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Q61183

- PAPOA_MOUSE

UniProt

Q61183 - PAPOA_MOUSE

Protein

Poly(A) polymerase alpha

Gene

Papola

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 4 (23 Jan 2007)
      Previous versions | rss
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    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

    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

    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. 2 Publications
    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

    ArrayExpressiQ61183.
    BgeeiQ61183.
    CleanExiMM_PAPOLA.
    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

    MPFPVTTQGS QQTQPPQRHY GITSPISLAA PKETDCLLTQ KLIETLKPFG    50
    VFEEEEELQR RILILGKLNN LVKEWIREIS ESKNLPQSVI ENVGGKIFTF 100
    GSYRLGVHTK GADIDALCVA PRHVDRSDFF TSFYDKLKLQ EEVKDLRAVE 150
    EAFVPVIKLC FDGIEIDILF ARLALQTIPE DLDLRDDSLL KNLDIRCIRS 200
    LNGCRVTDEI LHLVPNIDNF RLTLRAIKLW AKRHNIYSNI LGFLGGVSWA 250
    MLVARTCQLY PNAIASTLVH KFFLVFSKWE WPNPVLLKQP EECNLNLPVW 300
    DPRVNPSDRY HLMPIITPAY PQQNSTYNVS VSTRMVMVEE FKQGLAITDE 350
    ILLSKAEWSK LFEAPNFFQK YKHYIVLLAS APTEKQRLEW VGLVESKIRI 400
    LVGSLEKNEF ITLAHVNPQS FPAPKESPDR EEFRTMWVIG LVFKKTENSE 450
    NLSVDLTYDI QSFTDTVYRQ AINSKMFELD MKIAAMHVKR KQLHQLLPSH 500
    VLQKRKKHST EGVKLTALND SSLDLSMDSD NSMSVPSPTS AMKTSPLNSS 550
    GSSQGRNSPA PAVTAASVTS IQASEVSVPQ ANSSESPGGP SSESIPQTAT 600
    QPAISPPPKP TVSRVVSSTR LVNPSPRPSG NTATKVPNPI VGVKRTSSPN 650
    KEESPKKTKT EEDETSEDAN CLALSGHDKT ETKEQVDLET SAVQSETVPA 700
    SASLLASQKT SSTDLSDIPA LPANPIPVIK NSIKLRLNR 739
    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

    ArrayExpressi Q61183.
    Bgeei Q61183.
    CleanExi MM_PAPOLA.
    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 1, 2014
    This is version 110 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