Disprot - Database of Protein Disorder

DP00075: DNA topoisomerase 1

General information
DisProt:	DP00075
Name:	DNA topoisomerase 1
Synonym(s):	TOP1_HUMAN EC 5.99.1.2 DNA topoisomerase I Eukaryotic DNA topoisomerase I Human Top1 Human topo I HsTop1 hTop1p hTopo hTopol DNA topoisomerase 1B DNA topoisomerase type 1B TopIB
First appeared in release:	Release 2.2 (04/14/2005)
UniProt:	P11387
UniGene:	Hs.472737
SwissProt:	TOP1_HUMAN
TrEMBL:
NCBI (GI):	12644118
Source organism:	Homo sapiens (Human)
Sequence length:	765
Percent disordered:	42%
Homologues:

Native sequence

10 20 30 40 50 60
| | | | | |
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS NSEHKDSEKK - 60
HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA KIKKEKENGF SSPPQIKDEP - 120
EDDGYFVPPK EDIKPLKRPR DEDDADYKPK KIKTEDTKKE KKRKLEEEED GKLKKPKNKD - 180
KDKKVPEPDN KKKKPKKEEE QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF - 240
YYDGKVMKLS PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC - 300
DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI ANFKIEPPGL - 360
FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK WKEVRHDNKV TWLVSWTENI - 420
QGSIKYIMLN PSSRIKGEKD WQKYETARRL KKCVDKIRNQ YREDWKSKEM KVRQRAVALY - 480
FIDKLALRAG NEKEEGETAD TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK - 540
VPVEKRVFKN LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ - 600
QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK IDAKKEQLAD - 660
ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK LEVQATDREE NKQIALGTSK - 720
LNYLDPRITV AWCKKWGVPI EKIYNKTQRE KFAWAIDMAD EDYEF

Functional narrative

DNA topoisomerase I is a nuclear enzyme involved in transcription, replication, recombination, chromosome condensation, chromatin remodeling, and DNA damage recognition. Eukaryotic topoisomerase I and II can relax both negative and positive supercoils. DNA topoisomerase I catalyzes the ATP-independent breakage of single-stranded DNA, followed by passage and rejoining. DNA topoisomerase I also acts as a protein kinase for other proteins. DNA topoisomerase I is Involved in transcription, replication, recombination, chromosome condensation, chromatin remodeling, and DNA damage recognition. DNA topoisomerase I interacts with transcription factors, such as RNA polymerase I, nucleolin, TATA-binding protein, and p53. DNA topoisomerase I along with NUP98 are involved in a form of therapy-related myelodysplastic syndrome by a chromosomal translocation t(11;20)(p15;q11). DNA topoisomerase I is also involved with Ataxia-Telangiectasia mutated gene (ATM), Acute Myelogenous Leukemia (Familial AML), and Fanconi Anemia (FA) The functions of the disordered regions are: DNA binding, DNA topoisomerase type I activity, kinase activity, nuclear localization, and protein-protein interactions.

Map of ordered and disordered regions
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.

Region 1
Type:	Disordered - Extended
Name:
Location:	1 - 174
Length:	174
Region sequence:	MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKK HKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEP EDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLK
Modification type:
PDB:
Structural/functional type:	Function arises from the ordered state Function arises via a disorder to order transition
Functional classes:	Molecular assembly
Functional subclasses:	Disordered region is not essential for protein function Nuclear localization Autoregulatory Protein-protein binding
Detection methods: Circular dichroism (CD) spectroscopy, far-UV (310 K; KPO₄ ((pH 7.4)) 10 mM) Size exclusion/gel filtration chromatography (298 K; KPO₄ ((pH 7.4)) 200 mM; DTT 1 mM; EDTA 1 mM)
References: Bharti AK, Olson MO, Kufe DW, Rubin EH. "Identification of a nucleolin binding site in human topoisomerase I." J Biol Chem. 1996; 271(4): 1993-7. PubMed: 8567649 Shaiu WL, Hu T, Hsieh TS. "The hydrophilic, protease-sensitive terminal domains of eucaryotic DNA topoisomerases have essential intracellular functions." Pac Symp Biocomput. 1999: 578-589. PubMed: 10380229 Stewart L, Ireton GC, Parker LH, Madden KR, Champoux JJ. "Biochemical and biophysical analyses of recombinant forms of human topoisomerase I." J Biol Chem. 1996; 271(13): 7593-7601. PubMed: 8631793
Comments: Proposed functions of N-terminus include regulation of Topo I activity through the phosphorylation of the N-terminal domain, phosphorylation by a number of protein kinases, nuclear targeting (NLS), and possible protein-protein interactions between the Topo I N-terminus and other chromosomal proteins. Since this domain is flexible and extended, it may be proficient in providing an interacting surface to allow for binding with other proteins. A 44-residue segment in the human Topo I N-terminus can bind to an abundant nucleolar protein nucleolin. (Shaiu, et al.) The critical residues involved in nucleolin binding appear to be contained in the region of 166 - 210. Nucleolin binding to topo I may be the mechanism by which topo I enters the nucleus. While the 166 - 210 region of topo I does contain a NLS, the 140 - 167 and 1 - 139 regions of topo I also contain NLSs that do not bind nucleolin. (Bharti AK, et al.)

Region 2
Type:	Disordered - Extended
Name:
Location:	1 - 197
Length:	197
Region sequence:	MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKK HKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEP EDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKD KDKKVPEPDNKKKKPKK
Modification type:
PDB:
Structural/functional type:	Function arises from the disordered state
Functional classes:	Molecular assembly
Functional subclasses:	Autoregulatory Disordered region is not essential for protein function Nuclear localization Phosphorylation Protein-protein binding
Detection methods: Circular dichroism (CD) spectroscopy, far-UV (298 K; pH: 7.4; Jasco 3000 (spectropolarimeter); path length 0.1 cm; guanidine hypochlorite 6 M; KPO4 10 mM) Size exclusion/gel filtration chromatography (298 K; pH: 7.4; DTT 1 mM; EDTA 1 mM; flow rate 0.75 mL/min; KPO4 200 mM; Superose 12 ((Pharmacia) column )) Sensitivity to proteolysis
References: Bharti AK, Olson MO, Kufe DW, Rubin EH. "Identification of a nucleolin binding site in human topoisomerase I." J Biol Chem. 1996; 271(4): 1993-7. PubMed: 8567649 Labourier E, Rossi F, Gallouzi IE, Allemand E, Divita G, Tazi J. "Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor." Nucleic Acids Res. 1998; 26(12): 2955-2962. PubMed: 9611241 Shaiu WL, Hu T, Hsieh TS. "The hydrophilic, protease-sensitive terminal domains of eucaryotic DNA topoisomerases have essential intracellular functions." Pac Symp Biocomput. 1999: 578-589. PubMed: 10380229 Stewart L, Ireton GC, Champoux JJ. "The domain organization of human topoisomerase I." J Biol Chem. 1996; 271(13): 7602-7608. PubMed: 8631794 Stewart L, Ireton GC, Parker LH, Madden KR, Champoux JJ. "Biochemical and biophysical analyses of recombinant forms of human topoisomerase I." J Biol Chem. 1996; 271(13): 7593-7601. PubMed: 8631793
Comments: Charged residues contained within the interacting region of topo I/kinase (139 - 175) make electrostatic interactions with SF2/ASF (splice factor). Topo I/kinase phosphorylates at least six members of the SR protein family on serines contained in the RS domain of these proteins. Binding of SR proteins or other nuclear factors to DNA topoisomerase I may be a mechanism through which DNA topoisomerase I enters the nucleus. The N-terminal domain is highly extended and thereby accessible for specific interaction with other proteins. Human DNA topoisomerase I is a constitutively expressed nuclear phospho-protein that localizes to active transcription sites in which its kinase activity may allow this protein to participate in the coordination between transcription and splicing, since sites of transcription in the nucleus colocalize with sites of splicing. (Labourier, et al., 1998) Proposed functions of N-terminus include regulation of Topo I activity through the phosphorylation of the N-terminal domain, phosphorylation by a number of protein kinases, nuclear targeting (NLS), and possible protein-protein interactions between the Topo I N-terminus and other chromosomal proteins. Since this domain is flexible and extended, it may be proficient in providing an interacting surface to allow for binding with other proteins. A 44-residue segment in the human Topo I N-terminus can bind to an abundant nucleolar protein nucleolin. (Shaiu, et al.) The critical residues involved in nucleolin binding appear to be contained in the region of 166 - 210. Nucleolin binding to topo I may be the mechanism by which topo I enters the nucleus. While the 166 - 210 region of topo I does contain a NLS, the 140 - 167 and 1 - 139 regions of topo I also contain NLSs that do not bind nucleolin. (Bharti AK, et al.)

Region 3
Type:	Disordered - Extended
Name:
Location:	175 - 214
Length:	40
Region sequence:	KPKNKDKDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEG
Modification type:	Complex Engineered Fragment
PDB:	1A31:A, 1A35:A
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; water 3 uL; duplex oligonucleotide 1 uL)
References: Bharti AK, Olson MO, Kufe DW, Rubin EH. "Identification of a nucleolin binding site in human topoisomerase I." J Biol Chem. 1996; 271(4): 1993-7. PubMed: 8567649 Christensen MO, Barthelmes HU, Boege F, Mielke C. "Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitro." Nucleic Acids Res. 2003; 31(24): 7255-63. PubMed: 14654701 Frohlich RF, Andersen FF, Westergaard O, Andersen AH, Knudsen BR. "Regions within the N-terminal domain of human topoisomerase I exert important functions during strand rotation and DNA binding." J Mol Biol. 2004; 336(1): 93-103. PubMed: 14741206 Lisby M, Olesen JR, Skouboe C, Krogh BO, Straub T, Boege F, Velmurugan S, Martensen PM, Andersen AH, Jayaram M, Westergaard O, Knudsen BR. "Residues within the N-terminal domain of human topoisomerase I play a direct role in relaxation." J Biol Chem. 2001; 276(23): 20220-20227. PubMed: 11283003 Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. "Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA." Science. 1998; 279(5356): 1504-1153. PubMed: 9488644
Comments:

Region 4
Type:	Disordered - Extended
Name:
Location:	174 - 214
Length:	41
Region sequence:	KKPKNKDKDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEG
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 6 uL; duplex oligonucleotide 2 uL; protein 4 uL; water 2 uL)
References: Bharti AK, Olson MO, Kufe DW, Rubin EH. "Identification of a nucleolin binding site in human topoisomerase I." J Biol Chem. 1996; 271(4): 1993-7. PubMed: 8567649 Christensen MO, Barthelmes HU, Boege F, Mielke C. "Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitro." Nucleic Acids Res. 2003; 31(24): 7255-63. PubMed: 14654701 Frohlich RF, Andersen FF, Westergaard O, Andersen AH, Knudsen BR. "Regions within the N-terminal domain of human topoisomerase I exert important functions during strand rotation and DNA binding." J Mol Biol. 2004; 336(1): 93-103. PubMed: 14741206 Lisby M, Olesen JR, Skouboe C, Krogh BO, Straub T, Boege F, Velmurugan S, Martensen PM, Andersen AH, Jayaram M, Westergaard O, Knudsen BR. "Residues within the N-terminal domain of human topoisomerase I play a direct role in relaxation." J Biol Chem. 2001; 276(23): 20220-20227. PubMed: 11283003 Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ. "A model for the mechanism of human topoisomerase I." Science. 1998; 279(5356): 1534-1541. PubMed: 9488652
Comments:

Region 5
Type:	Disordered - Extended
Name:
Location:	627 - 659
Length:	33
Region sequence:	AILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLA
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 6 uL; duplex oligonucleotide 2 uL; protein 4 uL; water 2 uL)
References: Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ. "A model for the mechanism of human topoisomerase I." Science. 1998; 279(5356): 1534-1541. PubMed: 9488652
Comments:

Region 6
Type:	Disordered - Extended
Name:
Location:	636 - 659
Length:	24
Region sequence:	PPKTFEKSMMNLQTKIDAKKEQLA
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. "Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA." Science. 1998; 279(5356): 1504-1153. PubMed: 9488644
Comments:

Region 7
Type:	Disordered - Extended
Name:
Location:	634 - 640
Length:	7
Region sequence:	RAPPKTF
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 6 uL; duplex oligonucleotide 2 uL; protein 4 uL; water 2 uL) X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031 Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ. "A model for the mechanism of human topoisomerase I." Science. 1998; 279(5356): 1534-1541. PubMed: 9488652
Comments:

Region 8
Type:	Disordered - Extended
Name:
Location:	636 - 640
Length:	5
Region sequence:	PPKTF
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 6 uL; duplex oligonucleotide 2 uL; protein 4 uL; water 2 uL)
References: Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ. "A model for the mechanism of human topoisomerase I." Science. 1998; 279(5356): 1534-1541. PubMed: 9488652
Comments:

Region 9
Type:	Disordered - Extended
Name:
Location:	628 - 635
Length:	8
Region sequence:	ILCNHQRA
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. "Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA." Science. 1998; 279(5356): 1504-1153. PubMed: 9488644
Comments:

Region 10
Type:	Disordered - Extended
Name:
Location:	713 - 719
Length:	7
Region sequence:	QIALGTS
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. "Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA." Science. 1998; 279(5356): 1504-1153. PubMed: 9488644
Comments:

Region 11
Type:	Disordered - Extended
Name:
Location:	711 - 716
Length:	6
Region sequence:	NKQIAL
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 6 uL; duplex oligonucleotide 2 uL; protein 4 uL; water 2 uL)
References: Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ. "A model for the mechanism of human topoisomerase I." Science. 1998; 279(5356): 1534-1541. PubMed: 9488652
Comments:

Region 12
Type:	Disordered - Extended
Name:
Location:	715 - 719
Length:	5
Region sequence:	ALGTS
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. "Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA." Science. 1998; 279(5356): 1504-1153. PubMed: 9488644
Comments:

Region 13
Type:	Disordered - Extended
Name:
Location:	636 - 712
Length:	77
Region sequence:	PPKTFEKSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLE EQLMKLEVQATDREENK
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 14
Type:	Disordered - Extended
Name:
Location:	627 - 632
Length:	6
Region sequence:	AILCNH
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 15
Type:	Disordered - Extended
Name:
Location:	673 - 678
Length:	6
Region sequence:	KVMKDA
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 16
Type:	Disordered - Extended
Name:
Location:	708 - 721
Length:	14
Region sequence:	REENKQIALGTSKL
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 17
Type:	Disordered - Extended
Name:
Location:	712 - 718
Length:	7
Region sequence:	KQIALGT
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 18
Type:	Disordered - Extended
Name:
Location:	620 - 633
Length:	14
Region sequence:	NRANRAVAILCNHQ
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 19
Type:	Disordered - Extended
Name:
Location:	642 - 712
Length:	71
Region sequence:	KSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKL EVQATDREENK
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 20
Type:	Disordered - Extended
Name:
Location:	713 - 724
Length:	12
Region sequence:	QIALGTSKLNYL
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 21
Type:	Disordered - Extended
Name:
Location:	634 - 641
Length:	8
Region sequence:	RAPPKTFE
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 22
Type:	Disordered - Extended
Name:
Location:	626 - 721
Length:	96
Region sequence:	VAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVE SKKKAVQRLEEQLMKLEVQATDREENKQIALGTSKL
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 23
Type:	Disordered - Extended
Name:
Location:	633 - 641
Length:	9
Region sequence:	QRAPPKTFE
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments:

Region 24
Type:	Disordered - Extended
Name:
Location:	626 - 632
Length:	7
Region sequence:	VAILCNH
Modification type:
PDB:
Structural/functional type:
Functional classes:
Functional subclasses:
Detection methods: X-ray crystallography (295 K; crystallant 3 uL; duplex oligonucleotide 1 uL; water 3 uL)
References: Redinbo MR, Stewart L, Champoux JJ, Hol WG. "Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures." J Mol Biol. 1999; 292(3): 685-696. PubMed: 10497031
Comments: The loop leading up to His632 (residues 626- 632) is disordered in four out of five structures A-E. His632 may stabilize the transition state of the scissile phosphorus atom that was exposed through nucleophilic attack by an activated C4-oxygen atom of Tyr723.

Comments
Additional UniGene ID: Hs.712686 Additional synonyms that are not specific to humans: Deoxiribonucleate topoisomerase, Deoxiribonucleic topoisomerase, Late protein H6, Nicking-closing enzyme, Omega-protein, Relaxing enzyme, Reverse gyrase, Swivelase, and Untwisting enzyme.

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