P51003 (PAPOA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	745 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	mRNA processing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding RNA-binding
Molecular function	Transferase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mRNA polyadenylation Non-traceable author statement. Source: UniProtKB mRNA splicing, via spliceosome Traceable author statement. Source: Reactome termination of RNA polymerase II transcription Traceable author statement. Source: Reactome
Cellular_component	cytoplasm Traceable author statement Ref.3. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB RNA binding Non-traceable author statement. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB manganese ion binding Inferred from sequence or structural similarity. Source: UniProtKB polynucleotide adenylyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 745	745	Poly(A) polymerase alpha		PRO_0000051612
Regions
	Nucleotide binding	100 – 102	3	ATP By similarity
	Nucleotide binding	113 – 115	3	ATP By similarity
	Nucleotide binding	246 – 247	2	ATP By similarity
	Region	508 – 643	136	Ser/Thr-rich
	Region	677 – 745	69	Required for interaction with NUDT21
	Motif	490 – 507	18	Nuclear localization signal 1 By similarity
	Motif	650 – 665	16	Nuclear localization signal 2 By similarity
	Compositional bias	53 – 57	5	Poly-Glu
	Compositional bias	504 – 507	4	Poly-Lys
Sites
	Metal binding	113	1	Magnesium 1; catalytic By similarity
	Metal binding	113	1	Magnesium 2; catalytic By similarity
	Metal binding	115	1	Magnesium 1; catalytic By similarity
	Metal binding	115	1	Magnesium 2; catalytic By similarity
	Metal binding	167	1	Magnesium 2; catalytic By similarity
	Binding site	109	1	ATP By similarity
	Binding site	167	1	ATP By similarity
	Binding site	228	1	ATP By similarity
	Binding site	237	1	ATP By similarity
	Site	153	1	Interaction with RNA By similarity
	Site	158	1	Interaction with RNA By similarity
	Site	328	1	Interaction with RNA By similarity
	Site	399	1	Interaction with RNA By similarity
	Site	524	1	Interaction with RNA By similarity
Amino acid modifications
	Modified residue	24	1	Phosphoserine Ref.6 Ref.7
	Modified residue	537	1	Phosphoserine By similarity
	Modified residue	641	1	N6-acetyllysine By similarity
	Modified residue	650	1	N6-acetyllysine By similarity
	Modified residue	736	1	N6-acetyllysine; alternate By similarity
	Modified residue	740	1	N6-acetyllysine; alternate By similarity
	Cross-link	444		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
	Cross-link	445		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
	Cross-link	506		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
	Cross-link	507		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
	Cross-link	736		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
	Cross-link	740		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
Natural variations
	Alternative sequence	280 – 285	6	EWPNPV → YVFRLY in isoform 2.		VSP_012895
	Alternative sequence	286 – 745	460	Missing in isoform 2.		VSP_012896
Experimental info
	Sequence conflict	2 – 3	2	PF → GTSNSPGHSSFSAPSTKKIK TTRKQNIAWC in CAD62628. Ref.2
	Sequence conflict	204 – 238	35	CRVTD…HNIYS → MRKPTSFCVLQFLSDISCFY TSFVLKLFIAILLTQ in CAD61935. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 14A00CCCDAD9B374	FASTA	745	82,843
	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
	Isoform 2 [UniParc]. Checksum: 5967D93F0375C54C	FASTA	285	32,626
	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 LGFLGGVSWA MLVARTCQLY PNAIASTLVH KFFLVFSKWY VFRLY

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.
IPI	IPI00384028. IPI01025082.
RefSeq	NP_001238935.1. NM_001252006.1. NP_001238936.1. NM_001252007.1. NP_116021.2. NM_032632.4.
UniGene	Hs.253726.
3D structure databases
ProteinModelPortal	P51003.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27610N.
IntAct	P51003. 1 interaction.
MINT	MINT-125699.
STRING	9606.ENSP00000216277.
PTM databases
PhosphoSite	P51003.
Polymorphism databases
DMDM	59803092.
Proteomic databases
PaxDb	P51003.
PeptideAtlas	P51003.
PRIDE	P51003.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216277; ENSP00000216277; ENSG00000090060. ENST00000557320; ENSP00000450437; ENSG00000090060. ENST00000557471; ENSP00000450812; ENSG00000090060.
GeneID	10914.
KEGG	hsa:10914.
UCSC	uc001yfo.3. human. uc001yfq.3. human.
Organism-specific databases
CTD	10914.
GeneCards	GC14P096969.
HGNC	HGNC:14981. PAPOLA.
HPA	HPA001788.
MIM	605553. gene.
neXtProt	NX_P51003.
PharmGKB	PA32932.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5186.
HOVERGEN	HBG053502.
InParanoid	P51003.
KO	K14376.
OMA	SPVTTQG.
OrthoDB	EOG4J6RQB.
PhylomeDB	P51003.
Enzyme and pathway databases
Reactome	REACT_1675. mRNA Processing. REACT_1788. Transcription. REACT_71. Gene Expression. REACT_78. Post-Elongation Processing of the Transcript.
Gene expression databases
ArrayExpress	P51003.
Bgee	P51003.
CleanEx	HS_PAPOLA.
Genevestigator	P51003.
GermOnline	ENSG00000090060. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.590. 1 hit.
InterPro	IPR002934. Nucleotidyltransferase. IPR011068. NuclTrfase_I_C. IPR007012. PolA_pol_cen_dom. IPR007010. PolA_pol_RNA-bd_dom. IPR014492. PolyA_polymerase. [Graphical view]
Pfam	PF01909. NTP_transf_2. 1 hit. PF04928. PAP_central. 1 hit. PF04926. PAP_RNA-bind. 1 hit. [Graphical view]
PIRSF	PIRSF018425. PolyA_polymerase. 1 hit.
SUPFAM	SSF55003. PAP_C. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	PAPOLA. human.
GenomeRNAi	10914.
NextBio	41453.
SOURCE	Search...

Entry information

Entry name

PAPOA_HUMAN

Accession

Primary (citable) accession number: P51003
Secondary accession number(s): Q86SX4 , Q86TV0, Q8IYF5, Q9BVU2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 131 of the entry and version 4 of the sequence. [Complete history]

Entry status

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.