Q61183 (PAPOA_MOUSE) 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

Gene names

Name:	Papola
Synonyms:	Pap, Plap

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	739 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 By similarity. Ref.4 Ref.5
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.3
Subcellular location	Nucleus By similarity Ref.4.
Tissue specificity	Expressed in brain, thymus, lung, kidney, bladder, testis and spleen. Ref.4
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. Ref.4 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	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 Inferred from Biological aspect of Ancestor. Source: RefGenome mRNA splicing, via spliceosome Inferred from Biological aspect of Ancestor. Source: RefGenome termination of RNA polymerase II transcription Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB RNA binding Inferred from electronic annotation. Source: UniProtKB-KW 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 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q61183-1)

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: Q61183-2)

Also known as: III;

The sequence of this isoform differs from the canonical sequence as follows:
     373-375: HYI → YVK
     376-739: Missing.

Isoform 3 (identifier: Q61183-3)

Also known as: V;

The sequence of this isoform differs from the canonical sequence as follows:
     305-317: NPSDRYHLMPIIT → SVLFFPLQIHTIQ
     318-375: Missing.

Isoform 4 (identifier: Q61183-4)

Also known as: VI;

The sequence of this isoform differs from the canonical sequence as follows:
     280-293: EWPNPVLLKQPEEC → YVFRLYYNKIDCRH
     294-375: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 739	739	Poly(A) polymerase alpha		PRO_0000051613
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	671 – 739	69	Required for interaction with NUDT21
	Motif	490 – 507	18	Nuclear localization signal 1 By similarity
	Motif	644 – 659	16	Nuclear localization signal 2 By similarity
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 By similarity
	Modified residue	537	1	Phosphoserine; by MAPK Ref.5
	Modified residue	635	1	N6-acetyllysine By similarity
	Modified residue	644	1	N6-acetyllysine By similarity
	Modified residue	730	1	N6-acetyllysine; alternate By similarity
	Modified residue	734	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	730		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.4
	Cross-link	734		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.4
Natural variations
	Alternative sequence	280 – 293	14	EWPNP…QPEEC → YVFRLYYNKIDCRH in isoform 4.		VSP_004527
	Alternative sequence	294 – 375	82	Missing in isoform 4.		VSP_004528
	Alternative sequence	305 – 317	13	NPSDR…MPIIT → SVLFFPLQIHTIQ in isoform 3.		VSP_004529
	Alternative sequence	318 – 375	58	Missing in isoform 3.		VSP_004530
	Alternative sequence	373 – 375	3	HYI → YVK in isoform 2.		VSP_004531
	Alternative sequence	376 – 739	364	Missing in isoform 2.		VSP_004532
Experimental info
	Mutagenesis	444 – 445	2	KK → RR: Some loss of sumoylation. No change in nuclear localization. Ref.4
	Mutagenesis	537	1	S → A: Eliminates MAPK-mediated phosphorylation. Ref.4 Ref.5
	Mutagenesis	656 – 657	2	KK → RR: Some loss of sumoylation; Largely localized to the cytoplasm. Ref.4
	Sequence conflict	47	1	K → L in AAC52586. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: BABE406BDF8EBEE9	FASTA	739	82,309
	10 20 30 40 50 60 MPFPVTTQGS QQTQPPQRHY GITSPISLAA PKETDCLLTQ 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 FPAPKESPDR EEFRTMWVIG LVFKKTENSE NLSVDLTYDI QSFTDTVYRQ AINSKMFELD 490 500 510 520 530 540 MKIAAMHVKR KQLHQLLPSH VLQKRKKHST EGVKLTALND SSLDLSMDSD NSMSVPSPTS 550 560 570 580 590 600 AMKTSPLNSS GSSQGRNSPA PAVTAASVTS IQASEVSVPQ ANSSESPGGP SSESIPQTAT 610 620 630 640 650 660 QPAISPPPKP TVSRVVSSTR LVNPSPRPSG NTATKVPNPI VGVKRTSSPN KEESPKKTKT 670 680 690 700 710 720 EEDETSEDAN CLALSGHDKT ETKEQVDLET SAVQSETVPA SASLLASQKT SSTDLSDIPA 730 LPANPIPVIK NSIKLRLNR
	Isoform 2 (III) [UniParc]. Checksum: 09C195A8E639A0B2	FASTA	375	43,110
	10 20 30 40 50 60 MPFPVTTQGS QQTQPPQRHY GITSPISLAA PKETDCLLTQ 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 LFEAPNFFQK YKYVK
	Isoform 3 (V) [UniParc]. Checksum: AA7913AC868F72CF	FASTA	681	75,495
	10 20 30 40 50 60 MPFPVTTQGS QQTQPPQRHY GITSPISLAA PKETDCLLTQ 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 DPRVSVLFFP LQIHTIQVLL ASAPTEKQRL EWVGLVESKI RILVGSLEKN EFITLAHVNP 370 380 390 400 410 420 QSFPAPKESP DREEFRTMWV IGLVFKKTEN SENLSVDLTY DIQSFTDTVY RQAINSKMFE 430 440 450 460 470 480 LDMKIAAMHV KRKQLHQLLP SHVLQKRKKH STEGVKLTAL NDSSLDLSMD SDNSMSVPSP 490 500 510 520 530 540 TSAMKTSPLN SSGSSQGRNS PAPAVTAASV TSIQASEVSV PQANSSESPG GPSSESIPQT 550 560 570 580 590 600 ATQPAISPPP KPTVSRVVSS TRLVNPSPRP SGNTATKVPN PIVGVKRTSS PNKEESPKKT 610 620 630 640 650 660 KTEEDETSED ANCLALSGHD KTETKEQVDL ETSAVQSETV PASASLLASQ KTSSTDLSDI 670 680 PALPANPIPV IKNSIKLRLN R
	Isoform 4 (VI) [UniParc]. Checksum: 8EE01C27FBF14541	FASTA	657	72,874
	10 20 30 40 50 60 MPFPVTTQGS QQTQPPQRHY GITSPISLAA PKETDCLLTQ 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 KFFLVFSKWY VFRLYYNKID CRHVLLASAP 310 320 330 340 350 360 TEKQRLEWVG LVESKIRILV GSLEKNEFIT LAHVNPQSFP APKESPDREE FRTMWVIGLV 370 380 390 400 410 420 FKKTENSENL SVDLTYDIQS FTDTVYRQAI NSKMFELDMK IAAMHVKRKQ LHQLLPSHVL 430 440 450 460 470 480 QKRKKHSTEG VKLTALNDSS LDLSMDSDNS MSVPSPTSAM KTSPLNSSGS SQGRNSPAPA 490 500 510 520 530 540 VTAASVTSIQ ASEVSVPQAN SSESPGGPSS ESIPQTATQP AISPPPKPTV SRVVSSTRLV 550 560 570 580 590 600 NPSPRPSGNT ATKVPNPIVG VKRTSSPNKE ESPKKTKTEE DETSEDANCL ALSGHDKTET 610 620 630 640 650 KEQVDLETSA VQSETVPASA SLLASQKTSS TDLSDIPALP ANPIPVIKNS IKLRLNR

References

[1]	"Complex alternative RNA processing generates an unexpected diversity of poly(A) polymerase isoforms." Zhao W., Manley J.L. Mol. Cell. Biol. 16:2378-2386(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4). Tissue: Brain.
[2]	"Regulation of spermatogenesis by testis-specific, cytoplasmic poly(A) polymerase TPAP." Kashiwabara S., Noguchi J., Zhuang T., Ohmura K., Honda A., Sugiura S., Miyamoto K., Takahashi S., Inoue K., Ogura A., Baba T. Science 298:1999-2002(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). Strain: 129/SvJ.
[3]	"Interaction of poly(A) polymerase with the 25-kDa subunit of cleavage factor I." Kim H., Lee Y. Biochem. Biophys. Res. Commun. 289:513-518(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NUDT21.
[4]	"Sumoylation regulates multiple aspects of mammalian poly(A) polymerase function." Vethantham V., Rao N., Manley J.L. Genes Dev. 22:499-511(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-444; LYS-445; LYS-506; LYS-507; LYS-730 AND LYS-734, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, MUTAGENESIS OF 444-LYS-LYS-445; 506-LYS-LYS-507 AND 656-LYS-LYS-657.
[5]	"ERK is a novel regulatory kinase for poly(A) polymerase." Lee S.-H., Choi H.-S., Kim H., Lee Y. Nucleic Acids Res. 36:803-813(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-537, FUNCTION, MASS SPECTROMETRY, MUTAGENESIS OF SER-537.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U52197 mRNA. Translation: AAC52586.1. U58134 mRNA. Translation: AAC52608.1. U58135 mRNA. Translation: AAC52609.1. AB086650 Genomic DNA. Translation: BAC00996.1.
IPI	IPI00224655. IPI00224656. IPI00266738. IPI00467146.
RefSeq	NP_035242.1. NM_011112.3.
UniGene	Mm.255877.
3D structure databases
ProteinModelPortal	Q61183.
SMR	Q61183. Positions 19-498.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000098624.
PTM databases
PhosphoSite	Q61183.
Proteomic databases
PaxDb	Q61183.
PRIDE	Q61183.
Protocols and materials databases
DNASU	18789.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021535; ENSMUSP00000021535; ENSMUSG00000021111. ENSMUST00000109901; ENSMUSP00000105527; ENSMUSG00000021111. ENSMUST00000166735; ENSMUSP00000128908; ENSMUSG00000021111.
GeneID	18789.
KEGG	mmu:18789.
UCSC	uc007oyv.1. mouse. uc007oyx.1. mouse.
Organism-specific databases
CTD	10914.
MGI	MGI:109301. Papola.
Phylogenomic databases
eggNOG	COG5186.
GeneTree	ENSGT00390000017928.
HOGENOM	HOG000204376.
HOVERGEN	HBG053502.
InParanoid	Q61183.
KO	K14376.
OMA	SPVTTQG.
OrthoDB	EOG4J6RQB.
Gene expression databases
ArrayExpress	Q61183.
Bgee	Q61183.
CleanEx	MM_PAPOLA.
Genevestigator	Q61183.
GermOnline	ENSMUSG00000021111. Mus musculus.
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. mouse.
NextBio	295064.
SOURCE	Search...

Entry information

Entry name

PAPOA_MOUSE

Accession

Primary (citable) accession number: Q61183
Secondary accession number(s): Q61208, Q61209, Q8K4X2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 99 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program