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TOP1 (topoisomerase (DNA) 1)

Written2004-12Junko Horiguchi Yamada
Department of Oncology, Institute of DNA Medicine, The Jikei University, School of Medicine, Tokyo, Japan

(Note : for Links provided by Atlas : click)

Identity

HGNC (Hugo) TOP1
LocusID (NCBI) 7150
Atlas_Id 320
Location 20q12  [Link to chromosome band 20q12]
Location_base_pair Starts at 39657462 and ends at 39753126 bp from pter ( according to hg19-Feb_2009)  [Mapping TOP1.png]
Local_order centromer to telomer
Fusion genes
(updated 2016)
MRFAP1 (4p16.1) / TOP1 (20q12)NUP98 (11p15.4) / TOP1 (20q12)SENP6 (6q14.1) / TOP1 (20q12)
SHROOM2 (Xp22.2) / TOP1 (20q12)TOP1 (20q12) / C17orf64 (17q23.2)TOP1 (20q12) / CDH4 (20q13.33)
TOP1 (20q12) / NUP98 (11p15.4)TOP1 (20q12) / PZP (12p13.31)

DNA/RNA

Note The sequence is split into 21 exons over 85kbp. Introns are 0.2-30 kbp in size.
 
  The star denotes intron 7 where chromosome translocation occurs.
Description 21 exons with 20 introns
Transcription 3.8 kb (single band)
Pseudogene 2 pseudogenes. TOP1P1 on chromosome 1q23-q24, and TOP1P2 on chromosome 22q12-q13.1.

Protein

Note type I DNA topoisomerase, EC (5.99.1.2)
 
  The arrow indicates the breaking point of translocation, and the star denotes the sites of point mutation.
Description 765 amino acids, about 100kDa; contains NLS in the N-term, a core domain which recognizes its binding sequences, a link domain which connects the core and catalytic domains, and the catalytic domain in the C-term.
Expression Ubiquitous. The expression level is up-regulated along with cell proliferation signals.
Localisation Nucleus
Function TOP1 catalyzes the breaking and rejoining of single DNA strand.
Homology The core and catalytic domains are conserved between the human and S.cerevisiae enzyme.

Mutations

Somatic Translocation of chromosome t(11;20)(p15;q12) has been reported in hematological malignancies (see below).
Point mutations with amino acid substitution in the catalytic domain have been implicated in irinotecan-resistance.

Implicated in

Note
Entity t(11;20)(p15;q12)
Disease de novo acute myeloid leukemia, acute monocytic leukemia, therapy-related myelodysplastic syndrome/leukemia(t-MDS/AML)
Prognosis poor (?)
Hybrid/Mutated Gene NUP98/TOP1
 
Oncogenesis NUP98-TOP1 fusion protein has been proved to have leukemogenic activities independent of topoisomerase activity.
  

Breakpoints

 
  The breakpoints locate in intron 7, causing the fusion protein to lack the N-terminal 169 amino acids.The breakpoints locate in the repetitive elements or close to them which exist in intron 7 of TOP1 gene.

To be noted

Point mutations W736stop and G737S were detected in lung non-small cell carcinoma. The significance of mutations in catalytic domain has been suspected to be relevant to susceptibility to irinotecan.

Bibliography

Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.
Ahuja HG, Felix CA, Aplan PD
Genes, chromosomes & cancer. 2000 ; 29 (2) : 96-105.
PMID 10959088
 
Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia.
Chen S, Xue Y, Chen Z, Guo Y, Wu Y, Pan J
Cancer genetics and cytogenetics. 2003 ; 140 (2) : 153-156.
PMID 12645654
 
NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation.
Gurevich RM, Aplan PD, Humphries RK
Blood. 2004 ; 104 (4) : 1127-1136.
PMID 15100157
 
Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).
Iwase S, Akiyama N, Sekikawa T, Saito S, Arakawa Y, Horiguchi-Yamada J, Yamada H
Genes, chromosomes & cancer. 2003 ; 38 (1) : 102-105.
PMID 12874791
 
Structure of the human type I DNA topoisomerase gene.
Kunze N, Yang GC, Dölberg M, Sundarp R, Knippers R, Richter A
The Journal of biological chemistry. 1991 ; 266 (15) : 9610-9616.
PMID 1851751
 
Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).
Panagopoulos I, Fioretos T, Isaksson M, Larsson G, Billström R, Mitelman F, Johansson B
Genes, chromosomes & cancer. 2002 ; 34 (2) : 249-254.
PMID 11979559
 
A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia.
Potenza L, Sinigaglia B, Luppi M, Morselli M, Saviola A, Ferrari A, Riva G, Zucchini P, Giacobbi F, Emilia G, Temperani P, Torelli G
Cancer genetics and cytogenetics. 2004 ; 149 (2) : 164-168.
PMID 15036893
 
Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan.
Tsurutani J, Nitta T, Hirashima T, Komiya T, Uejima H, Tada H, Syunichi N, Tohda A, Fukuoka M, Nakagawa K
Lung cancer (Amsterdam, Netherlands). 2002 ; 35 (3) : 299-304.
PMID 11844605
 

Citation

This paper should be referenced as such :
Yamada, JH
TOP1 (topoisomerase (DNA) 1)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(1):12-14.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TOP1ID320ch20q11.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  del(20q) in myeloid malignancies
dic(17;20)(p11.2;q11.2)
t(4;11)(q21;p15) NUP98/RAP1GDS1
t(11;20)(p15;q11) NUP98/TOP1


External links

Nomenclature
HGNC (Hugo)TOP1   11986
Cards
AtlasTOP1ID320ch20q11
Entrez_Gene (NCBI)TOP1  7150  topoisomerase (DNA) I
AliasesTOPI
GeneCards (Weizmann)TOP1
Ensembl hg19 (Hinxton)ENSG00000198900 [Gene_View]  chr20:39657462-39753126 [Contig_View]  TOP1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000198900 [Gene_View]  chr20:39657462-39753126 [Contig_View]  TOP1 [Vega]
ICGC DataPortalENSG00000198900
TCGA cBioPortalTOP1
AceView (NCBI)TOP1
Genatlas (Paris)TOP1
WikiGenes7150
SOURCE (Princeton)TOP1
Genetics Home Reference (NIH)TOP1
Genomic and cartography
GoldenPath hg19 (UCSC)TOP1  -     chr20:39657462-39753126 +  20q12-q13.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TOP1  -     20q12-q13.1   [Description]    (hg38-Dec_2013)
EnsemblTOP1 - 20q12-q13.1 [CytoView hg19]  TOP1 - 20q12-q13.1 [CytoView hg38]
Mapping of homologs : NCBITOP1 [Mapview hg19]  TOP1 [Mapview hg38]
OMIM126420   
Gene and transcription
Genbank (Entrez)AK225095 AK292943 AK310508 AK310516 BC000943
RefSeq transcript (Entrez)NM_003286
RefSeq genomic (Entrez)NC_000020 NC_018931 NG_012262 NT_011362 NW_004929418
Consensus coding sequences : CCDS (NCBI)TOP1
Cluster EST : UnigeneHs.472737 [ NCBI ]
CGAP (NCI)Hs.472737
Alternative Splicing GalleryENSG00000198900
Gene ExpressionTOP1 [ NCBI-GEO ]   TOP1 [ EBI - ARRAY_EXPRESS ]   TOP1 [ SEEK ]   TOP1 [ MEM ]
Gene Expression Viewer (FireBrowse)TOP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7150
GTEX Portal (Tissue expression)TOP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP11387   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP11387  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP11387
Splice isoforms : SwissVarP11387
Catalytic activity : Enzyme5.99.1.2 [ Enzyme-Expasy ]   5.99.1.25.99.1.2 [ IntEnz-EBI ]   5.99.1.2 [ BRENDA ]   5.99.1.2 [ KEGG ]   
PhosPhoSitePlusP11387
Domaine pattern : Prosite (Expaxy)TOPOISOMERASE_I_EUK (PS00176)   
Domains : Interpro (EBI)DNA_brk_join_enz    DNA_topo_domain1    TopoI    TopoI_AS    TopoI_C_dom    TopoI_cat_a-hlx-sub_euk    TopoI_cat_a/b-sub_euk    TopoI_cat_euk    TopoI_DNA-bd_euk    TopoI_DNA-bd_mixed-a/b_euk    TopoI_euk   
Domain families : Pfam (Sanger)Topo_C_assoc (PF14370)    Topoisom_I (PF01028)    Topoisom_I_N (PF02919)   
Domain families : Pfam (NCBI)pfam14370    pfam01028    pfam02919   
Domain families : Smart (EMBL)TOPEUc (SM00435)  
Conserved Domain (NCBI)TOP1
DMDM Disease mutations7150
Blocks (Seattle)TOP1
PDB (SRS)1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
PDB (PDBSum)1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
PDB (IMB)1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
PDB (RSDB)1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
Structural Biology KnowledgeBase1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
SCOP (Structural Classification of Proteins)1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
CATH (Classification of proteins structures)1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
SuperfamilyP11387
Human Protein AtlasENSG00000198900
Peptide AtlasP11387
HPRD00535
IPIIPI00413611   
Protein Interaction databases
DIP (DOE-UCLA)P11387
IntAct (EBI)P11387
FunCoupENSG00000198900
BioGRIDTOP1
STRING (EMBL)TOP1
ZODIACTOP1
Ontologies - Pathways
QuickGOP11387
Ontology : AmiGOnuclear chromosome  cytoplasmic mRNA processing body  core promoter sequence-specific DNA binding  DNA binding  chromatin binding  DNA topoisomerase type I activity  DNA topoisomerase type I activity  DNA topoisomerase type II (ATP-hydrolyzing) activity  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  DNA replication  DNA topological change  chromatin remodeling  chromosome segregation  circadian rhythm  programmed cell death  viral process  phosphorylation  protein sumoylation  replication fork protection complex  circadian regulation of gene expression  embryonic cleavage  response to drug  perikaryon  poly(A) RNA binding  
Ontology : EGO-EBInuclear chromosome  cytoplasmic mRNA processing body  core promoter sequence-specific DNA binding  DNA binding  chromatin binding  DNA topoisomerase type I activity  DNA topoisomerase type I activity  DNA topoisomerase type II (ATP-hydrolyzing) activity  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  DNA replication  DNA topological change  chromatin remodeling  chromosome segregation  circadian rhythm  programmed cell death  viral process  phosphorylation  protein sumoylation  replication fork protection complex  circadian regulation of gene expression  embryonic cleavage  response to drug  perikaryon  poly(A) RNA binding  
NDEx NetworkTOP1
Atlas of Cancer Signalling NetworkTOP1
Wikipedia pathwaysTOP1
Orthology - Evolution
OrthoDB7150
GeneTree (enSembl)ENSG00000198900
Phylogenetic Trees/Animal Genes : TreeFamTOP1
HOVERGENP11387
HOGENOMP11387
Homologs : HomoloGeneTOP1
Homology/Alignments : Family Browser (UCSC)TOP1
Gene fusions - Rearrangements
Fusion : MitelmanNUP98/TOP1 [11p15.4/20q12]  [t(11;20)(p15;q12)]  
Fusion : MitelmanTOP1/C17orf64 [20q12/17q23.2]  [t(17;20)(q23;q12)]  
Fusion : MitelmanTOP1/CDH4 [20q12/20q13.33]  [t(20;20)(q12;q13)]  
Fusion : MitelmanTOP1/PZP [20q12/12p13.31]  [t(12;20)(p13;q12)]  
Fusion: TCGATOP1 20q12 C17orf64 17q23.2 BRCA
Fusion: TCGATOP1 20q12 CDH4 20q13.33 LUAD
Fusion: TCGATOP1 20q12 PZP 12p13.31 BRCA
Fusion : TICdbNUP98 [11p15.4]  -  TOP1 [20q12]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTOP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TOP1
dbVarTOP1
ClinVarTOP1
1000_GenomesTOP1 
Exome Variant ServerTOP1
ExAC (Exome Aggregation Consortium)TOP1 (select the gene name)
Genetic variants : HAPMAP7150
Genomic Variants (DGV)TOP1 [DGVbeta]
DECIPHER (Syndromes)20:39657462-39753126  ENSG00000198900
CONAN: Copy Number AnalysisTOP1 
Mutations
ICGC Data PortalTOP1 
TCGA Data PortalTOP1 
Broad Tumor PortalTOP1
OASIS PortalTOP1 [ Somatic mutations - Copy number]
Cancer Gene: CensusTOP1 
Somatic Mutations in Cancer : COSMICTOP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTOP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TOP1
DgiDB (Drug Gene Interaction Database)TOP1
DoCM (Curated mutations)TOP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TOP1 (select a term)
intoGenTOP1
NCG5 (London)TOP1
Cancer3DTOP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM126420   
Orphanet
MedgenTOP1
Genetic Testing Registry TOP1
NextProtP11387 [Medical]
TSGene7150
GENETestsTOP1
Huge Navigator TOP1 [HugePedia]
snp3D : Map Gene to Disease7150
BioCentury BCIQTOP1
ClinGenTOP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7150
Chemical/Pharm GKB GenePA353
Clinical trialTOP1
Miscellaneous
canSAR (ICR)TOP1 (select the gene name)
Probes
Litterature
PubMed272 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTOP1
EVEXTOP1
GoPubMedTOP1
iHOPTOP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Nov 18 20:01:53 CET 2016

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