Q13472 (TOP3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA topoisomerase 3-alpha
EC=5.99.1.2

Alternative name(s):
DNA topoisomerase III alpha

Gene names

Name:	TOP3A
Synonyms:	TOP3

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	1001 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. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells.
Catalytic activity	ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
Subunit structure	Directly interacts with BLM and RMI1. Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM.
Tissue specificity	High expression is found in testis, heart, skeletal muscle and pancreas.
Sequence similarities	Belongs to the type IA topoisomerase family. Contains 1 Toprim domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	ATP-binding DNA-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Isomerase Topoisomerase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA topological change Inferred from electronic annotation. Source: InterPro meiosis Traceable author statement. Source: ProtInc
Cellular component	PML body Inferred from direct assay. Source: UniProtKB chromosome Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA topoisomerase type I activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q13472-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: Q13472-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1001	1001	DNA topoisomerase 3-alpha		PRO_0000145190
Regions
	Domain	35 – 179	145	Toprim
	Repeat	812 – 839	28	1
	Repeat	896 – 923	28	2
	Zinc finger	658 – 685	28	C4-type Potential
	Region	812 – 923	112	2 X 27 AA approximate repeats
Sites
	Active site	362	1	O-(5'-phospho-DNA)-tyrosine intermediate By similarity
Amino acid modifications
	Modified residue	54	1	Phosphoserine Ref.9
	Modified residue	771	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	1 – 25	25	Missing in isoform Short.		VSP_006524
	Natural variant	459	1	D → N. Corresponds to variant rs28671051 [ dbSNP | Ensembl ].		VAR_052588
	Natural variant	596	1	C → Y.		VAR_007529
	Natural variant	742	1	D → N. Corresponds to variant rs9909732 [ dbSNP | Ensembl ].		VAR_052589
	Natural variant	773	1	N → D. Corresponds to variant rs9911283 [ dbSNP | Ensembl ].		VAR_052590

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 06558C749569E0C2	FASTA	1,001	112,372
	10 20 30 40 50 60 MIFPVARYAL RWLRRPEDRA FSRAAMEMAL RGVRKVLCVA EKNDAAKGIA DLLSNGRMRR 70 80 90 100 110 120 REGLSKFNKI YEFDYHLYGQ NVTMVMTSVS GHLLAHDFQM QFRKWQSCNP LVLFEAEIEK 130 140 150 160 170 180 YCPENFVDIK KTLERETRQC QALVIWTDCD REGENIGFEI IHVCKAVKPN LQVLRARFSE 190 200 210 220 230 240 ITPHAVRTAC ENLTEPDQRV SDAVDVRQEL DLRIGAAFTR FQTLRLQRIF PEVLAEQLIS 250 260 270 280 290 300 YGSCQFPTLG FVVERFKAIQ AFVPEIFHRI KVTHDHKDGI VEFNWKRHRL FNHTACLVLY 310 320 330 340 350 360 QLCVEDPMAT VVEVRSKPKS KWRPQALDTV ELEKLASRKL RINAKETMRI AEKLYTQGYI 370 380 390 400 410 420 SYPRTETNIF PRDLNLTVLV EQQTPDPRWG AFAQSILERG GPTPRNGNKS DQAHPPIHPT 430 440 450 460 470 480 KYTNNLQGDE QRLYEFIVRH FLACCSQDAQ GQETTVEIDI AQERFVAHGL MILARNYLDV 490 500 510 520 530 540 YPYDHWSDKI LPVYEQGSHF QPSTVEMVDG ETSPPKLLTE ADLIALMEKH GIGTDATHAE 550 560 570 580 590 600 HIETIKARMY VGLTPDKRFL PGHLGMGLVE GYDSMGYEMS KPDLRAELEA DLKLICDGKK 610 620 630 640 650 660 DKFVVLRQQV QKYKQVFIEA VAKAKKLDEA LAQYFGNGTE LAQQEDIYPA MPEPIRKCPQ 670 680 690 700 710 720 CNKDMVLKTK KNGGFYLSCM GFPECRSAVW LPDSVLEASR DSSVCPVCQP HPVYRLKLKF 730 740 750 760 770 780 KRGSLPPTMP LEFVCCIGGC DDTLREILDL RFSGGPPRAS QPSGRLQANQ SLNRMDNSQH 790 800 810 820 830 840 PQPADSRQTG SSKALAQTLP PPTAAGESNS VTCNCGQEAV LLTVRKEGPN RGRQFFKCNG 850 860 870 880 890 900 GSCNFFLWAD SPNPGAGGPP ALAYRPLGAS LGCPPGPGIH LGGFGNPGDG SGSGTSCLCS 910 920 930 940 950 960 QPSVTRTVQK DGPNKGRQFH TCAKPREQQC GFFQWVDENT APGTSGAPSW TGDRGRTLES 970 980 990 1000 EARSKRPRAS SSDMGSTAKK PRKCSLCHQP GHTRPFCPQN R
	Isoform Short [UniParc]. Checksum: 4AB9262B5DE7D05B	FASTA	976	109,341
	10 20 30 40 50 60 MEMALRGVRK VLCVAEKNDA AKGIADLLSN GRMRRREGLS KFNKIYEFDY HLYGQNVTMV 70 80 90 100 110 120 MTSVSGHLLA HDFQMQFRKW QSCNPLVLFE AEIEKYCPEN FVDIKKTLER ETRQCQALVI 130 140 150 160 170 180 WTDCDREGEN IGFEIIHVCK AVKPNLQVLR ARFSEITPHA VRTACENLTE PDQRVSDAVD 190 200 210 220 230 240 VRQELDLRIG AAFTRFQTLR LQRIFPEVLA EQLISYGSCQ FPTLGFVVER FKAIQAFVPE 250 260 270 280 290 300 IFHRIKVTHD HKDGIVEFNW KRHRLFNHTA CLVLYQLCVE DPMATVVEVR SKPKSKWRPQ 310 320 330 340 350 360 ALDTVELEKL ASRKLRINAK ETMRIAEKLY TQGYISYPRT ETNIFPRDLN LTVLVEQQTP 370 380 390 400 410 420 DPRWGAFAQS ILERGGPTPR NGNKSDQAHP PIHPTKYTNN LQGDEQRLYE FIVRHFLACC 430 440 450 460 470 480 SQDAQGQETT VEIDIAQERF VAHGLMILAR NYLDVYPYDH WSDKILPVYE QGSHFQPSTV 490 500 510 520 530 540 EMVDGETSPP KLLTEADLIA LMEKHGIGTD ATHAEHIETI KARMYVGLTP DKRFLPGHLG 550 560 570 580 590 600 MGLVEGYDSM GYEMSKPDLR AELEADLKLI CDGKKDKFVV LRQQVQKYKQ VFIEAVAKAK 610 620 630 640 650 660 KLDEALAQYF GNGTELAQQE DIYPAMPEPI RKCPQCNKDM VLKTKKNGGF YLSCMGFPEC 670 680 690 700 710 720 RSAVWLPDSV LEASRDSSVC PVCQPHPVYR LKLKFKRGSL PPTMPLEFVC CIGGCDDTLR 730 740 750 760 770 780 EILDLRFSGG PPRASQPSGR LQANQSLNRM DNSQHPQPAD SRQTGSSKAL AQTLPPPTAA 790 800 810 820 830 840 GESNSVTCNC GQEAVLLTVR KEGPNRGRQF FKCNGGSCNF FLWADSPNPG AGGPPALAYR 850 860 870 880 890 900 PLGASLGCPP GPGIHLGGFG NPGDGSGSGT SCLCSQPSVT RTVQKDGPNK GRQFHTCAKP 910 920 930 940 950 960 REQQCGFFQW VDENTAPGTS GAPSWTGDRG RTLESEARSK RPRASSSDMG STAKKPRKCS 970 LCHQPGHTRP FCPQNR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human TOP3: a single-copy gene encoding DNA topoisomerase III." Hanai R., Caron P.R., Wang J.C. Proc. Natl. Acad. Sci. U.S.A. 93:3653-3657(1996) [PubMed: 8622991] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
[2]	"Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing." Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., Speed T.P., Scharfe C. Nucleic Acids Res. 39:44-58(2011) [PubMed: 20843780] [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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Trachea.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM LONG). Tissue: Testis.
[6]	"BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity." Yin J., Sobeck A., Xu C., Meetei A.R., Hoatlin M., Li L., Wang W. EMBO J. 24:1465-1476(2005) [PubMed: 15775963] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH BLM AND RMI1.
[7]	"RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability." Xu D., Guo R., Sobeck A., Bachrati C.Z., Yang J., Enomoto T., Brown G.W., Hoatlin M.E., Hickson I.D., Wang W. Genes Dev. 22:2843-2855(2008) [PubMed: 18923082] [Abstract] Cited for: IDENTIFICATION IN THE RMI COMPLEX.
[8]	"BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome." Singh T.R., Ali A.M., Busygina V., Raynard S., Fan Q., Du C.-H., Andreassen P.R., Sung P., Meetei A.R. Genes Dev. 22:2856-2868(2008) [PubMed: 18923083] [Abstract] Cited for: IDENTIFICATION IN THE RMI COMPLEX.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-771, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U43431 mRNA. Translation: AAB03694.1. U43431 mRNA. Translation: AAB03695.1. HQ205026 Genomic DNA. Translation: ADP90454.1. HQ205027 Genomic DNA. Translation: ADP90455.1. HQ205028 Genomic DNA. Translation: ADP90456.1. HQ205029 Genomic DNA. Translation: ADP90457.1. HQ205030 Genomic DNA. Translation: ADP90458.1. HQ205031 Genomic DNA. Translation: ADP90459.1. HQ205032 Genomic DNA. Translation: ADP90460.1. HQ205033 Genomic DNA. Translation: ADP90461.1. HQ205034 Genomic DNA. Translation: ADP90462.1. HQ205035 Genomic DNA. Translation: ADP90463.1. HQ205036 Genomic DNA. Translation: ADP90464.1. HQ205037 Genomic DNA. Translation: ADP90465.1. HQ205038 Genomic DNA. Translation: ADP90466.1. HQ205039 Genomic DNA. Translation: ADP90467.1. HQ205040 Genomic DNA. Translation: ADP90468.1. HQ205041 Genomic DNA. Translation: ADP90469.1. HQ205042 Genomic DNA. Translation: ADP90470.1. HQ205043 Genomic DNA. Translation: ADP90471.1. HQ205044 Genomic DNA. Translation: ADP90472.1. HQ205045 Genomic DNA. Translation: ADP90473.1. HQ205046 Genomic DNA. Translation: ADP90474.1. HQ205047 Genomic DNA. Translation: ADP90475.1. HQ205048 Genomic DNA. Translation: ADP90476.1. HQ205049 Genomic DNA. Translation: ADP90477.1. HQ205050 Genomic DNA. Translation: ADP90478.1. HQ205051 Genomic DNA. Translation: ADP90479.1. HQ205052 Genomic DNA. Translation: ADP90480.1. HQ205053 Genomic DNA. Translation: ADP90481.1. HQ205054 Genomic DNA. Translation: ADP90482.1. HQ205055 Genomic DNA. Translation: ADP90483.1. HQ205056 Genomic DNA. Translation: ADP90484.1. HQ205057 Genomic DNA. Translation: ADP90485.1. HQ205058 Genomic DNA. Translation: ADP90486.1. HQ205059 Genomic DNA. Translation: ADP90487.1. HQ205060 Genomic DNA. Translation: ADP90488.1. HQ205061 Genomic DNA. Translation: ADP90489.1. HQ205062 Genomic DNA. Translation: ADP90490.1. HQ205063 Genomic DNA. Translation: ADP90491.1. HQ205064 Genomic DNA. Translation: ADP90492.1. HQ205065 Genomic DNA. Translation: ADP90493.1. AK292926 mRNA. Translation: BAF85615.1. CH471196 Genomic DNA. Translation: EAW55646.1. CH471196 Genomic DNA. Translation: EAW55648.1. CH471196 Genomic DNA. Translation: EAW55649.1. BC051748 mRNA. Translation: AAH51748.1.
IPI	IPI00013378. IPI00221295.
RefSeq	NP_004609.1. NM_004618.3.
UniGene	Hs.592115.
3D structure databases
ProteinModelPortal	Q13472.
SMR	Q13472. Positions 37-695.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-33323N.
IntAct	Q13472. 4 interactions.
MINT	MINT-6610291.
STRING	Q13472.
PTM databases
PhosphoSite	Q13472.
Polymorphism databases
DMDM	2501242.
Proteomic databases
PRIDE	Q13472.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000321105; ENSP00000321636; ENSG00000177302.
GeneID	7156.
KEGG	hsa:7156.
NMPDR	fig|9606.3.peg.13244.
UCSC	uc002gsx.1. human.
Organism-specific databases
CTD	7156.
GeneCards	GC17M018117.
H-InvDB	HIX0027125.
HGNC	HGNC:11992. TOP3A.
HPA	CAB002449.
MIM	601243. gene.
neXtProt	NX_Q13472.
PharmGKB	PA36673.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11894.
GeneTree	ENSGT00530000063430.
HOGENOM	HBG525547.
HOVERGEN	HBG056668.
InParanoid	Q13472.
OMA	CNCGQEA.
OrthoDB	EOG4K6G3F.
PhylomeDB	Q13472.
Enzyme and pathway databases
Reactome	REACT_111183. Meiosis.
Gene expression databases
ArrayExpress	Q13472.
Bgee	Q13472.
CleanEx	HS_TOP3A.
Genevestigator	Q13472.
GermOnline	ENSG00000177302. Homo sapiens.
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. IPR013826. Topo_IA_cen_sub3. IPR023405. Topo_IA_core_domain. IPR003602. Topo_IA_DNA-bd. IPR013498. Topo_IA_Znf. IPR006171. Toprim_domain. IPR001878. Znf_CCHC. IPR010666. Znf_GRF. [Graphical view]
Gene3D	G3DSA:1.10.460.10. Topo_IA_cen_sub1. 3 hits. G3DSA:1.10.290.10. Topo_IA_cen_sub3. 1 hit.
KO	K03165.
PANTHER	PTHR11390. Topo_IA. 1 hit.
Pfam	PF01131. Topoisom_bac. 1 hit. PF01751. Toprim. 1 hit. PF01396. zf-C4_Topoisom. 1 hit. PF06839. zf-GRF. 2 hits. [Graphical view]
PRINTS	PR00417. PRTPISMRASEI.
SMART	SM00437. TOP1Ac. 1 hit. SM00436. TOP1Bc. 1 hit. SM00493. TOPRIM. 1 hit. SM00343. ZnF_C2HC. 1 hit. [Graphical view]
SUPFAM	SSF56712. Topo_IA_core. 1 hit.
PROSITE	PS00396. TOPOISOMERASE_I_PROK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	28002.
SOURCE	Search...

Entry information

Entry name

TOP3A_HUMAN

Accession

Primary (citable) accession number: Q13472
Secondary accession number(s): A8KA61, D3DXC7, Q13473

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 106 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.