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    PAPOLA poly(A) polymerase alpha [ Homo sapiens (human) ]

    Gene ID: 10914, updated on 3-Nov-2024

    Summary

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    Official Symbol
    PAPOLAprovided by HGNC
    Official Full Name
    poly(A) polymerase alphaprovided by HGNC
    Primary source
    HGNC:HGNC:14981
    See related
    Ensembl:ENSG00000090060 MIM:605553; AllianceGenome:HGNC:14981
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PAP; PAP-alpha
    Summary
    The protein encoded by this gene belongs to the poly(A) polymerase family. It is required for the addition of adenosine residues for the creation of the 3'-poly(A) tail of mRNAs. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
    Expression
    Ubiquitous expression in testis (RPKM 27.7), thyroid (RPKM 22.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PAPOLA in Genome Data Viewer
    Location:
    14q32.2
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (96502376..96567116)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (90733979..90798717)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (96968713..97033453)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene adenylate kinase 7 Neighboring gene ribosomal protein L23a pseudogene 10 Neighboring gene MPRA-validated peak2245 silencer Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:96967424-96968020 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:96968021-96968615 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:96968616-96969211 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:96970367-96970868 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:96970869-96971368 Neighboring gene PAPOLA divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6056 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8988 Neighboring gene RN7SK pseudogene 108 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8989 Neighboring gene uncharacterized LOC105370645 Neighboring gene NANOG hESC enhancer GRCh37_chr14:97142464-97143129

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase. Pendurthi UR, et al. Proc Natl Acad Sci U S A, 1997 Nov 11. PMID 9356495, Free PMC Article
    2. Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence. Yamauchi T, et al. J Hum Genet, 1999. PMID 10429366
    3. The structure of the 5'-untranslated region of mammalian poly(A) polymerase-alpha mRNA suggests a mechanism of translational regulation. Rapti A, et al. Mol Cell Biochem, 2010 Jul. PMID 20174964
    4. PAPOLA contributes to cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cell proliferation. Komini C, et al. J Cell Sci, 2021 Apr 1. PMID 33712453
    5. 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. Varani L, et al. Nat Struct Biol, 2000 Apr. PMID 10742179

    See all (60) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PAPOLA contributes to cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cell proliferation.
      Title: PAPOLA contributes to cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cell proliferation.
    2. Whereas PABPN1 strongly increases the activity of its cognate poly(A) polymerase in vitro, Pab2 was unable to stimulate Pla1 to any significant extent.
      Title: The nuclear poly(A) binding protein of mammals, but not of fission yeast, participates in mRNA polyadenylation.
    3. Lack of CstF-64 binding excludes PAPalpha from Star-PAP target pre-mRNA UTRs.CstF-64 and 3'-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding poly A polymerase.
      Title: CstF-64 and 3'-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα.
    4. The ability of PABPN1 to promote splicing requires its RNA binding and, to a lesser extent, poly(A)polymerase (PAP) - stimulatory functions.
      Title: Poly(A) Polymerase and the Nuclear Poly(A) Binding Protein, PABPN1, Coordinate the Splicing and Degradation of a Subset of Human Pre-mRNAs.
    5. Observations imply that translational regulation is among the conserved mechanisms regulating PAPOLA expression.
      Title: The structure of the 5'-untranslated region of mammalian poly(A) polymerase-alpha mRNA suggests a mechanism of translational regulation.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat The poly(A) site in the HIV-1 5'-LTR is occluded in a Tat-dependent manner, suggesting a role for Tat in regulating this nucleotide signal PubMed
    Vpr vpr HIV-1 Vpr dephosphorylates poly(A) polymerase (PAP), presumably through inhibition of the p34cdc2/cyclin B kinase complex, leading to enhanced PAP activity PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC5378, FLJ33067

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables RNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables magnesium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables manganese ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables poly(A) RNA polymerase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables poly(A) RNA polymerase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables poly(A) RNA polymerase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables poly(A) RNA polymerase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in co-transcriptional mRNA 3'-end processing, cleavage and polyadenylation pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cytosolic mRNA polyadenylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mRNA 3'-end processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mRNA 3'-end processing TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    poly(A) polymerase alpha
    Names
    polynucleotide adenylyltransferase alpha
    NP_001238935.1
    NP_001238936.1
    NP_001280556.1
    NP_001280557.1
    NP_001280561.1
    NP_001350591.1
    NP_001350593.1
    NP_001350594.1
    NP_001350595.1
    NP_116021.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_030439.1 RefSeqGene

      Range
      5007..69741
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001252006.1 → NP_001238935.1  poly(A) polymerase alpha isoform 2

      See identical proteins and their annotated locations for NP_001238935.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks multiple exons and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 2 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL163051, BX089817, BX248753, DB045100
      Consensus CDS
      CCDS58334.1
      UniProtKB/Swiss-Prot
      P51003
      Related
      ENSP00000450437.1, ENST00000557320.5
      Conserved Domains (1) summary
      pfam04928
      Location:21 → 279
      PAP_central; Poly(A) polymerase central domain

    2. NM_001252007.1 → NP_001238936.1  poly(A) polymerase alpha isoform 3

      See identical proteins and their annotated locations for NP_001238936.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks multiple exons and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 3 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL163051, BX089817, BX161482, DB045100
      Consensus CDS
      CCDS58335.1
      UniProtKB/TrEMBL
      A0A0C4DGK1
      Related
      ENSP00000450812.1, ENST00000557471.5
      Conserved Domains (1) summary
      cl11966
      Location:21 → 205
      NT_Pol-beta-like; Nucleotidyltransferase (NT) domain of DNA polymerase beta and similar proteins

    3. NM_001293627.1 → NP_001280556.1  poly(A) polymerase alpha isoform 4

      See identical proteins and their annotated locations for NP_001280556.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has an alternate splice site in the 3' coding region, compared to variant 1. The resulting isoform (4) lacks an internal aa, compared to isoform 1.
      Source sequence(s)
      BC015150, BC036014, CD655865, DB483858
      UniProtKB/TrEMBL
      B4DYF4
      Conserved Domains (2) summary
      pfam04926
      Location:366 → 495
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain
      pfam04928
      Location:21 → 363
      PAP_central; Poly(A) polymerase central domain

    4. NM_001293628.2 → NP_001280557.1  poly(A) polymerase alpha isoform 5

      See identical proteins and their annotated locations for NP_001280557.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) has an alternate 5' terminal exon, which results in a downstream AUG start codon, compared to variant 1. The resulting isoform (5) has a shorter N-terminus, compared to isoform 1. Both variants 5 and 6 encode the same isoform 5.
      Source sequence(s)
      AL163051, BC036014, BX248301, CD655865
      Conserved Domains (3) summary
      cl11966
      Location:1 → 113
      NT_Pol-beta-like; Nucleotidyltransferase (NT) domain of DNA polymerase beta and similar proteins
      cl26091
      Location:251 → 396
      MotB_plug; Membrane MotB of proton-channel complex MotA/MotB
      cl27098
      Location:1 → 317
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain

    5. NM_001293632.3 → NP_001280561.1  poly(A) polymerase alpha isoform 5

      See identical proteins and their annotated locations for NP_001280561.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks two consecutive exons in the 5' region, which results in a downstream AUG start codon, compared to variant 1. The resulting isoform (5) has a shorter N-terminus, compared to isoform 1. Both variants 5 and 6 encode the same isoform 5.
      Source sequence(s)
      AK307659, AL163051, BC036014, DB483858
      Conserved Domains (3) summary
      cl11966
      Location:1 → 113
      NT_Pol-beta-like; Nucleotidyltransferase (NT) domain of DNA polymerase beta and similar proteins
      cl26091
      Location:251 → 396
      MotB_plug; Membrane MotB of proton-channel complex MotA/MotB
      cl27098
      Location:1 → 317
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain

    6. NM_001363662.3 → NP_001350591.1  poly(A) polymerase alpha isoform 6

      Status: REVIEWED

      Source sequence(s)
      AL163051
      Consensus CDS
      CCDS86431.1
      UniProtKB/TrEMBL
      B4DHB8, G3XAH6
      Related
      ENSP00000376716.2, ENST00000392990.6
      Conserved Domains (3) summary
      PRK12799
      Location:501 → 646
      motB; flagellar motor protein MotB; Reviewed
      pfam04926
      Location:366 → 495
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain
      pfam04928
      Location:21 → 363
      PAP_central; Poly(A) polymerase central domain

    7. NM_001363664.3 → NP_001350593.1  poly(A) polymerase alpha isoform 7

      Status: REVIEWED

      Source sequence(s)
      AL163051
      UniProtKB/TrEMBL
      B4DHB8
      Conserved Domains (3) summary
      pfam04926
      Location:366 → 495
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain
      pfam04928
      Location:21 → 363
      PAP_central; Poly(A) polymerase central domain
      cl26091
      Location:501 → 645
      MotB_plug; Membrane MotB of proton-channel complex MotA/MotB

    8. NM_001363665.3 → NP_001350594.1  poly(A) polymerase alpha isoform 8

      Status: REVIEWED

      Source sequence(s)
      AL163051
      UniProtKB/TrEMBL
      B4DHB8
      Conserved Domains (3) summary
      PRK12799
      Location:501 → 646
      motB; flagellar motor protein MotB; Reviewed
      pfam04926
      Location:366 → 495
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain
      pfam04928
      Location:21 → 363
      PAP_central; Poly(A) polymerase central domain

    9. NM_001363666.3 → NP_001350595.1  poly(A) polymerase alpha isoform 9

      Status: REVIEWED

      Source sequence(s)
      AL163051
      UniProtKB/TrEMBL
      B4DHB8
      Conserved Domains (3) summary
      pfam04926
      Location:366 → 495
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain
      pfam04928
      Location:21 → 363
      PAP_central; Poly(A) polymerase central domain
      cl26091
      Location:501 → 645
      MotB_plug; Membrane MotB of proton-channel complex MotA/MotB

    10. NM_032632.5 → NP_116021.2  poly(A) polymerase alpha isoform 1

      See identical proteins and their annotated locations for NP_116021.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AL163051
      Consensus CDS
      CCDS9946.1
      UniProtKB/Swiss-Prot
      P51003, Q86SX4, Q86TV0, Q8IYF5, Q9BVU2
      UniProtKB/TrEMBL
      B4DYF4
      Related
      ENSP00000216277.8, ENST00000216277.13
      Conserved Domains (3) summary
      PRK12799
      Location:501 → 646
      motB; flagellar motor protein MotB; Reviewed
      pfam04926
      Location:366 → 495
      PAP_RNA-bind; Poly(A) polymerase predicted RNA binding domain
      pfam04928
      Location:21 → 363
      PAP_central; Poly(A) polymerase central domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      96502376..96567116
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      90733979..90798717
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51003.4 GenPept UniProtKB/Swiss-Prot:P51003

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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