Search Results

Overview

Uniprot IDQ92547
Protein NameDNA topoisomerase 2-binding protein 1
Gene NameTOPBP1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
461 VSHKPESKAALLKKK
475 KNSSFSKKDFAPSEK
825 LHLDTPSKFLSKDKL
856 PGRPSQQKRKPSTPL

Function

Scaffold protein that acts as a key protein-protein adapter in DNA replication and DNA repair (PubMed:10498869, PubMed:11395493, PubMed:11714696, PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:33592542, PubMed:35597237, PubMed:37674080). Composed of multiple BRCT domains, which specifically recognize and bind phosphorylated proteins, bringing proteins together into functional combinations (PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:35597237, PubMed:37674080). Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages (By similarity). Necessary for the loading of replication factors onto chromatin, including GMNC, CDC45, DNA polymerases and components of the GINS complex (By similarity). Plays a central role in DNA repair by bridging proteins and promoting recruitment of proteins to DNA damage sites (PubMed:30898438, PubMed:35597237, PubMed:37674080). Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the exchange between the DNA replication factor A (RPA) complex and RAD51 (PubMed:26811421, PubMed:35597237). Mechanistically, TOPBP1 is recruited to DNA damage sites in S-phase via interaction with phosphorylated HTATSF1, and promotes the loading of RAD51, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination (PubMed:35597237). Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis (PubMed:37674080). MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair DSBs in DNA that originate in S-phase (PubMed:37674080). Recognizes and binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for subsequent repair (PubMed:37674080). Involved in G1 DNA damage checkpoint by acting as a molecular adapter that couples TP53BP1 and the 9-1-1 complex (PubMed:31135337). In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the CHEK1 signaling pathway and block S-phase progression (PubMed:16530042, PubMed:21777809). Acts as an activator of the kinase activity of ATR (PubMed:16530042, PubMed:21777809). Also required for chromosomal stability when DSBs occur during mitosis by forming filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Together with CIP2A, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei (PubMed:35121901, PubMed:35842428, PubMed:37165191, PubMed:37316668). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss (PubMed:37165191, PubMed:37316668). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters, thereby down-regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage (PubMed:12697828, PubMed:15075294)

Protein Sequence

10 MSRNDKEPFF 20 VKFLKSSDNS 30 KCFFKALESI 40 KEFQSEEYLQ 50 IITEEEALKI 60 KENDRSLYIC 70 DPFSGVVFDH 80 LKKLGCRIVG 90 PQVVIFCMHH 100 QRCVPRAEHP 110 VYNMVMSDVT 120 ISCTSLEKEK 130 REEVHKYVQM 140 MGGRVYRDLN 150 VSVTHLIAGE 160 VGSKKYLVAA 170 NLKKPILLPS 180 WIKTLWEKSQ 190 EKKITRYTDI 200 NMEDFKCPIF 210 LGCIICVTGL 220 CGLDRKEVQQ 230 LTVKHGGQYM 240 GQLKMNECTH 250 LIVQEPKGQK 260 YECAKRWNVH 270 CVTTQWFFDS 280 IEKGFCQDES 290 IYKTEPRPEA 300 KTMPNSSTPT 310 SQINTIDSRT 320 LSDVSNISNI 330 NASCVSESIC 340 NSLNSKLEPT 350 LENLENLDVS 360 AFQAPEDLLD 370 GCRIYLCGFS 380 GRKLDKLRRL 390 INSGGGVRFN 400 QLNEDVTHVI 410 VGDYDDELKQ 420 FWNKSAHRPH 430 VVGAKWLLEC 440 FSKGYMLSEE 450 PYIHANYQPV 460 EIPVSHKPES 470 KAALLKKKNS 480 SFSKKDFAPS 490 EKHEQADEDL 500 LSQYENGSST 510 VVEAKTSEAR 520 PFNDSTHAEP 530 LNDSTHISLQ 540 EENQSSVSHC 550 VPDVSTITEE 560 GLFSQKSFLV 570 LGFSNENESN 580 IANIIKENAG 590 KIMSLLSRTV 600 ADYAVVPLLG 610 CEVEATVGEV 620 VTNTWLVTCI 630 DYQTLFDPKS 640 NPLFTPVPVM 650 TGMTPLEDCV 660 ISFSQCAGAE 670 KESLTFLANL 680 LGASVQEYFV 690 RKSNAKKGMF 700 ASTHLILKER 710 GGSKYEAAKK 720 WNLPAVTIAW 730 LLETARTGKR 740 ADESHFLIEN 750 STKEERSLET 760 EITNGINLNS 770 DTAEHPGTRL 780 QTHRKTVVTP 790 LDMNRFQSKA 800 FRAVVSQHAR 810 QVAASPAVGQ 820 PLQKEPSLHL 830 DTPSKFLSKD 840 KLFKPSFDVK 850 DALAALETPG 860 RPSQQKRKPS 870 TPLSEVIVKN 880 LQLALANSSR 890 NAVALSASPQ 900 LKEAQSEKEE 910 APKPLHKVVV 920 CVSKKLSKKQ 930 SELNGIAASL 940 GADYRWSFDE 950 TVTHFIYQGR 960 PNDTNREYKS 970 VKERGVHIVS 980 EHWLLDCAQE 990 CKHLPESLYP 1000 HTYNPKMSLD 1010 ISAVQDGRLC 1020 NSRLLSAVSS 1030 TKDDEPDPLI 1040 LEENDVDNMA 1050 TNNKESAPSN 1060 GSGKNDSKGV 1070 LTQTLEMREN 1080 FQKQLQEIMS 1090 ATSIVKPQGQ 1100 RTSLSRSGCN 1110 SASSTPDSTR 1120 SARSGRSRVL 1130 EALRQSRQTV 1140 PDVNTEPSQN 1150 EQIIWDDPTA 1160 REERARLASN 1170 LQWPSCPTQY 1180 SELQVDIQNL 1190 EDSPFQKPLH 1200 DSEIAKQAVC 1210 DPGNIRVTEA 1220 PKHPISEELE 1230 TPIKDSHLIP 1240 TPQAPSIAFP 1250 LANPPVAPHP 1260 REKIITIEET 1270 HEELKKQYIF 1280 QLSSLNPQER 1290 IDYCHLIEKL 1300 GGLVIEKQCF 1310 DPTCTHIVVG 1320 HPLRNEKYLA 1330 SVAAGKWVLH 1340 RSYLEACRTA 1350 GHFVQEEDYE 1360 WGSSSILDVL 1370 TGINVQQRRL 1380 ALAAMRWRKK 1390 IQQRQESGIV 1400 EGAFSGWKVI 1410 LHVDQSREAG 1420 FKRLLQSGGA 1430 KVLPGHSVPL 1440 FKEATHLFSD 1450 LNKLKPDDSG 1460 VNIAEAAAQN 1470 VYCLRTEYIA 1480 DYLMQESPPH 1490 VENYCLPEAI 1500 SFIQNNKELG 1510 TGLSQKRKAP 1520 TEKNKIKRPR VH

Gene Ontology

Classification GO ID Description
Biological Process GO:1990166 protein localization to site of double-strand break
Cellular Component GO:0070532 BRCA1-B complex
Cellular Component GO:0005813 centrosome
Cellular Component GO:0005694 chromosome
Cellular Component GO:0000794 condensed nuclear chromosome
Cellular Component GO:0001673 male germ cell nucleus
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0016605 PML body
Cellular Component GO:0090734 site of DNA damage
Cellular Component GO:0035861 site of double-strand break
Cellular Component GO:0000922 spindle pole
Molecular Function GO:0140463 chromatin-protein adaptor activity
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0140031 phosphorylation-dependent protein binding
Molecular Function GO:0043539 protein serine/threonine kinase activator activity
Biological Process GO:0141112 broken chromosome clustering
Biological Process GO:0051276 chromosome organization
Biological Process GO:0000077 DNA damage checkpoint signaling
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006259 DNA metabolic process
Biological Process GO:0006281 DNA repair
Biological Process GO:0000076 DNA replication checkpoint signaling
Biological Process GO:0006270 DNA replication initiation
Biological Process GO:0097681 double-strand break repair via alternative nonhomologous end joining
Biological Process GO:0097680 double-strand break repair via classical nonhomologous end joining
Biological Process GO:0000724 double-strand break repair via homologous recombination
Biological Process GO:0035825 homologous recombination
Biological Process GO:0033314 mitotic DNA replication checkpoint signaling
Biological Process GO:0007095 mitotic G2 DNA damage checkpoint signaling
Biological Process GO:0010212 response to ionizing radiation

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.