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Protein

Poly(A) polymerase alpha

Gene

PAPOLA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.1 Publication

Catalytic activityi

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

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium ions. Also active with manganese.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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

mRNA processing

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiREACT_1096. Processing of Intronless Pre-mRNAs.
REACT_1849. mRNA 3'-end processing.
REACT_387. Cleavage of Growing Transcript in the Termination Region.
REACT_467. mRNA Splicing - Major Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Poly(A) polymerase alpha (EC:2.7.7.19)
Short name:
PAP-alpha
Alternative name(s):
Polynucleotide adenylyltransferase alpha
Gene namesi
Name:PAPOLA
Synonyms:PAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:14981. PAPOLA.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: The 90 kDa form is nuclear while the 100 kDa and the 106 kDa forms are both nuclear and cytoplasmic.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA32932.

Polymorphism and mutation databases

BioMutaiPAPOLA.
DMDMi59803092.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 745745Poly(A) polymerase alphaPRO_0000051612Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei24 – 241Phosphoserine2 Publications
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 – 5371PhosphoserineBy similarity
Modified residuei558 – 5581Phosphoserine1 Publication
Modified residuei641 – 6411N6-acetyllysineBy similarity
Modified residuei650 – 6501N6-acetyllysineBy similarity
Modified residuei736 – 7361N6-acetyllysine; alternateBy similarity
Cross-linki736 – 736Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Modified residuei740 – 7401N6-acetyllysine; alternateBy similarity
Cross-linki740 – 740Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity

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 (By similarity).By similarity
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

MaxQBiP51003.
PaxDbiP51003.
PeptideAtlasiP51003.
PRIDEiP51003.

PTM databases

PhosphoSiteiP51003.

Expressioni

Gene expression databases

BgeeiP51003.
CleanExiHS_PAPOLA.
ExpressionAtlasiP51003. baseline and differential.
GenevisibleiP51003. HS.

Organism-specific databases

HPAiHPA001788.

Interactioni

Subunit structurei

Monomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with AHCYL1 and FIP1L1; the interaction with AHCYL1 seems to increase interaction with FIP1L1 (PubMed:19224921). 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 similarity1 Publication

Protein-protein interaction databases

BioGridi116119. 29 interactions.
DIPiDIP-27610N.
DIP-40865N.
IntActiP51003. 8 interactions.
MINTiMINT-125699.
STRINGi9606.ENSP00000216277.

Structurei

3D structure databases

ProteinModelPortaliP51003.
SMRiP51003. Positions 19-498.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni508 – 643136Ser/Thr-richAdd
BLAST
Regioni677 – 74569Required for interaction with NUDT21Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi490 – 50718Nuclear localization signal 1By similarityAdd
BLAST
Motifi650 – 66516Nuclear localization signal 2By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi53 – 575Poly-Glu
Compositional biasi504 – 5074Poly-Lys

Sequence similaritiesi

Belongs to the poly(A) polymerase family.Curated

Phylogenomic databases

eggNOGiCOG5186.
GeneTreeiENSGT00390000017928.
HOVERGENiHBG053502.
InParanoidiP51003.
KOiK14376.
OMAiEEYRTMW.
OrthoDBiEOG7XH6PT.
PhylomeDBiP51003.
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]
PANTHERiPTHR10682. PTHR10682. 1 hit.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51003-1) [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 QQTQPPQKHY GITSPISLAA PKETDCVLTQ 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 FPAPKENPDK EEFRTMWVIG LVFKKTENSE
460 470 480 490 500
NLSVDLTYDI QSFTDTVYRQ AINSKMFEVD MKIAAMHVKR KQLHQLLPNH
510 520 530 540 550
VLQKKKKHST EGVKLTALND SSLDLSMDSD NSMSVPSPTS ATKTSPLNSS
560 570 580 590 600
GSSQGRNSPA PAVTAASVTN IQATEVSVPQ VNSSESSGGT SSESIPQTAT
610 620 630 640 650
QPAISPPPKP TVSRVVSSTR LVNPPPRSSG NAATSGNAAT KIPTPIVGVK
660 670 680 690 700
RTSSPHKEES PKKTKTEEDE TSEDANCLAL SGHDKTEAKE QLDTETSTTQ
710 720 730 740
SETIQTAASL LASQKTSSTD LSDIPALPAN PIPVIKNSIK LRLNR
Length:745
Mass (Da):82,843
Last modified:January 23, 2007 - v4
Checksum:i14A00CCCDAD9B374
GO
Isoform 2 (identifier: P51003-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     280-285: EWPNPV → YVFRLY
     286-745: Missing.

Show »
Length:285
Mass (Da):32,626
Checksum:i5967D93F0375C54C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 32PF → GTSNSPGHSSFSAPSTKKIK TTRKQNIAWC in CAD62628 (Ref. 2) Curated
Sequence conflicti204 – 23835CRVTD…HNIYS → MRKPTSFCVLQFLSDISCFY TSFVLKLFIAILLTQ in CAD61935 (Ref. 2) CuratedAdd
BLAST

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei280 – 2856EWPNPV → YVFRLY in isoform 2. 2 PublicationsVSP_012895
Alternative sequencei286 – 745460Missing in isoform 2. 2 PublicationsVSP_012896Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC000927 mRNA. Translation: AAH00927.1.
BC036014 mRNA. Translation: AAH36014.1.
BX248301 mRNA. Translation: CAD62628.1.
BX248753 mRNA. Translation: CAD66560.1.
BX161482 mRNA. Translation: CAD61935.1.
X76770 mRNA. No translation available.
CCDSiCCDS58334.1. [P51003-2]
CCDS9946.1. [P51003-1]
RefSeqiNP_001238935.1. NM_001252006.1. [P51003-2]
NP_001238936.1. NM_001252007.1.
NP_001280556.1. NM_001293627.1.
NP_001280557.1. NM_001293628.1.
NP_001280561.1. NM_001293632.1.
NP_116021.2. NM_032632.4. [P51003-1]
UniGeneiHs.253726.

Genome annotation databases

EnsembliENST00000216277; ENSP00000216277; ENSG00000090060.
ENST00000557320; ENSP00000450437; ENSG00000090060. [P51003-2]
GeneIDi10914.
KEGGihsa:10914.
UCSCiuc001yfo.3. human. [P51003-2]
uc001yfq.3. human. [P51003-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC000927 mRNA. Translation: AAH00927.1.
BC036014 mRNA. Translation: AAH36014.1.
BX248301 mRNA. Translation: CAD62628.1.
BX248753 mRNA. Translation: CAD66560.1.
BX161482 mRNA. Translation: CAD61935.1.
X76770 mRNA. No translation available.
CCDSiCCDS58334.1. [P51003-2]
CCDS9946.1. [P51003-1]
RefSeqiNP_001238935.1. NM_001252006.1. [P51003-2]
NP_001238936.1. NM_001252007.1.
NP_001280556.1. NM_001293627.1.
NP_001280557.1. NM_001293628.1.
NP_001280561.1. NM_001293632.1.
NP_116021.2. NM_032632.4. [P51003-1]
UniGeneiHs.253726.

3D structure databases

ProteinModelPortaliP51003.
SMRiP51003. Positions 19-498.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116119. 29 interactions.
DIPiDIP-27610N.
DIP-40865N.
IntActiP51003. 8 interactions.
MINTiMINT-125699.
STRINGi9606.ENSP00000216277.

PTM databases

PhosphoSiteiP51003.

Polymorphism and mutation databases

BioMutaiPAPOLA.
DMDMi59803092.

Proteomic databases

MaxQBiP51003.
PaxDbiP51003.
PeptideAtlasiP51003.
PRIDEiP51003.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216277; ENSP00000216277; ENSG00000090060.
ENST00000557320; ENSP00000450437; ENSG00000090060. [P51003-2]
GeneIDi10914.
KEGGihsa:10914.
UCSCiuc001yfo.3. human. [P51003-2]
uc001yfq.3. human. [P51003-1]

Organism-specific databases

CTDi10914.
GeneCardsiGC14P096969.
HGNCiHGNC:14981. PAPOLA.
HPAiHPA001788.
MIMi605553. gene.
neXtProtiNX_P51003.
PharmGKBiPA32932.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5186.
GeneTreeiENSGT00390000017928.
HOVERGENiHBG053502.
InParanoidiP51003.
KOiK14376.
OMAiEEYRTMW.
OrthoDBiEOG7XH6PT.
PhylomeDBiP51003.
TreeFamiTF300842.

Enzyme and pathway databases

ReactomeiREACT_1096. Processing of Intronless Pre-mRNAs.
REACT_1849. mRNA 3'-end processing.
REACT_387. Cleavage of Growing Transcript in the Termination Region.
REACT_467. mRNA Splicing - Major Pathway.

Miscellaneous databases

ChiTaRSiPAPOLA. human.
GeneWikiiPAPOLA.
GenomeRNAii10914.
NextBioi41453.
PROiP51003.
SOURCEiSearch...

Gene expression databases

BgeeiP51003.
CleanExiHS_PAPOLA.
ExpressionAtlasiP51003. baseline and differential.
GenevisibleiP51003. HS.

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]
PANTHERiPTHR10682. PTHR10682. 1 hit.
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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Placenta and Testis.
  2. "Full-length cDNA libraries and normalization."
    Li W.B., Gruber C., Jessee J., Polayes D.
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-725 (ISOFORMS 1 AND 2).
    Tissue: B-cell and Fetal brain.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-660 (ISOFORM 1).
  4. "Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization."
    Dettwiler S., Aringhieri C., Cardinale S., Keller W., Barabino S.M.
    J. Biol. Chem. 279:35788-35797(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NUDT21/CPSF5.
  5. "Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase."
    Kaufmann I., Martin G., Friedlein A., Langen H., Keller W.
    EMBO J. 23:616-626(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH CPSF1 AND FIP1L1, INTERACTION WITH FIP1L1.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. "Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation."
    Kiefer H., Mizutani A., Iemura S., Natsume T., Ando H., Kuroda Y., Mikoshiba K.
    J. Biol. Chem. 284:10694-10705(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AHCYL1 AND FIP1L1, FUNCTION.
  8. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  9. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-558, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiPAPOA_HUMAN
AccessioniPrimary (citable) accession number: P51003
Secondary accession number(s): Q86SX4
, Q86TV0, Q8IYF5, Q9BVU2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: July 22, 2015
This is version 152 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.