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Protein

Poly(A) polymerase alpha

Gene

PAPOLA

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

Keywordsi

Molecular functionRNA-binding, Transferase
Biological processmRNA processing
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000090060.17
HGNCiHGNC:14981 PAPOLA
MIMi605553 gene
neXtProtiNX_P51003

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi10914
OpenTargetsiENSG00000090060
PharmGKBiPA32932

Chemistry databases

DrugBankiDB02153 3-Sulfinoalanine
DB01860 Cordycepin Triphosphate
DB03896 Triphospate

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
ProteomicsDBi56276
56277 [P51003-2]

PTM databases

iPTMnetiP51003
PhosphoSitePlusiP51003

Expressioni

Gene expression databases

BgeeiENSG00000090060 Expressed in 232 organ(s), highest expression level in testis
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, 50 interactors
CORUMiP51003
DIPiDIP-27610N
DIP-40865N
IntActiP51003, 13 interactors
MINTiP51003
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
OMAiQLEWCGL
OrthoDBiEOG091G0571
PhylomeDBiP51003
TreeFamiTF300842

Family and domain databases

InterProiView protein in InterPro
IPR011068 NuclTrfase_I-like_C
IPR007012 PolA_pol_cen_dom
IPR007010 PolA_pol_RNA-bd_dom
IPR014492 PolyA_polymerase
IPR002934 Polymerase_NTP_transf_dom
PANTHERiPTHR10682 PTHR10682, 1 hit
PfamiView protein in Pfam
PF01909 NTP_transf_2, 1 hit
PF04928 PAP_central, 1 hit
PF04926 PAP_RNA-bind, 1 hit
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

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3XAH6G3XAH6_HUMAN
Poly(A) polymerase alpha
PAPOLA
724Annotation score:
G3V2A0G3V2A0_HUMAN
Poly(A) polymerase alpha
PAPOLA
475Annotation score:
H0YJL4H0YJL4_HUMAN
Poly(A) polymerase alpha
PAPOLA
181Annotation score:
A0A0C4DGK1A0A0C4DGK1_HUMAN
Poly(A) polymerase alpha, isoform C...
PAPOLA hCG_24516
238Annotation score:
G3V457G3V457_HUMAN
Poly(A) polymerase alpha
PAPOLA
111Annotation score:
H0YJ00H0YJ00_HUMAN
Poly(A) polymerase alpha
PAPOLA
203Annotation score:
G3V3I9G3V3I9_HUMAN
Poly(A) polymerase alpha
PAPOLA
177Annotation score:
H0YJZ9H0YJZ9_HUMAN
Poly(A) polymerase alpha
PAPOLA
73Annotation score:

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

Similar proteinsi

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, 50 interactors
CORUMiP51003
DIPiDIP-27610N
DIP-40865N
IntActiP51003, 13 interactors
MINTiP51003
STRINGi9606.ENSP00000216277

Chemistry databases

DrugBankiDB02153 3-Sulfinoalanine
DB01860 Cordycepin Triphosphate
DB03896 Triphospate

PTM databases

iPTMnetiP51003
PhosphoSitePlusiP51003

Polymorphism and mutation databases

BioMutaiPAPOLA
DMDMi59803092

Proteomic databases

EPDiP51003
MaxQBiP51003
PaxDbiP51003
PeptideAtlasiP51003
PRIDEiP51003
ProteomicsDBi56276
56277 [P51003-2]

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
EuPathDBiHostDB:ENSG00000090060.17
GeneCardsiPAPOLA
HGNCiHGNC:14981 PAPOLA
HPAiHPA001788
MIMi605553 gene
neXtProtiNX_P51003
OpenTargetsiENSG00000090060
PharmGKBiPA32932
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2245 Eukaryota
COG5186 LUCA
GeneTreeiENSGT00390000017928
HOVERGENiHBG053502
InParanoidiP51003
KOiK14376
OMAiQLEWCGL
OrthoDBiEOG091G0571
PhylomeDBiP51003
TreeFamiTF300842

Enzyme and pathway databases

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
PROiPR:P51003
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000090060 Expressed in 232 organ(s), highest expression level in testis
CleanExiHS_PAPOLA
ExpressionAtlasiP51003 baseline and differential
GenevisibleiP51003 HS

Family and domain databases

InterProiView protein in InterPro
IPR011068 NuclTrfase_I-like_C
IPR007012 PolA_pol_cen_dom
IPR007010 PolA_pol_RNA-bd_dom
IPR014492 PolyA_polymerase
IPR002934 Polymerase_NTP_transf_dom
PANTHERiPTHR10682 PTHR10682, 1 hit
PfamiView protein in Pfam
PF01909 NTP_transf_2, 1 hit
PF04928 PAP_central, 1 hit
PF04926 PAP_RNA-bind, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 180 of the entry and version 4 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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