UniProtKB - P51003 (PAPOA_HUMAN)
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Protein
Poly(A) polymerase alpha
Gene
PAPOLA
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 109 | ATPBy similarity | 1 | |
Metal bindingi | 113 | Magnesium 1; catalyticBy similarity | 1 | |
Metal bindingi | 113 | Magnesium 2; catalyticBy similarity | 1 | |
Metal bindingi | 115 | Magnesium 1; catalyticBy similarity | 1 | |
Metal bindingi | 115 | Magnesium 2; catalyticBy similarity | 1 | |
Metal bindingi | 167 | Magnesium 2; catalyticBy similarity | 1 | |
Binding sitei | 167 | ATPBy similarity | 1 | |
Binding sitei | 228 | ATPBy similarity | 1 | |
Binding sitei | 237 | ATPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 100 – 102 | ATPBy similarity | 3 | |
Nucleotide bindingi | 113 – 115 | ATPBy similarity | 3 | |
Nucleotide bindingi | 246 – 247 | ATPBy similarity | 2 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- magnesium ion binding Source: UniProtKB
- manganese ion binding Source: UniProtKB
- polynucleotide adenylyltransferase activity Source: UniProtKB
- RNA binding Source: UniProtKB-KW
GO - Biological processi
- mRNA 3'-end processing Source: Reactome
- mRNA polyadenylation Source: UniProtKB
- mRNA splicing, via spliceosome Source: Reactome
- regulation of mRNA 3'-end processing Source: UniProtKB
- RNA polyadenylation Source: UniProtKB
- termination of RNA polymerase II transcription Source: Reactome
Keywordsi
Molecular function | RNA-binding, Transferase |
Biological process | mRNA processing |
Ligand | ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-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. |
SIGNORi | P51003. |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000090060.17. |
HGNCi | HGNC:14981. PAPOLA. |
MIMi | 605553. gene. |
neXtProti | NX_P51003. |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 10914. |
OpenTargetsi | ENSG00000090060. |
PharmGKBi | PA32932. |
Chemistry databases
DrugBanki | DB02153. 3-Sulfinoalanine. DB01860. Cordycepin Triphosphate. DB03896. Triphospate. |
Polymorphism and mutation databases
BioMutai | PAPOLA. |
DMDMi | 59803092. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000051612 | 2 – 745 | Poly(A) polymerase alphaAdd BLAST | 744 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 10 | PhosphoserineCombined sources | 1 | |
Modified residuei | 24 | PhosphoserineCombined sources | 1 | |
Cross-linki | 444 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated | ||
Cross-linki | 445 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated | ||
Cross-linki | 506 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated | ||
Cross-linki | 507 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated | ||
Modified residuei | 537 | PhosphoserineBy similarity | 1 | |
Modified residuei | 558 | PhosphoserineCombined sources | 1 | |
Modified residuei | 641 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 650 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 736 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 736 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity | ||
Modified residuei | 738 | PhosphoserineCombined sources | 1 | |
Modified residuei | 740 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 740 | Glycyl 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 conjugationProteomic databases
EPDi | P51003. |
MaxQBi | P51003. |
PaxDbi | P51003. |
PeptideAtlasi | P51003. |
PRIDEi | P51003. |
PTM databases
iPTMneti | P51003. |
PhosphoSitePlusi | P51003. |
Expressioni
Gene expression databases
Bgeei | ENSG00000090060. |
CleanExi | HS_PAPOLA. |
ExpressionAtlasi | P51003. baseline and differential. |
Genevisiblei | P51003. HS. |
Organism-specific databases
HPAi | HPA001788. |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 153 | Interaction with RNABy similarity | 1 | |
Sitei | 158 | Interaction with RNABy similarity | 1 | |
Sitei | 328 | Interaction with RNABy similarity | 1 | |
Sitei | 399 | Interaction with RNABy similarity | 1 | |
Sitei | 524 | Interaction with RNABy similarity | 1 |
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
Ywhae | P62259 | 3 | EBI-359376,EBI-356480 | From Mus musculus. |
Protein-protein interaction databases
BioGridi | 116119. 50 interactors. |
CORUMi | P51003. |
DIPi | DIP-27610N. DIP-40865N. |
IntActi | P51003. 13 interactors. |
MINTi | P51003. |
STRINGi | 9606.ENSP00000216277. |
Structurei
3D structure databases
ProteinModelPortali | P51003. |
SMRi | P51003. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 508 – 643 | Ser/Thr-richAdd BLAST | 136 | |
Regioni | 677 – 745 | Required for interaction with NUDT21Add BLAST | 69 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 490 – 507 | Nuclear localization signal 1By similarityAdd BLAST | 18 | |
Motifi | 650 – 665 | Nuclear localization signal 2By similarityAdd BLAST | 16 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 53 – 57 | Poly-Glu | 5 | |
Compositional biasi | 504 – 507 | Poly-Lys | 4 |
Sequence similaritiesi
Belongs to the poly(A) polymerase family.Curated
Phylogenomic databases
eggNOGi | KOG2245. Eukaryota. COG5186. LUCA. |
GeneTreei | ENSGT00390000017928. |
HOVERGENi | HBG053502. |
InParanoidi | P51003. |
KOi | K14376. |
OMAi | MGIVVRH. |
OrthoDBi | EOG091G0571. |
PhylomeDBi | P51003. |
TreeFami | TF300842. |
Family and domain databases
InterProi | View 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. |
PANTHERi | PTHR10682. PTHR10682. 1 hit. |
Pfami | View protein in Pfam PF01909. NTP_transf_2. 1 hit. PF04928. PAP_central. 1 hit. PF04926. PAP_RNA-bind. 1 hit. |
PIRSFi | PIRSF018425. PolyA_polymerase. 1 hit. |
SUPFAMi | SSF55003. SSF55003. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative 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.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 2 – 3 | PF → GTSNSPGHSSFSAPSTKKIK TTRKQNIAWC in CAD62628 (Ref. 2) Curated | 2 | |
Sequence conflicti | 204 – 238 | CRVTD…HNIYS → MRKPTSFCVLQFLSDISCFY TSFVLKLFIAILLTQ in CAD61935 (Ref. 2) CuratedAdd BLAST | 35 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_012895 | 280 – 285 | EWPNPV → YVFRLY in isoform 2. 2 Publications | 6 | |
Alternative sequenceiVSP_012896 | 286 – 745 | Missing in isoform 2. 2 PublicationsAdd BLAST | 460 |
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. |
CCDSi | CCDS58334.1. [P51003-2] CCDS9946.1. [P51003-1] |
RefSeqi | NP_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] |
UniGenei | Hs.253726. |
Genome annotation databases
Ensembli | ENST00000216277; ENSP00000216277; ENSG00000090060. [P51003-1] ENST00000557320; ENSP00000450437; ENSG00000090060. [P51003-2] |
GeneIDi | 10914. |
KEGGi | hsa:10914. |
UCSCi | uc001yfo.5. human. [P51003-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | PAPOA_HUMAN | |
Accessioni | P51003Primary (citable) accession number: P51003 Secondary accession number(s): Q86SX4 Q9BVU2 | |
Entry historyi | Integrated 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 statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |