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    PARN poly(A)-specific ribonuclease [ Homo sapiens (human) ]

    Gene ID: 5073, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PARNprovided by HGNC
    Official Full Name
    poly(A)-specific ribonucleaseprovided by HGNC
    Primary source
    HGNC:HGNC:8609
    See related
    Ensembl:ENSG00000140694 MIM:604212; AllianceGenome:HGNC:8609
    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
    DAN; DKCB6; PFBMFT4
    Summary
    The protein encoded by this gene is a 3'-exoribonuclease, with similarity to the RNase D family of 3'-exonucleases. It prefers poly(A) as the substrate, hence, efficiently degrades poly(A) tails of mRNAs. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs. This protein is also involved in silencing of certain maternal mRNAs during oocyte maturation and early embryonic development, as well as in nonsense-mediated decay (NMD) of mRNAs that contain premature stop codons. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 11.4), testis (RPKM 9.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PARN in Genome Data Viewer
    Location:
    16p13.12
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (14435701..14630260, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (14473312..14667845, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (14529558..14724117, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:14458211-14458712 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:14466520-14467096 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:14468174-14468349 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:14469696-14470196 Neighboring gene long intergenic non-protein coding RNA 2130 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:14487195-14487694 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:14499557-14500058 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10498 Neighboring gene Sharpr-MPRA regulatory region 5329 Neighboring gene Sharpr-MPRA regulatory region 2182 Neighboring gene long intergenic non-protein coding RNA 3107 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:14539490-14539990 Neighboring gene Sharpr-MPRA regulatory region 750 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14579525-14580460 Neighboring gene uncharacterized LOC105371094 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14589500-14590022 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14590023-14590545 Neighboring gene NFE2L2 motif-containing MPRA enhancer 233 Neighboring gene Sharpr-MPRA regulatory regions 10217 and 14533 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr16:14616510-14617247 Neighboring gene uncharacterized LOC107984865 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14626034-14626783 Neighboring gene RNA, 7SL, cytoplasmic 274, pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14723085-14723608 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14723609-14724130 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14724131-14724653 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14726253-14726820 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:14726821-14727390 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr16:14730046-14730899 Neighboring gene RNA, U7 small nuclear 125 pseudogene Neighboring gene bifunctional apoptosis regulator Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:14781374-14781874 Neighboring gene phospholipase A2 group X

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Recognition of adenosine residues by the active site of poly(A)-specific ribonuclease. Henriksson N, et al. J Biol Chem, 2010 Jan 1. PMID 19901024, Free PMC Article
    2. Structural insight into poly(A) binding and catalytic mechanism of human PARN. Wu M, et al. EMBO J, 2005 Dec 7. PMID 16281054, Free PMC Article
    3. Translation Efficiency and Degradation of ER-Associated mRNAs Modulated by ER-Anchored poly(A)-Specific Ribonuclease (PARN). Duan TL, et al. Cells, 2020 Jan 9. PMID 31936572, Free PMC Article
    4. PARN Modulates Y RNA Stability and Its 3'-End Formation. Shukla S, et al. Mol Cell Biol, 2017 Oct 15. PMID 28760775, Free PMC Article
    5. The Intrinsically Disordered C-Terminal Domain Triggers Nucleolar Localization and Function Switch of PARN in Response to DNA Damage. Duan TL, et al. Cells, 2019 Aug 5. PMID 31387300, Free PMC Article

    See all (115) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Translation Efficiency and Degradation of ER-Associated mRNAs Modulated by ER-Anchored poly(A)-Specific Ribonuclease (PARN).
      Title: Translation Efficiency and Degradation of ER-Associated mRNAs Modulated by ER-Anchored poly(A)-Specific Ribonuclease (PARN).
    2. Regulation of poly(a)-specific ribonuclease activity by reversible lysine acetylation.
      Title: Regulation of poly(a)-specific ribonuclease activity by reversible lysine acetylation.
    3. PARN regulates miRNA levels by stabilizing either mature or precursor miRNAs by removing oligo(A) tails added by the poly(A) polymerase PAPD5, which if remaining recruit the exonuclease DIS3L or DIS3L2 to degrade the miRNA. PARN knockdown destabilizes multiple miRNAs that repress p53 translation, leading to p53 accumulation.
      Title: The RNase PARN Controls the Levels of Specific miRNAs that Contribute to p53 Regulation.
    4. Study reports a family with idiopathic pulmonary fibrosis with a rare missense mutation, p.Y91C, and a novel insertion, p.(I274*) in PARN gene. PARN p.Y91C had reduced deadenylase activity and the p.(I274*) transcript was depleted.
      Title: From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants.
    5. Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models.
      Title: Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models.
    6. Intrinsically disordered PARN C-terminal domain is required for PARN nuclear localization in response to DNA damage.
      Title: The Intrinsically Disordered C-Terminal Domain Triggers Nucleolar Localization and Function Switch of PARN in Response to DNA Damage.
    7. We find that mature hTR derives from extended precursors but that in PARN-mutant cells hTR maturation kinetically stalls and unprocessed precursors are degraded. Loss of poly(A)polymerase PAPD5 in PARN-mutant cells accelerates hTR maturation and restores hTR processing, indicating that oligoadenylation and deadenylation set rates of hTR maturation
      Title: Disruption of Telomerase RNA Maturation Kinetics Precipitates Disease.
    8. PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs).
      Title: PARN and TOE1 Constitute a 3' End Maturation Module for Nuclear Non-coding RNAs.
    9. PARN-mediated shortening is pervasive across most miRNAs and appears to be a conserved mechanism contributing to the 3' end formation of vertebrate miRNAs. Our findings add miRNAs to the expanding list of noncoding RNAs whose 3' end formation depends on PARN.
      Title: Poly(A)-specific ribonuclease sculpts the 3' ends of microRNAs.
    10. Processing of 3' telomerase RNA occurs in two steps with longer forms first being trimmed by RRP6 and shorter forms then being processed by PARN.
      Title: The H/ACA complex disrupts triplex in hTR precursor to permit processing by RRP6 and PARN.
    Submit: New GeneRIF Correction See all GeneRIFs (45)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3'-5'-RNA exonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA binding HDA PubMed 
    enables RNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cation binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables mRNA 3'-UTR binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nuclease activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables poly(A)-specific ribonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables poly(A)-specific ribonuclease activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables telomerase RNA binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in RNA modification TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in box H/ACA sno(s)RNA 3'-end processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in female gamete generation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in lncRNA processing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in miRNA catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nuclear-transcribed mRNA poly(A) tail shortening IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in poly(A)-dependent snoRNA 3'-end processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of telomere maintenance via telomerase IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in priRNA 3'-end processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of telomerase RNA localization to Cajal body IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in siRNA 3'-end processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in telomerase RNA stabilization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    poly(A)-specific ribonuclease PARN
    Names
    deadenylating nuclease
    deadenylation nuclease
    polyadenylate-specific ribonuclease
    NP_001127949.1
    NP_001229921.1
    NP_002573.1
    XP_011520816.1
    XP_047290137.1
    XP_047290138.1
    XP_047290139.1
    XP_047290140.1
    XP_047290141.1
    XP_054185071.1
    XP_054185072.1
    XP_054185073.1
    XP_054185074.1
    XP_054185075.1
    XP_054185076.1
    XP_054236386.1
    XP_054236387.1
    XP_054236388.1
    XP_054236389.1
    XP_054236390.1
    XP_054236391.1
    XP_054236392.1
    XP_054236393.1
    XP_054236394.1
    XP_054236395.1
    XP_054236396.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_042871.1 RefSeqGene

      Range
      5012..199571
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1286

    mRNA and Protein(s)

    1. NM_001134477.3 → NP_001127949.1  poly(A)-specific ribonuclease PARN isoform 2

      See identical proteins and their annotated locations for NP_001127949.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate donor splice site in the 5' terminal exon compared to transcript variant 1, resulting in translation initiation from an alternate, in-frame downstream AUG and a shorter isoform (2) compared to isoform 1.
      Source sequence(s)
      AK023866, AK293189, BF435512
      Consensus CDS
      CCDS45420.1
      UniProtKB/TrEMBL
      A0A494C0W0
      Related
      ENSP00000345456.7, ENST00000341484.11
      Conserved Domains (2) summary
      pfam04857
      Location:1 → 329
      CAF1; CAF1 family ribonuclease
      pfam08675
      Location:377 → 451
      RNA_bind; RNA binding domain

    2. NM_001242992.2 → NP_001229921.1  poly(A)-specific ribonuclease PARN isoform 3

      See identical proteins and their annotated locations for NP_001229921.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses two alternate in-frame splice sites and lacks an alternate exon in the 5' coding region compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.
      Source sequence(s)
      AK023866, AK301648, BF435512, DA308295
      Consensus CDS
      CCDS58425.1
      UniProtKB/TrEMBL
      A0A494C0K5
      Related
      ENSP00000410525.2, ENST00000420015.6
      Conserved Domains (2) summary
      pfam04857
      Location:3 → 344
      CAF1; CAF1 family ribonuclease
      pfam08675
      Location:392 → 466
      RNA_bind; RNA binding domain

    3. NM_002582.4 → NP_002573.1  poly(A)-specific ribonuclease PARN isoform 1

      See identical proteins and their annotated locations for NP_002573.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AK023866, AK315020, BF435512
      Consensus CDS
      CCDS45419.1
      UniProtKB/Swiss-Prot
      B2RCB3, B4DDG8, B4DSB0, B4DWR4, B4E1H6, O95453
      UniProtKB/TrEMBL
      A0A494C0W0
      Related
      ENSP00000387911.2, ENST00000437198.7
      Conserved Domains (2) summary
      pfam08675
      Location:438 → 512
      RNA_bind; RNA binding domain
      pfam04857
      Location:3 → 390
      CAF1; CAF1 family ribonuclease

    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_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      14435701..14630260 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047434184.1 → XP_047290140.1  poly(A)-specific ribonuclease PARN isoform X4

      UniProtKB/TrEMBL
      A0A494BZU6

    2. XM_047434183.1 → XP_047290139.1  poly(A)-specific ribonuclease PARN isoform X3

      UniProtKB/TrEMBL
      A0A494BZU6

    3. XM_047434181.1 → XP_047290137.1  poly(A)-specific ribonuclease PARN isoform X1

      UniProtKB/TrEMBL
      A0A494BZW7
      Related
      ENSP00000499078.1, ENST00000651634.1

    4. XM_047434182.1 → XP_047290138.1  poly(A)-specific ribonuclease PARN isoform X2

      UniProtKB/TrEMBL
      A0A494BZW7, A0A494C1N1
      Related
      ENSP00000499110.1, ENST00000650960.1

    5. XM_011522514.3 → XP_011520816.1  poly(A)-specific ribonuclease PARN isoform X5

      See identical proteins and their annotated locations for XP_011520816.1

      UniProtKB/TrEMBL
      A0A494C156
      Related
      ENSP00000498898.1, ENST00000652051.1
      Conserved Domains (1) summary
      pfam04857
      Location:3 → 390
      CAF1; CAF1 family ribonuclease

    6. XM_047434185.1 → XP_047290141.1  poly(A)-specific ribonuclease PARN isoform X6

      UniProtKB/TrEMBL
      A0A494C002
      Related
      ENSP00000498315.1, ENST00000651348.1

    RNA

    1. XR_007064884.1 RNA Sequence

    2. XR_007064883.1 RNA Sequence

    3. XR_007064882.1 RNA Sequence

    4. XR_007064881.1 RNA Sequence

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187607.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      8558..203161 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054329096.1 → XP_054185071.1  poly(A)-specific ribonuclease PARN isoform X1

      UniProtKB/TrEMBL
      A0A494BZW7

    2. XM_054329097.1 → XP_054185072.1  poly(A)-specific ribonuclease PARN isoform X2

      UniProtKB/TrEMBL
      A0A494BZW7, A0A494C1N1

    3. XM_054329099.1 → XP_054185074.1  poly(A)-specific ribonuclease PARN isoform X4

      UniProtKB/TrEMBL
      A0A494BZU6

    4. XM_054329098.1 → XP_054185073.1  poly(A)-specific ribonuclease PARN isoform X3

      UniProtKB/TrEMBL
      A0A494BZU6

    5. XM_054329100.1 → XP_054185075.1  poly(A)-specific ribonuclease PARN isoform X5

      UniProtKB/TrEMBL
      A0A494C156

    6. XM_054329101.1 → XP_054185076.1  poly(A)-specific ribonuclease PARN isoform X6

      UniProtKB/TrEMBL
      A0A494C002

    RNA

    1. XR_008485621.1 RNA Sequence

    2. XR_008485620.1 RNA Sequence

    3. XR_008485619.1 RNA Sequence

    4. XR_008485622.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      14473312..14667845 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054380414.1 → XP_054236389.1  poly(A)-specific ribonuclease PARN isoform X8

      UniProtKB/TrEMBL
      A0A494BZW7, A0A494C1K5

    2. XM_054380413.1 → XP_054236388.1  poly(A)-specific ribonuclease PARN isoform X7

      UniProtKB/TrEMBL
      A0A494BZW7, A0A494C0Q2

    3. XM_054380417.1 → XP_054236392.1  poly(A)-specific ribonuclease PARN isoform X9

      UniProtKB/TrEMBL
      A0A494BZU6

    4. XM_054380421.1 → XP_054236396.1  poly(A)-specific ribonuclease PARN isoform X11

    5. XM_054380420.1 → XP_054236395.1  poly(A)-specific ribonuclease PARN isoform X10

    6. XM_054380411.1 → XP_054236386.1  poly(A)-specific ribonuclease PARN isoform X1

      UniProtKB/TrEMBL
      A0A494BZW7

    7. XM_054380412.1 → XP_054236387.1  poly(A)-specific ribonuclease PARN isoform X2

      UniProtKB/TrEMBL
      A0A494BZW7, A0A494C1N1

    8. XM_054380416.1 → XP_054236391.1  poly(A)-specific ribonuclease PARN isoform X4

      UniProtKB/TrEMBL
      A0A494BZU6

    9. XM_054380415.1 → XP_054236390.1  poly(A)-specific ribonuclease PARN isoform X3

      UniProtKB/TrEMBL
      A0A494BZU6

    10. XM_054380418.1 → XP_054236393.1  poly(A)-specific ribonuclease PARN isoform X5

      UniProtKB/TrEMBL
      A0A494C156

    11. XM_054380419.1 → XP_054236394.1  poly(A)-specific ribonuclease PARN isoform X6

      UniProtKB/TrEMBL
      A0A494C002
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95453.1 GenPept UniProtKB/Swiss-Prot:O95453

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