DNA topoisomerase 2-binding protein 1 (DNA topoisomerase 2-beta-binding protein 1, TopBP1, KIAA0259)

Function: 1) required for DNA replication 2) role in rescue of stalled replication forks & checkpoint control 3) binds double-stranded DNA breaks & nicks as well as single-stranded DNA 4) recruits SWI/SNF chromatin remodeling complex to E2F1- responsive promoters 5) down-regulates E2F1 activity & inhibits E2F1-dependent apoptosis during G1/S transition & after DNA damage 6) induces kinase activity of ATR 7) binds EDD, E2F1, PML, RAD9A, SMARCA2, SMARCA4 & POLE 8) may interact with TOP2B 9) phosphorylated on Ser & Thr in response to X-ray irradiation 10) ubiquitinated & degraded by the proteasome - X-ray irradiation reduces ubiquitination Structure: - contains 8 BRCT domains Compartment: - nucleus - detected on unpaired autosomes in meiotic prophase cells. - detected on X & Y chromosomes during later stages of prophase - colocalizes with ATR & H2AFX at unsynapsed chromosome cores during prophase - uniform nuclear distribution during G phase - colocalizes with BRCA1 at stalled replication forks during S phase - in mitotic cells, colocalizes with BRCA1 at spindle poles & centrosomes during metaphase & anaphase - detected in discrete foci together with PML & numerous DNA repair enzymes after DNA damage by alkylating agents, UV or gamma irradiation Expression: - expressed in heart, brain, placenta, lung, kidney - up-regulated during the S phase of the cell cycle - up-regulated by E2F1 & interferon

General

DNA-binding protein phosphoprotein

Properties

SIZE: MW = 171 kD entity length = 1522 aa COMPARTMENT: cell nucleus MOTIF: BRCA1 C-terminal (BRCT) motif SITE: 101-189 BRCA1 C-terminal (BRCT) motif SITE: 195-284 BRCA1 C-terminal (BRCT) motif SITE: 354-444 BRCA1 C-terminal (BRCT) motif SITE: 548-633 BRCA1 C-terminal (BRCT) motif SITE: 641-738 Ser phosphorylation site {S805} nuclear translocation signal {852-858} Ser phosphorylation site {S888} BRCT 6 {900-991} BRCT 7 {1259-1351} BRCT 8 {1389-1486} nuclear translocation signal {1517-1520}

Database Correlations

OMIM 607760 UniProt Q92547 Pfam PF00533

References

UniProt :accession Q92547