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P51003 (PAPOA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Poly(A) polymerase alpha

Short name=PAP-alpha
EC=2.7.7.19
Alternative name(s):
Polynucleotide adenylyltransferase alpha
Gene names
Name:PAPOLA
Synonyms:PAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length745 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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

Cofactor

Binds 2 magnesium ions. Also active with manganese By similarity.

Subunit structure

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. Ref.4 Ref.5

Subcellular location

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

Post-translational modification

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.

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.

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.

Sequence similarities

Belongs to the poly(A) polymerase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51003-1)

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.
Isoform 2 (identifier: P51003-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 745745Poly(A) polymerase alpha
PRO_0000051612

Regions

Nucleotide binding100 – 1023ATP By similarity
Nucleotide binding113 – 1153ATP By similarity
Nucleotide binding246 – 2472ATP By similarity
Region508 – 643136Ser/Thr-rich
Region677 – 74569Required for interaction with NUDT21
Motif490 – 50718Nuclear localization signal 1 By similarity
Motif650 – 66516Nuclear localization signal 2 By similarity
Compositional bias53 – 575Poly-Glu
Compositional bias504 – 5074Poly-Lys

Sites

Metal binding1131Magnesium 1; catalytic By similarity
Metal binding1131Magnesium 2; catalytic By similarity
Metal binding1151Magnesium 1; catalytic By similarity
Metal binding1151Magnesium 2; catalytic By similarity
Metal binding1671Magnesium 2; catalytic By similarity
Binding site1091ATP By similarity
Binding site1671ATP By similarity
Binding site2281ATP By similarity
Binding site2371ATP By similarity
Site1531Interaction with RNA By similarity
Site1581Interaction with RNA By similarity
Site3281Interaction with RNA By similarity
Site3991Interaction with RNA By similarity
Site5241Interaction with RNA By similarity

Amino acid modifications

Modified residue241Phosphoserine Ref.6 Ref.7
Modified residue5371Phosphoserine By similarity
Modified residue6411N6-acetyllysine By similarity
Modified residue6501N6-acetyllysine By similarity
Modified residue7361N6-acetyllysine; alternate By similarity
Modified residue7401N6-acetyllysine; alternate By similarity
Cross-link444Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
Cross-link445Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
Cross-link506Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
Cross-link507Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
Cross-link736Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
Cross-link740Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity

Natural variations

Alternative sequence280 – 2856EWPNPV → YVFRLY in isoform 2.
VSP_012895
Alternative sequence286 – 745460Missing in isoform 2.
VSP_012896

Experimental info

Sequence conflict2 – 32PF → GTSNSPGHSSFSAPSTKKIK TTRKQNIAWC in CAD62628. Ref.2
Sequence conflict204 – 23835CRVTD…HNIYS → MRKPTSFCVLQFLSDISCFY TSFVLKLFIAILLTQ in CAD61935. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 14A00CCCDAD9B374

FASTA74582,843
        10         20         30         40         50         60 
MPFPVTTQGS QQTQPPQKHY GITSPISLAA PKETDCVLTQ KLIETLKPFG VFEEEEELQR 

        70         80         90        100        110        120 
RILILGKLNN LVKEWIREIS ESKNLPQSVI ENVGGKIFTF GSYRLGVHTK GADIDALCVA 

       130        140        150        160        170        180 
PRHVDRSDFF TSFYDKLKLQ EEVKDLRAVE EAFVPVIKLC FDGIEIDILF ARLALQTIPE 

       190        200        210        220        230        240 
DLDLRDDSLL KNLDIRCIRS LNGCRVTDEI LHLVPNIDNF RLTLRAIKLW AKRHNIYSNI 

       250        260        270        280        290        300 
LGFLGGVSWA MLVARTCQLY PNAIASTLVH KFFLVFSKWE WPNPVLLKQP EECNLNLPVW 

       310        320        330        340        350        360 
DPRVNPSDRY HLMPIITPAY PQQNSTYNVS VSTRMVMVEE FKQGLAITDE ILLSKAEWSK 

       370        380        390        400        410        420 
LFEAPNFFQK YKHYIVLLAS APTEKQRLEW VGLVESKIRI LVGSLEKNEF ITLAHVNPQS 

       430        440        450        460        470        480 
FPAPKENPDK EEFRTMWVIG LVFKKTENSE NLSVDLTYDI QSFTDTVYRQ AINSKMFEVD 

       490        500        510        520        530        540 
MKIAAMHVKR KQLHQLLPNH VLQKKKKHST EGVKLTALND SSLDLSMDSD NSMSVPSPTS 

       550        560        570        580        590        600 
ATKTSPLNSS GSSQGRNSPA PAVTAASVTN IQATEVSVPQ VNSSESSGGT SSESIPQTAT 

       610        620        630        640        650        660 
QPAISPPPKP TVSRVVSSTR LVNPPPRSSG NAATSGNAAT KIPTPIVGVK RTSSPHKEES 

       670        680        690        700        710        720 
PKKTKTEEDE TSEDANCLAL SGHDKTEAKE QLDTETSTTQ SETIQTAASL LASQKTSSTD 

       730        740 
LSDIPALPAN PIPVIKNSIK LRLNR 

« Hide

Isoform 2 [UniParc].

Checksum: 5967D93F0375C54C
Show »

FASTA28532,626

References

« Hide 'large scale' references
[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]"Multiple forms of poly(A) polymerases in human cells."
Thuresson A.-C., Aastroem J., Aastroem A., Groenvik K.-O., Virtanen A.
Proc. Natl. Acad. Sci. U.S.A. 91:979-983(1994) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"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.
[8]"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.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001238935.1. NM_001252006.1.
NP_001238936.1. NM_001252007.1.
NP_116021.2. NM_032632.4.
UniGeneHs.253726.

3D structure databases

ProteinModelPortalP51003.
SMRP51003. Positions 19-498.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116119. 27 interactions.
DIPDIP-27610N.
DIP-40865N.
IntActP51003. 7 interactions.
MINTMINT-125699.
STRING9606.ENSP00000216277.

PTM databases

PhosphoSiteP51003.

Polymorphism databases

DMDM59803092.

Proteomic databases

PaxDbP51003.
PeptideAtlasP51003.
PRIDEP51003.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216277; ENSP00000216277; ENSG00000090060. [P51003-1]
ENST00000557320; ENSP00000450437; ENSG00000090060. [P51003-2]
ENST00000557471; ENSP00000450812; ENSG00000090060.
GeneID10914.
KEGGhsa:10914.
UCSCuc001yfo.3. human. [P51003-2]
uc001yfq.3. human. [P51003-1]

Organism-specific databases

CTD10914.
GeneCardsGC14P096969.
HGNCHGNC:14981. PAPOLA.
HPAHPA001788.
MIM605553. gene.
neXtProtNX_P51003.
PharmGKBPA32932.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5186.
HOVERGENHBG053502.
InParanoidP51003.
KOK14376.
OMASPVTTQG.
OrthoDBEOG7XH6PT.
PhylomeDBP51003.
TreeFamTF300842.

Enzyme and pathway databases

ReactomeREACT_1788. Transcription.
REACT_71. Gene Expression.
REACT_78. Post-Elongation Processing of the Transcript.

Gene expression databases

ArrayExpressP51003.
BgeeP51003.
CleanExHS_PAPOLA.
GenevestigatorP51003.

Family and domain databases

Gene3D3.30.70.590. 1 hit.
InterProIPR002934. Nucleotidyltransferase.
IPR011068. NuclTrfase_I_C.
IPR007012. PolA_pol_cen_dom.
IPR007010. PolA_pol_RNA-bd_dom.
IPR014492. PolyA_polymerase.
[Graphical view]
PfamPF01909. NTP_transf_2. 1 hit.
PF04928. PAP_central. 1 hit.
PF04926. PAP_RNA-bind. 1 hit.
[Graphical view]
PIRSFPIRSF018425. PolyA_polymerase. 1 hit.
SUPFAMSSF55003. SSF55003. 1 hit.
ProtoNetSearch...

Other

ChiTaRSPAPOLA. human.
GeneWikiPAPOLA.
GenomeRNAi10914.
NextBio41453.
PROP51003.
SOURCESearch...

Entry information

Entry namePAPOA_HUMAN
AccessionPrimary (citable) accession number: P51003
Secondary accession number(s): Q86SX4 expand/collapse secondary AC list , Q86TV0, Q8IYF5, Q9BVU2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 137 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM