TOPBP1
entrez
11073
canonical
uniprot
Q92547
canonical
ensembl
ENSG00000163781
resolver
ensp
ENSP00000260810
resolver
ensp
ENSP00000493612
resolver
ensp
ENSP00000551720
resolver
ensp
ENSP00000551722
resolver
ensp
ENSP00000623740
resolver
ensp
ENSP00000729091
resolver
ensp
ENSP00000782991
resolver
ensp
ENSP00000782992
resolver
enst
ENST00000260810
resolver
enst
ENST00000642236
resolver
enst
ENST00000881661
resolver
enst
ENST00000881663
resolver
enst
ENST00000953681
resolver
genesymbol
TOPBP1
resolver
genesymbol_syn
KIAA0259
resolver
hgnc
HGNC:17008
resolver
uniprot
A0A2R8YD63
resolver
uniprot
A0AV47
resolver
uniprot
A7E2X7
resolver
uniprot
B7Z7W8
resolver
uniprot
Q05BV8
resolver
uniprot
Q7LGC1
resolver
uniprot
Q9UEB9
resolver
uniprot_entry
A0A2R8YD63_HUMAN
resolver
uniprot_entry
A0AV47_HUMAN
resolver
uniprot_entry
A7E2X7_HUMAN
resolver
uniprot_entry
Q05BV8_HUMAN
resolver
uniprot_entry
TOPB1_HUMAN
resolver
uniprot_sec
B7Z7W8
resolver
uniprot_sec
Q7LGC1
resolver
uniprot_sec
Q9UEB9
resolver
amino_acid_sequence
MSRNDKEPFFVKFLKSSDNSKCFFKALESIKEFQSEEYLQIITEEEALKIKENDRSLYICDPFSGVVFDHLKKLGCRIVGPQVVIFCMHHQRCVPRAEHPVYNMVMSDVTISCTSLEKEKREEVHKYVQMMGGRVYRDLNVSVTHLIAGEVGSKKYLVAANLKKPILLPSWIKTLWEKSQEKKITRYTDINMEDFKCPIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLKMNECTHLIVQEPKGQKYECAKRWNVHCVTTQWFFDSIEKGFCQDESIYKTEPRPEAKTMPNSSTPTSQINTIDSRTLSDVSNISNINASCVSESICNSLNSKLEPTLENLENLDVSAFQAPEDLLDGCRIYLCGFSGRKLDKLRRLINSGGGVRFNQLNEDVTHVIVGDYDDELKQFWNKSAHRPHVVGAKWLLECFSKGYMLSEEPYIHANYQPVEIPVSHKPESKAALLKKKNSSFSKKDFAPSEKHEQADEDLLSQYENGSSTVVEAKTSEARPFNDSTHAEPLNDSTHISLQEENQSSVSHCVPDVSTITEEGLFSQKSFLVLGFSNENESNIANIIKENAGKIMSLLSRTVADYAVVPLLGCEVEATVGEVVTNTWLVTCIDYQTLFDPKSNPLFTPVPVMTGMTPLEDCVISFSQCAGAEKESLTFLANLLGASVQEYFVRKSNAKKGMFASTHLILKERGGSKYEAAKKWNLPAVTIAWLLETARTGKRADESHFLIENSTKEERSLETEITNGINLNSDTAEHPGTRLQTHRKTVVTPLDMNRFQSKAFRAVVSQHARQVAASPAVGQPLQKEPSLHLDTPSKFLSKDKLFKPSFDVKDALAALETPGRPSQQKRKPSTPLSEVIVKNLQLALANSSRNAVALSASPQLKEAQSEKEEAPKPLHKVVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFIYQGRPNDTNREYKSVKERGVHIVSEHWLLDCAQECKHLPESLYPHTYNPKMSLDISAVQDGRLCNSRLLSAVSSTKDDEPDPLILEENDVDNMATNNKESAPSNGSGKNDSKGVLTQTLEMRENFQKQLQEIMSATSIVKPQGQRTSLSRSGCNSASSTPDSTRSARSGRSRVLEALRQSRQTVPDVNTEPSQNEQIIWDDPTAREERARLASNLQWPSCPTQYSELQVDIQNLEDSPFQKPLHDSEIAKQAVCDPGNIRVTEAPKHPISEELETPIKDSHLIPTPQAPSIAFPLANPPVAPHPREKIITIEETHEELKKQYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDPTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAGHFVQEEDYEWGSSSILDVLTGINVQQRRLALAAMRWRKKIQQRQESGIVEGAFSGWKVILHVDQSREAGFKRLLQSGGAKVLPGHSVPLFKEATHLFSDLNKLKPDDSGVNIAEAAAQNVYCLRTEYIADYLMQESPPHVENYCLPEAISFIQNNKELGTGLSQKRKAPTEKNKIKRPRVH
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q800K6, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}.
uniprot
proteins
mass_dalton
170679
uniprot
proteins
mutagenesis
MUTAGEN 155; /note="K->E: Impaired interaction with phosphorylated MDC1. Does not affect interaction with phosphorylated TP53BP1."; /evidence="ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337"; MUTAGEN 250; /note="K->A: Abolished interaction with phosphorylated HTATSF1."; /evidence="ECO:0000269|PubMed:35597237"; MUTAGEN 250; /note="K->E: Abolished interaction with phosphorylated TP53BP1."; /evidence="ECO:0000269|PubMed:31135337"; MUTAGEN 564; /note="S->A: Does not affect interaction with MDC1."; /evidence="ECO:0000269|PubMed:23891287"; MUTAGEN 681..682; /note="RK->EE: Decreased interaction with MDC1."; /evidence="ECO:0000269|PubMed:23891287"; MUTAGEN 704; /note="K->A: Decreased interaction with MDC1. Does not affect interaction with phosphorylated HTATSF1."; /evidence="ECO:0000269|PubMed:23891287, ECO:0000269|PubMed:35597237"; MUTAGEN 837..839; /note="FDV->AAA: Decreased interaction with CIP2A."; /evidence="ECO:0000269|PubMed:35121901"; MUTAGEN 1273; /note="S->A: Decreased interaction with autophosphorylated ATR."; /evidence="ECO:0000269|PubMed:21777809"; MUTAGEN 1280; /note="R->Q: Decreased interaction with autophosphorylated ATR."; /evidence="ECO:0000269|PubMed:21777809"; MUTAGEN 1317; /note="K->A: Does not affect interaction with phosphorylated HTATSF1."; /evidence="ECO:0000269|PubMed:35597237"; MUTAGEN 1317; /note="K->M: Decreased interaction with autophosphorylated ATR."; /evidence="ECO:0000269|PubMed:21777809
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on serine and threonine residues in response to X-ray irradiation. {ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696}.; PTM: Ubiquitinated and degraded by the proteasome. X-ray irradiation reduces ubiquitination (PubMed:11714696). Deubiquitinated by USP13; leading to TOPBP1 stabilizion and activation of the ATR-TOPBP1 axis pathway (PubMed:33592542). {ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:33592542}.
uniprot
proteins
protein_family
TOPBP1 family
uniprot
proteins
pubmed
10498869
uniprot
proteins
pubmed
11395493
uniprot
proteins
pubmed
11714696
uniprot
proteins
pubmed
12697828
uniprot
proteins
pubmed
12773567
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15075294
uniprot
proteins
pubmed
15138768
uniprot
proteins
pubmed
16530042
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17575048
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19937654
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20080954
uniprot
proteins
pubmed
20545769
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21482717
uniprot
proteins
pubmed
21659603
uniprot
proteins
pubmed
21777809
uniprot
proteins
pubmed
22730300
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23891287
uniprot
proteins
pubmed
25602520
uniprot
proteins
pubmed
25933514
uniprot
proteins
pubmed
26811421
uniprot
proteins
pubmed
30898438
uniprot
proteins
pubmed
31135337
uniprot
proteins
pubmed
33592542
uniprot
proteins
pubmed
35121901
uniprot
proteins
pubmed
35597237
uniprot
proteins
pubmed
35842428
uniprot
proteins
pubmed
37165191
uniprot
proteins
pubmed
37316668
uniprot
proteins
pubmed
37674080
uniprot
proteins
pubmed
9039502
uniprot
proteins
pubmed
9461304
uniprot
proteins
sequence_length
1522
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:12773567}. Chromosome {ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:15138768, ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:15138768}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:15138768}. Note=Localizes to sites of DNA damage, such as double-stranded breaks (DSBs) (PubMed:10498869, PubMed:21482717, PubMed:21659603, PubMed:21777809, PubMed:30898438, PubMed:35842428, PubMed:37674080). Recruited to DNA double-strand break (DSBs) during S-phase following interaction with phosphorylated HTATSF1 (PubMed:35597237). Recruited to DSBs during mitosis following interaction with phosphorylated MDC1 (PubMed:30898438). Has a uniform nuclear distribution during G phase (PubMed:11395493). Colocalizes with BRCA1 at stalled replication forks during S phase (PubMed:11395493). In mitotic cells it colocalizes with BRCA1 at spindle poles and centrosomes during metaphase and anaphase (PubMed:11395493). Detected in discrete foci together with PML and numerous DNA repair enzymes after DNA damage by alkylating agents, UV or gamma irradiation (PubMed:12773567). Detected on unpaired autosomes in meiotic prophase cells (By similarity). Detected on X and Y chromosomes during later stages of prophase (By similarity). Colocalizes with ATR and H2AX at unsynapsed chromosome cores during prophase (By similarity). Localizes to broken chromosomes within micronuclei during interphase and following chromothripsis (PubMed:37165191, PubMed:37316668). Localization to broken chromosomes is mainly independent of MDC1 (PubMed:35121901, PubMed:37165191). {ECO:0000250|UniProtKB:Q6ZQF0, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:12773567, ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}.
uniprot
proteins