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Tdp1 tyrosyl-DNA phosphodiesterase 1 [ Mus musculus (house mouse) ]

Gene ID: 104884, updated on 2-Nov-2024

Summary

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Official Symbol
Tdp1provided by MGI
Official Full Name
tyrosyl-DNA phosphodiesterase 1provided by MGI
Primary source
MGI:MGI:1920036
See related
Ensembl:ENSMUSG00000021177 AllianceGenome:MGI:1920036
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
SCAN1; Gm40556; MLZ-501; 2810481F14Rik; 4921509N21Rik; E430034L06Rik
Summary
Predicted to enable 3'-tyrosyl-DNA phosphodiesterase activity; double-stranded DNA binding activity; and single-stranded DNA binding activity. Acts upstream of or within single strand break repair. Located in nucleus. Is expressed in ovary and testis. Used to study spinocerebellar ataxia with axonal neuropathy 1. Human ortholog(s) of this gene implicated in spinocerebellar ataxia with axonal neuropathy 1. Orthologous to human TDP1 (tyrosyl-DNA phosphodiesterase 1). [provided by Alliance of Genome Resources, Nov 2024]
Expression
Broad expression in testis adult (RPKM 14.7), CNS E14 (RPKM 6.9) and 22 other tissues See more
Orthologs
human all
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Genomic context

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See Tdp1 in Genome Data Viewer
Location:
12; 12 E
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 12 NC_000078.7 (99850767..99921482)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 12 NC_000078.6 (99884515..99955223)

Chromosome 12 - NC_000078.7Genomic Context describing neighboring genes Neighboring gene predicted gene, 53756 Neighboring gene predicted gene, 19951 Neighboring gene EF-hand calcium binding domain 11 Neighboring gene STARR-seq mESC enhancer starr_33027 Neighboring gene STARR-seq mESC enhancer starr_33028 Neighboring gene phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoribosylaminoimidazole, succinocarboxamide synthetase pseudogene Neighboring gene STARR-positive B cell enhancer mm9_chr12:101121576-101121877 Neighboring gene STARR-seq mESC enhancer starr_33029 Neighboring gene STARR-positive B cell enhancer mm9_chr12:101140770-101141071 Neighboring gene predicted gene, 57807 Neighboring gene STARR-seq mESC enhancer starr_33030 Neighboring gene potassium channel, subfamily K, member 13 Neighboring gene malate dehydrogenase 1, NAD (soluble) pseudogene Neighboring gene predicted gene, 51957

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy. Khomenko TM, et al. Int J Mol Sci, 2019 Dec 23. PMID 31878088, Free PMC Article
  2. Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage. Chiang SC, et al. Sci Adv, 2017 Apr. PMID 28508041, Free PMC Article
  3. In vitro complementation of Tdp1 deficiency indicates a stabilized enzyme-DNA adduct from tyrosyl but not glycolate lesions as a consequence of the SCAN1 mutation. Hawkins AJ, et al. DNA Repair (Amst), 2009 May 1. PMID 19211312, Free PMC Article
  4. TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. Katyal S, et al. EMBO J, 2007 Nov 14. PMID 17914460, Free PMC Article
  5. TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1. Zeng Z, et al. Nucleic Acids Res, 2012 Sep 1. PMID 22740648, Free PMC Article

See all (36) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy.
    Title: Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy.
  2. These findings provide evidence for TDP1 as a novel mitochondrial enzyme.
    Title: Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria.
  3. The interaction with Lig3alpha is promoted by serine 81 that is located within a putative S/TQ site in the N-terminus domain of TDP1.
    Title: TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage.
  4. Tdp1(-/-) fibroblasts exhibited deficiencies in processing 3'-phosphotyrosyl single-strand breaks and 3'-phosphoglycolate double-strand breaks, but not 3'-phosphoglycolate single-strand breaks.
    Title: In vitro complementation of Tdp1 deficiency indicates a stabilized enzyme-DNA adduct from tyrosyl but not glycolate lesions as a consequence of the SCAN1 mutation.
  5. Data indicate that TDP1 is required for neural homeostasis and reveal a widespread requisite for TDP1 function in response to acutely elevated levels of DNA topoisomerase I (Top1)-associated DNA strand breaks.
    Title: TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo.
  6. This study provides a direct demonstration that Tdp1 repairs Topo I covalent lesions in vivo and suggests that spinocerebellar ataxia with axonal neuropathy (SCAN1) arises from the recessive neomorphic mutation H493R.
    Title: Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?
Submit: New GeneRIF Correction

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Endonuclease-mediated (2) 
  • Gene trapped (3)  1 citation

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 MGI

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 ISO
Inferred from Sequence Orthology
more info
  
enables 3'-tyrosyl-DNA phosphodiesterase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables double-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables double-stranded DNA binding ISO
Inferred from Sequence Orthology
more info
  
enables exonuclease activity IEA
Inferred from Electronic Annotation
more info
  
enables single-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables single-stranded DNA binding ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
involved_in DNA repair IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within DNA repair IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in DNA repair ISO
Inferred from Sequence Orthology
more info
  
involved_in double-strand break repair ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within single strand break repair IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in single strand break repair ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
NOT located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm ISO
Inferred from Sequence Orthology
more info
  
located_in intracellular membrane-bounded organelle ISO
Inferred from Sequence Orthology
more info
  
located_in nucleoplasm ISO
Inferred from Sequence Orthology
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
tyrosyl-DNA phosphodiesterase 1
Names
protein expressed in male leptotene and zygotene spermatocytes 501
tyr-DNA phosphodiesterase 1
tyrosyl-DNA phodphodiesterase 1
NP_001366001.1
NP_082630.2
XP_030102366.1
XP_030102367.1
XP_036013044.1
XP_036013045.1
XP_036013046.1

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.

mRNA and Protein(s)

  1. NM_001379072.1 → NP_001366001.1  tyrosyl-DNA phosphodiesterase 1 isoform 1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC160931, CT010436
    UniProtKB/Swiss-Prot
    Q8BJ37, Q8VE39
    Conserved Domains (1) summary
    pfam06087
    Location:167 → 548
    Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

  2. NM_028354.5 → NP_082630.2  tyrosyl-DNA phosphodiesterase 1 isoform 2

    See identical proteins and their annotated locations for NP_082630.2

    Status: VALIDATED

    Source sequence(s)
    AC160931, CT010436
    Consensus CDS
    CCDS26105.2
    UniProtKB/Swiss-Prot
    Q8BJ37, Q8VE39
    UniProtKB/TrEMBL
    B8JJC1
    Related
    ENSMUSP00000118656.2, ENSMUST00000153627.8
    Conserved Domains (1) summary
    pfam06087
    Location:167 → 580
    Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000078.7 Reference GRCm39 C57BL/6J

    Range
    99850767..99921482
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_036157151.1 → XP_036013044.1  tyrosyl-DNA phosphodiesterase 1 isoform X3

    UniProtKB/Swiss-Prot
    Q8BJ37, Q8VE39
    Conserved Domains (1) summary
    pfam06087
    Location:171 → 584
    Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

  2. XM_030246506.2 → XP_030102366.1  tyrosyl-DNA phosphodiesterase 1 isoform X1

    UniProtKB/Swiss-Prot
    Q8BJ37, Q8VE39
    Conserved Domains (1) summary
    pfam06087
    Location:171 → 554
    Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

  3. XM_036157152.1 → XP_036013045.1  tyrosyl-DNA phosphodiesterase 1 isoform X4

    UniProtKB/Swiss-Prot
    Q8BJ37, Q8VE39
    UniProtKB/TrEMBL
    B8JJC1
    Conserved Domains (1) summary
    pfam06087
    Location:167 → 580
    Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

  4. XM_030246507.2 → XP_030102367.1  tyrosyl-DNA phosphodiesterase 1 isoform X2

    UniProtKB/Swiss-Prot
    Q8BJ37, Q8VE39
    Conserved Domains (1) summary
    pfam06087
    Location:199 → 612
    Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase

  5. XM_036157153.1 → XP_036013046.1  tyrosyl-DNA phosphodiesterase 1 isoform X5

    UniProtKB/Swiss-Prot
    Q8BJ37, Q8VE39
    Conserved Domains (1) summary
    pfam06087
    Location:167 → 548
    Tyr-DNA_phospho; Tyrosyl-DNA phosphodiesterase
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8BJ37.2 GenPept UniProtKB/Swiss-Prot:Q8BJ37

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