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    TDP1 tyrosyl-DNA phosphodiesterase 1 [ Homo sapiens (human) ]

    Gene ID: 55775, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TDP1provided by HGNC
    Official Full Name
    tyrosyl-DNA phosphodiesterase 1provided by HGNC
    Primary source
    HGNC:HGNC:18884
    See related
    Ensembl:ENSG00000042088 MIM:607198; AllianceGenome:HGNC:18884
    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
    Summary
    The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). [provided by RefSeq, Aug 2016]
    Expression
    Broad expression in testis (RPKM 7.3), lymph node (RPKM 4.5) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TDP1 in Genome Data Viewer
    Location:
    14q32.11
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (89954968..90044764)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (84179088..84268965)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (90422271..90511108)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene EF-hand calcium binding domain 11 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:90359151-90359706 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:90377489-90378106 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:90378107-90378722 Neighboring gene Sharpr-MPRA regulatory region 15055 Neighboring gene uncharacterized LOC124903358 Neighboring gene RAB42, member RAS oncogene family, pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:90420803-90421303 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6004 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:90424329-90424837 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr14:90429220-90430419 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:90473008-90473175 Neighboring gene uncharacterized LOC124903406 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6005 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:90527279-90527780 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:90527781-90528280 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:90555766-90556266 Neighboring gene potassium two pore domain channel subfamily K member 13 Neighboring gene glutaredoxin pseudogene 2

    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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks.
      Title: TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks.
    2. Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus.
      Title: Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus.
    3. Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro.
      Title: Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro.
    4. TDP1 and TOP1 as targets in anticancer treatment of NSCLC: Activity and protein level in normal and tumor tissue from 150 NSCLC patients correlated to clinical data.
      Title: TDP1 and TOP1 as targets in anticancer treatment of NSCLC: Activity and protein level in normal and tumor tissue from 150 NSCLC patients correlated to clinical data.
    5. New Hybrid Compounds Combining Fragments of Usnic Acid and Monoterpenoids for Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibition.
      Title: New Hybrid Compounds Combining Fragments of Usnic Acid and Monoterpenoids for Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibition.
    6. Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
      Title: Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
    7. Data suggest that tyrosyl-DNA phosphodiesterase 1 (TDP1) in mitochondria creates a pathological state that allows neurons to turn on mitophagy to rescue fit mitochondria as a mechanism of survival.
      Title: SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy.
    8. These results demonstrate that fragment-based methods can be a highly feasible approach toward the discovery of small-molecule chemical scaffolds to target TDP1, and for the first time, we provide co-crystal structures of small molecule inhibitors bound to TDP1, which could serve for the rational development of medicinal TDP1 inhibitors.
      Title: Identification of a ligand binding hot spot and structural motifs replicating aspects of tyrosyl-DNA phosphodiesterase I (TDP1) phosphoryl recognition by crystallographic fragment cocktail screening.
    9. This article reviews TDP1 and TDP2 in the context of mitochondrial DNA repair. [review]
      Title: Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair.
    10. Data suggest that tyrosyl-DNA Phosphodiesterases 1 (TDP1) and 2 (TDP2) are promising therapeutic targets and their inhibitors are expected to significantly synergize the effects of current anti-tumor therapies [Review].
      Title: Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.
    Submit: New GeneRIF Correction See all GeneRIFs (67)

    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

    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

    • FLJ11090, MGC104252

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3'-tyrosyl-DNA phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3'-tyrosyl-DNA phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables double-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables exonuclease activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables single-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables single-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in single strand break repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in single strand break repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    tyrosyl-DNA phosphodiesterase 1
    Names
    tyr-DNA phosphodiesterase 1
    NP_001008744.1
    NP_001317134.1
    NP_060789.2
    XP_005267905.1
    XP_006720260.1
    XP_011535244.1
    XP_016876929.1
    XP_047287524.1
    XP_047287525.1
    XP_047287526.1
    XP_047287528.1
    XP_047287529.1
    XP_047287530.1
    XP_047287531.1
    XP_047287532.1
    XP_047287533.1
    XP_047287534.1
    XP_047287535.1
    XP_054232334.1
    XP_054232335.1
    XP_054232336.1
    XP_054232337.1
    XP_054232338.1
    XP_054232339.1
    XP_054232340.1
    XP_054232341.1
    XP_054232342.1
    XP_054232343.1
    XP_054232344.1

    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_009164.1 RefSeqGene

      Range
      5026..93863
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001008744.2 → NP_001008744.1  tyrosyl-DNA phosphodiesterase 1 isoform a

      See identical proteins and their annotated locations for NP_001008744.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (a).
      Source sequence(s)
      AK001952, AK023514, AL137128, BC015474, BM661793, BU849335
      Consensus CDS
      CCDS9888.1
      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8
      UniProtKB/TrEMBL
      B2RDI0
      Related
      ENSP00000377099.2, ENST00000393454.6
      Conserved Domains (3) summary
      cd09193
      Location:162 → 330
      PLDc_mTdp1_1; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase
      cd09195
      Location:352 → 545
      PLDc_mTdp1_2; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase
      pfam06087
      Location:166 → 582
      Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

    2. NM_001330205.2 → NP_001317134.1  tyrosyl-DNA phosphodiesterase 1 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' and 3' UTRs, and lacks an alternate exon in the 3' coding region resulting in a frameshift and a novel 3' coding region, compared to variant 1. The encoded isoform (b) is shorter, and has a distinct C-terminus, compared to isoform a.
      Source sequence(s)
      AL137128, BM661793
      Consensus CDS
      CCDS81836.1
      UniProtKB/TrEMBL
      E7EPD8, G3V2F4
      Conserved Domains (3) summary
      cd09193
      Location:162 → 330
      PLDc_mTdp1_1; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase
      cd09195
      Location:352 → 545
      PLDc_mTdp1_2; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase
      pfam06087
      Location:166 → 550
      Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

    3. NM_018319.4 → NP_060789.2  tyrosyl-DNA phosphodiesterase 1 isoform a

      See identical proteins and their annotated locations for NP_060789.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (a). Variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AK023514, AL137128, BC015474, BM661793, BU849335
      Consensus CDS
      CCDS9888.1
      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8
      UniProtKB/TrEMBL
      B2RDI0
      Related
      ENSP00000337353.4, ENST00000335725.9
      Conserved Domains (3) summary
      cd09193
      Location:162 → 330
      PLDc_mTdp1_1; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase
      cd09195
      Location:352 → 545
      PLDc_mTdp1_2; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase
      pfam06087
      Location:166 → 582
      Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

    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
      89954968..90044764
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047431570.1 → XP_047287526.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    2. XM_011536942.4 → XP_011535244.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      See identical proteins and their annotated locations for XP_011535244.1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8
      UniProtKB/TrEMBL
      B2RDI0
      Conserved Domains (3) summary
      cd09193
      Location:162 → 330
      PLDc_mTdp1_1; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase
      cd09195
      Location:352 → 545
      PLDc_mTdp1_2; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase
      pfam06087
      Location:166 → 582
      Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

    3. XM_047431568.1 → XP_047287524.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    4. XM_047431576.1 → XP_047287532.1  tyrosyl-DNA phosphodiesterase 1 isoform X2

      UniProtKB/TrEMBL
      G3V2F4

    5. XM_047431569.1 → XP_047287525.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    6. XM_006720197.5 → XP_006720260.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      See identical proteins and their annotated locations for XP_006720260.1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8
      UniProtKB/TrEMBL
      B2RDI0
      Conserved Domains (3) summary
      cd09193
      Location:162 → 330
      PLDc_mTdp1_1; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase
      cd09195
      Location:352 → 545
      PLDc_mTdp1_2; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase
      pfam06087
      Location:166 → 582
      Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

    7. XM_047431577.1 → XP_047287533.1  tyrosyl-DNA phosphodiesterase 1 isoform X2

      UniProtKB/TrEMBL
      G3V2F4

    8. XM_047431573.1 → XP_047287529.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    9. XM_005267848.4 → XP_005267905.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      See identical proteins and their annotated locations for XP_005267905.1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8
      UniProtKB/TrEMBL
      B2RDI0
      Conserved Domains (3) summary
      cd09193
      Location:162 → 330
      PLDc_mTdp1_1; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase
      cd09195
      Location:352 → 545
      PLDc_mTdp1_2; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase
      pfam06087
      Location:166 → 582
      Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

    10. XM_047431572.1 → XP_047287528.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    11. XM_017021440.3 → XP_016876929.1  tyrosyl-DNA phosphodiesterase 1 isoform X2

      UniProtKB/TrEMBL
      E7EPD8, G3V2F4
      Related
      ENSP00000450628.1, ENST00000555880.5
      Conserved Domains (3) summary
      cd09193
      Location:162 → 330
      PLDc_mTdp1_1; Catalytic domain, repeat 1, of metazoan tyrosyl-DNA phosphodiesterase
      cd09195
      Location:352 → 545
      PLDc_mTdp1_2; Catalytic domain, repeat 2, of metazoan tyrosyl-DNA phosphodiesterase
      pfam06087
      Location:166 → 550
      Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

    12. XM_047431579.1 → XP_047287535.1  tyrosyl-DNA phosphodiesterase 1 isoform X4

    13. XM_047431578.1 → XP_047287534.1  tyrosyl-DNA phosphodiesterase 1 isoform X3

    14. XM_047431574.1 → XP_047287530.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    15. XM_047431575.1 → XP_047287531.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    RNA

    1. XR_007064032.1 RNA Sequence

    2. XR_007064034.1 RNA Sequence

    3. XR_007064035.1 RNA Sequence

    4. XR_007064033.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      84179088..84268965
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376362.1 → XP_054232337.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    2. XM_054376361.1 → XP_054232336.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    3. XM_054376360.1 → XP_054232335.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    4. XM_054376367.1 → XP_054232342.1  tyrosyl-DNA phosphodiesterase 1 isoform X2

      UniProtKB/TrEMBL
      G3V2F4

    5. XM_054376363.1 → XP_054232338.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    6. XM_054376359.1 → XP_054232334.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    7. XM_054376366.1 → XP_054232341.1  tyrosyl-DNA phosphodiesterase 1 isoform X2

      UniProtKB/TrEMBL
      G3V2F4

    8. XM_054376369.1 → XP_054232344.1  tyrosyl-DNA phosphodiesterase 1 isoform X4

    9. XM_054376368.1 → XP_054232343.1  tyrosyl-DNA phosphodiesterase 1 isoform X3

    10. XM_054376364.1 → XP_054232339.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    11. XM_054376365.1 → XP_054232340.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

      UniProtKB/Swiss-Prot
      Q2HXX4, Q86TV8, Q96BK7, Q9NUW8, Q9NZM7, Q9NZM8

    RNA

    1. XR_008488883.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NUW8.2 GenPept UniProtKB/Swiss-Prot:Q9NUW8

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