Q969P6 (TOP1M_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA topoisomerase I, mitochondrial
Short name=TOP1mt
EC=5.99.1.2

Gene names

Name:

TOP1MT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	601 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Releases the supercoiling and torsional tension of DNA introduced during duplication of mitochondrial DNA 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 than 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. Ref.1
Catalytic activity	ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
Cofactor	Divalent metal ions (calcium or magnesium). Ref.1
Subcellular location	Mitochondrion Ref.1.
Tissue specificity	Ubiquitous; highest in skeletal muscle, heart, brain and fetal liver. Ref.1
Sequence similarities	Belongs to the type IB topoisomerase family.
Sequence caution	The sequence AAH44646.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
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 Biological aspect of Ancestor. Source: RefGenome
Cellular component	chromosome Inferred from electronic annotation. Source: InterPro mitochondrial nucleoid Inferred from direct assay. Source: BHF-UCL
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA topoisomerase (ATP-hydrolyzing) activity Inferred from electronic annotation. Source: InterPro DNA topoisomerase type I activity Inferred from Biological aspect of Ancestor. Source: RefGenome chromatin DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 50	50	Mitochondrion Probable
	Chain	51 – 601	551	DNA topoisomerase I, mitochondrial		PRO_0000034797
Sites
	Active site	559	1	O-(3'-phospho-DNA)-tyrosine intermediate By similarity
Natural variations
	Natural variant	256	1	V → I. Ref.2 Corresponds to variant rs11544484 [ dbSNP | Ensembl ].		VAR_052593
	Natural variant	525	1	R → W. Corresponds to variant rs2293925 [ dbSNP | Ensembl ].		VAR_021863

Sequences

	Sequence		Length	Mass (Da)
	Q969P6 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: A012248D4250C675	FASTA	601	69,872
	10 20 30 40 50 60 MRVVRLLRLR AALTLLGEVP RRPASRGVPG SRRTQKGSGA RWEKEKHEDG VKWRQLEHKG 70 80 90 100 110 120 PYFAPPYEPL PDGVRFFYEG RPVRLSVAAE EVATFYGRML DHEYTTKEVF RKNFFNDWRK 130 140 150 160 170 180 EMAVEEREVI KSLDKCDFTE IHRYFVDKAA ARKVLSREEK QKLKEEAEKL QQEFGYCILD 190 200 210 220 230 240 GHQEKIGNFK IEPPGLFRGR GDHPKMGMLK RRITPEDVVI NCSRDSKIPE PPAGHQWKEV 250 260 270 280 290 300 RSDNTVTWLA AWTESVQNSI KYIMLNPCSK LKGETAWQKF ETARRLRGFV DEIRSQYRAD 310 320 330 340 350 360 WKSREMKTRQ RAVALYFIDK LALRAGNEKE DGEAADTVGC CSLRVEHVQL HPEADGCQHV 370 380 390 400 410 420 VEFDFLGKDC IRYYNRVPVE KPVYKNLQLF MENKDPRDDL FDRLTTTSLN KHLQELMDGL 430 440 450 460 470 480 TAKVFRTYNA SITLQEQLRA LTRAEDSIAA KILSYNRANR VVAILCNHQR ATPSTFEKSM 490 500 510 520 530 540 QNLQTKIQAK KEQVAEARAE LRRARAEHKA QGDGKSRSVL EKKRRLLEKL QEQLAQLSVQ 550 560 570 580 590 600 ATDKEENKQV ALGTSKLNYL DPRISIAWCK RFRVPVEKIY SKTQRERFAW ALAMAGEDFE F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human mitochondrial topoisomerase I." Zhang H., Barcelo J.M., Lee B., Kohlhagen G., Zimonjic D.B., Popescu N.C., Pommier Y. Proc. Natl. Acad. Sci. U.S.A. 98:10608-10613(2001) [PubMed: 11526219] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, COFACTOR, SUBCELLULAR LOCATION, PROBABLE TRANSIT PEPTIDE, TISSUE SPECIFICITY.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-256. Tissue: Brain and Lung.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF349031 , AF349018, AF349019, AF349020, AF349021, AF349022, AF349023, AF349024, AF349025, AF349026, AF349027, AF349028, AF349029, AF349030 Genomic DNA. Translation: AAL10791.1. AF349017 mRNA. Translation: AAL05624.1. BC044646 mRNA. Translation: AAH44646.1. Different initiation. BC052285 mRNA. Translation: AAH52285.1. BC071914 mRNA. Translation: AAH71914.1.
IPI	IPI00465141.
RefSeq	NP_443195.1. NM_052963.1.
UniGene	Hs.528574.
3D structure databases
ProteinModelPortal	Q969P6.
SMR	Q969P6. Positions 42-601.
ModBase	Search...
Protein-protein interaction databases
STRING	Q969P6.
PTM databases
PhosphoSite	Q969P6.
Polymorphism databases
DMDM	20140694.
Proteomic databases
PRIDE	Q969P6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000329245; ENSP00000328835; ENSG00000184428.
GeneID	116447.
KEGG	hsa:116447.
NMPDR	fig|9606.3.peg.30831.
UCSC	uc003yxz.1. human.
Organism-specific databases
CTD	116447.
GeneCards	GC08M144391.
H-InvDB	HIX0025544.
HGNC	HGNC:29787. TOP1MT.
HPA	HPA001915. HPA021542.
MIM	606387. gene.
neXtProt	NX_Q969P6.
PharmGKB	PA134922772.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000016347.
HOVERGEN	HBG007988.
InParanoid	Q969P6.
OMA	PVEKIYS.
OrthoDB	EOG49S667.
PhylomeDB	Q969P6.
Gene expression databases
ArrayExpress	Q969P6.
Bgee	Q969P6.
CleanEx	HS_TOP1MT.
Genevestigator	Q969P6.
GermOnline	ENSG00000184428. Homo sapiens.
Family and domain databases
InterPro	IPR011010. DNA_brk_join_enz. IPR013034. DNA_topo_domain1. IPR018521. TopoI_AS. IPR001631. TopoI_C. IPR013499. TopoI_C_euk. 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. IPR009054. TopoI_insert_euk. [Graphical view]
Gene3D	G3DSA:3.90.15.10. TopoI_cat_a-hlx-sub_euk. 1 hit. G3DSA:1.10.132.10. TopoI_cat_a/b-sub_euk. 1 hit. G3DSA:1.10.10.41. TopoI_DNA-bd_a-hlx_euk. 1 hit. G3DSA:2.170.11.10. TopoI_DNA-bd_mixed-a/b_euk. 2 hits.
KO	K03163.
Pfam	PF01028. Topoisom_I. 1 hit. PF02919. Topoisom_I_N. 1 hit. [Graphical view]
PRINTS	PR00416. EUTPISMRASEI.
SMART	SM00435. TOPEUc. 1 hit. [Graphical view]
SUPFAM	SSF56349. DNA_brk_join_enz. 1 hit. SSF46596. Topismrse_insert. 1 hit. SSF56741. TopoI_DNA_bd_euk. 1 hit.
PROSITE	PS00176. TOPOISOMERASE_I_EUK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00762. Irinotecan. DB01030. Topotecan.
NextBio	79927.
SOURCE	Search...

Entry information

Entry name

TOP1M_HUMAN

Accession

Primary (citable) accession number: Q969P6
Secondary accession number(s): Q86ST4, Q86V82

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.