O95985 (TOP3B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA topoisomerase 3-beta-1
EC=5.99.1.2

Alternative name(s):
DNA topoisomerase III beta-1

Gene names

Name:	TOP3B
Synonyms:	TOP3B1

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	862 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. Possesses negatively supercoiled DNA relaxing activity.
Catalytic activity	ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
Tissue specificity	Isoform 1 is found in testis, heart and skeletal muscle. A 4 kb transcript which probably represents isoform 2 is found in thymus, kidney and pancreas. Ref.1
Sequence similarities	Belongs to the type IA topoisomerase family. Contains 1 Toprim domain.
Sequence caution	The sequence BAA20009.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
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
Cellular component	nucleus Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA topoisomerase type I activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95985-1)

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 2 (identifier: O95985-2)

The sequence of this isoform differs from the canonical sequence as follows:
     703-730: GMGCNECTHPSCQHSLSMLGIGQCVECE → GECSHSLLSTGSCSLFSVPTPALHQAGL
     731-862: Missing.

Isoform 3 (identifier: O95985-3)

The sequence of this isoform differs from the canonical sequence as follows:
     703-707: GMGCN → VVPCV
     708-862: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 862	862	DNA topoisomerase 3-beta-1		PRO_0000145192
Regions
	Domain	3 – 153	151	Toprim
Sites
	Active site	336	1	O-(5'-phospho-DNA)-tyrosine intermediate By similarity
Natural variations
	Alternative sequence	703 – 730	28	GMGCN…CVECE → GECSHSLLSTGSCSLFSVPT PALHQAGL in isoform 2.		VSP_006525
	Alternative sequence	703 – 707	5	GMGCN → VVPCV in isoform 3.		VSP_006527
	Alternative sequence	708 – 862	155	Missing in isoform 3.		VSP_006528
	Alternative sequence	731 – 862	132	Missing in isoform 2.		VSP_006526
	Natural variant	365	1	D → N. Ref.6 Corresponds to variant rs9610728 [ dbSNP | Ensembl ].		VAR_052591

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 75532827856CFF8F	FASTA	862	96,662
	10 20 30 40 50 60 MKTVLMVAEK PSLAQSIAKI LSRGSLSSHK GLNGACSVHE YTGTFAGQPV RFKMTSVCGH 70 80 90 100 110 120 VMTLDFLGKY NKWDKVDPAE LFSQAPTEKK EANPKLNMVK FLQVEGRGCD YIVLWLDCDK 130 140 150 160 170 180 EGENICFEVL DAVLPVMNKA HGGEKTVFRA RFSSITDTDI CNAMACLGEP DHNEALSVDA 190 200 210 220 230 240 RQELDLRIGC AFTRFQTKYF QGKYGDLDSS LISFGPCQTP TLGFCVERHD KIQSFKPETY 250 260 270 280 290 300 WVLQAKVNTD KDRSLLLDWD RVRVFDREIA QMFLNMTKLE KEAQVEATSR KEKAKQRPLA 310 320 330 340 350 360 LNTVEMLRVA SSSLGMGPQH AMQTAERLYT QGYISYPRTE TTHYPENFDL KGSLRQQANH 370 380 390 400 410 420 PYWADTVKRL LAEGINRPRK GHDAGDHPPI TPMKSATEAE LGGDAWRLYE YITRHFIATV 430 440 450 460 470 480 SHDCKYLQST ISFRIGPELF TCSGKTVLSP GFTEVMPWQS VPLEESLPTC QRGDAFPVGE 490 500 510 520 530 540 VKMLEKQTNP PDYLTEAELI TLMEKHGIGT DASIPVHINN ICQRNYVTVE SGRRLKPTNL 550 560 570 580 590 600 GIVLVHGYYK IDAELVLPTI RSAVEKQLNL IAQGKADYRQ VLGHTLDVFK RKFHYFVDSI 610 620 630 640 650 660 AGMDELMEVS FSPLAATGKP LSRCGKCHRF MKYIQAKPSR LHCSHCDETY TLPQNGTIKL 670 680 690 700 710 720 YKELRCPLDD FELVLWSSGS RGKSYPLCPY CYNHPPFRDM KKGMGCNECT HPSCQHSLSM 730 740 750 760 770 780 LGIGQCVECE SGVLVLDPTS GPKWKVACNK CNVVAHCFEN AHRVRVSADT CSVCEAALLD 790 800 810 820 830 840 VDFNKAKSPL PGDETQHMGC VFCDPVFQEL VELKHAASCH PMHRGGPGRR QGRGRGRARR 850 860 PPGKPNPRRP KDKMSALAAY FV
	Isoform 2 [UniParc]. Checksum: 8CC2903C7C4304E6	FASTA	730	82,123
	10 20 30 40 50 60 MKTVLMVAEK PSLAQSIAKI LSRGSLSSHK GLNGACSVHE YTGTFAGQPV RFKMTSVCGH 70 80 90 100 110 120 VMTLDFLGKY NKWDKVDPAE LFSQAPTEKK EANPKLNMVK FLQVEGRGCD YIVLWLDCDK 130 140 150 160 170 180 EGENICFEVL DAVLPVMNKA HGGEKTVFRA RFSSITDTDI CNAMACLGEP DHNEALSVDA 190 200 210 220 230 240 RQELDLRIGC AFTRFQTKYF QGKYGDLDSS LISFGPCQTP TLGFCVERHD KIQSFKPETY 250 260 270 280 290 300 WVLQAKVNTD KDRSLLLDWD RVRVFDREIA QMFLNMTKLE KEAQVEATSR KEKAKQRPLA 310 320 330 340 350 360 LNTVEMLRVA SSSLGMGPQH AMQTAERLYT QGYISYPRTE TTHYPENFDL KGSLRQQANH 370 380 390 400 410 420 PYWADTVKRL LAEGINRPRK GHDAGDHPPI TPMKSATEAE LGGDAWRLYE YITRHFIATV 430 440 450 460 470 480 SHDCKYLQST ISFRIGPELF TCSGKTVLSP GFTEVMPWQS VPLEESLPTC QRGDAFPVGE 490 500 510 520 530 540 VKMLEKQTNP PDYLTEAELI TLMEKHGIGT DASIPVHINN ICQRNYVTVE SGRRLKPTNL 550 560 570 580 590 600 GIVLVHGYYK IDAELVLPTI RSAVEKQLNL IAQGKADYRQ VLGHTLDVFK RKFHYFVDSI 610 620 630 640 650 660 AGMDELMEVS FSPLAATGKP LSRCGKCHRF MKYIQAKPSR LHCSHCDETY TLPQNGTIKL 670 680 690 700 710 720 YKELRCPLDD FELVLWSSGS RGKSYPLCPY CYNHPPFRDM KKGECSHSLL STGSCSLFSV 730 PTPALHQAGL
	Isoform 3 [UniParc]. Checksum: BE43F9D46B50AA85	FASTA	707	79,839
	10 20 30 40 50 60 MKTVLMVAEK PSLAQSIAKI LSRGSLSSHK GLNGACSVHE YTGTFAGQPV RFKMTSVCGH 70 80 90 100 110 120 VMTLDFLGKY NKWDKVDPAE LFSQAPTEKK EANPKLNMVK FLQVEGRGCD YIVLWLDCDK 130 140 150 160 170 180 EGENICFEVL DAVLPVMNKA HGGEKTVFRA RFSSITDTDI CNAMACLGEP DHNEALSVDA 190 200 210 220 230 240 RQELDLRIGC AFTRFQTKYF QGKYGDLDSS LISFGPCQTP TLGFCVERHD KIQSFKPETY 250 260 270 280 290 300 WVLQAKVNTD KDRSLLLDWD RVRVFDREIA QMFLNMTKLE KEAQVEATSR KEKAKQRPLA 310 320 330 340 350 360 LNTVEMLRVA SSSLGMGPQH AMQTAERLYT QGYISYPRTE TTHYPENFDL KGSLRQQANH 370 380 390 400 410 420 PYWADTVKRL LAEGINRPRK GHDAGDHPPI TPMKSATEAE LGGDAWRLYE YITRHFIATV 430 440 450 460 470 480 SHDCKYLQST ISFRIGPELF TCSGKTVLSP GFTEVMPWQS VPLEESLPTC QRGDAFPVGE 490 500 510 520 530 540 VKMLEKQTNP PDYLTEAELI TLMEKHGIGT DASIPVHINN ICQRNYVTVE SGRRLKPTNL 550 560 570 580 590 600 GIVLVHGYYK IDAELVLPTI RSAVEKQLNL IAQGKADYRQ VLGHTLDVFK RKFHYFVDSI 610 620 630 640 650 660 AGMDELMEVS FSPLAATGKP LSRCGKCHRF MKYIQAKPSR LHCSHCDETY TLPQNGTIKL 670 680 690 700 YKELRCPLDD FELVLWSSGS RGKSYPLCPY CYNHPPFRDM KKVVPCV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new human topoisomerase III that interacts with SGS1 protein." Ng S.-W., Liu Y., Hasselblatt K.T., Mok S.C., Berkowitz R.S. Nucleic Acids Res. 27:993-1000(1999) [PubMed: 9927731] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[2]	"One-megabase sequence analysis of the human immunoglobulin lambda gene locus." Kawasaki K., Minoshima S., Nakato E., Shibuya K., Shintani A., Schmeits J.L., Wang J., Shimizu N. Genome Res. 7:250-261(1997) [PubMed: 9074928] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Hanai R., Li W., Wang J.C. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	Riou J.F., Goulaouic H., Grondard L. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"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 1), VARIANT ASN-365. Tissue: Skin.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF053082 mRNA. Translation: AAD15791.1. D87012 Genomic DNA. Translation: BAA20009.1. Sequence problems. AF017146 mRNA. Translation: AAD01614.1. AF125216 mRNA. Translation: AAD29670.1. CR456596 mRNA. Translation: CAG30482.1. BC002432 mRNA. Translation: AAH02432.1.
IPI	IPI00216815. IPI00216816. IPI00292671.
RefSeq	NP_003926.1. NM_003935.3.
UniGene	Hs.436401.
3D structure databases
ProteinModelPortal	O95985.
SMR	O95985. Positions 3-599.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95985. 3 interactions.
MINT	MINT-1458306.
STRING	O95985.
Proteomic databases
PRIDE	O95985.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357179; ENSP00000349705; ENSG00000100038. ENST00000398793; ENSP00000381773; ENSG00000100038. ENST00000403680; ENSP00000385197; ENSG00000100038.
GeneID	8940.
KEGG	hsa:8940.
UCSC	uc002zvs.1. human.
Organism-specific databases
CTD	8940.
GeneCards	GC22M022309.
H-InvDB	HIX0016284.
HGNC	HGNC:11993. TOP3B.
HPA	CAB009198.
MIM	603582. gene.
neXtProt	NX_O95985.
PharmGKB	PA36674.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13424.
GeneTree	ENSGT00530000063430.
HOVERGEN	HBG059857.
InParanoid	O95985.
OMA	RRPKDKM.
OrthoDB	EOG4ZPDTK.
PhylomeDB	O95985.
Gene expression databases
ArrayExpress	O95985.
Bgee	O95985.
CleanEx	HS_TOP3B.
Genevestigator	O95985.
GermOnline	ENSG00000100038. 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. IPR006171. Toprim_domain. [Graphical view]
Gene3D	G3DSA:1.10.460.10. Topo_IA_cen_sub1. 2 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. [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.
PROSITE	PS00396. TOPOISOMERASE_I_PROK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	33622.
SOURCE	Search...

Entry information

Entry name

TOP3B_HUMAN

Accession

Primary (citable) accession number: O95985
Secondary accession number(s): A0M8Q3, Q9BUP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 109 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.