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Protein

DNA topoisomerase 2-binding protein 1

Gene

TOPBP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:16530042).6 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • protein C-terminus binding Source: ProtInc

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA metabolic process Source: ProtInc
  • DNA repair Source: UniProtKB
  • mitotic DNA replication checkpoint Source: GO_Central
  • response to ionizing radiation Source: UniProtKB

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair

Enzyme and pathway databases

ReactomeiR-HSA-5685938 HDR through Single Strand Annealing (SSA)
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-69473 G2/M DNA damage checkpoint
SignaLinkiQ92547
SIGNORiQ92547

Names & Taxonomyi

Protein namesi
Recommended name:
DNA topoisomerase 2-binding protein 1
Alternative name(s):
DNA topoisomerase II-beta-binding protein 1
Short name:
TopBP1
DNA topoisomerase II-binding protein 1
Gene namesi
Name:TOPBP1
Synonyms:KIAA0259
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000163781.12
HGNCiHGNC:17008 TOPBP1
MIMi607760 gene
neXtProtiNX_Q92547

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi11073
OpenTargetsiENSG00000163781
PharmGKBiPA134934073

Chemistry databases

ChEMBLiCHEMBL3175

Polymorphism and mutation databases

BioMutaiTOPBP1
DMDMi296453012

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000726311 – 1522DNA topoisomerase 2-binding protein 1Add BLAST1522

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei298PhosphothreonineCombined sources1
Modified residuei301PhosphoserineCombined sources1
Modified residuei779PhosphothreonineCombined sources1
Modified residuei848PhosphothreonineCombined sources1
Modified residuei860PhosphoserineCombined sources1
Modified residuei861PhosphothreonineCombined sources1
Modified residuei864PhosphoserineCombined sources1
Modified residuei886PhosphoserineCombined sources1
Modified residuei888PhosphoserineCombined sources1
Modified residuei1002PhosphoserineCombined sources1
Modified residuei1064PhosphothreonineCombined sources1
Modified residuei1504PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on serine and threonine residues in response to X-ray irradiation.2 Publications
Ubiquitinated and degraded by the proteasome. X-ray irradiation reduces ubiquitination.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ92547
MaxQBiQ92547
PaxDbiQ92547
PeptideAtlasiQ92547
PRIDEiQ92547
ProteomicsDBi75308

PTM databases

iPTMnetiQ92547
PhosphoSitePlusiQ92547

Expressioni

Tissue specificityi

Highly expressed in heart, brain, placenta, lung and kidney.1 Publication

Inductioni

Up-regulated during the S phase of the cell cycle. Up-regulated by E2F1 and interferon.1 Publication

Gene expression databases

BgeeiENSG00000163781 Expressed in 225 organ(s), highest expression level in intestine
CleanExiHS_TOPBP1
ExpressionAtlasiQ92547 baseline and differential
GenevisibleiQ92547 HS

Organism-specific databases

HPAiCAB022451
HPA036738
HPA036739

Interactioni

Subunit structurei

Interacts with POLE (PubMed:11395493). Interacts with RAD9A (PubMed:11395493). Interacts with UBR5 (PubMed:11714696). Interacts with E2F1 (PubMed:12697828, PubMed:15075294). Interacts with PML (PubMed:12773567). Interacts with SMARCA2 (PubMed:15075294). Interacts with SMARCA4 (PubMed:15075294). Interacts with RHNO1 (PubMed:21659603). May interact with TOP2B (PubMed:9461304). Interacts with TICRR (PubMed:20080954). Interacts with HELB (PubMed:25933514).9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116256, 59 interactors
CORUMiQ92547
DIPiDIP-24263N
IntActiQ92547, 26 interactors
MINTiQ92547
STRINGi9606.ENSP00000260810

Chemistry databases

BindingDBiQ92547

Structurei

Secondary structure

11522
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ92547
SMRiQ92547
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92547

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini101 – 189BRCT 1PROSITE-ProRule annotationAdd BLAST89
Domaini195 – 284BRCT 2PROSITE-ProRule annotationAdd BLAST90
Domaini354 – 444BRCT 3PROSITE-ProRule annotationAdd BLAST91
Domaini548 – 633BRCT 4PROSITE-ProRule annotationAdd BLAST86
Domaini641 – 738BRCT 5PROSITE-ProRule annotationAdd BLAST98
Domaini900 – 991BRCT 6PROSITE-ProRule annotationAdd BLAST92
Domaini1259 – 1351BRCT 7PROSITE-ProRule annotationAdd BLAST93
Domaini1389 – 1486BRCT 8PROSITE-ProRule annotationAdd BLAST98

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi852 – 858Nuclear localization signalSequence analysis7
Motifi1517 – 1520Nuclear localization signalSequence analysis4

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1929 Eukaryota
ENOG410XPFH LUCA
GeneTreeiENSGT00840000129846
HOGENOMiHOG000154662
HOVERGENiHBG067053
InParanoidiQ92547
KOiK10728
OMAiCAQEYKH
OrthoDBiEOG091G02MY
PhylomeDBiQ92547
TreeFamiTF326403

Family and domain databases

CDDicd00027 BRCT, 6 hits
Gene3Di3.40.50.10190, 9 hits
InterProiView protein in InterPro
IPR001357 BRCT_dom
IPR036420 BRCT_dom_sf
IPR035960 Secretoglobin_sf
PfamiView protein in Pfam
PF00533 BRCT, 4 hits
PF12738 PTCB-BRCT, 2 hits
SMARTiView protein in SMART
SM00292 BRCT, 7 hits
SUPFAMiSSF48201 SSF48201, 1 hit
SSF52113 SSF52113, 6 hits
PROSITEiView protein in PROSITE
PS50172 BRCT, 7 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q92547-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSRNDKEPFF VKFLKSSDNS KCFFKALESI KEFQSEEYLQ IITEEEALKI
60 70 80 90 100
KENDRSLYIC DPFSGVVFDH LKKLGCRIVG PQVVIFCMHH QRCVPRAEHP
110 120 130 140 150
VYNMVMSDVT ISCTSLEKEK REEVHKYVQM MGGRVYRDLN VSVTHLIAGE
160 170 180 190 200
VGSKKYLVAA NLKKPILLPS WIKTLWEKSQ EKKITRYTDI NMEDFKCPIF
210 220 230 240 250
LGCIICVTGL CGLDRKEVQQ LTVKHGGQYM GQLKMNECTH LIVQEPKGQK
260 270 280 290 300
YECAKRWNVH CVTTQWFFDS IEKGFCQDES IYKTEPRPEA KTMPNSSTPT
310 320 330 340 350
SQINTIDSRT LSDVSNISNI NASCVSESIC NSLNSKLEPT LENLENLDVS
360 370 380 390 400
AFQAPEDLLD GCRIYLCGFS GRKLDKLRRL INSGGGVRFN QLNEDVTHVI
410 420 430 440 450
VGDYDDELKQ FWNKSAHRPH VVGAKWLLEC FSKGYMLSEE PYIHANYQPV
460 470 480 490 500
EIPVSHKPES KAALLKKKNS SFSKKDFAPS EKHEQADEDL LSQYENGSST
510 520 530 540 550
VVEAKTSEAR PFNDSTHAEP LNDSTHISLQ EENQSSVSHC VPDVSTITEE
560 570 580 590 600
GLFSQKSFLV LGFSNENESN IANIIKENAG KIMSLLSRTV ADYAVVPLLG
610 620 630 640 650
CEVEATVGEV VTNTWLVTCI DYQTLFDPKS NPLFTPVPVM TGMTPLEDCV
660 670 680 690 700
ISFSQCAGAE KESLTFLANL LGASVQEYFV RKSNAKKGMF ASTHLILKER
710 720 730 740 750
GGSKYEAAKK WNLPAVTIAW LLETARTGKR ADESHFLIEN STKEERSLET
760 770 780 790 800
EITNGINLNS DTAEHPGTRL QTHRKTVVTP LDMNRFQSKA FRAVVSQHAR
810 820 830 840 850
QVAASPAVGQ PLQKEPSLHL DTPSKFLSKD KLFKPSFDVK DALAALETPG
860 870 880 890 900
RPSQQKRKPS TPLSEVIVKN LQLALANSSR NAVALSASPQ LKEAQSEKEE
910 920 930 940 950
APKPLHKVVV CVSKKLSKKQ SELNGIAASL GADYRWSFDE TVTHFIYQGR
960 970 980 990 1000
PNDTNREYKS VKERGVHIVS EHWLLDCAQE CKHLPESLYP HTYNPKMSLD
1010 1020 1030 1040 1050
ISAVQDGRLC NSRLLSAVSS TKDDEPDPLI LEENDVDNMA TNNKESAPSN
1060 1070 1080 1090 1100
GSGKNDSKGV LTQTLEMREN FQKQLQEIMS ATSIVKPQGQ RTSLSRSGCN
1110 1120 1130 1140 1150
SASSTPDSTR SARSGRSRVL EALRQSRQTV PDVNTEPSQN EQIIWDDPTA
1160 1170 1180 1190 1200
REERARLASN LQWPSCPTQY SELQVDIQNL EDSPFQKPLH DSEIAKQAVC
1210 1220 1230 1240 1250
DPGNIRVTEA PKHPISEELE TPIKDSHLIP TPQAPSIAFP LANPPVAPHP
1260 1270 1280 1290 1300
REKIITIEET HEELKKQYIF QLSSLNPQER IDYCHLIEKL GGLVIEKQCF
1310 1320 1330 1340 1350
DPTCTHIVVG HPLRNEKYLA SVAAGKWVLH RSYLEACRTA GHFVQEEDYE
1360 1370 1380 1390 1400
WGSSSILDVL TGINVQQRRL ALAAMRWRKK IQQRQESGIV EGAFSGWKVI
1410 1420 1430 1440 1450
LHVDQSREAG FKRLLQSGGA KVLPGHSVPL FKEATHLFSD LNKLKPDDSG
1460 1470 1480 1490 1500
VNIAEAAAQN VYCLRTEYIA DYLMQESPPH VENYCLPEAI SFIQNNKELG
1510 1520
TGLSQKRKAP TEKNKIKRPR VH
Length:1,522
Mass (Da):170,679
Last modified:May 18, 2010 - v3
Checksum:i02C25880EDCD6AC7
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8YD63A0A2R8YD63_HUMAN
DNA topoisomerase 2-binding protein...
TOPBP1
1,517Annotation score:
I3L1F2I3L1F2_HUMAN
DNA topoisomerase 2-binding protein...
TOPBP1
50Annotation score:

Sequence cautioni

The sequence BAA13389 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAA34202 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti457K → Q in BAA34202 (PubMed:9461304).Curated1
Sequence conflicti457K → Q in BAA13389 (PubMed:9039502).Curated1
Sequence conflicti911C → R in BAH13754 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059733817S → L. Corresponds to variant dbSNP:rs17301766Ensembl.1
Natural variantiVAR_057007955N → S. Corresponds to variant dbSNP:rs10935070Ensembl.1
Natural variantiVAR_0597341042N → S. Corresponds to variant dbSNP:rs10935070Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB019397 mRNA Translation: BAA34202.1 Different initiation.
D87448 mRNA Translation: BAA13389.1 Different initiation.
AK302584 mRNA Translation: BAH13754.1
AC016255 Genomic DNA No translation available.
AC083905 Genomic DNA No translation available.
CCDSiCCDS46919.1
RefSeqiNP_008958.2, NM_007027.3
XP_016861125.1, XM_017005636.1
UniGeneiHs.593379

Genome annotation databases

EnsembliENST00000260810; ENSP00000260810; ENSG00000163781
GeneIDi11073
KEGGihsa:11073
UCSCiuc003eps.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB019397 mRNA Translation: BAA34202.1 Different initiation.
D87448 mRNA Translation: BAA13389.1 Different initiation.
AK302584 mRNA Translation: BAH13754.1
AC016255 Genomic DNA No translation available.
AC083905 Genomic DNA No translation available.
CCDSiCCDS46919.1
RefSeqiNP_008958.2, NM_007027.3
XP_016861125.1, XM_017005636.1
UniGeneiHs.593379

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WF6NMR-A326-444[»]
2XNHX-ray2.80A1-287[»]
2XNKX-ray2.60A/B/C/D1-290[»]
3AL2X-ray2.00A1264-1493[»]
3AL3X-ray2.15A1264-1493[»]
3JVEX-ray1.34A893-996[»]
3OLCX-ray2.40X1-290[»]
3PD7X-ray1.26A/B893-994[»]
3UENX-ray1.90A549-746[»]
3UEOX-ray2.60A/B/C/D549-746[»]
ProteinModelPortaliQ92547
SMRiQ92547
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116256, 59 interactors
CORUMiQ92547
DIPiDIP-24263N
IntActiQ92547, 26 interactors
MINTiQ92547
STRINGi9606.ENSP00000260810

Chemistry databases

BindingDBiQ92547
ChEMBLiCHEMBL3175

PTM databases

iPTMnetiQ92547
PhosphoSitePlusiQ92547

Polymorphism and mutation databases

BioMutaiTOPBP1
DMDMi296453012

Proteomic databases

EPDiQ92547
MaxQBiQ92547
PaxDbiQ92547
PeptideAtlasiQ92547
PRIDEiQ92547
ProteomicsDBi75308

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260810; ENSP00000260810; ENSG00000163781
GeneIDi11073
KEGGihsa:11073
UCSCiuc003eps.4 human

Organism-specific databases

CTDi11073
DisGeNETi11073
EuPathDBiHostDB:ENSG00000163781.12
GeneCardsiTOPBP1
H-InvDBiHIX0003693
HGNCiHGNC:17008 TOPBP1
HPAiCAB022451
HPA036738
HPA036739
MIMi607760 gene
neXtProtiNX_Q92547
OpenTargetsiENSG00000163781
PharmGKBiPA134934073
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1929 Eukaryota
ENOG410XPFH LUCA
GeneTreeiENSGT00840000129846
HOGENOMiHOG000154662
HOVERGENiHBG067053
InParanoidiQ92547
KOiK10728
OMAiCAQEYKH
OrthoDBiEOG091G02MY
PhylomeDBiQ92547
TreeFamiTF326403

Enzyme and pathway databases

ReactomeiR-HSA-5685938 HDR through Single Strand Annealing (SSA)
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-69473 G2/M DNA damage checkpoint
SignaLinkiQ92547
SIGNORiQ92547

Miscellaneous databases

ChiTaRSiTOPBP1 human
EvolutionaryTraceiQ92547
GeneWikiiTOPBP1
GenomeRNAii11073
PROiPR:Q92547
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163781 Expressed in 225 organ(s), highest expression level in intestine
CleanExiHS_TOPBP1
ExpressionAtlasiQ92547 baseline and differential
GenevisibleiQ92547 HS

Family and domain databases

CDDicd00027 BRCT, 6 hits
Gene3Di3.40.50.10190, 9 hits
InterProiView protein in InterPro
IPR001357 BRCT_dom
IPR036420 BRCT_dom_sf
IPR035960 Secretoglobin_sf
PfamiView protein in Pfam
PF00533 BRCT, 4 hits
PF12738 PTCB-BRCT, 2 hits
SMARTiView protein in SMART
SM00292 BRCT, 7 hits
SUPFAMiSSF48201 SSF48201, 1 hit
SSF52113 SSF52113, 6 hits
PROSITEiView protein in PROSITE
PS50172 BRCT, 7 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTOPB1_HUMAN
AccessioniPrimary (citable) accession number: Q92547
Secondary accession number(s): B7Z7W8, Q7LGC1, Q9UEB9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 173 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
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