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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)DescriptionActionsGraphical viewLength
Binding sitei109ATPBy similarity1
Metal bindingi113Magnesium 1; catalyticBy similarity1
Metal bindingi113Magnesium 2; catalyticBy similarity1
Metal bindingi115Magnesium 1; catalyticBy similarity1
Metal bindingi115Magnesium 2; catalyticBy similarity1
Metal bindingi167Magnesium 2; catalyticBy similarity1
Binding sitei167ATPBy similarity1
Binding sitei228ATPBy similarity1
Binding sitei237ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi100 – 102ATPBy similarity3
Nucleotide bindingi113 – 115ATPBy similarity3
Nucleotide bindingi246 – 247ATPBy similarity2

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

BioCyciZFISH:HS01674-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
R-HSA-77595. Processing of Intronless Pre-mRNAs.
SIGNORiP51003.

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
Proteomesi
  • UP000005640 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

DisGeNETi10914.
OpenTargetsiENSG00000090060.
PharmGKBiPA32932.

Polymorphism and mutation databases

BioMutaiPAPOLA.
DMDMi59803092.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000516122 – 745Poly(A) polymerase alphaAdd BLAST744

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineCombined sources1
Modified residuei24PhosphoserineCombined sources1
Cross-linki444Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Cross-linki445Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Cross-linki506Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Cross-linki507Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Modified residuei537PhosphoserineBy similarity1
Modified residuei558PhosphoserineCombined sources1
Modified residuei641N6-acetyllysineBy similarity1
Modified residuei650N6-acetyllysineBy similarity1
Modified residuei736N6-acetyllysine; alternateBy similarity1
Cross-linki736Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Modified residuei738PhosphoserineCombined sources1
Modified residuei740N6-acetyllysine; alternateBy similarity1
Cross-linki740Glycyl 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

EPDiP51003.
MaxQBiP51003.
PaxDbiP51003.
PeptideAtlasiP51003.
PRIDEiP51003.

PTM databases

iPTMnetiP51003.
PhosphoSitePlusiP51003.

Expressioni

Gene expression databases

BgeeiENSG00000090060.
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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei153Interaction with RNABy similarity1
Sitei158Interaction with RNABy similarity1
Sitei328Interaction with RNABy similarity1
Sitei399Interaction with RNABy similarity1
Sitei524Interaction with RNABy similarity1

Protein-protein interaction databases

BioGridi116119. 49 interactors.
DIPiDIP-27610N.
DIP-40865N.
IntActiP51003. 10 interactors.
MINTiMINT-125699.
STRINGi9606.ENSP00000216277.

Structurei

3D structure databases

ProteinModelPortaliP51003.
SMRiP51003.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni508 – 643Ser/Thr-richAdd BLAST136
Regioni677 – 745Required for interaction with NUDT21Add BLAST69

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi490 – 507Nuclear localization signal 1By similarityAdd BLAST18
Motifi650 – 665Nuclear localization signal 2By similarityAdd BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi53 – 57Poly-Glu5
Compositional biasi504 – 507Poly-Lys4

Sequence similaritiesi

Belongs to the poly(A) polymerase family.Curated

Phylogenomic databases

eggNOGiKOG2245. Eukaryota.
COG5186. LUCA.
GeneTreeiENSGT00390000017928.
HOVERGENiHBG053502.
InParanoidiP51003.
KOiK14376.
OMAiDMKIAAR.
OrthoDBiEOG091G0571.
PhylomeDBiP51003.
TreeFamiTF300842.

Family and domain databases

Gene3Di3.30.70.590. 1 hit.
InterProiIPR011068. NuclTrfase_I_C.
IPR007012. PolA_pol_cen_dom.
IPR007010. PolA_pol_RNA-bd_dom.
IPR014492. PolyA_polymerase.
IPR002934. Polymerase_NTP_transf_dom.
[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.

Sequence processingi: The displayed sequence is further processed into a mature form.

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)DescriptionActionsGraphical viewLength
Sequence conflicti2 – 3PF → GTSNSPGHSSFSAPSTKKIK TTRKQNIAWC in CAD62628 (Ref. 2) Curated2
Sequence conflicti204 – 238CRVTD…HNIYS → MRKPTSFCVLQFLSDISCFY TSFVLKLFIAILLTQ in CAD61935 (Ref. 2) CuratedAdd BLAST35

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012895280 – 285EWPNPV → YVFRLY in isoform 2. 2 Publications6
Alternative sequenceiVSP_012896286 – 745Missing in isoform 2. 2 PublicationsAdd BLAST460

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. [P51003-1]
ENST00000557320; ENSP00000450437; ENSG00000090060. [P51003-2]
GeneIDi10914.
KEGGihsa:10914.
UCSCiuc001yfo.5. 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116119. 49 interactors.
DIPiDIP-27610N.
DIP-40865N.
IntActiP51003. 10 interactors.
MINTiMINT-125699.
STRINGi9606.ENSP00000216277.

PTM databases

iPTMnetiP51003.
PhosphoSitePlusiP51003.

Polymorphism and mutation databases

BioMutaiPAPOLA.
DMDMi59803092.

Proteomic databases

EPDiP51003.
MaxQBiP51003.
PaxDbiP51003.
PeptideAtlasiP51003.
PRIDEiP51003.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216277; ENSP00000216277; ENSG00000090060. [P51003-1]
ENST00000557320; ENSP00000450437; ENSG00000090060. [P51003-2]
GeneIDi10914.
KEGGihsa:10914.
UCSCiuc001yfo.5. human. [P51003-1]

Organism-specific databases

CTDi10914.
DisGeNETi10914.
GeneCardsiPAPOLA.
HGNCiHGNC:14981. PAPOLA.
HPAiHPA001788.
MIMi605553. gene.
neXtProtiNX_P51003.
OpenTargetsiENSG00000090060.
PharmGKBiPA32932.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2245. Eukaryota.
COG5186. LUCA.
GeneTreeiENSGT00390000017928.
HOVERGENiHBG053502.
InParanoidiP51003.
KOiK14376.
OMAiDMKIAAR.
OrthoDBiEOG091G0571.
PhylomeDBiP51003.
TreeFamiTF300842.

Enzyme and pathway databases

BioCyciZFISH:HS01674-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
R-HSA-77595. Processing of Intronless Pre-mRNAs.
SIGNORiP51003.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000090060.
CleanExiHS_PAPOLA.
ExpressionAtlasiP51003. baseline and differential.
GenevisibleiP51003. HS.

Family and domain databases

Gene3Di3.30.70.590. 1 hit.
InterProiIPR011068. NuclTrfase_I_C.
IPR007012. PolA_pol_cen_dom.
IPR007010. PolA_pol_RNA-bd_dom.
IPR014492. PolyA_polymerase.
IPR002934. Polymerase_NTP_transf_dom.
[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...

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: November 2, 2016
This is version 165 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

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 one 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.