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TOP1 (topoisomerase (DNA) 1)

Identity

HGNC (Hugo) TOP1
Location 20q12-q13.1
Location_base_pair Starts at 39090876 and ends at 39186540 bp from pter ( according to hg18-Mar_2006)  [Mapping]
Local_order centromer to telomer

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

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.

External links

Nomenclature
HGNC (Hugo)TOP1   11986
Entrez_Gene (NCBI)TOP1  7150  topoisomerase (DNA) I
Cards
AtlasTOP1ID320ch20q11
GeneCards (Weizmann)TOP1
Ensembl (Hinxton)ENSG00000198900 [Gene_View]  TOP1 [Vega]
AceView (NCBI)TOP1
Genatlas (Paris)TOP1
euGene (Indiana)7150
SOURCE (Stanford)NM_003286
Genomic and cartography
GoldenPath (UCSC)TOP1  -     chr20:39090876-39186540 +  20q12-q13.1   [Description]    (hg18-Mar_2006)
EnsemblTOP1 - 20q12-q13.1 [CytoView]
Mapping of homologs : NCBITOP1 [Mapview]
OMIM126420   
Gene and transcription
Gene : Genbank (Entrez)AK225095 AK292943 AK310508 BC000943 BC004475
Reference sequence (RefSeq transcript) :SRSNM_003286
Reference transcript : EntrezNM_003286
RefSeq genomic : SRSAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
RefSeq genomic : EntrezAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
Consensus coding sequences : CCDS NCBITOP1
Cluster EST : UnigeneHs.472737 [ SRS ] Hs.472737 [ NCBI ]
Alternative Splicing : Fast-db (Paris)11362
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP11387 (SRS) P11387 (Expasy) P11387 (Uniprot)
With graphics : InterProP11387
Splice isoforms : VarSplice FASTAP11387(VarSplice FASTA)
Domaine pattern : Prosite (SRS)TOPOISOMERASE_I_EUK (PS00176)   
Domain pattern : Prosite (Expaxy)TOPOISOMERASE_I_EUK (PS00176)   
Domains : Interpro (SRS)TopoI_C    TopoI_C_euk    TopoI_cat_a-hlx-sub_euk    TopoI_cat_a/b-sub_euk    TopoI_cat_euk    TopoI_DNA-bd_mixed-a/b_euk    TopoI_DNA_bd_euk   
Domains : Interpro (EBI)TopoI_C    TopoI_C_euk    TopoI_cat_a-hlx-sub_euk    TopoI_cat_a/b-sub_euk    TopoI_cat_euk    TopoI_DNA-bd_mixed-a/b_euk    TopoI_DNA_bd_euk   
Related proteins : CluSTrP11387
Domain families : Pfam SRSTopoisom_I (PF01028)    Topoisom_I_N (PF02919)   
Domain families : Pfam SangerTopoisom_I (PF01028)    Topoisom_I_N (PF02919)   
Domain families : Pfam NCBIpfam01028    pfam02919   
Domain families : Smart EMBLTOPEUc (SM00435)
Blocks (Seattle)P11387
Crystal structure of protein : PDB SRS1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
Crystal structure of protein : PDBSum1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
Crystal structure of protein : IMB1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
Crystal structure of protein : PDB RSDB1A31    1A35    1A36    1EJ9    1K4S    1K4T    1LPQ    1NH3    1R49    1RR8    1RRJ    1SC7    1SEU    1T8I    1TL8   
HPRD00535
Protein Interaction databases
DIP (DOE-UCLA)P11387
IntAct (EBI)P11387
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBITOP1
SNP : GeneSNP UtahTOP1
SNP : HGBaseTOP1
Genetic variants : HAPMAPTOP1
Somatic Mutations in Cancer : COSMICTOP1 
Translocation Breakpoints in Cancer : TICdbTOP1 
Mutations and Diseases : HGMDTOP1
Hereditary diseases : OMIM126420   
Hereditary diseases : GENETests126420   
Diseases : Genetic AssociationTOP1
General knowledge
Homologs : HomoloGeneTOP1
Homology/Alignments : Family Browser UCSCTOP1
Phylogenetic Trees/Animal Genes : TreeFamTOP1
Catalytic activity : Enzyme5.99.1.2 [ Enzyme-Expasy ]   5.99.1.2 [ Enzyme-SRS ]   5.99.1.2 [ IntEnz-EBI ]   5.99.1.2 [ BRENDA ]   5.99.1.2 [ KEGG ]   
Chemical/Protein Interactions : CTD7150
Keywords Ontology : AmiGOchromatin binding  DNA topoisomerase type I activity  DNA topoisomerase (ATP-hydrolyzing) activity  protein binding  nucleus  nucleoplasm  chromosome  nucleolus  cytoplasm  DNA replication  DNA topological change  DNA unwinding during replication  programmed cell death  phosphorylation  embryonic cleavage  response to drug  perikaryon  
Keywords Ontology : EGO-EBIchromatin binding  DNA topoisomerase type I activity  DNA topoisomerase (ATP-hydrolyzing) activity  protein binding  nucleus  nucleoplasm  chromosome  nucleolus  cytoplasm  DNA replication  DNA topological change  DNA unwinding during replication  programmed cell death  phosphorylation  embryonic cleavage  response to drug  perikaryon  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesTOP1 Related clones (RZPD - Berlin)
Literature
PubMed132 Pubmed reference(s) in Entrez
PubGeneTOP1

Bibliography

Structure of the human type I DNA topoisomerase gene.
Kunze N, Yang GC, Dlberg M, Sundarp R, Knippers R, Richter A
The Journal of biological chemistry. 1991 ; 266 (15) : 9610-9616.
PMID 1851751
 
The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion.
Ahuja HG, Felix CA, Aplan PD
Blood. 1999 ; 94 (9) : 3258-3261.
PMID 10556215
 
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
 
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, Billstrm R, Mitelman F, Johansson B
Genes, chromosomes & cancer. 2002 ; 34 (2) : 249-254.
PMID 11979559
 
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
 
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
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-2004Junko Horiguchi Yamada
Department of Oncology, Institute of DNA Medicine, The Jikei University, School of Medicine, Tokyo, Japan

Citation

This paper should be referenced as such :
Yamada JH . TOP1 (topoisomerase (DNA) 1). Atlas Genet Cytogenet Oncol Haematol. December 2004 .
URL : http://AtlasGeneticsOncology.org/Genes/TOP1ID320ch20q11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jun 27 16:38:42 CEST 2009

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