ID:TOP3A_HUMAN DESCRIPTION: RecName: Full=DNA topoisomerase 3-alpha; EC=5.99.1.2; AltName: Full=DNA topoisomerase III alpha; 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 than 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 (By similarity). 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. CATALYTIC ACTIVITY: ATP-independent breakage of single-stranded DNA, followed by passage and rejoining. SUBUNIT: Directly interacts with BLM and RMI1. Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM. TISSUE SPECIFICITY: High expression is found in testis, heart, skeletal muscle and pancreas. SIMILARITY: Belongs to the type IA topoisomerase family. SIMILARITY: Contains 1 Toprim domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 56712 - Prokaryotic type I DNA topoisomerase 57756 - Retrovirus zinc finger-like domains 57783 - Zinc beta-ribbon
ModBase Predicted Comparative 3D Structure on Q13472
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
DQ597686 - Homo sapiens piRNA piR-35752, complete sequence. DQ578786 - Homo sapiens piRNA piR-46898, complete sequence. DQ593881 - Homo sapiens piRNA piR-33993, complete sequence. DQ590993 - Homo sapiens piRNA piR-58105, complete sequence. JD264194 - Sequence 245218 from Patent EP1572962. JD420243 - Sequence 401267 from Patent EP1572962. JD105356 - Sequence 86380 from Patent EP1572962. JD383843 - Sequence 364867 from Patent EP1572962. JD420242 - Sequence 401266 from Patent EP1572962. JD319323 - Sequence 300347 from Patent EP1572962. DQ588945 - Homo sapiens piRNA piR-56057, complete sequence. AF086042 - Homo sapiens full length insert cDNA clone YX60A04. BC051748 - Homo sapiens topoisomerase (DNA) III alpha, mRNA (cDNA clone MGC:51761 IMAGE:6044661), complete cds. AK126869 - Homo sapiens cDNA FLJ44921 fis, clone BRAMY3011581, highly similar to DNA topoisomerase 3-alpha (EC 5.99.1.2). JD522247 - Sequence 503271 from Patent EP1572962. JD556293 - Sequence 537317 from Patent EP1572962. JD319171 - Sequence 300195 from Patent EP1572962. JD319172 - Sequence 300196 from Patent EP1572962. JD556292 - Sequence 537316 from Patent EP1572962. JD211162 - Sequence 192186 from Patent EP1572962. JD217612 - Sequence 198636 from Patent EP1572962. U43431 - Human DNA topoisomerase III mRNA, complete cds. AK290513 - Homo sapiens cDNA FLJ77764 complete cds. JD521420 - Sequence 502444 from Patent EP1572962. JD534002 - Sequence 515026 from Patent EP1572962. AK292926 - Homo sapiens cDNA FLJ77247 complete cds, highly similar to Homo sapiens topoisomerase (DNA) III alpha (TOP3A), mRNA. JD226763 - Sequence 207787 from Patent EP1572962. JD121133 - Sequence 102157 from Patent EP1572962. JD134657 - Sequence 115681 from Patent EP1572962. JD206237 - Sequence 187261 from Patent EP1572962. JD325761 - Sequence 306785 from Patent EP1572962. JD049799 - Sequence 30823 from Patent EP1572962. JD429393 - Sequence 410417 from Patent EP1572962. AK299764 - Homo sapiens cDNA FLJ56242 complete cds, highly similar to DNA topoisomerase 3-alpha (EC 5.99.1.2). AK296437 - Homo sapiens cDNA FLJ60620 complete cds, highly similar to DNA topoisomerase 3-alpha (EC 5.99.1.2). JD226577 - Sequence 207601 from Patent EP1572962. JD307442 - Sequence 288466 from Patent EP1572962. JD521276 - Sequence 502300 from Patent EP1572962. AK311668 - Homo sapiens cDNA, FLJ18710. JD217410 - Sequence 198434 from Patent EP1572962. JD222349 - Sequence 203373 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13472 (Reactome details) participates in the following event(s):
R-HSA-5686398 SPIDR binds BLM:TOP3A:RMI1:RMI2 R-HSA-5685985 EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment R-HSA-5686410 BLM mediates dissolution of double Holliday junction R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693589 D-loop dissociation and strand annealing R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs R-HSA-5685994 Long-range resection of DNA DSBs by EXO1 or DNA2 R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5685341 BCDX2 complex stabilizes RAD51 filament R-HSA-5685838 CX3 complex binds D-loop structures R-HSA-5693620 D-loop formation mediated by PALB2, BRCA2 and RAD51 R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-912446 Meiotic recombination R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-1500620 Meiosis R-HSA-5693537 Resolution of D-Loop Structures R-HSA-1474165 Reproduction R-HSA-1640170 Cell Cycle R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693538 Homology Directed Repair R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-73894 DNA Repair R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69481 G2/M Checkpoints R-HSA-5633007 Regulation of TP53 Activity R-HSA-69620 Cell Cycle Checkpoints R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)