TOP3B DNA topoisomerase III beta [Homo sapiens (human)] - Gene

Summary

Official Symbol: TOP3Bprovided by HGNC
Official Full Name: DNA topoisomerase III betaprovided by HGNC
Primary source: HGNC:HGNC:11993
See related: Ensembl:ENSG00000100038 MIM:603582; AllianceGenome:HGNC:11993
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: TOP3B1
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 relaxing the supercoils and altering the topology of DNA. The enzyme interacts with DNA helicase SGS1 and plays a role in DNA recombination, cellular aging and maintenance of genome stability. Low expression of this gene may be related to higher survival rates in breast cancer patients. This gene has a pseudogene on chromosome 22. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Aug 2013]
Expression: Ubiquitous expression in spleen (RPKM 4.6), lymph node (RPKM 3.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q11.22

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (21957025..21982787, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (22370556..22396320, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (22311397..22337184, complement)

Chromosome 22 - NC_000022.11 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
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?

A dual-activity topoisomerase complex regulates mRNA translation and turnover.
Title: A dual-activity topoisomerase complex regulates mRNA translation and turnover.
Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3beta.
Title: Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3β.
DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks.
Title: DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks.
Further evidence of GABRA4 and TOP3B as autism susceptibility genes.
Title: Further evidence of GABRA4 and TOP3B as autism susceptibility genes.
Topoisomerase III-beta is required for efficient replication of positive-sense RNA viruses.
Title: Topoisomerase III-β is required for efficient replication of positive-sense RNA viruses.
Our data show that TOP3B is necessary to prevent the accumulation of excessive R-loops and identify TOP3B as a putative cancer gene, and support recent data showing that R-loops are involved in cancer aetiology.
Title: Loss of TOP3B leads to increased R-loop formation and genome instability.
Findings indicate the regulation of DNA topoisomerase III beta (TOP3B) activity by post-translational modification (PTM).
Title: Arginine methylation of the C-terminus RGG motif promotes TOP3B topoisomerase activity and stress granule localization.
Structural basis of the interaction between TOP3B and the TDRD3 auxiliary factor has been reported.
Title: Structural basis of the interaction between Topoisomerase IIIβ and the TDRD3 auxiliary factor.
Results identified TOP3B gene deletion as candidate gene in the etiology of neurodevelopmental disorders including juvenile myoclonic epilepsy.
Title: TOP3B: A Novel Candidate Gene in Juvenile Myoclonic Epilepsy?
Top3beta mutants lacking either its RNA-binding domain or catalytic residue fail to promote synapse formation, suggesting that Top3beta requires both its mRNA-binding and catalytic activity to facilitate neurodevelopment.
Title: Topoisomerase 3β is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction.

Submit: New GeneRIF Correction See all GeneRIFs (15)

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

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2022-07-13) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2022-07-13) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of topoisomerase (DNA) III beta (TOP3B) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Top3b (e-PCR), detects polymorphism
- UniSTS:259698

Gene Ontology Provided by GOA

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

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	NAS Non-traceable Author Statement more info	PubMed
involved_in chromosome segregation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of DNA topoisomerase III-beta-TDRD3 complex	IPI Inferred from Physical Interaction more info	PubMed
located_in condensed chromosome	IEA Inferred from Electronic Annotation 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

General protein information

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Preferred Names: DNA topoisomerase 3-beta-1

Names: DNA topoisomerase III beta-1; topoisomerase (DNA) III beta; topoisomerase III beta

NP_001269041.1

EC 5.6.2.1

NP_001269042.1

EC 5.6.2.1

NP_001336774.1

EC 5.6.2.1

NP_001336776.1

EC 5.6.2.1

NP_001336777.1

EC 5.6.2.1

NP_001336779.1

EC 5.6.2.1

NP_001336780.1

EC 5.6.2.1

NP_001336781.1

EC 5.6.2.1

NP_003926.1

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_001282112.2 → NP_001269041.1 DNA topoisomerase 3-beta-1 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. Variants 1-5 encode the same protein (isoform 1).

Source sequence(s)

AC245452, AF053082, BQ270362, DA025312

Consensus CDS

CCDS13797.1

UniProtKB/Swiss-Prot

A0M8Q3, O95985, Q9BUP5

UniProtKB/TrEMBL

A8K4N2

Related

ENSP00000349705.5, ENST00000357179.10

Conserved Domains (2) summary

cd03362
Location:3 → 167

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 ...

cd00186
Location:172 → 593

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 ...
NM_001282113.2 → NP_001269042.1 DNA topoisomerase 3-beta-1 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 5' terminal exon and uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1-5 encode the same protein (isoform 1).

Source sequence(s)

AC245452, AK290997, BQ270362

Consensus CDS

CCDS13797.1

UniProtKB/Swiss-Prot

A0M8Q3, O95985, Q9BUP5

UniProtKB/TrEMBL

A8K4N2

Conserved Domains (2) summary

cd03362
Location:3 → 167

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 ...

cd00186
Location:172 → 593

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 ...
NM_001349845.2 → NP_001336774.1 DNA topoisomerase 3-beta-1 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1-5 encode the same protein (isoform 1).

Source sequence(s)

AC245452, AK290997, BQ270362, DA025312, DA124773

Consensus CDS

CCDS13797.1

UniProtKB/Swiss-Prot

A0M8Q3, O95985, Q9BUP5

UniProtKB/TrEMBL

A8K4N2

Conserved Domains (2) summary

cd03362
Location:3 → 167

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 ...

cd00186
Location:172 → 593

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 ...
NM_001349847.2 → NP_001336776.1 DNA topoisomerase 3-beta-1 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1-5 encode the same protein (isoform 1).

Source sequence(s)

AC245452, AK290997, BQ270362, DA025312, DB134726

Consensus CDS

CCDS13797.1

UniProtKB/Swiss-Prot

A0M8Q3, O95985, Q9BUP5

UniProtKB/TrEMBL

A8K4N2

Conserved Domains (2) summary

cd03362
Location:3 → 167

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 ...

cd00186
Location:172 → 593

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 ...
NM_001349848.2 → NP_001336777.1 DNA topoisomerase 3-beta-1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses an alternate splice site in its 5' terminal exon and contains an alternate exon in its 5' UTR, resulting in the use of a downstream start codon compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1. Variants 6 and 7 encode the same protein (isoform 2).

Source sequence(s)

AC245452, AK290997, BQ270362, DA025312, DB165571, DR003213

UniProtKB/TrEMBL

A8K4N2

Conserved Domains (2) summary

cd00186
Location:36 → 457

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 ...

cl00718
Location:6 → 31

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_001349850.2 → NP_001336779.1 DNA topoisomerase 3-beta-1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (7) contains an alternate exon structure in the 5' region and contains an alternate exon in its 5' UTR, resulting in the use of a downstream start codon compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1. Variants 6 and 7 encode the same protein (isoform 2).

Source sequence(s)

AC245452, AK290997, BQ270362, DA025312, DA124773, DB146985, DB150453

UniProtKB/TrEMBL

A8K4N2

Conserved Domains (2) summary

cd00186
Location:36 → 457

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 ...

cl00718
Location:6 → 31

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_001349851.2 → NP_001336780.1 DNA topoisomerase 3-beta-1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (8) differs in its 5' UTR, resulting in the use of a downstream start codon, and its 3' terminal exon extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3) has a shorter N-terminus and a shorter and distinct C-terminus comparted to isoform 1. Variants 8 and 9 encode the same protein (isoform 3).

Source sequence(s)

AI361851, AK290997, BQ270362, CF137541, CN302239, CN353231, CN353232, CR980357, CT002728, DA025312, DR003213

UniProtKB/TrEMBL

H0Y6W0

Related

ENSP00000408282.1, ENST00000457270.5

Conserved Domains (2) summary

cd00186
Location:36 → 457

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 ...

cl00718
Location:6 → 31

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_001349852.2 → NP_001336781.1 DNA topoisomerase 3-beta-1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (9) differs in its 5' UTR, resulting in the use of a downstream start codon, and its 3' terminal exon extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3) has a shorter N-terminus and a shorter and distinct C-terminus comparted to isoform 1. Variants 8 and 9 encode the same protein (isoform 3).

Source sequence(s)

AI361851, AK290997, BQ270362, CF137541, CN302239, CN353231, CN353232, CR980357, CT002728, DA025312, DA124773, DB146985, DB150453, DR003213

UniProtKB/TrEMBL

H0Y6W0

Conserved Domains (2) summary

cd00186
Location:36 → 457

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 ...

cl00718
Location:6 → 31

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_003935.5 → NP_003926.1 DNA topoisomerase 3-beta-1 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1-5 encode the same protein (isoform 1).

Source sequence(s)

BC002432, BQ270362, CR456596, DA025312

Consensus CDS

CCDS13797.1

UniProtKB/Swiss-Prot

A0M8Q3, O95985, Q9BUP5

UniProtKB/TrEMBL

A8K4N2

Related

ENSP00000381773.2, ENST00000398793.6

Conserved Domains (2) summary

cd03362
Location:3 → 167

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 ...

cd00186
Location:172 → 593

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 ...

RNA

NR_146277.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (10) contains multiple differences, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC245452, AI361851, AK290997, BI908256, BQ270362, CF137541, CN353231, CN353232, CR980357, CT002728, DA796433, DB137508

Related

ENST00000444502.5