P0A620 (TOP1_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA topoisomerase 1
EC=5.99.1.2

Alternative name(s):
DNA topoisomerase I
Omega-protein
Relaxing enzyme
Swivelase
Untwisting enzyme

Gene names

Name:	topA
Ordered Locus Names:	Rv3646c, MT3749
ORF Names:	MTCY15C10.06

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	934 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand than undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone By similarity. Ref.5 The C-terminus (residues 622-934) inhibits RNA cleavage by MazF4. Ref.5
Catalytic activity	ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
Enzyme regulation	SsDNA cleavage is inhibited by MazF4.
Subunit structure	Monomer By similarity. Interacts with mRNA interferase MazF4. Ref.5
Miscellaneous	Was identified as a high-confidence drug target.
Sequence similarities	Belongs to the type IA topoisomerase family. Contains 1 Toprim domain.

Ontologies

Keywords
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Isomerase Topoisomerase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA topological change Inferred from electronic annotation. Source: InterPro growth Inferred from mutant phenotype. Source: MTBBASE
Cellular component	cell wall Inferred from direct assay. Source: MTBBASE chromosome Inferred from electronic annotation. Source: InterPro cytosol Inferred from direct assay. Source: MTBBASE plasma membrane Inferred from direct assay. Source: MTBBASE
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA topoisomerase type I activity Inferred from direct assay Ref.3. Source: MTBBASE magnesium ion binding Inferred from direct assay Ref.3. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 934	934	DNA topoisomerase 1		PRO_0000145159
Regions
	Domain	18 – 140	123	Toprim
Sites
	Active site	342	1	O-(5'-phospho-DNA)-tyrosine intermediate By similarity
Experimental info
	Sequence conflict	1	1	M → MERGAQL in AAC44599. Ref.3
	Sequence conflict	53 – 61	9	PRAASDVPA → RGPRRCTR in AAC44599. Ref.3
	Sequence conflict	255 – 281	27	RDFDS…ATALA → AISTRWARCAKATKSLCSTR GARPRWP in AAC44599. Ref.3
	Sequence conflict	369 – 372	4	EYVA → GVRR in AAC44599. Ref.3
	Sequence conflict	797	1	G → V in AAC44599. Ref.3
	Sequence conflict	853 – 895	43	PLREL…DDVAS → ACASWEQIRRRASQWSSRTA DSGRTSPTVRPMPACVRATT WLP in AAC44599. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P0A620 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: B29E2C17897781BA	FASTA	934	102,336
	10 20 30 40 50 60 MADPKTKGRG SGGNGSGRRL VIVESPTKAR KLASYLGSGY IVESSRGHIR DLPRAASDVP 70 80 90 100 110 120 AKYKSQPWAR LGVNVDADFE PLYIISPEKR STVSELRGLL KDVDELYLAT DGDREGEAIA 130 140 150 160 170 180 WHLLETLKPR IPVKRMVFHE ITEPAIRAAA EHPRDLDIDL VDAQETRRIL DRLYGYEVSP 190 200 210 220 230 240 VLWKKVAPKL SAGRVQSVAT RIIVARERDR MAFRSAAYWD ILAKLDASVS DPDAAPPTFS 250 260 270 280 290 300 ARLTAVAGRR VATGRDFDSL GTLRKGDEVI VLDEGSATAL AAGLDGTQLT VASAEEKPYA 310 320 330 340 350 360 RRPYPPFMTS TLQQEASRKL RFSAERTMSI AQRLYENGYI TYMRTDSTTL SESAINAART 370 380 390 400 410 420 QARQLYGDEY VAPAPRQYTR KVKNAQEAHE AIRPAGETFA TPDAVRRELD GPNIDDFRLY 430 440 450 460 470 480 ELIWQRTVAS QMADARGMTL SLRITGMSGH QEVVFSATGR TLTFPGFLKA YVETVDELVG 490 500 510 520 530 540 GEADDAERRL PHLTPGQRLD IVELTPDGHA TNPPARYTEA SLVKALEELG IGRPSTYSSI 550 560 570 580 590 600 IKTIQDRGYV HKKGSALVPS WVAFAVTGLL EQHFGRLVDY DFTAAMEDEL DEIAAGNERR 610 620 630 640 650 660 TNWLNNFYFG GDHGVPDSVA RSGGLKKLVG INLEGIDARE VNSIKLFDDT HGRPIYVRVG 670 680 690 700 710 720 KNGPYLERLV AGDTGEPTPQ RANLSDSITP DELTLQVAEE LFATPQQGRT LGLDPETGHE 730 740 750 760 770 780 IVAREGRFGP YVTEILPEPA ADAAAAAQGV KKRQKAAGPK PRTGSLLRSM DLQTVTLEDA 790 800 810 820 830 840 LRLLSLPRVV GVDPASGEEI TAQNGRYGPY LKRGNDSRSL VTEDQIFTIT LDEALKIYAE 850 860 870 880 890 900 PKRRGRQSAS APPLRELGTD PASGKPMVIK DGRFGPYVTD GETNASLRKG DDVASITDER 910 920 930 AAELLADRRA RGPAKRPARK AARKVPAKKA AKRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Cloning, expression, purification and characterization of DNA topoisomerase I of Mycobacterium tuberculosis." Yang F.D., Lu G., Rubin H. Gene 178:63-69(1996) [PubMed: 8921893] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-895. Strain: ATCC 35801 / TMC 107 / Erdman.
[4]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed: 19099550] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[5]	"Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495 and its sole DNA topoisomerase I." Huang F., He Z.G. Nucleic Acids Res. 38:8219-8230(2010) [PubMed: 20724443] [Abstract] Cited for: FUNCTION AS A TOPOISOMERASE, DNA CLEAVAGE, SSDNA-BINDING, INTERACTION WITH MAZF4, INHIBITION BY MAZF4, INHIBITION OF MAZF ACTIVITY. Strain: ATCC 25618 / H37Rv.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842583 Genomic DNA. Translation: CAB08843.1. AE000516 Genomic DNA. Translation: AAK48109.1. U40159 Genomic DNA. Translation: AAC44599.1.
PIR	G70563.
RefSeq	NP_218163.1. NC_000962.2. NP_338295.1. NC_002755.2.
3D structure databases
ProteinModelPortal	P0A620.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	EBMYCT00000003850; EBMYCP00000003850; EBMYCG00000003848. EBMYCT00000070990; EBMYCP00000069049; EBMYCG00000070985.
GeneID	885608. 922741.
GenomeReviews	Gene locus MT3749 in contig AE000516_GR. Gene locus Rv3646c in contig AL123456_GR.
KEGG	mtc:MT3749. mtu:Rv3646c.
PATRIC	18130002. VBIMycTub22151_4094.
TIGR	MT3749.
Organism-specific databases
TubercuList	Rv3646c.
Phylogenomic databases
GeneTree	EBGT00050000016895.
HOGENOM	HBG512935.
OMA	KKVMPRL.
PhylomeDB	P0A620.
ProtClustDB	PRK07561.
Family and domain databases
InterPro	IPR000380. Topo_IA. IPR003601. Topo_IA_2. IPR023406. Topo_IA_AS. IPR013497. Topo_IA_cen. IPR013824. Topo_IA_cen_sub1. IPR013825. Topo_IA_cen_sub2. IPR023405. Topo_IA_core_domain. IPR003602. Topo_IA_DNA-bd. IPR005733. TopoI_bac-type. IPR006171. Toprim_domain. [Graphical view]
Gene3D	G3DSA:1.10.460.10. Topo_IA_cen_sub1. 2 hits. G3DSA:2.70.20.10. Topo_IA_cen_sub2. 2 hits.
KO	K03168.
PANTHER	PTHR11390. Topo_IA. 1 hit.
Pfam	PF01131. Topoisom_bac. 1 hit. PF01751. Toprim. 1 hit. [Graphical view]
PRINTS	PR00417. PRTPISMRASEI.
SMART	SM00437. TOP1Ac. 1 hit. SM00436. TOP1Bc. 1 hit. SM00493. TOPRIM. 1 hit. [Graphical view]
SUPFAM	SSF56712. Topo_IA_core. 1 hit.
TIGRFAMs	TIGR01051. TopA_bact. 1 hit.
PROSITE	PS00396. TOPOISOMERASE_I_PROK. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

TOP1_MYCTU

Accession

Primary (citable) accession number: P0A620
Secondary accession number(s): O08383, Q59567

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	January 25, 2012
This is version 50 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program