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P11387

- TOP1_HUMAN

UniProt

P11387 - TOP1_HUMAN

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Protein

DNA topoisomerase 1

Gene

TOP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein 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 (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.By similarity5 Publications

Catalytic activityi

ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.3 PublicationsPROSITE-ProRule annotation

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei316 – 3161Interaction with DNA
Sitei364 – 3641Interaction with DNA
Sitei412 – 4121Interaction with DNA
Sitei443 – 4431Interaction with DNA
Sitei501 – 5011Interaction with DNA
Sitei532 – 5321Interaction with DNA
Sitei574 – 5741Interaction with DNA
Sitei632 – 6321Interaction with DNA
Sitei650 – 6501Interaction with DNA
Active sitei723 – 7231O-(3'-phospho-DNA)-tyrosine intermediate7 PublicationsPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  1. chromatin remodeling Source: RefGenome
  2. chromosome segregation Source: RefGenome
  3. DNA replication Source: RefGenome
  4. DNA topological change Source: UniProtKB
  5. embryonic cleavage Source: Ensembl
  6. phosphorylation Source: UniProtKB
  7. programmed cell death Source: UniProtKB
  8. response to drug Source: UniProtKB
  9. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Topoisomerase

Keywords - Biological processi

Biological rhythms, Host-virus interaction

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:11986. TOP1.

Subcellular locationi

Nucleusnucleolus 1 Publication. Nucleusnucleoplasm 1 Publication
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.

GO - Cellular componenti

  1. cytoplasmic mRNA processing body Source: UniProtKB
  2. nucleolus Source: UniProtKB
  3. nucleoplasm Source: UniProtKB
  4. nucleus Source: UniProtKB
  5. perikaryon Source: Ensembl
  6. replication fork protection complex Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi103 – 1031K → R: Localizes in both nucleoplasm and nucleoli; when associated with R-117 or R-153. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-117 and R-153. 1 Publication
Mutagenesisi117 – 1171K → R: 5-fold decrease in sumoylation. Localizes in both nucleoplasm and nucleoli; when associated with or without R-103 or R-153. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-103 and R-153. 1 Publication
Mutagenesisi153 – 1531K → R: Localizes in both nucleoplasm and nucleoli; when associated with R-103 or R-117. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-103 and R-117. 1 Publication
Mutagenesisi532 – 5321K → A: Almost abolishes enzyme activity. 1 Publication
Mutagenesisi532 – 5321K → R: Strongly reduced enzyme activity. 1 Publication
Mutagenesisi723 – 7231Y → F: No change in CPT-induced clearing from nuclei. 1 Publication

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA353.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed3 Publications
Chaini2 – 765764DNA topoisomerase 1PRO_0000145201Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine3 Publications
Modified residuei10 – 101Phosphoserine2 Publications
Modified residuei57 – 571Phosphoserine1 Publication
Cross-linki103 – 103Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Modified residuei112 – 1121Phosphoserine1 Publication
Cross-linki117 – 117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Cross-linki153 – 153Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
Modified residuei172 – 1721N6-acetyllysineBy similarity
Modified residuei280 – 2801N6-acetyllysine1 Publication
Modified residuei506 – 5061Phosphoserine; by CK21 Publication

Post-translational modificationi

Sumoylated. Lys-117 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.1 Publication
Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP11387.
PaxDbiP11387.
PeptideAtlasiP11387.
PRIDEiP11387.

2D gel databases

SWISS-2DPAGEP11387.

PTM databases

PhosphoSiteiP11387.

Miscellaneous databases

PMAP-CutDBP11387.

Expressioni

Tissue specificityi

Endothelial cells.1 Publication

Gene expression databases

BgeeiP11387.
CleanExiHS_TOP1.
ExpressionAtlasiP11387. baseline and differential.
GenevestigatoriP11387.

Organism-specific databases

HPAiCAB009058.
HPA019039.

Interactioni

Subunit structurei

Monomer. Interacts with SV40 Large T antigen; this interactions allows viral DNA replication.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABL1P005197EBI-876302,EBI-375543
MYCP011062EBI-876302,EBI-447544
NKX3-1Q998016EBI-876302,EBI-1385894

Protein-protein interaction databases

BioGridi113003. 133 interactions.
IntActiP11387. 56 interactions.
MINTiMINT-94018.
STRINGi9606.ENSP00000354522.

Structurei

Secondary structure

1
765
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi205 – 2073Combined sources
Beta strandi220 – 2223Combined sources
Beta strandi236 – 2383Combined sources
Beta strandi240 – 2423Combined sources
Beta strandi245 – 2473Combined sources
Helixi251 – 26111Combined sources
Turni262 – 2654Combined sources
Helixi267 – 2704Combined sources
Helixi272 – 28514Combined sources
Helixi288 – 2936Combined sources
Helixi297 – 2993Combined sources
Helixi303 – 31715Combined sources
Helixi321 – 33818Combined sources
Beta strandi339 – 3435Combined sources
Beta strandi346 – 3516Combined sources
Beta strandi358 – 3603Combined sources
Beta strandi364 – 3663Combined sources
Turni368 – 3714Combined sources
Helixi379 – 3813Combined sources
Beta strandi383 – 3853Combined sources
Beta strandi396 – 3983Combined sources
Beta strandi402 – 4054Combined sources
Beta strandi413 – 4175Combined sources
Turni419 – 4213Combined sources
Beta strandi424 – 4274Combined sources
Beta strandi431 – 4333Combined sources
Helixi434 – 46431Combined sources
Helixi470 – 48516Combined sources
Turni495 – 4973Combined sources
Helixi504 – 5063Combined sources
Helixi509 – 5113Combined sources
Beta strandi514 – 5185Combined sources
Beta strandi521 – 53010Combined sources
Helixi532 – 5343Combined sources
Beta strandi536 – 5427Combined sources
Helixi545 – 5539Combined sources
Turni554 – 5574Combined sources
Turni564 – 5674Combined sources
Helixi570 – 58011Combined sources
Beta strandi581 – 5833Combined sources
Helixi586 – 60520Combined sources
Beta strandi608 – 6103Combined sources
Helixi612 – 62514Combined sources
Turni626 – 6316Combined sources
Helixi640 – 6434Combined sources
Helixi644 – 67330Combined sources
Helixi678 – 71033Combined sources
Beta strandi712 – 7143Combined sources
Turni721 – 7233Combined sources
Helixi726 – 73510Combined sources
Helixi740 – 7423Combined sources
Helixi746 – 7516Combined sources
Helixi753 – 7586Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A31X-ray2.10A175-765[»]
1A35X-ray2.50A175-765[»]
1A36X-ray2.80A175-765[»]
1EJ9X-ray2.60A203-765[»]
1K4SX-ray3.20A174-765[»]
1K4TX-ray2.10A174-765[»]
1LPQX-ray3.14A202-765[»]
1NH3X-ray3.10A203-765[»]
1R49X-ray3.13A174-765[»]
1RR8X-ray2.60C203-765[»]
1RRJX-ray2.30A201-765[»]
1SC7X-ray3.00A174-765[»]
1SEUX-ray3.00A174-765[»]
1T8IX-ray3.00A174-765[»]
1TL8X-ray3.10A174-765[»]
DisProtiDP00075.
ProteinModelPortaliP11387.
SMRiP11387. Positions 201-765.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11387.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni425 – 4262Interaction with DNA
Regioni488 – 4936Interaction with DNA
Regioni585 – 5873Interaction with DNA

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi23 – 204182Lys-richAdd
BLAST

Sequence similaritiesi

Belongs to the type IB topoisomerase family.Curated

Phylogenomic databases

eggNOGiCOG3569.
GeneTreeiENSGT00390000016347.
HOVERGENiHBG007988.
InParanoidiP11387.
KOiK03163.
OMAiEFDFPGK.
OrthoDBiEOG7CVPX5.
PhylomeDBiP11387.
TreeFamiTF105281.

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.

P11387-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS
60 70 80 90 100
NSEHKDSEKK HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA
110 120 130 140 150
KIKKEKENGF SSPPQIKDEP EDDGYFVPPK EDIKPLKRPR DEDDADYKPK
160 170 180 190 200
KIKTEDTKKE KKRKLEEEED GKLKKPKNKD KDKKVPEPDN KKKKPKKEEE
210 220 230 240 250
QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF YYDGKVMKLS
260 270 280 290 300
PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC
310 320 330 340 350
DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI
360 370 380 390 400
ANFKIEPPGL FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK
410 420 430 440 450
WKEVRHDNKV TWLVSWTENI QGSIKYIMLN PSSRIKGEKD WQKYETARRL
460 470 480 490 500
KKCVDKIRNQ YREDWKSKEM KVRQRAVALY FIDKLALRAG NEKEEGETAD
510 520 530 540 550
TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK VPVEKRVFKN
560 570 580 590 600
LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ
610 620 630 640 650
QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK
660 670 680 690 700
IDAKKEQLAD ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK
710 720 730 740 750
LEVQATDREE NKQIALGTSK LNYLDPRITV AWCKKWGVPI EKIYNKTQRE
760
KFAWAIDMAD EDYEF
Length:765
Mass (Da):90,726
Last modified:December 1, 2000 - v2
Checksum:i6FBED540BCF7BE28
GO

Sequence cautioni

The sequence CAA36834.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti145 – 1451A → V in AAA61207. (PubMed:2833744)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti214 – 2141G → S.
Corresponds to variant rs6029542 [ dbSNP | Ensembl ].
VAR_052592
Natural varianti326 – 3261K → R in breast cancer; somatic mutation. 1 Publication
VAR_036555
Natural varianti370 – 3701M → T in CPT-resistant leukemia. 1 Publication
VAR_010666
Natural varianti533 – 5331D → G in CPT-resistant leukemia. 1 Publication
VAR_007530
Natural varianti722 – 7221N → S in CPT-resistant leukemia. 1 Publication
VAR_010667
Natural varianti729 – 7291T → A in CPT-resistant lung cancer. 1 Publication
VAR_007531

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03250 mRNA. Translation: AAA61207.1.
M60706
, M60688, M60689, M60690, M60691, M60692, M60693, M60694, M60695, M60696, M60697, M60698, M60699, M60700, M60701, M60702, M60703, M60704, M60705 Genomic DNA. Translation: AAA61206.1.
AK292943 mRNA. Translation: BAF85632.1.
AL035652, AL022394 Genomic DNA. Translation: CAI19767.1.
AL022394, AL035652 Genomic DNA. Translation: CAI42886.1.
CH471077 Genomic DNA. Translation: EAW75994.1.
CH471077 Genomic DNA. Translation: EAW75995.1.
X52601 Genomic DNA. Translation: CAA36834.1. Sequence problems.
U07804 mRNA. Translation: AAB60379.1.
U07806 mRNA. Translation: AAB60380.1.
X16479 mRNA. Translation: CAA34500.2.
M27913 mRNA. Translation: AAA61208.1.
CCDSiCCDS13312.1.
PIRiA30887. ISHUT1.
RefSeqiNP_003277.1. NM_003286.2.
UniGeneiHs.472737.

Genome annotation databases

EnsembliENST00000361337; ENSP00000354522; ENSG00000198900.
GeneIDi7150.
KEGGihsa:7150.
UCSCiuc002xjl.3. human.

Polymorphism databases

DMDMi12644118.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03250 mRNA. Translation: AAA61207.1 .
M60706
, M60688 , M60689 , M60690 , M60691 , M60692 , M60693 , M60694 , M60695 , M60696 , M60697 , M60698 , M60699 , M60700 , M60701 , M60702 , M60703 , M60704 , M60705 Genomic DNA. Translation: AAA61206.1 .
AK292943 mRNA. Translation: BAF85632.1 .
AL035652 , AL022394 Genomic DNA. Translation: CAI19767.1 .
AL022394 , AL035652 Genomic DNA. Translation: CAI42886.1 .
CH471077 Genomic DNA. Translation: EAW75994.1 .
CH471077 Genomic DNA. Translation: EAW75995.1 .
X52601 Genomic DNA. Translation: CAA36834.1 . Sequence problems.
U07804 mRNA. Translation: AAB60379.1 .
U07806 mRNA. Translation: AAB60380.1 .
X16479 mRNA. Translation: CAA34500.2 .
M27913 mRNA. Translation: AAA61208.1 .
CCDSi CCDS13312.1.
PIRi A30887. ISHUT1.
RefSeqi NP_003277.1. NM_003286.2.
UniGenei Hs.472737.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1A31 X-ray 2.10 A 175-765 [» ]
1A35 X-ray 2.50 A 175-765 [» ]
1A36 X-ray 2.80 A 175-765 [» ]
1EJ9 X-ray 2.60 A 203-765 [» ]
1K4S X-ray 3.20 A 174-765 [» ]
1K4T X-ray 2.10 A 174-765 [» ]
1LPQ X-ray 3.14 A 202-765 [» ]
1NH3 X-ray 3.10 A 203-765 [» ]
1R49 X-ray 3.13 A 174-765 [» ]
1RR8 X-ray 2.60 C 203-765 [» ]
1RRJ X-ray 2.30 A 201-765 [» ]
1SC7 X-ray 3.00 A 174-765 [» ]
1SEU X-ray 3.00 A 174-765 [» ]
1T8I X-ray 3.00 A 174-765 [» ]
1TL8 X-ray 3.10 A 174-765 [» ]
DisProti DP00075.
ProteinModelPortali P11387.
SMRi P11387. Positions 201-765.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113003. 133 interactions.
IntActi P11387. 56 interactions.
MINTi MINT-94018.
STRINGi 9606.ENSP00000354522.

Chemistry

BindingDBi P11387.
ChEMBLi CHEMBL1781.
DrugBanki DB00762. Irinotecan.
DB04967. Lucanthone.
DB05630. Sodium stibogluconate.
DB01030. Topotecan.

PTM databases

PhosphoSitei P11387.

Polymorphism databases

DMDMi 12644118.

2D gel databases

SWISS-2DPAGE P11387.

Proteomic databases

MaxQBi P11387.
PaxDbi P11387.
PeptideAtlasi P11387.
PRIDEi P11387.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000361337 ; ENSP00000354522 ; ENSG00000198900 .
GeneIDi 7150.
KEGGi hsa:7150.
UCSCi uc002xjl.3. human.

Organism-specific databases

CTDi 7150.
GeneCardsi GC20P039657.
H-InvDB HIX0015818.
HIX0040702.
HGNCi HGNC:11986. TOP1.
HPAi CAB009058.
HPA019039.
MIMi 126420. gene.
neXtProti NX_P11387.
PharmGKBi PA353.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG3569.
GeneTreei ENSGT00390000016347.
HOVERGENi HBG007988.
InParanoidi P11387.
KOi K03163.
OMAi EFDFPGK.
OrthoDBi EOG7CVPX5.
PhylomeDBi P11387.
TreeFami TF105281.

Miscellaneous databases

ChiTaRSi TOP1. human.
EvolutionaryTracei P11387.
GeneWikii TOP1.
GenomeRNAii 7150.
NextBioi 27982.
PMAP-CutDB P11387.
PROi P11387.
SOURCEi Search...

Gene expression databases

Bgeei P11387.
CleanExi HS_TOP1.
ExpressionAtlasi P11387. baseline and differential.
Genevestigatori P11387.

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

« Hide 'large scale' publications
  1. "cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment."
    D'Arpa P., Machlin P.S., Ratrie H. III, Rothfield N.F., Cleveland D.W., Earnshaw W.C.
    Proc. Natl. Acad. Sci. U.S.A. 85:2543-2547(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY.
  2. "Structure of the human type I DNA topoisomerase gene."
    Kunze N., Yang G., Dolberg M., Sundarp R., Knippers R., Richter A.
    J. Biol. Chem. 266:9610-9616(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Trachea.
  4. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Structural characterisation of the human DNA topoisomerase I gene promoter."
    Kunze N., Klein M., Richter A., Knippers R.
    Eur. J. Biochem. 194:323-330(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
  7. Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.
    Submitted (DEC-2008) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 2-17; 107-117; 224-239; 253-262; 292-299; 355-362; 426-434; 476-484; 509-532; 550-587; 591-615; 625-634; 656-663; 694-712; 721-734 AND 736-742, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Ovarian carcinoma.
  8. "Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin."
    Fujimori A., Harker W.G., Kohlhagen G., Hoki Y., Pommier Y.
    Cancer Res. 55:1339-1346(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-765, VARIANTS CPT-RESISTANT LEUKEMIA THR-370 AND SER-722.
    Tissue: Peripheral blood.
  9. "Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activity."
    Oddou P., Schmidt U., Knippers R., Richter A.
    Eur. J. Biochem. 177:523-529(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 344-765.
  10. "Characterization of the 3' region of the human DNA topoisomerase I gene."
    Zhou B.S., Bastow K.F., Cheng Y.C.
    Cancer Res. 49:3922-3927(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 541-765.
  11. "Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis."
    Maul G.G., Jimenez S.A., Riggs E., Ziemnicka-Kotula D.
    Proc. Natl. Acad. Sci. U.S.A. 86:8492-8496(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 657-765.
  12. "The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion."
    Ahuja H.G., Felix C.A., Aplan P.D.
    Blood 94:3258-3261(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHROMOSOMAL TRANSLOCATION WITH NUP98.
  13. "Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin."
    Rallabhandi P., Hashimoto K., Mo Y.-Y., Beck W.T., Moitra P.K., D'Arpa P.
    J. Biol. Chem. 277:40020-40026(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-117, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-103; LYS-117; LYS-153 AND TYR-723.
  14. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  15. "Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen."
    Khopde S., Simmons D.T.
    J. Virol. 82:1136-1145(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SV40 LARGE T ANTIGEN.
  16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  17. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  18. "Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells."
    Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S., Poller W., Schultheiss H.P., Rauch U.
    Circ. Res. 104:589-599(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  19. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-57 AND SER-112, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period."
    Onishi Y., Kawano Y.
    Nucleic Acids Res. 40:9482-9492(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  24. "CK2-mediated hyperphosphorylation of topoisomerase I targets serine 506, enhances topoisomerase I-DNA Binding, and increases cellular camptothecin sensitivity."
    Bandyopadhyay K., Li P., Gjerset R.A.
    PLoS ONE 7:E50427-E50427(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-506.
  25. "Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA."
    Redinbo M.R., Stewart L., Kuhn P., Champoux J.J., Hol W.G.J.
    Science 279:1504-1513(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 175-765 IN COMPLEX WITH DNA, ACTIVE SITE.
  26. "A model for the mechanism of human topoisomerase I."
    Stewart L., Redinbo M.R., Qiu X., Hol W.G.J., Champoux J.J.
    Science 279:1534-1541(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 215-765 OF MUTANT PHE-723 IN COMPLEX WITH DNA.
  27. "Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA."
    Redinbo M.R., Champoux J.J., Hol W.G.J.
    Biochemistry 39:6832-6840(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 203-765 IN COMPLEX WITH DNA, ACTIVE SITE.
  28. "8-Oxoguanine rearranges the active site of human topoisomerase I."
    Lesher D.T., Pommier Y., Stewart L., Redinbo M.R.
    Proc. Natl. Acad. Sci. U.S.A. 99:12102-12107(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.14 ANGSTROMS) OF 202-765 IN COMPLEX WITH DNA.
  29. Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND TOPOTECAN, ACTIVE SITE.
  30. "Structural impact of the leukemia drug 1-beta-D-arabinofuranosylcytosine (Ara-C) on the covalent human topoisomerase I-DNA complex."
    Chrencik J.E., Burgin A.B., Pommier Y., Stewart L., Redinbo M.R.
    J. Biol. Chem. 278:12461-12466(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 203-764 IN COMPLEX WITH DNA, ACTIVE SITE.
  31. "The role of lysine 532 in the catalytic mechanism of human topoisomerase I."
    Interthal H., Quigley P.M., Hol W.G., Champoux J.J.
    J. Biol. Chem. 279:2984-2992(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.13 ANGSTROMS) OF 174-765, MUTAGENESIS OF LYS-532, CATALYTIC ACTIVITY, FUNCTION.
  32. "Mechanisms of camptothecin resistance by human topoisomerase I mutations."
    Chrencik J.E., Staker B.L., Burgin A.B., Pourquier P., Pommier Y., Stewart L., Redinbo M.R.
    J. Mol. Biol. 339:773-784(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 201-765 IN COMPLEX WITH DNA AND TOPOTECAN, ACTIVE SITE.
  33. "Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex."
    Staker B.L., Feese M.D., Cushman M., Pommier Y., Zembower D., Stewart L., Burgin A.B.
    J. Med. Chem. 48:2336-2345(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND SYNTHETIC INHIBITORS, ACTIVE SITE.
  34. "Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA-enzyme-inhibitor complex as determined by X-ray crystallographic analysis."
    Ioanoviciu A., Antony S., Pommier Y., Staker B.L., Stewart L., Cushman M.
    J. Med. Chem. 48:4803-4814(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 174-765 IN COMPLEX WITH DNA AND SYNTHETIC INHIBITORS, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE.
  35. "Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites."
    Tamura H., Kohchi C., Yamada R., Ikeda T., Koiwai O., Patterson E., Keene J.D., Okada K., Kjeldsen E., Nishikawa K.
    Nucleic Acids Res. 19:69-75(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CPT-RESISTANT LEUKEMIA GLY-533.
  36. "Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line."
    Kubota N., Kanzawa F., Nishio K., Takeda Y., Ohmori T., Fujiwara Y., Terashima Y., Saijo N.
    Biochem. Biophys. Res. Commun. 188:571-577(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CPT-RESISTANT LUNG CANCER ALA-729.
  37. Cited for: VARIANT [LARGE SCALE ANALYSIS] BREAST CANCER ARG-326.

Entry informationi

Entry nameiTOP1_HUMAN
AccessioniPrimary (citable) accession number: P11387
Secondary accession number(s): A8KA78
, E1P5W3, O43256, Q12855, Q12856, Q15610, Q5TFY3, Q9UJN0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: December 1, 2000
Last modified: November 26, 2014
This is version 171 of the entry and version 2 of the sequence. [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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: 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
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3