with
CC NUDT21; the interaction is diminished by acetylation. Interacts with
CC KPNB1; the interaction promotes PAP nuclear import and is inhibited by
CC acetylation of PAP (By similarity). {ECO:0000250|UniProtKB:P25500,
CC ECO:0000250|UniProtKB:P51003, ECO:0000269|PubMed:19224921}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q61183-1; Sequence=Displayed;
CC Name=2; Synonyms=III;
CC IsoId=Q61183-2; Sequence=VSP_004531, VSP_004532;
CC Name=3; Synonyms=V;
CC IsoId=Q61183-3; Sequence=VSP_004529, VSP_004530;
CC Name=4; Synonyms=VI;
CC IsoId=Q61183-4; Sequence=VSP_004527, VSP_004528;
CC -!- TISSUE SPECIFICITY: Expressed in brain, thymus, lung, kidney, bladder,
CC testis and spleen. {ECO:0000269|PubMed:18281463}.
CC -!- PTM: Polysumoylated. Varying sumolyation depending on tissue- and cell-
CC type. Highly sumoylated in bladder and NIH 3T3 cells. Sumoylation is
CC required for nuclear localization and enhances PAP stability.
CC Desumoylated by SENP1. Inhibits polymerase activity.
CC {ECO:0000269|PubMed:18281463}.
CC -!- PTM: Hyperphosphorylation on multiple CDK2 consensus and non-consensus
CC sites in the C-terminal Ser/Thr-rich region represses PAP activity in
CC late M-phase. Phosphorylation/dephosphorylation may regulate the
CC interaction between PAP and CPSF (By similarity). {ECO:0000250}.
CC -!- PTM: Acetylated in the C-terminus. Acetylation decreases interaction
CC with NUDT21 and KPNB1, and inhibits nuclear localization through
CC inhibiting binding to the importin alpha/beta complex (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the poly(A) polymerase family. {ECO:0000305}.
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DR EMBL; U52197; AAC52586.1; -; mRNA.
DR EMBL; U58134; AAC52608.1; -; mRNA.
DR EMBL; U58135; AAC52609.1; -; mRNA.
DR EMBL; AB086650; BAC00996.1; -; Genomic_DNA.
DR CCDS; CCDS49163.1; -. [Q61183-1]
DR RefSeq; NP_035242.1; NM_011112.4. [Q61183-1]
DR AlphaFoldDB; Q61183; -.
DR SMR; Q61183; -.
DR BioGRID; 202227; 1.
DR ELM; Q61183; -.
DR STRING; 10090.ENSMUSP00000105527; -.
DR iPTMnet; Q61183; -.
DR PhosphoSitePlus; Q61183; -.
DR EPD; Q61183; -.
DR jPOST; Q61183; -.
DR MaxQB; Q61183; -.
DR PaxDb; Q61183; -.
DR PeptideAtlas; Q61183; -.
DR PRIDE; Q61183; -.
DR ProteomicsDB; 287880; -. [Q61183-1]
DR ProteomicsDB; 287881; -. [Q61183-2]
DR ProteomicsDB; 287882; -. [Q61183-3]
DR ProteomicsDB; 287883; -. [Q61183-4]
DR Antibodypedia; 86; 148 antibodies from 22 providers.
DR DNASU; 18789; -.
DR Ensembl; ENSMUST00000021535; ENSMUSP00000021535; ENSMUSG00000021111. [Q61183-1]
DR Ensembl; ENSMUST00000109901; ENSMUSP00000105527; ENSMUSG00000021111. [Q61183-1]
DR GeneID; 18789; -.
DR KEGG; mmu:18789; -.
DR UCSC; uc007oyv.1; mouse. [Q61183-2]
DR UCSC; uc007oyz.2; mouse. [Q61183-1]
DR CTD; 10914; -.
DR MGI; MGI:109301; Papola.
DR VEuPathDB; HostDB:ENSMUSG00000021111; -.
DR eggNOG; KOG2245; Eukaryota.
DR GeneTree; ENSGT00940000154598; -.
DR InParanoid; Q61183; -.
DR OMA; PAYPAMC; -.
DR OrthoDB; 326577at2759; -.
DR PhylomeDB; Q61183; -.
DR TreeFam; TF300842; -.
DR Reactome; R-MMU-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-MMU-72187; mRNA 3'-end processing.
DR Reactome; R-MMU-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-MMU-77595; Processing of Intronless Pre-mRNAs.
DR BioGRID-ORCS; 18789; 10 hits in 43 CRISPR screens.
DR ChiTaRS; Papola; mouse.
DR PRO; PR:Q61183; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q61183; protein.
DR Bgee; ENSMUSG00000021111; Expressed in undifferentiated genital tubercle and 276 other tissues.
DR ExpressionAtlas; Q61183; baseline and differential.
DR Genevisible; Q61183; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0004652; F:polynucleotide adenylyltransferase activity; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
DR GO; GO:0031440; P:regulation of mRNA 3'-end processing; ISS:UniProtKB.
DR GO; GO:0043631; P:RNA polyadenylation; IDA:MGI.
DR Gene3D; 3.30.460.10; -; 1.
DR InterPro; IPR043519; NT_sf.
DR InterPro; IPR011068; NuclTrfase_I-like_C.
DR InterPro; IPR007012; PolA_pol_cen_dom.
DR InterPro; IPR007010; PolA_pol_RNA-bd_dom.
DR InterPro; IPR014492; PolyA_polymerase.
DR InterPro; IPR002934; Polymerase_NTP_transf_dom.
DR Pfam; PF01909; NTP_transf_2; 1.
DR Pfam; PF04928; PAP_central; 1.
DR Pfam; PF04926; PAP_RNA-bind; 1.
DR PIRSF; PIRSF018425; PolyA_polymerase; 1.
DR SUPFAM; SSF55003; SSF55003; 1.
DR SUPFAM; SSF81301; SSF81301; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Isopeptide bond; Magnesium;
KW Manganese; Metal-binding; mRNA processing; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; Transferase;
KW Ubl conjugation.
FT CHAIN 1..739
FT /note="Poly(A) polymerase alpha"
FT /id="PRO_0000051613"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..643
FT /note="Ser/Thr-rich"
FT REGION 523..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..739
FT /note="Required for interaction with NUDT21"
FT /evidence="ECO:0000269|PubMed:11716503"
FT MOTIF 490..507
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 644..659
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 523..600
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 649..666
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 687..718
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 100..102
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 113..115
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 237
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 246..247
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 153
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250"
FT SITE 158
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250"
FT SITE 328
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250"
FT SITE 399
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250"
FT SITE 524
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51003"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 537
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:18084034"
FT MOD_RES 558
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51003"
FT MOD_RES 635
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25500"
FT MOD_RES 644
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25500"
FT MOD_RES 730
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25500"
FT MOD_RES 732
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51003"
FT MOD_RES 734
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25500"
FT CROSSLNK 444
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:18281463"
FT CROSSLNK 445
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:18281463"
FT CROSSLNK 506
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:18281463"
FT CROSSLNK 507
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:18281463"
FT CROSSLNK 730
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 734
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT VAR_SEQ 280..293
FT /note="EWPNPVLLKQPEEC -> YVFRLYYNKIDCRH (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:8628305"
FT /id="VSP_004527"
FT VAR_SEQ 294..375
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:8628305"
FT /id="VSP_004528"
FT VAR_SEQ 305..317
FT /note="NPSDRYHLMPIIT -> SVLFFPLQIHTIQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8628305"
FT /id="VSP_004529"
FT VAR_SEQ 318..375
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8628305"
FT /id="VSP_004530"
FT VAR_SEQ 373..375
FT /note="HYI -> YVK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8628305"
FT /id="VSP_004531"
FT VAR_SEQ 376..739
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8628305"
FT /id="VSP_004532"
FT MUTAGEN 444..445
FT /note="KK->RR: Some loss of sumoylation. No change in
FT nuclear localization."
FT /evidence="ECO:0000269|PubMed:18281463"
FT MUTAGEN 537
FT /note="S->A: Eliminates MAPK-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:18084034"
FT MUTAGEN 656..657
FT /note="KK->RR: Some loss of sumoylation; Largely localized
FT to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:18281463"
FT CONFLICT 47
FT /note="K -> L (in Ref. 1; AAC52586)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 739 AA; 82309 MW; BABE406BDF8EBEE9 CRC64;
MPFPVTTQGS QQTQPPQRHY GITSPISLAA PKETDCLLTQ KLIETLKPFG VFEEEEELQR
RILILGKLNN LVKEWIREIS ESKNLPQSVI ENVGGKIFTF GSYRLGVHTK GADIDALCVA
PRHVDRSDFF TSFYDKLKLQ EEVKDLRAVE EAFVPVIKLC FDGIEIDILF ARLALQTIPE
DLDLRDDSLL KNLDIRCIRS LNGCRVTDEI LHLVPNIDNF RLTLRAIKLW AKRHNIYSNI
LGFLGGVSWA MLVARTCQLY PNAIASTLVH KFFLVFSKWE WPNPVLLKQP EECNLNLPVW
DPRVNPSDRY HLMPIITPAY PQQNSTYNVS VSTRMVMVEE FKQGLAITDE ILLSKAEWSK
LFEAPNFFQK YKHYIVLLAS APTEKQRLEW VGLVESKIRI LVGSLEKNEF ITLAHVNPQS
FPAPKESPDR EEFRTMWVIG LVFKKTENSE NLSVDLTYDI QSFTDTVYRQ AINSKMFELD
MKIAAMHVKR KQLHQLLPSH VLQKRKKHST EGVKLTALND SSLDLSMDSD NSMSVPSPTS
AMKTSPLNSS GSSQGRNSPA PAVTAASVTS IQASEVSVPQ ANSSESPGGP SSESIPQTAT
QPAISPPPKP TVSRVVSSTR LVNPSPRPSG NTATKVPNPI VGVKRTSSPN KEESPKKTKT
EEDETSEDAN CLALSGHDKT ETKEQVDLET SAVQSETVPA SASLLASQKT SSTDLSDIPA
LPANPIPVIK NSIKLRLNR
