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UniProtKB - P51003 (PAPOA_HUMAN)

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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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
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.

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

Binary interactionsi

WithEntry#Exp.IntActNotes
YwhaeP622593EBI-359376,EBI-356480From Mus musculus.

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.
OMAiMGIVVRH.
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

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

Similar proteinsi

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: March 28, 2018
This is version 175 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