TOPBP1
DNA topoisomerase 2-binding protein 1
Also known as: Dpb11, KIAA0259, TOP2BP1, TOPB1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q92547
- Gene
- TOPBP1
- Ensembl
- ENSG00000163781
- Chromosome
- 3
- Canonical length
- 1522 aa
- Protein class
- Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nuclear bodies,Plasma membrane
OverviewNCBI Gene
This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
1522 residues, UniProt reviewed canonical sequence.
>Q92547|TOPBP1
1 MSRNDKEPFF VKFLKSSDNS KCFFKALESI KEFQSEEYLQ IITEEEALKI KENDRSLYIC
61 DPFSGVVFDH LKKLGCRIVG PQVVIFCMHH QRCVPRAEHP VYNMVMSDVT ISCTSLEKEK
121 REEVHKYVQM MGGRVYRDLN VSVTHLIAGE VGSKKYLVAA NLKKPILLPS WIKTLWEKSQ
181 EKKITRYTDI NMEDFKCPIF LGCIICVTGL CGLDRKEVQQ LTVKHGGQYM GQLKMNECTH
241 LIVQEPKGQK YECAKRWNVH CVTTQWFFDS IEKGFCQDES IYKTEPRPEA KTMPNSSTPT
301 SQINTIDSRT LSDVSNISNI NASCVSESIC NSLNSKLEPT LENLENLDVS AFQAPEDLLD
361 GCRIYLCGFS GRKLDKLRRL INSGGGVRFN QLNEDVTHVI VGDYDDELKQ FWNKSAHRPH
421 VVGAKWLLEC FSKGYMLSEE PYIHANYQPV EIPVSHKPES KAALLKKKNS SFSKKDFAPS
481 EKHEQADEDL LSQYENGSST VVEAKTSEAR PFNDSTHAEP LNDSTHISLQ EENQSSVSHC
541 VPDVSTITEE GLFSQKSFLV LGFSNENESN IANIIKENAG KIMSLLSRTV ADYAVVPLLG
601 CEVEATVGEV VTNTWLVTCI DYQTLFDPKS NPLFTPVPVM TGMTPLEDCV ISFSQCAGAE
661 KESLTFLANL LGASVQEYFV RKSNAKKGMF ASTHLILKER GGSKYEAAKK WNLPAVTIAW
721 LLETARTGKR ADESHFLIEN STKEERSLET EITNGINLNS DTAEHPGTRL QTHRKTVVTP
781 LDMNRFQSKA FRAVVSQHAR QVAASPAVGQ PLQKEPSLHL DTPSKFLSKD KLFKPSFDVK
841 DALAALETPG RPSQQKRKPS TPLSEVIVKN LQLALANSSR NAVALSASPQ LKEAQSEKEE
901 APKPLHKVVV CVSKKLSKKQ SELNGIAASL GADYRWSFDE TVTHFIYQGR PNDTNREYKS
961 VKERGVHIVS EHWLLDCAQE CKHLPESLYP HTYNPKMSLD ISAVQDGRLC NSRLLSAVSS
1021 TKDDEPDPLI LEENDVDNMA TNNKESAPSN GSGKNDSKGV LTQTLEMREN FQKQLQEIMS
1081 ATSIVKPQGQ RTSLSRSGCN SASSTPDSTR SARSGRSRVL EALRQSRQTV PDVNTEPSQN
1141 EQIIWDDPTA REERARLASN LQWPSCPTQY SELQVDIQNL EDSPFQKPLH DSEIAKQAVC
1201 DPGNIRVTEA PKHPISEELE TPIKDSHLIP TPQAPSIAFP LANPPVAPHP REKIITIEET
1261 HEELKKQYIF QLSSLNPQER IDYCHLIEKL GGLVIEKQCF DPTCTHIVVG HPLRNEKYLA
1321 SVAAGKWVLH RSYLEACRTA GHFVQEEDYE WGSSSILDVL TGINVQQRRL ALAAMRWRKK
1381 IQQRQESGIV EGAFSGWKVI LHVDQSREAG FKRLLQSGGA KVLPGHSVPL FKEATHLFSD
1441 LNKLKPDDSG VNIAEAAAQN VYCLRTEYIA DYLMQESPPH VENYCLPEAI SFIQNNKELG
1501 TGLSQKRKAP TEKNKIKRPR VHLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TOPBP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 31 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 31 nTPM
- thymus: 27 nTPM
- testis: 21 nTPM
- lymph node: 18 nTPM
- tonsil: 17 nTPM
- appendix: 12 nTPM
Single-cell type
- neutrophil progenitors: 204 nCPM
- monocyte progenitors: 170 nCPM
- late spermatids: 156 nCPM
- erythrocyte progenitors: 129 nCPM
- megakaryocyte progenitors: 105 nCPM
- early primary spermatocytes: 87 nCPM
Immune cell
- eosinophil: 2.2 nTPM
- basophil: 1.8 nTPM
- T-reg: 1.5 nTPM
- MAIT T-cell: 1 nTPM
- NK-cell: 1 nTPM
- plasmacytoid DC: 1 nTPM
Brain region
- cerebellum: 13 nTPM
- cerebral cortex: 12 nTPM
- white matter: 12 nTPM
- basal ganglia: 11 nTPM
- medulla oblongata: 11 nTPM
- pons: 11 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.09
- gnomAD pLI
- 1
- gnomAD missense Z
- 1.97
- DepMap mean gene effect
- -1.42
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 11% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- broken chromosome clustering
- chromosome organization
- DNA damage checkpoint signaling
- DNA damage response
- DNA metabolic process
- DNA repair
- DNA replication checkpoint signaling
- DNA replication initiation
- double-strand break repair via alternative nonhomologous end joining
- double-strand break repair via classical nonhomologous end joining
- double-strand break repair via homologous recombination
- homologous recombination
- mitotic DNA replication checkpoint signaling
- mitotic G2 DNA damage checkpoint signaling
- protein localization to site of double-strand break
- response to ionizing radiation
Molecular functions
- chromatin-protein adaptor activity
- DNA binding
- identical protein binding
- phosphorylation-dependent protein binding
- protein serine/threonine kinase activator activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- BRCT domain
- Secretoglobin superfamily
- BRCT domain superfamily
- TopBP1/SLF1, BRCT domain
- BRCA1 C Terminus (BRCT) domain
- TopBP1/SLF1, BRCT domain
- TopBP1, first BRCT domain
- TopBP1-like, BRCT0 domain
- TopBP1, eighth BRCT domain
- DNA topoisomerase 2-binding protein 1-like, second BRCT domain
- TopBP1, BRCT0 domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TOPBP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TOPBP1 as an antibody target. Whether an autoantibody or antibody against TOPBP1 could matter depends on whether native TOPBP1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TOPBP1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label TOPBP1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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