TOP3A DNA topoisomerase III alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: TOP3Aprovided by HGNC
Official Full Name: DNA topoisomerase III alphaprovided by HGNC
Primary source: HGNC:HGNC:11992
See related: Ensembl:ENSG00000177302 MIM:601243; AllianceGenome:HGNC:11992
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: TOP3; PEOB5; ZGRF7; MGRISCE2
Summary: This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
Expression: Ubiquitous expression in testis (RPKM 4.1), bone marrow (RPKM 3.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p11.2

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (18271428..18314994, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (18218234..18261800, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (18174742..18218308, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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?

Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability.
Title: Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability.
Prediction of recurrence from metabolites and expression of TOP2A and EZH2 in prostate cancer patients treated with radiotherapy.
Title: Prediction of recurrence from metabolites and expression of TOP2A and EZH2 in prostate cancer patients treated with radiotherapy.
The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins.
Title: The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins.
Two type I topoisomerases maintain DNA topology in human mitochondria.
Title: Two type I topoisomerases maintain DNA topology in human mitochondria.
TOP3A amplification and ATRX inactivation are mutually exclusive events in pediatric osteosarcomas using ALT.
Title: TOP3A amplification and ATRX inactivation are mutually exclusive events in pediatric osteosarcomas using ALT.
The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom's syndrome helicase for efficient disruption of D-loops.
Title: The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom's syndrome helicase for efficient disruption of D-loops.
Duplex DNA and BLM regulate gate opening by the human TopoIIIalpha-RMI1-RMI2 complex.
Title: Duplex DNA and BLM regulate gate opening by the human TopoIIIα-RMI1-RMI2 complex.
Predominant cellular mitochondrial dysfunction in the TOP3A gene-caused Bloom syndrome-like disorder.
Title: Predominant cellular mitochondrial dysfunction in the TOP3A gene-caused Bloom syndrome-like disorder.
Long interspersed element-1 ribonucleoprotein particles protect telomeric ends in alternative lengthening of telomeres dependent cells.
Title: Long interspersed element-1 ribonucleoprotein particles protect telomeric ends in alternative lengthening of telomeres dependent cells.
Top3alpha is shown to be an essential component of the mitochondrial DNA replication machinery and as the first component of the mitochondrial DNA separation machinery.
Title: Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA.

Submit: New GeneRIF Correction See all GeneRIFs (26)

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

Associated conditions

Description	Tests
Microcephaly, growth restriction, and increased sister chromatid exchange 2 MedGen: C4748176 OMIM: 618097 GeneReviews: Not available	Compare labs
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5 MedGen: C4748184 OMIM: 618098 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH47004 (e-PCR)
- UniSTS:87050

SHGC-80056 (e-PCR)
- UniSTS:101662

D8S2279 (e-PCR)
- UniSTS:473907

TOP3A__3878 (e-PCR)
- UniSTS:462935

D11S3430 (e-PCR)
- UniSTS:152671

G59869 (e-PCR)
- UniSTS:137152

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	TAS Traceable Author Statement more info	PubMed
enables DNA topoisomerase type I (single strand cut, ATP-independent) activity	IBA Inferred from Biological aspect of Ancestor more info
enables DNA topoisomerase type I (single strand cut, ATP-independent) activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA recombination	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA topological change	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA topological change	IDA Inferred from Direct Assay more info	PubMed
involved_in chromosome separation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
involved_in meiotic cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in mitochondrial DNA metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in resolution of DNA recombination intermediates	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in PML body	IDA Inferred from Direct Assay more info	PubMed
part_of RecQ family helicase-topoisomerase III complex	IBA Inferred from Biological aspect of Ancestor more info
part_of RecQ family helicase-topoisomerase III complex	IPI Inferred from Physical Interaction more info	PubMed
located_in mitochondrial matrix	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HTP more info	PubMed
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	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: DNA topoisomerase 3-alpha

Names: topo III-alpha; topoisomerase (DNA) III alpha; zinc finger, GRF-type containing 7

NP_001307688.1

EC 5.6.2.1

NP_004609.1

EC 5.6.2.1

XP_047292589.1

EC 5.6.2.1

XP_047292590.1

EC 5.6.2.1

XP_047292591.1

EC 5.6.2.1

XP_054173011.1

EC 5.6.2.1

XP_054173012.1

EC 5.6.2.1

XP_054173013.1

EC 5.6.2.1

XP_054188088.1

EC 5.6.2.1

XP_054188089.1

EC 5.6.2.1

XP_054188090.1

EC 5.6.2.1

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)

NM_001320759.2 → NP_001307688.1 DNA topoisomerase 3-alpha isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 5' coding region, resulting in a novel 5' UTR and the use of an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter, compared to isoform 1.

Source sequence(s)

AC127537, AF086042, AK296437, AW294300, BM462184, BY996313

UniProtKB/Swiss-Prot

Q13472

Conserved Domains (6) summary

COG0551
Location:557 → 633

YrdD; ssDNA-binding Zn-finger and Zn-ribbon domains of topoisomerase 1 [Replication, recombination and repair]

cd00186
Location:107 → 522

TOP1Ac; DNA Topoisomerase, subtype IA; DNA-binding, ATP-binding and catalytic domain of bacterial DNA topoisomerases I and III, and eukaryotic DNA topoisomerase III and eubacterial and archael reverse gyrases. Topoisomerases clevage single or double stranded DNA ...

pfam01131
Location:100 → 507

Topoisom_bac; DNA topoisomerase

pfam01396
Location:560 → 599

zf-C4_Topoisom; Topoisomerase DNA binding C4 zinc finger

pfam06839
Location:800 → 844

zf-GRF; GRF zinc finger

cl00718
Location:18 → 98

TOPRIM; Topoisomerase-primase domain. This is a nucleotidyl transferase/hydrolase domain found in type IA, type IIA and type IIB topoisomerases, bacterial DnaG-type primases, small primase-like proteins from bacteria and archaea, OLD family nucleases from ...
NM_004618.5 → NP_004609.1 DNA topoisomerase 3-alpha isoform 1

See identical proteins and their annotated locations for NP_004609.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC127537, AF086042, AW294300, BC051748, BM462184

Consensus CDS

CCDS11194.1

UniProtKB/Swiss-Prot

A8KA61, B4DK80, D3DXC7, Q13472, Q13473

Related

ENSP00000321636.5, ENST00000321105.10

Conserved Domains (6) summary

cd03362
Location:35 → 193

TOPRIM_TopoIA_TopoIII; TOPRIM_TopoIA_TopoIII: The topoisomerase-primase (TORPIM) domain found in members of the type IA family of DNA topoisomerases (Topo IA) similar to topoisomerase III. Type IA DNA topoisomerases remove (relax) negative supercoils in the DNA by: cleaving ...

COG0550
Location:35 → 634

TopA; DNA topoisomerase IA [Replication, recombination and repair]

COG0551
Location:652 → 728

YrdD; ssDNA-binding Zn-finger and Zn-ribbon domains of topoisomerase 1 [Replication, recombination and repair]

cd00186
Location:202 → 617

TOP1Ac; DNA Topoisomerase, subtype IA; DNA-binding, ATP-binding and catalytic domain of bacterial DNA topoisomerases I and III, and eukaryotic DNA topoisomerase III and eubacterial and archael reverse gyrases. Topoisomerases clevage single or double stranded DNA ...

pfam01396
Location:655 → 694

zf-C4_Topoisom; Topoisomerase DNA binding C4 zinc finger

pfam06839
Location:895 → 939

zf-GRF; GRF zinc finger