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{{Underlinked|date=March 2014}}
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{{Infobox_gene}}
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'''Poly(A) polymerase alpha''' is an [[enzyme]] that in humans is encoded by the ''PAPOLA'' [[gene]].<ref name="pmid8302877">{{cite journal | vauthors = Thuresson AC, Astrom J, Astrom A, Gronvik KO, Virtanen A | title = Multiple forms of poly(A) polymerases in human cells | journal = Proc Natl Acad Sci U S A | volume = 91 | issue = 3 | pages = 979–83 |date=Mar 1994 | pmid = 8302877 | pmc = 521437 | doi =10.1073/pnas.91.3.979  }}</ref><ref name="pmid10429366">{{cite journal | vauthors = Yamauchi T, Sugimoto J, Hatakeyama T, Asakawa S, Shimizu N, Isobe M | title = Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence | journal = J Hum Genet | volume = 44 | issue = 4 | pages = 253–5 |date=Sep 1999 | pmid = 10429366 | pmc = | doi = 10.1007/s100380050154 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PAPOLA poly(A) polymerase alpha| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10914| accessdate = }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
PAPOLA binds to [[FIP1L1]] (Factor interacting with PAPOLA and CPSF1), a subunit of the [[CPSF1|cleavage and polyadenylation specificity factor subunit 1]] (CPSF1) complex. This complex polyadenylates the [[Directionality (molecular biology)|3' end]] of [[precursor mRNA]]s (pre-mRNA) (see [[CPSF]]). CPSF1 is an [[RNA]] processing protein that binds to [[uracil]]-rich sequences in pre-mRNA, binds with and stimulates POPOLA's [[Polynucleotide adenylyltransferase]] activity, and thereby adds [[Adenosine monophosphate|adenylyl]] residues to pre-mRNA. This poly-adenylyl action increases pre mRNA's maturation and movement from the nucleus to cytoplasm while dramatically increasing the stability of the mRNA formed from pre-mRNA: FIP1L1 is a Pre-mRNA 3'-end-processing factor. ''FIP1L1'' [[Fusion gene|gene fusions]] between it and either the [[PDGFRA|platelet-derived growth factor receptor, alpha (''PGDFRA'')]] or [[Retinoic acid receptor alpha]] (RARA) genes are causes of certain human [[Hypereosinophilia|diseases associated with pathologically increased levels of blood eosinophils]] and/or [[Leukemia]]s.<ref>https://www.ncbi.nlm.nih.gov/gene/81608</ref><ref>https://www.ncbi.nlm.nih.gov/gene/81608</ref>
{{GNF_Protein_box
| image = PBB_Protein_PAPOLA_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1f5a.
| PDB = {{PDB2|1f5a}}, {{PDB2|1q78}}, {{PDB2|1q79}}
| Name = Poly(A) polymerase alpha
| HGNCid = 14981
| Symbol = PAPOLA
| AltSymbols =; PAP; MGC5378
| OMIM = 605553
| ECnumber = 
| Homologene = 23389
| MGIid = 109301
| GeneAtlas_image1 = PBB_GE_PAPOLA_212718_at_tn.png
| GeneAtlas_image2 = PBB_GE_PAPOLA_212720_at_tn.png
| GeneAtlas_image3 = PBB_GE_PAPOLA_222035_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003723 |text = RNA binding}} {{GNF_GO|id=GO:0004652 |text = polynucleotide adenylyltransferase activity}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006378 |text = mRNA polyadenylation}} {{GNF_GO|id=GO:0006397 |text = mRNA processing}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 10914
    | Hs_Ensembl = ENSG00000090060
    | Hs_RefseqProtein = NP_116021
    | Hs_RefseqmRNA = NM_032632
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 14
    | Hs_GenLoc_start = 96038471
    | Hs_GenLoc_end = 96103178
    | Hs_Uniprot = P51003
    | Mm_EntrezGene = 18789
    | Mm_Ensembl = ENSMUSG00000021111
    | Mm_RefseqmRNA = NM_011112
    | Mm_RefseqProtein = NP_035242
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 12
    | Mm_GenLoc_start = 106181750
    | Mm_GenLoc_end = 106239989
    | Mm_Uniprot = Q3V141
  }}
}}
'''Poly(A) polymerase alpha''', also known as '''PAPOLA''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PAPOLA poly(A) polymerase alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10914| accessdate = }}</ref>


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==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Thuresson AC, Aström J, Aström A, ''et al.'' |title=Multiple forms of poly(A) polymerases in human cells. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 3 |pages= 979-83 |year= 1994 |pmid= 8302877 |doi=  }}
*{{cite journal  | vauthors=Weichs an der Glon C, Ashe M, Eggermont J, Proudfoot NJ |title=Tat-dependent occlusion of the HIV poly(A) site. |journal=EMBO J. |volume=12 |issue= 5 |pages= 2119–28 |year= 1993 |pmid= 8491200 |doi= | pmc=413433 }}
*{{cite journal  | author=Weichs an der Glon C, Ashe M, Eggermont J, Proudfoot NJ |title=Tat-dependent occlusion of the HIV poly(A) site. |journal=EMBO J. |volume=12 |issue= 5 |pages= 2119-28 |year= 1993 |pmid= 8491200 |doi=  }}
*{{cite journal  | vauthors=Pendurthi UR, Alok D, Rao LV |title=Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 23 |pages= 12598–603 |year= 1997 |pmid= 9356495 |doi=10.1073/pnas.94.23.12598  | pmc=25051 }}
*{{cite journal  | author=Pendurthi UR, Alok D, Rao LV |title=Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 23 |pages= 12598-603 |year= 1997 |pmid= 9356495 |doi= }}
*{{cite journal   |vauthors=Varani L, Gunderson SI, Mattaj IW, etal |title=The NMR structure of the 38 kDa U1A protein - PIE RNA complex reveals the basis of cooperativity in regulation of polyadenylation by human U1A protein. |journal=Nat. Struct. Biol. |volume=7 |issue= 4 |pages= 329–35 |year= 2000 |pmid= 10742179 |doi= 10.1038/74101 }}
*{{cite journal  | author=Yamauchi T, Sugimoto J, Hatakeyama T, ''et al.'' |title=Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence. |journal=J. Hum. Genet. |volume=44 |issue= 4 |pages= 253-5 |year= 1999 |pmid= 10429366 |doi=  }}
*{{cite journal  | vauthors=Mouland AJ, Coady M, Yao XJ, Cohen EA |title=Hypophosphorylation of poly(A) polymerase and increased polyadenylation activity are associated with human immunodeficiency virus type 1 Vpr expression. |journal=Virology |volume=292 |issue= 2 |pages= 321–30 |year= 2002 |pmid= 11878934 |doi= 10.1006/viro.2001.1261 }}
*{{cite journal | author=Varani L, Gunderson SI, Mattaj IW, ''et al.'' |title=The NMR structure of the 38 kDa U1A protein - PIE RNA complex reveals the basis of cooperativity in regulation of polyadenylation by human U1A protein. |journal=Nat. Struct. Biol. |volume=7 |issue= 4 |pages= 329-35 |year= 2000 |pmid= 10742179 |doi= 10.1038/74101 }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal  | author=Mouland AJ, Coady M, Yao XJ, Cohen EA |title=Hypophosphorylation of poly(A) polymerase and increased polyadenylation activity are associated with human immunodeficiency virus type 1 Vpr expression. |journal=Virology |volume=292 |issue= 2 |pages= 321-30 |year= 2002 |pmid= 11878934 |doi= 10.1006/viro.2001.1261 }}
*{{cite journal  | vauthors=Kim H, Lee JH, Lee Y |title=Regulation of poly(A) polymerase by 14-3-3epsilon. |journal=EMBO J. |volume=22 |issue= 19 |pages= 5208–19 |year= 2003 |pmid= 14517258 |doi= 10.1093/emboj/cdg486 | pmc=204469 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Kim H, Lee JH, Lee Y |title=Regulation of poly(A) polymerase by 14-3-3epsilon. |journal=EMBO J. |volume=22 |issue= 19 |pages= 5208-19 |year= 2003 |pmid= 14517258 |doi= 10.1093/emboj/cdg486 }}
*{{cite journal   |vauthors=Bouwmeester T, Bauch A, Ruffner H, etal |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97–105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal   |vauthors=Kaufmann I, Martin G, Friedlein A, etal |title=Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. |journal=EMBO J. |volume=23 |issue= 3 |pages= 616–26 |year= 2005 |pmid= 14749727 |doi= 10.1038/sj.emboj.7600070 | pmc=1271804 }}
*{{cite journal | author=Bouwmeester T, Bauch A, Ruffner H, ''et al.'' |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97-105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 }}
*{{cite journal   |vauthors=Dettwiler S, Aringhieri C, Cardinale S, etal |title=Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization. |journal=J. Biol. Chem. |volume=279 |issue= 34 |pages= 35788–97 |year= 2005 |pmid= 15169763 |doi= 10.1074/jbc.M403927200 }}
*{{cite journal | author=Kaufmann I, Martin G, Friedlein A, ''et al.'' |title=Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. |journal=EMBO J. |volume=23 |issue= 3 |pages= 616-26 |year= 2005 |pmid= 14749727 |doi= 10.1038/sj.emboj.7600070 }}
*{{cite journal   |vauthors=Colland F, Jacq X, Trouplin V, etal |title=Functional proteomics mapping of a human signaling pathway. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324–32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 | pmc=442148 }}
*{{cite journal | author=Dettwiler S, Aringhieri C, Cardinale S, ''et al.'' |title=Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization. |journal=J. Biol. Chem. |volume=279 |issue= 34 |pages= 35788-97 |year= 2005 |pmid= 15169763 |doi= 10.1074/jbc.M403927200 }}
*{{cite journal   |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D, etal |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 }}
*{{cite journal | author=Colland F, Jacq X, Trouplin V, ''et al.'' |title=Functional proteomics mapping of a human signaling pathway. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324-32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal | author=Beausoleil SA, Jedrychowski M, Schwartz D, ''et al.'' |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130-5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 }}
*{{cite journal   |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
}}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=10914}}
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Revision as of 17:32, 7 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Poly(A) polymerase alpha is an enzyme that in humans is encoded by the PAPOLA gene.[1][2][3]

PAPOLA binds to FIP1L1 (Factor interacting with PAPOLA and CPSF1), a subunit of the cleavage and polyadenylation specificity factor subunit 1 (CPSF1) complex. This complex polyadenylates the 3' end of precursor mRNAs (pre-mRNA) (see CPSF). CPSF1 is an RNA processing protein that binds to uracil-rich sequences in pre-mRNA, binds with and stimulates POPOLA's Polynucleotide adenylyltransferase activity, and thereby adds adenylyl residues to pre-mRNA. This poly-adenylyl action increases pre mRNA's maturation and movement from the nucleus to cytoplasm while dramatically increasing the stability of the mRNA formed from pre-mRNA: FIP1L1 is a Pre-mRNA 3'-end-processing factor. FIP1L1 gene fusions between it and either the platelet-derived growth factor receptor, alpha (PGDFRA) or Retinoic acid receptor alpha (RARA) genes are causes of certain human diseases associated with pathologically increased levels of blood eosinophils and/or Leukemias.[4][5]


References

  1. ↑ Thuresson AC, Astrom J, Astrom A, Gronvik KO, Virtanen A (Mar 1994). "Multiple forms of poly(A) polymerases in human cells". Proc Natl Acad Sci U S A. 91 (3): 979–83. doi:10.1073/pnas.91.3.979. PMC 521437. PMID 8302877.
  2. ↑ Yamauchi T, Sugimoto J, Hatakeyama T, Asakawa S, Shimizu N, Isobe M (Sep 1999). "Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence". J Hum Genet. 44 (4): 253–5. doi:10.1007/s100380050154. PMID 10429366.
  3. ↑ "Entrez Gene: PAPOLA poly(A) polymerase alpha".
  4. ↑ https://www.ncbi.nlm.nih.gov/gene/81608
  5. ↑ https://www.ncbi.nlm.nih.gov/gene/81608

Further reading



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