This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands. [provided by RefSeq, Jul 2008] See more...

Aliases for TOPBP1 Gene

Aliases for TOPBP1 Gene

  • DNA Topoisomerase II Binding Protein 1 2 3 5
  • DNA Topoisomerase II-Beta-Binding Protein 1 3 4
  • Topoisomerase (DNA) II Binding Protein 1 2 3
  • DNA Topoisomerase 2-Binding Protein 1 3 4
  • KIAA0259 2 4
  • TOP2BP1 2 3
  • Dpb11 2 3
  • DNA Topoisomerase II-Binding Protein 1 4
  • TOPBP1 5
  • TopBP1 4

External Ids for TOPBP1 Gene

Previous GeneCards Identifiers for TOPBP1 Gene

  • GC03M130264
  • GC03M134064
  • GC03M134601
  • GC03M134640
  • GC03M134802
  • GC03M133319
  • GC03M130698

Summaries for TOPBP1 Gene

Entrez Gene Summary for TOPBP1 Gene

  • This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands. [provided by RefSeq, Jul 2008]

GeneCards Summary for TOPBP1 Gene

TOPBP1 (DNA Topoisomerase II Binding Protein 1) is a Protein Coding gene. Diseases associated with TOPBP1 include Ataxia-Telangiectasia and Fanconi Anemia, Complementation Group A. Among its related pathways are DNA Double-Strand Break Repair and Cell Cycle, Mitotic. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein C-terminus binding. An important paralog of this gene is SLF1.

UniProtKB/Swiss-Prot Summary for TOPBP1 Gene

  • Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR (PubMed:16530042).

Gene Wiki entry for TOPBP1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TOPBP1 Gene

Genomics for TOPBP1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TOPBP1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TOPBP1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TOPBP1

Top Transcription factor binding sites by QIAGEN in the TOPBP1 gene promoter:
  • FOXL1
  • GATA-1
  • HFH-1
  • HSF1 (long)
  • HSF1short
  • NRF-2
  • p53
  • TBP
  • TFIID
  • Zic3

Genomic Locations for TOPBP1 Gene

Latest Assembly
chr3:133,598,175-133,662,380
(GRCh38/hg38)
Size:
64,206 bases
Orientation:
Minus strand

Previous Assembly
chr3:133,319,082-133,380,785
(GRCh37/hg19 by Entrez Gene)
Size:
61,704 bases
Orientation:
Minus strand

chr3:133,317,019-133,380,737
(GRCh37/hg19 by Ensembl)
Size:
63,719 bases
Orientation:
Minus strand

Genomic View for TOPBP1 Gene

Genes around TOPBP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TOPBP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TOPBP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TOPBP1 Gene

Proteins for TOPBP1 Gene

  • Protein details for TOPBP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92547-TOPB1_HUMAN
    Recommended name:
    DNA topoisomerase 2-binding protein 1
    Protein Accession:
    Q92547
    Secondary Accessions:
    • B7Z7W8
    • Q7LGC1
    • Q9UEB9

    Protein attributes for TOPBP1 Gene

    Size:
    1522 amino acids
    Molecular mass:
    170679 Da
    Quaternary structure:
    • Interacts with POLE (PubMed:11395493). Interacts with RAD9A (PubMed:11395493). Interacts with UBR5 (PubMed:11714696). Interacts with E2F1 (PubMed:12697828, PubMed:15075294). Interacts with PML (PubMed:12773567). Interacts with SMARCA2 (PubMed:15075294). Interacts with SMARCA4 (PubMed:15075294). Interacts with RHNO1 (PubMed:21659603). May interact with TOP2B (PubMed:9461304). Interacts with TICRR (PubMed:20080954). Interacts with HELB (PubMed:25933514).
    SequenceCaution:
    • Sequence=BAA13389.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAA34202.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TOPBP1 Gene

neXtProt entry for TOPBP1 Gene

Post-translational modifications for TOPBP1 Gene

  • Phosphorylated on serine and threonine residues in response to X-ray irradiation.
  • Ubiquitinated and degraded by the proteasome. X-ray irradiation reduces ubiquitination.
  • Ubiquitination at Lys224 and Lys1421
  • Modification sites at PhosphoSitePlus

Other Protein References for TOPBP1 Gene

No data available for DME Specific Peptides for TOPBP1 Gene

Domains & Families for TOPBP1 Gene

Gene Families for TOPBP1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for TOPBP1 Gene

InterPro:
Blocks:
  • BRCT domain

Suggested Antigen Peptide Sequences for TOPBP1 Gene

GenScript: Design optimal peptide antigens:
  • Topoisomerase (DNA) II binding protein 1 (A0AV47_HUMAN)
  • Topoisomerase (DNA) II binding protein 1 (A7E2X7_HUMAN)
  • TOPBP1 protein (Q05BV8_HUMAN)
  • DNA topoisomerase II-binding protein 1 (TOPB1_HUMAN)
genes like me logo Genes that share domains with TOPBP1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TOPBP1 Gene

Function for TOPBP1 Gene

Molecular function for TOPBP1 Gene

UniProtKB/Swiss-Prot Function:
Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR (PubMed:16530042).
UniProtKB/Swiss-Prot Induction:
Up-regulated during the S phase of the cell cycle. Up-regulated by E2F1 and interferon.

Phenotypes From GWAS Catalog for TOPBP1 Gene

Gene Ontology (GO) - Molecular Function for TOPBP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
GO:0005515 protein binding IPI 12773567
GO:0008022 protein C-terminus binding TAS 9461304
GO:0042802 identical protein binding IPI 17006541
genes like me logo Genes that share ontologies with TOPBP1: view
genes like me logo Genes that share phenotypes with TOPBP1: view

Animal Models for TOPBP1 Gene

MGI Knock Outs for TOPBP1:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TOPBP1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TOPBP1 Gene

Localization for TOPBP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TOPBP1 Gene

Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Chromosome. Note=Detected on unpaired autosomes in meiotic prophase cells. Detected on X and Y chromosomes during later stages of prophase. Colocalizes with ATR and H2AX at unsynapsed chromosome cores during prophase (By similarity). Has a uniform nuclear distribution during G phase. Colocalizes with BRCA1 at stalled replication forks during S phase. In mitotic cells it colocalizes with BRCA1 at spindle poles and centrosomes during metaphase and anaphase. Detected in discrete foci together with PML and numerous DNA repair enzymes after DNA damage by alkylating agents, UV or gamma irradiation. Localizes to sites of DNA damage in a H2AX- independent manner. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TOPBP1 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
plasma membrane 4
cytosol 3
mitochondrion 2
golgi apparatus 2
extracellular 1
lysosome 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TOPBP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000794 condensed nuclear chromosome IEA --
GO:0000922 spindle pole IEA --
GO:0001673 male germ cell nucleus IEA --
GO:0005634 nucleus TAS 9461304
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with TOPBP1: view

Pathways & Interactions for TOPBP1 Gene

genes like me logo Genes that share pathways with TOPBP1: view

Pathways by source for TOPBP1 Gene

1 KEGG pathway for TOPBP1 Gene
1 Cell Signaling Technology pathway for TOPBP1 Gene

SIGNOR curated interactions for TOPBP1 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for TOPBP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006259 DNA metabolic process TAS 9461304
GO:0006260 DNA replication TAS --
GO:0006270 DNA replication initiation IBA 21873635
GO:0006281 DNA repair NAS 12773567
GO:0006974 cellular response to DNA damage stimulus IEA,IDA 12773567
genes like me logo Genes that share ontologies with TOPBP1: view

Drugs & Compounds for TOPBP1 Gene

(3) Drugs for TOPBP1 Gene - From: ApexBio and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Amrubicin Investigational Pharma Topoisomerase II inhibitor, anthracycline agent 20
Mitoxantrone HCl Pharma Topoisomerase II inhibitor, anti-neoplastic drug 0

(2) ApexBio Compounds for TOPBP1 Gene

Compound Action Cas Number
Amrubicin Topoisomerase II inhibitor, anthracycline agent 110267-81-7
Mitoxantrone HCl Topoisomerase II inhibitor, anti-neoplastic drug 70476-82-3
genes like me logo Genes that share compounds with TOPBP1: view

Drug products for research

Transcripts for TOPBP1 Gene

mRNA/cDNA for TOPBP1 Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TOPBP1

Alternative Splicing Database (ASD) splice patterns (SP) for TOPBP1 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4a · 4b ^ 5a · 5b · 5c · 5d ^ 6a · 6b ^ 7 ^ 8a · 8b · 8c · 8d · 8e ^ 9a · 9b · 9c · 9d ^ 10 ^ 11a · 11b ^
SP1:
SP2:
SP3:
SP4:
SP5: -
SP6:
SP7:
SP8:
SP9:
SP10:
SP11: - - - - -
SP12: - -
SP13:
SP14: - -
SP15: - - - - -
SP16: -
SP17: - -
SP18: - - -
SP19:
SP20:
SP21:

ExUns: 12 ^ 13a · 13b ^ 14a · 14b ^ 15a · 15b ^ 16a · 16b ^ 17 ^ 18 ^ 19 ^ 20 ^ 21a · 21b ^ 22a · 22b ^ 23 ^ 24a · 24b ^ 25a · 25b ^ 26a · 26b ^ 27 ^ 28 ^
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9: -
SP10: -
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:
SP19:
SP20:
SP21:

ExUns: 29 ^ 30 ^ 31
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:
SP19:
SP20:
SP21:

Relevant External Links for TOPBP1 Gene

GeneLoc Exon Structure for
TOPBP1

Expression for TOPBP1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TOPBP1 Gene

Protein differential expression in normal tissues from HIPED for TOPBP1 Gene

This gene is overexpressed in Liver (43.8) and Tlymphocyte (14.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TOPBP1 Gene



Protein tissue co-expression partners for TOPBP1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TOPBP1

SOURCE GeneReport for Unigene cluster for TOPBP1 Gene:

Hs.593379

mRNA Expression by UniProt/SwissProt for TOPBP1 Gene:

Q92547-TOPB1_HUMAN
Tissue specificity: Highly expressed in heart, brain, placenta, lung and kidney.

Evidence on tissue expression from TISSUES for TOPBP1 Gene

  • Bone marrow(4.4)
  • Nervous system(3.9)
  • Skin(2.3)
  • Intestine(2.3)
  • Kidney(2.2)
genes like me logo Genes that share expression patterns with TOPBP1: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TOPBP1 Gene

Orthologs for TOPBP1 Gene

This gene was present in the common ancestor of animals.

Orthologs for TOPBP1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TOPBP1 29 30
  • 99.56 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TOPBP1 29 30
  • 91.51 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TOPBP1 29 30
  • 90.69 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Topbp1 29
  • 81.43 (n)
Mouse
(Mus musculus)
Mammalia Topbp1 29 16 30
  • 80.97 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 73 (a)
OneToMany
-- 30
  • 59 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia TOPBP1 30
  • 71 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TOPBP1 29 30
  • 71.6 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 63 (a)
OneToMany
-- 30
  • 56 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia topbp1 29
  • 66.58 (n)
Zebrafish
(Danio rerio)
Actinopterygii topbp1 29 30
  • 58 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta mus101 30 31
  • 17 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea mus-101 30
  • 16 (a)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 28 (a)
OneToMany
-- 30
  • 14 (a)
OneToMany
Species where no ortholog for TOPBP1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for TOPBP1 Gene

ENSEMBL:
Gene Tree for TOPBP1 (if available)
TreeFam:
Gene Tree for TOPBP1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TOPBP1: view image
Alliance of Genome Resources:
Additional Orthologs for TOPBP1

Paralogs for TOPBP1 Gene

Paralogs for TOPBP1 Gene

(1) SIMAP similar genes for TOPBP1 Gene using alignment to 6 proteins:

  • TOPB1_HUMAN
  • A0AV47_HUMAN
  • A7E2X7_HUMAN
  • H0Y8I7_HUMAN
  • I3L1F2_HUMAN
  • Q05BV8_HUMAN
genes like me logo Genes that share paralogs with TOPBP1: view

Variants for TOPBP1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TOPBP1 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs17301766 Benign: not provided 133,637,946(-) G/Ap.Ser817Leu
NM_007027.4(TOPBP1):c.2450C>T (p.Ser817Leu)
MISSENSE
rs10935070 -- p.Asn955Serp.Asn1042Ser

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TOPBP1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for TOPBP1 Gene

Variant ID Type Subtype PubMed ID
esv2677101 CNV deletion 23128226
esv2725942 CNV deletion 23290073
esv3562577 CNV deletion 23714750
esv3597847 CNV loss 21293372

Variation tolerance for TOPBP1 Gene

Residual Variation Intolerance Score: 93.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.63; 78.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TOPBP1 Gene

Human Gene Mutation Database (HGMD)
TOPBP1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TOPBP1
Leiden Open Variation Database (LOVD)
TOPBP1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TOPBP1 Gene

Disorders for TOPBP1 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TOPBP1 Gene - From: COP and GCD

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TOPBP1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TOPBP1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TOPBP1 Gene

Publications for TOPBP1 Gene

  1. A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator. (PMID: 9461304) Yamane K … Tsuruo T (European journal of biochemistry 1997) 2 3 4 22
  2. A vertebrate gene, ticrr, is an essential checkpoint and replication regulator. (PMID: 20080954) Sansam CL … Lees JA (Genes & development 2010) 3 4 22
  3. Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer. (PMID: 16930991) Karppinen SM … Winqvist R (European journal of cancer (Oxford, England : 1990) 2006) 3 22 40
  4. TopBP1 activates the ATR-ATRIP complex. (PMID: 16530042) Kumagai A … Dunphy WG (Cell 2006) 3 4 22
  5. TopBP1 localises to centrosomes in mitosis and to chromosome cores in meiosis. (PMID: 15138768) Reini K … Syväoja JE (Chromosoma 2004) 3 4 22

Products for TOPBP1 Gene

Sources for TOPBP1 Gene