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Q07050

- TOP1_CRIGR

UniProt

Q07050 - TOP1_CRIGR

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Protein
DNA topoisomerase 1
Gene
TOP1, TOP-1
Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells By similarity.

Catalytic activityi

ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.

Enzyme regulationi

Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei318 – 3181Interaction with DNA By similarity
Sitei366 – 3661Interaction with DNA By similarity
Sitei414 – 4141Interaction with DNA By similarity
Sitei445 – 4451Interaction with DNA By similarity
Sitei503 – 5031Interaction with DNA By similarity
Sitei534 – 5341Interaction with DNA By similarity
Sitei576 – 5761Interaction with DNA By similarity
Sitei634 – 6341Interaction with DNA By similarity
Sitei652 – 6521Interaction with DNA By similarity
Active sitei725 – 7251O-(3'-phospho-DNA)-tyrosine intermediate By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. DNA binding Source: UniProtKB
  3. DNA topoisomerase type I activity Source: UniProtKB
  4. DNA topoisomerase type II (ATP-hydrolyzing) activity Source: InterPro
  5. chromatin binding Source: UniProtKB

GO - Biological processi

  1. DNA topological change Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Topoisomerase

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
DNA topoisomerase 1 (EC:5.99.1.2)
Alternative name(s):
DNA topoisomerase I
Gene namesi
Name:TOP1
Synonyms:TOP-1
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus

Subcellular locationi

Nucleusnucleolus. Nucleusnucleoplasm
Note: Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumolyated forms found in both nucleoplasm and nucleoli By similarity.

GO - Cellular componenti

  1. chromosome Source: InterPro
  2. nucleolus Source: UniProtKB
  3. nucleoplasm Source: UniProtKB
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 767766DNA topoisomerase 1
PRO_0000145200Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine By similarity
Modified residuei10 – 101Phosphoserine By similarity
Modified residuei59 – 591Phosphoserine By similarity
Cross-linki105 – 105Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Inferred
Modified residuei114 – 1141Phosphoserine By similarity
Cross-linki119 – 119Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-linki155 – 155Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Inferred
Modified residuei174 – 1741N6-acetyllysine By similarity
Modified residuei282 – 2821N6-acetyllysine By similarity
Modified residuei508 – 5081Phosphoserine; by CK2 By similarity

Post-translational modificationi

Sumoylated. Lys-119 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment By similarity.
Phosphorylation at Ser-508 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin By similarity.

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ07050.

Interactioni

Subunit structurei

Monomer.

Structurei

3D structure databases

ProteinModelPortaliQ07050.
SMRiQ07050. Positions 201-767.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni427 – 4282Interaction with DNA By similarity
Regioni490 – 4956Interaction with DNA By similarity
Regioni587 – 5893Interaction with DNA By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi23 – 206184Lys-rich
Add
BLAST

Sequence similaritiesi

Phylogenomic databases

HOVERGENiHBG007988.
KOiK03163.

Family and domain databases

Gene3Di1.10.10.41. 1 hit.
1.10.132.10. 1 hit.
2.170.11.10. 2 hits.
3.90.15.10. 1 hit.
InterProiIPR011010. DNA_brk_join_enz.
IPR013034. DNA_topo_domain1.
IPR001631. TopoI.
IPR018521. TopoI_AS.
IPR025834. TopoI_C_dom.
IPR014711. TopoI_cat_a-hlx-sub_euk.
IPR014727. TopoI_cat_a/b-sub_euk.
IPR013500. TopoI_cat_euk.
IPR008336. TopoI_DNA-bd_euk.
IPR013030. TopoI_DNA-bd_mixed-a/b_euk.
IPR013499. TopoI_euk.
[Graphical view]
PfamiPF14370. Topo_C_assoc. 1 hit.
PF01028. Topoisom_I. 1 hit.
PF02919. Topoisom_I_N. 1 hit.
[Graphical view]
PRINTSiPR00416. EUTPISMRASEI.
SMARTiSM00435. TOPEUc. 1 hit.
[Graphical view]
SUPFAMiSSF56349. SSF56349. 2 hits.
SSF56741. SSF56741. 1 hit.
PROSITEiPS00176. TOPOISOMERASE_I_EUK. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q07050-1 [UniParc]FASTAAdd to Basket

« Hide

MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK DKEKDREKSK    50
HSNSEHKDSE KKHKEKEKTK HKDGSSEKHK DKHKDRDKEK RKEEKIRASG 100
DAKIKKEKEN GFSSPPRIKD EPDDDGYFAP PKEDIKPLKR PRDEDDADYK 150
PKKIKTEDIK KEKKRKLEEE EDGKLKKTKN KDKDKKGAES DNKKKKPKKE 200
EEQKWKWWEE ERYPEGIKWK FLEHKGPVFA PPYEPLPEGV KFYYDGKVMK 250
LSPKAEEVAT FFAKMLDHEY TTKEIFRKNF FKDWRKEMTN DEKNVITNLS 300
KCDFTQMSQY FKDQSEARKQ MSKEEKLKIK EENEKLLKEY GFCVMDNHRE 350
RIANFKIEPP GLFRGRGNHP KMGMLKRRIM PEDIIINCSK DAKVPSPPPG 400
HKWKEVRHDN KVTWLVSWTE NIQGSIKYIM LNPSSRIKGE KDWQKYETAR 450
RLKKCVDKIR NQYREDWKSK EMKVRQRAVA LYFIDKLALR AGNEKEEGET 500
ADTVSCCSLR VEHINLHPEL DGQEYVVEFD FPGKDSIRYY NKVPVEKRVF 550
KNLQLFMENK QPEDDLFDRL NTGILNKHLQ DLMEGLTAKV FRTYNASITL 600
QQQLKELTAP DENVPAKILS YNRANRAVAI LCNHQRAPPK TFEKSMMNLQ 650
SKIDAKKDQL ADARRDLKSA KADAKVMKDA KTKKVVESKK KAVQRLEEQL 700
MKLEVQATDR EENKQIALGT SKLNYLDPRI TVAWCKKWGV PIEKIYNKTQ 750
REKFAWAIDM TDEDYEF 767
Length:767
Mass (Da):90,868
Last modified:October 1, 1994 - v1
Checksum:i347336D424EF35A9
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti505 – 5051S → G in CPT-resistant cell.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z21624 mRNA. Translation: CAA79747.1.
Z21625 mRNA. Translation: CAA79748.1.
PIRiA49546.
RefSeqiNP_001230963.1. NM_001244034.1.

Genome annotation databases

GeneIDi100689046.
KEGGicge:100689046.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z21624 mRNA. Translation: CAA79747.1 .
Z21625 mRNA. Translation: CAA79748.1 .
PIRi A49546.
RefSeqi NP_001230963.1. NM_001244034.1.

3D structure databases

ProteinModelPortali Q07050.
SMRi Q07050. Positions 201-767.
ModBasei Search...
MobiDBi Search...

Proteomic databases

PRIDEi Q07050.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100689046.
KEGGi cge:100689046.

Organism-specific databases

CTDi 7150.

Phylogenomic databases

HOVERGENi HBG007988.
KOi K03163.

Family and domain databases

Gene3Di 1.10.10.41. 1 hit.
1.10.132.10. 1 hit.
2.170.11.10. 2 hits.
3.90.15.10. 1 hit.
InterProi IPR011010. DNA_brk_join_enz.
IPR013034. DNA_topo_domain1.
IPR001631. TopoI.
IPR018521. TopoI_AS.
IPR025834. TopoI_C_dom.
IPR014711. TopoI_cat_a-hlx-sub_euk.
IPR014727. TopoI_cat_a/b-sub_euk.
IPR013500. TopoI_cat_euk.
IPR008336. TopoI_DNA-bd_euk.
IPR013030. TopoI_DNA-bd_mixed-a/b_euk.
IPR013499. TopoI_euk.
[Graphical view ]
Pfami PF14370. Topo_C_assoc. 1 hit.
PF01028. Topoisom_I. 1 hit.
PF02919. Topoisom_I_N. 1 hit.
[Graphical view ]
PRINTSi PR00416. EUTPISMRASEI.
SMARTi SM00435. TOPEUc. 1 hit.
[Graphical view ]
SUPFAMi SSF56349. SSF56349. 2 hits.
SSF56741. SSF56741. 1 hit.
PROSITEi PS00176. TOPOISOMERASE_I_EUK. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistance."
    Tanizawa A., Bertrand R., Kohlhagen G., Tabuchi A., Jenkins J., Pommier Y.
    J. Biol. Chem. 268:25463-25468(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiTOP1_CRIGR
AccessioniPrimary (citable) accession number: Q07050
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: July 9, 2014
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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