ID:TOPB1_HUMAN DESCRIPTION: RecName: Full=DNA topoisomerase 2-binding protein 1; AltName: Full=DNA topoisomerase II-beta-binding protein 1; Short=TopBP1; AltName: Full=DNA topoisomerase II-binding protein 1; 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. SUBUNIT: Binds E2F1, PML, RAD9A, RHNO1, SMARCA2, SMARCA4, POLE and UBR5. May interact with TOP2B. Interacts with TICRR. INTERACTION: O75419:CDC45; NbExp=6; IntAct=EBI-308302, EBI-374969; SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, 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 H2AFX 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. TISSUE SPECIFICITY: Highly expressed in heart, brain, placenta, lung and kidney. INDUCTION: Up-regulated during the S phase of the cell cycle. Up- regulated by E2F1 and interferon. PTM: Phosphorylated on serine and threonine residues in response to X-ray irradiation. PTM: Ubiquitinated and degraded by the proteasome. X-ray irradiation reduces ubiquitination. SIMILARITY: Contains 8 BRCT domains. SEQUENCE CAUTION: Sequence=BAA13389.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAA34202.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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.
ModBase Predicted Comparative 3D Structure on Q92547
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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.
Biological Process: GO:0006259 DNA metabolic process GO:0006270 DNA replication initiation GO:0006281 DNA repair GO:0006974 cellular response to DNA damage stimulus GO:0007095 mitotic G2 DNA damage checkpoint GO:0010212 response to ionizing radiation GO:0033314 mitotic DNA replication checkpoint
JD224609 - Sequence 205633 from Patent EP1572962. BC151237 - Homo sapiens topoisomerase (DNA) II binding protein 1, mRNA (cDNA clone MGC:167825 IMAGE:8860504), complete cds. D87448 - Homo sapiens mRNA for KIAA0259 gene. BC017552 - Homo sapiens topoisomerase (DNA) II binding protein 1, mRNA (cDNA clone IMAGE:3911342), with apparent retained intron. AB019397 - Homo sapiens mRNA for DNA topoisomerase II binding protein, complete cds. AK026229 - Homo sapiens cDNA: FLJ22576 fis, clone HSI02511. JD354420 - Sequence 335444 from Patent EP1572962. BC126209 - Homo sapiens topoisomerase (DNA) II binding protein 1, mRNA (cDNA clone MGC:161487 IMAGE:8991925), complete cds. JD509932 - Sequence 490956 from Patent EP1572962. JD184595 - Sequence 165619 from Patent EP1572962. AK302584 - Homo sapiens cDNA FLJ61726 complete cds, highly similar to DNA topoisomerase 2-binding protein 1. JD168050 - Sequence 149074 from Patent EP1572962. JD088698 - Sequence 69722 from Patent EP1572962. JD305699 - Sequence 286723 from Patent EP1572962. JD403664 - Sequence 384688 from Patent EP1572962. KJ902195 - Synthetic construct Homo sapiens clone ccsbBroadEn_11589 TOPBP1 gene, encodes complete protein. KR711734 - Synthetic construct Homo sapiens clone CCSBHm_00030070 TOPBP1 (TOPBP1) mRNA, encodes complete protein. AB384453 - Synthetic construct DNA, clone: pF1KA0259, Homo sapiens TOPBP1 gene for DNA topoisomerase 2-binding protein 1, complete cds, without stop codon, in Flexi system. Y18557 - Homo sapiens mRNA for KIAA0259 protein, partial, 3' UTR. BC032633 - Homo sapiens topoisomerase (DNA) II binding protein 1, mRNA (cDNA clone IMAGE:5395690), partial cds. JD321429 - Sequence 302453 from Patent EP1572962. JD248458 - Sequence 229482 from Patent EP1572962. JD312925 - Sequence 293949 from Patent EP1572962. JD226452 - Sequence 207476 from Patent EP1572962. JD054398 - Sequence 35422 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q92547 (Reactome details) participates in the following event(s):
R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-5693538 Homology Directed Repair R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-69481 G2/M Checkpoints R-HSA-5633007 Regulation of TP53 Activity R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-69620 Cell Cycle Checkpoints R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-73894 DNA Repair R-HSA-1640170 Cell Cycle R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)