Q13472 (TOP3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 120.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: DNA topoisomerase 3-alpha EC=5.99.1.2 Alternative name(s): DNA topoisomerase III alpha | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1001 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity. Ref.1 Ref.10 |
| Catalytic activity | ATP-independent breakage of single-stranded DNA, followed by passage and rejoining. Ref.1 Ref.10 |
| Cofactor | Magnesium. Ref.10 |
| Subunit structure | Directly interacts with BLM and RMI1. Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM. Ref.6 Ref.7 Ref.8 Ref.10 |
| Tissue specificity | High expression is found in testis, heart, skeletal muscle and pancreas. |
| Sequence similarities | Belongs to the type IA topoisomerase family. Contains 1 Toprim domain. |
Ontologies
| Keywords | |
|---|---|
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Repeat Zinc-finger |
| Ligand | ATP-binding DNA-binding Magnesium Metal-binding Nucleotide-binding Zinc |
| Molecular function | Isomerase Topoisomerase |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological_process | DNA topological change Inferred from direct assay Ref.10. Source: UniProtKB meiosisTraceable author statement Ref.1. Source: ProtInc |
| Cellular_component | PML body Inferred from direct assay PubMed 10728666. Source: UniProtKB chromosomeInferred from electronic annotation. Source: InterPro |
| Molecular_function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA topoisomerase type I activityInferred from direct assay Ref.10. Source: UniProtKB zinc ion bindingInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform Long (identifier: Q13472-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform Short (identifier: Q13472-2) The sequence of this isoform differs from the canonical sequence as follows: 1-25: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1001 | 1001 | DNA topoisomerase 3-alpha | PRO_0000145190 | |||||
Regions | |||||||||
| Domain | 35 – 179 | 145 | Toprim | ||||||
| Repeat | 812 – 839 | 28 | 1 | ||||||
| Repeat | 896 – 923 | 28 | 2 | ||||||
| Zinc finger | 658 – 685 | 28 | C4-type Potential | ||||||
| Region | 812 – 923 | 112 | 2 X 27 AA approximate repeats | ||||||
Sites | |||||||||
| Active site | 362 | 1 | O-(5'-phospho-DNA)-tyrosine intermediate By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 25 | 25 | Missing in isoform Short. | VSP_006524 | |||||
| Natural variant | 459 | 1 | D → N. Corresponds to variant rs28671051 [ dbSNP | Ensembl ]. | VAR_052588 | |||||
| Natural variant | 596 | 1 | C → Y. | VAR_007529 | |||||
| Natural variant | 742 | 1 | D → N. Corresponds to variant rs9909732 [ dbSNP | Ensembl ]. | VAR_052589 | |||||
| Natural variant | 773 | 1 | N → D. Corresponds to variant rs9911283 [ dbSNP | Ensembl ]. | VAR_052590 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human TOP3: a single-copy gene encoding DNA topoisomerase III." Hanai R., Caron P.R., Wang J.C. Proc. Natl. Acad. Sci. U.S.A. 93:3653-3657(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), FUNCTION, CATALYTIC ACTIVITY. |
| [2] | "Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing." Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., Speed T.P., Scharfe C. Nucleic Acids Res. 39:44-58(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Trachea. |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Testis. |
| [6] | "BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity." Yin J., Sobeck A., Xu C., Meetei A.R., Hoatlin M., Li L., Wang W. EMBO J. 24:1465-1476(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH BLM AND RMI1. |
| [7] | "RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability." Xu D., Guo R., Sobeck A., Bachrati C.Z., Yang J., Enomoto T., Brown G.W., Hoatlin M.E., Hickson I.D., Wang W. Genes Dev. 22:2843-2855(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE RMI COMPLEX. |
| [8] | "BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome." Singh T.R., Ali A.M., Busygina V., Raynard S., Fan Q., Du C.-H., Andreassen P.R., Sung P., Meetei A.R. Genes Dev. 22:2856-2868(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE RMI COMPLEX. |
| [9] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| [10] | "Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1." Yang J., Bachrati C.Z., Ou J., Hickson I.D., Brown G.W. J. Biol. Chem. 285:21426-21436(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, INTERACTION WITH RMI1. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U43431 mRNA. Translation: AAB03694.1. U43431 mRNA. Translation: AAB03695.1. HQ205026 Genomic DNA. Translation: ADP90454.1. HQ205027 Genomic DNA. Translation: ADP90455.1. HQ205028 Genomic DNA. Translation: ADP90456.1. HQ205029 Genomic DNA. Translation: ADP90457.1. HQ205030 Genomic DNA. Translation: ADP90458.1. HQ205031 Genomic DNA. Translation: ADP90459.1. HQ205032 Genomic DNA. Translation: ADP90460.1. HQ205033 Genomic DNA. Translation: ADP90461.1. HQ205034 Genomic DNA. Translation: ADP90462.1. HQ205035 Genomic DNA. Translation: ADP90463.1. HQ205036 Genomic DNA. Translation: ADP90464.1. HQ205037 Genomic DNA. Translation: ADP90465.1. HQ205038 Genomic DNA. Translation: ADP90466.1. HQ205039 Genomic DNA. Translation: ADP90467.1. HQ205040 Genomic DNA. Translation: ADP90468.1. HQ205041 Genomic DNA. Translation: ADP90469.1. HQ205042 Genomic DNA. Translation: ADP90470.1. HQ205043 Genomic DNA. Translation: ADP90471.1. HQ205044 Genomic DNA. Translation: ADP90472.1. HQ205045 Genomic DNA. Translation: ADP90473.1. HQ205046 Genomic DNA. Translation: ADP90474.1. HQ205047 Genomic DNA. Translation: ADP90475.1. HQ205048 Genomic DNA. Translation: ADP90476.1. HQ205049 Genomic DNA. Translation: ADP90477.1. HQ205050 Genomic DNA. Translation: ADP90478.1. HQ205051 Genomic DNA. Translation: ADP90479.1. HQ205052 Genomic DNA. Translation: ADP90480.1. HQ205053 Genomic DNA. Translation: ADP90481.1. HQ205054 Genomic DNA. Translation: ADP90482.1. HQ205055 Genomic DNA. Translation: ADP90483.1. HQ205056 Genomic DNA. Translation: ADP90484.1. HQ205057 Genomic DNA. Translation: ADP90485.1. HQ205058 Genomic DNA. Translation: ADP90486.1. HQ205059 Genomic DNA. Translation: ADP90487.1. HQ205060 Genomic DNA. Translation: ADP90488.1. HQ205061 Genomic DNA. Translation: ADP90489.1. HQ205062 Genomic DNA. Translation: ADP90490.1. HQ205063 Genomic DNA. Translation: ADP90491.1. HQ205064 Genomic DNA. Translation: ADP90492.1. HQ205065 Genomic DNA. Translation: ADP90493.1. AK292926 mRNA. Translation: BAF85615.1. CH471196 Genomic DNA. Translation: EAW55646.1. CH471196 Genomic DNA. Translation: EAW55648.1. CH471196 Genomic DNA. Translation: EAW55649.1. BC051748 mRNA. Translation: AAH51748.1. |
| IPI | IPI00013378. IPI00221295. |
| RefSeq | NP_004609.1. NM_004618.3. |
| UniGene | Hs.592115. |
3D structure databases | |
| ProteinModelPortal | Q13472. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-33323N. |
| IntAct | Q13472. 4 interactions. |
| MINT | MINT-6610291. |
| STRING | 9606.ENSP00000321636. |
PTM databases | |
| PhosphoSite | Q13472. |
Polymorphism databases | |
| DMDM | 2501242. |
Proteomic databases | |
| PaxDb | Q13472. |
| PRIDE | Q13472. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000321105; ENSP00000321636; ENSG00000177302. ENST00000580095; ENSP00000462790; ENSG00000177302. |
| GeneID | 7156. |
| KEGG | hsa:7156. |
| UCSC | uc002gsx.1. human. |
Organism-specific databases | |
| CTD | 7156. |
| GeneCards | GC17M018175. |
| HGNC | HGNC:11992. TOP3A. |
| HPA | CAB002449. |
| MIM | 601243. gene. |
| neXtProt | NX_Q13472. |
| PharmGKB | PA36673. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG0550. |
| HOGENOM | HOG000184377. |
| HOVERGEN | HBG056668. |
| InParanoid | Q13472. |
| KO | K03165. |
| OMA | KPRKCSL. |
| OrthoDB | EOG4K6G3F. |
| PhylomeDB | Q13472. |
Enzyme and pathway databases | |
| Reactome | REACT_111183. Meiosis. |
Gene expression databases | |
| ArrayExpress | Q13472. |
| Bgee | Q13472. |
| CleanEx | HS_TOP3A. |
| Genevestigator | Q13472. |
| GermOnline | ENSG00000177302. Homo sapiens. |
Family and domain databases | |
| Gene3D | 1.10.460.10. 2 hits. 2.70.20.10. 3 hits. |
| InterPro | IPR000380. Topo_IA. IPR003601. Topo_IA_2. IPR023406. Topo_IA_AS. IPR013497. Topo_IA_cen. IPR013824. Topo_IA_cen_sub1. IPR013825. Topo_IA_cen_sub2. IPR023405. Topo_IA_core_domain. IPR003602. Topo_IA_DNA-bd. IPR013498. Topo_IA_Znf. IPR006171. Toprim_domain. IPR001878. Znf_CCHC. IPR010666. Znf_GRF. [Graphical view] |
| PANTHER | PTHR11390. PTHR11390. 1 hit. |
| Pfam | PF01131. Topoisom_bac. 1 hit. PF01751. Toprim. 1 hit. PF01396. zf-C4_Topoisom. 1 hit. PF06839. zf-GRF. 2 hits. [Graphical view] |
| PRINTS | PR00417. PRTPISMRASEI. |
| SMART | SM00437. TOP1Ac. 1 hit. SM00436. TOP1Bc. 1 hit. SM00493. TOPRIM. 1 hit. SM00343. ZnF_C2HC. 1 hit. [Graphical view] |
| SUPFAM | SSF56712. Topo_IA_core. 1 hit. |
| PROSITE | PS00396. TOPOISOMERASE_I_PROK. 1 hit. PS50880. TOPRIM. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| GenomeRNAi | 7156. |
| NextBio | 28002. |
| SOURCE | Search... |
Entry information
| Entry name | TOP3A_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13472 Secondary accession number(s): A8KA61, D3DXC7, Q13473 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
