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P25500 (PAPOA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length739 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. Ref.5

Catalytic activity

ATP + RNA(n) = diphosphate + RNA(n+1). Ref.8

Cofactor

Binds 2 magnesium ions. Also active with manganese. Ref.8

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. Ref.6

Subcellular location

Nucleus Ref.6.

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. Ref.6

Sequence similarities

Belongs to the poly(A) polymerase family.

Biophysicochemical properties

Kinetic parameters:

KM=0.229 mM for ATP Ref.8

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Long (identifier: P25500-1)

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 Short (identifier: P25500-2)

The sequence of this isoform differs from the canonical sequence as follows:
     663-683: Missing.
     709-710: KT → II
     711-739: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 739739Poly(A) polymerase alpha
PRO_0000051611

Regions

Nucleotide binding100 – 1023ATP
Nucleotide binding113 – 1153ATP
Nucleotide binding246 – 2472ATP
Region508 – 643136Ser/Thr-rich
Region671 – 73969Required for interaction with NUDT21
Motif490 – 50718Nuclear localization signal 1
Motif644 – 65916Nuclear localization signal 2

Sites

Metal binding1131Magnesium 1; catalytic
Metal binding1131Magnesium 2; catalytic
Metal binding1151Magnesium 1; catalytic
Metal binding1151Magnesium 2; catalytic
Metal binding1671Magnesium 2; catalytic
Binding site1091ATP
Binding site1671ATP
Binding site2281ATP
Binding site2371ATP
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 By similarity
Modified residue5371Phosphoserine; by MAPK By similarity
Modified residue6351N6-acetyllysine Ref.6
Modified residue6441N6-acetyllysine Ref.6
Modified residue7301N6-acetyllysine; alternate Ref.6
Modified residue7341N6-acetyllysine; alternate Ref.6
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-link730Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
Cross-link734Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity

Natural variations

Alternative sequence663 – 68321Missing in isoform Short.
VSP_004524
Alternative sequence709 – 7102KT → II in isoform Short.
VSP_004525
Alternative sequence711 – 73929Missing in isoform Short.
VSP_004526

Experimental info

Mutagenesis1001F → D: Strongly decreased enzyme activity. Strongly reduced affinity for RNA. Ref.8
Mutagenesis113 – 1153DID → AIA: Abolishes most of the specific and non-specific polyadenylation activity. Ref.4
Mutagenesis1131D → H: Abolishes most of the specific and non-specific polyadenylation activity. Ref.4
Mutagenesis1151D → H: Abolishes most of the specific and non-specific polyadenylation activity. Ref.4
Mutagenesis1531F → A: Strongly reduced affinity for RNA. Ref.8
Mutagenesis1561V → A: Strongly decreased enzyme activity. Strongly reduced affinity for RNA. Ref.8
Mutagenesis162 – 1632DG → HA: Small decrease in non-specific and specific polyadenylation activity.
Mutagenesis1671D → A: Loss of enzyme activity. Ref.4 Ref.8
Mutagenesis1671D → H: Abolishes most of the specific and non-specific polyadenylation activity. Ref.4 Ref.8
Mutagenesis1671D → N: Strongly decreased enzyme activity. Strongly reduced affinity for RNA. Ref.4 Ref.8
Mutagenesis1861D → H: Small decrease in non-specific and specific polyadenylation activity. Ref.4
Mutagenesis1941D → H: No change in non-specific and specific polyadenylation activity. Ref.4
Mutagenesis1991R → A: Strongly reduced affinity for RNA. Ref.8
Mutagenesis2021N → A: Strongly decreased enzyme activity. Strongly reduced affinity for RNA. Ref.8
Mutagenesis2031G → H: Loss of enzyme activity. Strongly reduced affinity for RNA. Ref.8
Mutagenesis208 – 2092DE → AA: Reduces by 60% non-specific and specific polyadenylation activity. Ref.4
Mutagenesis2081D → A: Reduces by 60% non-specific rf and specific polyadenylation activity. Ref.4
Mutagenesis2081D → H: Reduces by 20% non-specific and specific polyadenylation activity. Ref.4
Mutagenesis2091E → A: No change in non-specific and specific polyadenylation activity. Ref.4
Mutagenesis2281K → A: Strongly decreased affinity for ATP. Ref.8
Mutagenesis2321K → A: Decreased affinity for ATP. Ref.8
Mutagenesis2371Y → A: Strongly decreased affinity for ATP. Ref.8
Mutagenesis2471V → A or R: Strongly reduced affinity for RNA. Ref.8
Mutagenesis291 – 2922EE → AA: Abolishes most of non-specific polyadenylation activity. Ref.4
Mutagenesis2911E → A: Reduces by 60% non-specific polyadenylation activity. Ref.4
Mutagenesis2921E → A: No change in non-specific polyadenylation activity. Ref.4
Mutagenesis3081D → A: No change in non-specific and specific polyadenylation activity.
Mutagenesis3171T → G: Strongly decreased affinity for ATP.
Mutagenesis431 – 4322EE → AA: No change in non-specific and specific polyadenylation activity.
Mutagenesis4551D → A: Reduces by 30% non-specific polyadenylation activity. Ref.4
Mutagenesis4591D → A: No change in non-specific polyadenylation activity. Ref.4
Mutagenesis4651D → A: No change in non-specific and specific polyadenylation activity. Ref.4
Mutagenesis6351K → Q: Weak binding to KPBN1. Cytoplasmic location; when associated with Q-644; Q-730 and Q-734. Ref.6
Mutagenesis6351K → R: Some decrease in acetylation. Binds KPBN1 and localizes to the nucleus; when associated with R-644; R-730 and R-734. Ref.6
Mutagenesis6441K → Q: Weak binding to KPBN1. Cytoplasmic location; when associated with Q-635; Q-730 and Q-734. Ref.6
Mutagenesis6441K → R: Large decrease in acetylation. Binds KPBN1 and localizes to the nucleus; when associated with R-635; R-730 and R-734. Ref.6
Mutagenesis7301K → Q: Weak binding to KPBN1. Cytoplasmic location; when associated with Q-635; Q-644 and Q-734. Ref.6
Mutagenesis7301K → R: Some decrease in acetylation. Binds KPBN1 and localizes to the nucleus; when associated with R-635; R-644 and R-734. Ref.6
Mutagenesis7341K → Q: Weak binding to KPBN1. Cytoplasmic location; when associated with Q-635; Q-644 and Q-730. Ref.6
Mutagenesis7341K → R: Some decrease in acetylation. Binds KPBN1 and localizes to the nucleus; when associated with R-635; R-644 and R-730. Ref.6
Sequence conflict801S → R in CAA45031. Ref.3

Secondary structure

.......................................................................... 739
Helix Strand Turn

Details...

Sequences

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

Last modified January 23, 2007. Version 3.
Checksum: 7C89C15E33232CFF

FASTA73982,441
        10         20         30         40         50         60 
MPFPVTTQGS QQTQPPQKHY GITSPISLAA PKETDCLLTQ KLVETLKPFG 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 KQLHQLLPSH VLQKKKKHST EGVKLTPLND SSLDLSMDSD NSMSVPSPTS 

       550        560        570        580        590        600 
AMKTSPLNSS GSSQGRNSPA PAVTAASVTN IQATEVSLPQ INSSESSGGT SSESIPQTAT 

       610        620        630        640        650        660 
QPAISSPPKP TVSRVVSSTR LVNPPPRPSG NAAAKIPNPI VGVKRTSSPH KEESPKKTKT 

       670        680        690        700        710        720 
EEDETSEDAN CLALSGHDKT ETKEQLDTET STTQSETIQT ATSLLASQKT SSTDLSDIPA 

       730 
LPANPIPVIK NSIKLRLNR 

« Hide

Isoform Short [UniParc].

Checksum: 20BECA9A51B9ED1A
Show »

FASTA68977,066

References

[1]"Isolation and expression of cDNA clones encoding mammalian poly(A) polymerase."
Wahle E., Martin G., Schiltz E., Keller W.
EMBO J. 10:4251-4257(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), PROTEIN SEQUENCE OF 1-21; 207-255 AND 386-397.
Tissue: Thymus.
[2]Wahle E.
Submitted (AUG-1992) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Primary structure and expression of bovine poly(A) polymerase."
Raabe T., Bollum F.J., Manley J.L.
Nature 353:229-234(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 97-103 AND 445-468.
Tissue: Heart muscle.
[4]"Mutational analysis of mammalian poly(A) polymerase identifies a region for primer binding and catalytic domain, homologous to the family X polymerases, and to other nucleotidyltransferases."
Martin G., Keller W.
EMBO J. 15:2593-2603(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAINS, MUTAGENESIS OF ASP-113; ASP-115; 162-ASP-GLY-163; ASP-167; ASP-186; ASP-194; ASP-208; GLU-209; GLU-291; GLU-292; 431-GLU-GLU-432; ASP-455; ASP-459 AND ASP-465.
[5]"Inhibition of poly(A) polymerase requires p34cdc2/cyclin B phosphorylation of multiple consensus and non-consensus sites."
Colgan D.F., Murthy K.G., Zhao W., Prives C., Manley J.L.
EMBO J. 17:1053-1062(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, FUNCTION.
[6]"Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing."
Shimazu T., Horinouchi S., Yoshida M.
J. Biol. Chem. 282:4470-4478(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-635; LYS-644; LYS-730 AND LYS-734, INTERACTION WITH NUDT21 AND KPBN1, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF LYS-635; LYS-644; LYS-730 AND LYS-734.
[7]"Crystal structure of mammalian poly(A) polymerase in complex with an analog of ATP."
Martin G., Keller W., Doublie S.
EMBO J. 19:4193-4203(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-513 IN COMPLEX WITH ATP ANALOG AND MANGANESE IONS.
[8]"Biochemical and structural insights into substrate binding and catalytic mechanism of mammalian poly(A) polymerase."
Martin G., Moglich A., Keller W., Doublie S.
J. Mol. Biol. 341:911-925(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-513 IN COMPLEX WITH MAGNESIUM IONS; MANGANESE IONS AND ATP ANALOG, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF PHE-100; PHE-153; VAL-156; ASP-167; ARG-199; ASN-202; GLY-203; LYS-228; LYS-232; TYR-237 AND VAL-247.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X61585 mRNA. Translation: CAA43782.1.
X63436 mRNA. Translation: CAA45031.1.
PIRS17875.
S17925.
S18642.
RefSeqNP_788820.1. NM_176647.2.
UniGeneBt.109586.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1F5AX-ray2.50A1-513[»]
1Q78X-ray2.80A1-514[»]
1Q79X-ray2.15A1-513[»]
ProteinModelPortalP25500.
SMRP25500. Positions 19-498.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000005300.

Proteomic databases

PRIDEP25500.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000005300; ENSBTAP00000005300; ENSBTAG00000004054. [P25500-1]
GeneID338051.
KEGGbta:338051.

Organism-specific databases

CTD10914.

Phylogenomic databases

eggNOGCOG5186.
GeneTreeENSGT00390000017928.
HOGENOMHOG000204376.
HOVERGENHBG053502.
InParanoidP25500.
KOK14376.
OMASPVTTQG.
TreeFamTF300842.

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

EvolutionaryTraceP25500.
NextBio20812502.

Entry information

Entry namePAPOA_BOVIN
AccessionPrimary (citable) accession number: P25500
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 122 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references