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Q61183

- PAPOA_MOUSE

UniProt

Q61183 - PAPOA_MOUSE

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Protein

Poly(A) polymerase alpha

Gene

Papola

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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 By similarity.By similarity

Catalytic activityi

ATP + RNA(n) = diphosphate + RNA(n+1).

Cofactori

Binds 2 magnesium ions. Also active with manganese By similarity.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei109 – 1091ATPBy similarity
Metal bindingi113 – 1131Magnesium 1; catalyticBy similarity
Metal bindingi113 – 1131Magnesium 2; catalyticBy similarity
Metal bindingi115 – 1151Magnesium 1; catalyticBy similarity
Metal bindingi115 – 1151Magnesium 2; catalyticBy similarity
Sitei153 – 1531Interaction with RNABy similarity
Sitei158 – 1581Interaction with RNABy similarity
Metal bindingi167 – 1671Magnesium 2; catalyticBy similarity
Binding sitei167 – 1671ATPBy similarity
Binding sitei228 – 2281ATPBy similarity
Binding sitei237 – 2371ATPBy similarity
Sitei328 – 3281Interaction with RNABy similarity
Sitei399 – 3991Interaction with RNABy similarity
Sitei524 – 5241Interaction with RNABy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi100 – 1023ATPBy similarity
Nucleotide bindingi113 – 1153ATPBy similarity
Nucleotide bindingi246 – 2472ATPBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. magnesium ion binding Source: UniProtKB
  3. manganese ion binding Source: UniProtKB
  4. polynucleotide adenylyltransferase activity Source: UniProtKB
  5. RNA binding Source: UniProtKB-KW

GO - Biological processi

  1. mRNA polyadenylation Source: RefGenome
  2. mRNA splicing, via spliceosome Source: RefGenome
  3. RNA polyadenylation Source: UniProtKB
  4. termination of RNA polymerase II transcription Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

mRNA processing

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding, RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Poly(A) polymerase alpha (EC:2.7.7.19)
Short name:
PAP-alpha
Alternative name(s):
Polynucleotide adenylyltransferase
Gene namesi
Name:Papola
Synonyms:Pap, Plap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 12

Organism-specific databases

MGIiMGI:109301. Papola.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
  2. nucleus Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi444 – 4452KK → RR: Some loss of sumoylation. No change in nuclear localization. 1 Publication
Mutagenesisi537 – 5371S → A: Eliminates MAPK-mediated phosphorylation. 1 Publication
Mutagenesisi656 – 6572KK → RR: Some loss of sumoylation; Largely localized to the cytoplasm. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 739739Poly(A) polymerase alphaPRO_0000051613Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei24 – 241PhosphoserineBy similarity
Cross-linki444 – 444Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Cross-linki445 – 445Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Cross-linki506 – 506Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Cross-linki507 – 507Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Modified residuei537 – 5371Phosphoserine; by MAPK1 Publication
Modified residuei635 – 6351N6-acetyllysineBy similarity
Modified residuei644 – 6441N6-acetyllysineBy similarity
Modified residuei730 – 7301N6-acetyllysine; alternateBy similarity
Cross-linki730 – 730Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Modified residuei734 – 7341N6-acetyllysine; alternateBy similarity
Cross-linki734 – 734Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate

Post-translational modificationi

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.1 Publication
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 By similarity.By similarity
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 By similarity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ61183.
PaxDbiQ61183.
PRIDEiQ61183.

PTM databases

PhosphoSiteiQ61183.

Expressioni

Tissue specificityi

Expressed in brain, thymus, lung, kidney, bladder, testis and spleen.1 Publication

Gene expression databases

BgeeiQ61183.
CleanExiMM_PAPOLA.
ExpressionAtlasiQ61183. baseline and differential.
GenevestigatoriQ61183.

Interactioni

Subunit structurei

Monomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with FIP1L1 By similarity. Interacts with NUDT21; the interaction is diminished by acetylation. Interacts with KPNB1; the interaction promotes PAP nuclear import and is inhibited by acetylation of PAP By similarity.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000098624.

Structurei

3D structure databases

ProteinModelPortaliQ61183.
SMRiQ61183. Positions 19-498.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni508 – 643136Ser/Thr-richAdd
BLAST
Regioni671 – 73969Required for interaction with NUDT21Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi490 – 50718Nuclear localization signal 1By similarityAdd
BLAST
Motifi644 – 65916Nuclear localization signal 2By similarityAdd
BLAST

Sequence similaritiesi

Belongs to the poly(A) polymerase family.Curated

Phylogenomic databases

eggNOGiCOG5186.
GeneTreeiENSGT00390000017928.
HOGENOMiHOG000204376.
HOVERGENiHBG053502.
InParanoidiQ61183.
KOiK14376.
OMAiSPVTTQG.
OrthoDBiEOG7XH6PT.
PhylomeDBiQ61183.
TreeFamiTF300842.

Family and domain databases

Gene3Di3.30.70.590. 1 hit.
InterProiIPR002934. Nucleotidyltransferase.
IPR011068. NuclTrfase_I_C.
IPR007012. PolA_pol_cen_dom.
IPR007010. PolA_pol_RNA-bd_dom.
IPR014492. PolyA_polymerase.
[Graphical view]
PfamiPF01909. NTP_transf_2. 1 hit.
PF04928. PAP_central. 1 hit.
PF04926. PAP_RNA-bind. 1 hit.
[Graphical view]
PIRSFiPIRSF018425. PolyA_polymerase. 1 hit.
SUPFAMiSSF55003. SSF55003. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q61183-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPFPVTTQGS QQTQPPQRHY GITSPISLAA PKETDCLLTQ KLIETLKPFG
60 70 80 90 100
VFEEEEELQR RILILGKLNN LVKEWIREIS ESKNLPQSVI ENVGGKIFTF
110 120 130 140 150
GSYRLGVHTK GADIDALCVA PRHVDRSDFF TSFYDKLKLQ EEVKDLRAVE
160 170 180 190 200
EAFVPVIKLC FDGIEIDILF ARLALQTIPE DLDLRDDSLL KNLDIRCIRS
210 220 230 240 250
LNGCRVTDEI LHLVPNIDNF RLTLRAIKLW AKRHNIYSNI LGFLGGVSWA
260 270 280 290 300
MLVARTCQLY PNAIASTLVH KFFLVFSKWE WPNPVLLKQP EECNLNLPVW
310 320 330 340 350
DPRVNPSDRY HLMPIITPAY PQQNSTYNVS VSTRMVMVEE FKQGLAITDE
360 370 380 390 400
ILLSKAEWSK LFEAPNFFQK YKHYIVLLAS APTEKQRLEW VGLVESKIRI
410 420 430 440 450
LVGSLEKNEF ITLAHVNPQS FPAPKESPDR EEFRTMWVIG LVFKKTENSE
460 470 480 490 500
NLSVDLTYDI QSFTDTVYRQ AINSKMFELD MKIAAMHVKR KQLHQLLPSH
510 520 530 540 550
VLQKRKKHST EGVKLTALND SSLDLSMDSD NSMSVPSPTS AMKTSPLNSS
560 570 580 590 600
GSSQGRNSPA PAVTAASVTS IQASEVSVPQ ANSSESPGGP SSESIPQTAT
610 620 630 640 650
QPAISPPPKP TVSRVVSSTR LVNPSPRPSG NTATKVPNPI VGVKRTSSPN
660 670 680 690 700
KEESPKKTKT EEDETSEDAN CLALSGHDKT ETKEQVDLET SAVQSETVPA
710 720 730
SASLLASQKT SSTDLSDIPA LPANPIPVIK NSIKLRLNR
Length:739
Mass (Da):82,309
Last modified:January 23, 2007 - v4
Checksum:iBABE406BDF8EBEE9
GO
Isoform 2 (identifier: Q61183-2) [UniParc]FASTAAdd to Basket

Also known as: III

The sequence of this isoform differs from the canonical sequence as follows:
     373-375: HYI → YVK
     376-739: Missing.

Show »
Length:375
Mass (Da):43,110
Checksum:i09C195A8E639A0B2
GO
Isoform 3 (identifier: Q61183-3) [UniParc]FASTAAdd to Basket

Also known as: V

The sequence of this isoform differs from the canonical sequence as follows:
     305-317: NPSDRYHLMPIIT → SVLFFPLQIHTIQ
     318-375: Missing.

Show »
Length:681
Mass (Da):75,495
Checksum:iAA7913AC868F72CF
GO
Isoform 4 (identifier: Q61183-4) [UniParc]FASTAAdd to Basket

Also known as: VI

The sequence of this isoform differs from the canonical sequence as follows:
     280-293: EWPNPVLLKQPEEC → YVFRLYYNKIDCRH
     294-375: Missing.

Show »
Length:657
Mass (Da):72,874
Checksum:i8EE01C27FBF14541
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti47 – 471K → L in AAC52586. (PubMed:8628305)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei280 – 29314EWPNP…QPEEC → YVFRLYYNKIDCRH in isoform 4. 1 PublicationVSP_004527Add
BLAST
Alternative sequencei294 – 37582Missing in isoform 4. 1 PublicationVSP_004528Add
BLAST
Alternative sequencei305 – 31713NPSDR…MPIIT → SVLFFPLQIHTIQ in isoform 3. 1 PublicationVSP_004529Add
BLAST
Alternative sequencei318 – 37558Missing in isoform 3. 1 PublicationVSP_004530Add
BLAST
Alternative sequencei373 – 3753HYI → YVK in isoform 2. 1 PublicationVSP_004531
Alternative sequencei376 – 739364Missing in isoform 2. 1 PublicationVSP_004532Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U52197 mRNA. Translation: AAC52586.1.
U58134 mRNA. Translation: AAC52608.1.
U58135 mRNA. Translation: AAC52609.1.
AB086650 Genomic DNA. Translation: BAC00996.1.
CCDSiCCDS49163.1. [Q61183-1]
RefSeqiNP_035242.1. NM_011112.3. [Q61183-1]
UniGeneiMm.255877.

Genome annotation databases

EnsembliENSMUST00000021535; ENSMUSP00000021535; ENSMUSG00000021111. [Q61183-1]
ENSMUST00000109901; ENSMUSP00000105527; ENSMUSG00000021111. [Q61183-1]
ENSMUST00000166735; ENSMUSP00000128908; ENSMUSG00000021111.
GeneIDi18789.
KEGGimmu:18789.
UCSCiuc007oyv.1. mouse. [Q61183-2]
uc007oyz.2. mouse. [Q61183-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U52197 mRNA. Translation: AAC52586.1 .
U58134 mRNA. Translation: AAC52608.1 .
U58135 mRNA. Translation: AAC52609.1 .
AB086650 Genomic DNA. Translation: BAC00996.1 .
CCDSi CCDS49163.1. [Q61183-1 ]
RefSeqi NP_035242.1. NM_011112.3. [Q61183-1 ]
UniGenei Mm.255877.

3D structure databases

ProteinModelPortali Q61183.
SMRi Q61183. Positions 19-498.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000098624.

PTM databases

PhosphoSitei Q61183.

Proteomic databases

MaxQBi Q61183.
PaxDbi Q61183.
PRIDEi Q61183.

Protocols and materials databases

DNASUi 18789.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000021535 ; ENSMUSP00000021535 ; ENSMUSG00000021111 . [Q61183-1 ]
ENSMUST00000109901 ; ENSMUSP00000105527 ; ENSMUSG00000021111 . [Q61183-1 ]
ENSMUST00000166735 ; ENSMUSP00000128908 ; ENSMUSG00000021111 .
GeneIDi 18789.
KEGGi mmu:18789.
UCSCi uc007oyv.1. mouse. [Q61183-2 ]
uc007oyz.2. mouse. [Q61183-1 ]

Organism-specific databases

CTDi 10914.
MGIi MGI:109301. Papola.

Phylogenomic databases

eggNOGi COG5186.
GeneTreei ENSGT00390000017928.
HOGENOMi HOG000204376.
HOVERGENi HBG053502.
InParanoidi Q61183.
KOi K14376.
OMAi SPVTTQG.
OrthoDBi EOG7XH6PT.
PhylomeDBi Q61183.
TreeFami TF300842.

Miscellaneous databases

ChiTaRSi PAPOLA. mouse.
NextBioi 295064.
PROi Q61183.
SOURCEi Search...

Gene expression databases

Bgeei Q61183.
CleanExi MM_PAPOLA.
ExpressionAtlasi Q61183. baseline and differential.
Genevestigatori Q61183.

Family and domain databases

Gene3Di 3.30.70.590. 1 hit.
InterProi IPR002934. Nucleotidyltransferase.
IPR011068. NuclTrfase_I_C.
IPR007012. PolA_pol_cen_dom.
IPR007010. PolA_pol_RNA-bd_dom.
IPR014492. PolyA_polymerase.
[Graphical view ]
Pfami PF01909. NTP_transf_2. 1 hit.
PF04928. PAP_central. 1 hit.
PF04926. PAP_RNA-bind. 1 hit.
[Graphical view ]
PIRSFi PIRSF018425. PolyA_polymerase. 1 hit.
SUPFAMi SSF55003. SSF55003. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Complex alternative RNA processing generates an unexpected diversity of poly(A) polymerase isoforms."
    Zhao W., Manley J.L.
    Mol. Cell. Biol. 16:2378-2386(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
    Tissue: Brain.
  2. "Regulation of spermatogenesis by testis-specific, cytoplasmic poly(A) polymerase TPAP."
    Kashiwabara S., Noguchi J., Zhuang T., Ohmura K., Honda A., Sugiura S., Miyamoto K., Takahashi S., Inoue K., Ogura A., Baba T.
    Science 298:1999-2002(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    Strain: 129/SvJ.
  3. "Interaction of poly(A) polymerase with the 25-kDa subunit of cleavage factor I."
    Kim H., Lee Y.
    Biochem. Biophys. Res. Commun. 289:513-518(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NUDT21.
  4. "Sumoylation regulates multiple aspects of mammalian poly(A) polymerase function."
    Vethantham V., Rao N., Manley J.L.
    Genes Dev. 22:499-511(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-444; LYS-445; LYS-506; LYS-507; LYS-730 AND LYS-734, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, MUTAGENESIS OF 444-LYS-LYS-445; 506-LYS-LYS-507 AND 656-LYS-LYS-657.
  5. "ERK is a novel regulatory kinase for poly(A) polymerase."
    Lee S.-H., Choi H.-S., Kim H., Lee Y.
    Nucleic Acids Res. 36:803-813(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-537, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-537.

Entry informationi

Entry nameiPAPOA_MOUSE
AccessioniPrimary (citable) accession number: Q61183
Secondary accession number(s): Q61208, Q61209, Q8K4X2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: January 23, 2007
Last modified: October 29, 2014
This is version 111 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3