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Q01320

- TOP2A_MOUSE

UniProt

Q01320 - TOP2A_MOUSE

Protein

DNA topoisomerase 2-alpha

Gene

Top2a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 2 (14 Dec 2011)
      Previous versions | rss
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    Functioni

    Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes.1 Publication

    Catalytic activityi

    ATP-dependent breakage, passage and rejoining of double-stranded DNA.1 PublicationPROSITE-ProRule annotation

    Cofactori

    Magnesium. Binds two Mg2+ per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn2+ and Ca2+.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei90 – 901ATPBy similarity
    Binding sitei119 – 1191ATPBy similarity
    Metal bindingi460 – 4601Magnesium 1; catalyticPROSITE-ProRule annotation
    Sitei488 – 4881Interaction with DNAPROSITE-ProRule annotation
    Sitei491 – 4911Interaction with DNAPROSITE-ProRule annotation
    Metal bindingi540 – 5401Magnesium 1; catalyticPROSITE-ProRule annotation
    Metal bindingi540 – 5401Magnesium 2PROSITE-ProRule annotation
    Metal bindingi542 – 5421Magnesium 2PROSITE-ProRule annotation
    Sitei660 – 6601Interaction with DNAPROSITE-ProRule annotation
    Sitei661 – 6611Interaction with DNAPROSITE-ProRule annotation
    Sitei722 – 7221Interaction with DNAPROSITE-ProRule annotation
    Sitei756 – 7561Interaction with DNAPROSITE-ProRule annotation
    Sitei762 – 7621Interaction with DNAPROSITE-ProRule annotation
    Sitei803 – 8031Transition state stabilizerBy similarity
    Active sitei804 – 8041O-(5'-phospho-DNA)-tyrosine intermediateBy similarity
    Sitei855 – 8551Important for DNA bending; intercalates between base pairs of target DNABy similarity
    Sitei930 – 9301Interaction with DNAPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi147 – 1493ATPBy similarity
    Nucleotide bindingi160 – 1678ATPBy similarity
    Nucleotide bindingi375 – 3773ATPBy similarity

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. chromatin binding Source: Ensembl
    3. DNA binding, bending Source: UniProtKB
    4. DNA topoisomerase type II (ATP-hydrolyzing) activity Source: MGI
    5. drug binding Source: Ensembl
    6. magnesium ion binding Source: UniProtKB

    GO - Biological processi

    1. apoptotic chromosome condensation Source: RefGenome
    2. ATP catabolic process Source: GOC
    3. cellular response to DNA damage stimulus Source: Ensembl
    4. chromosome condensation Source: MGI
    5. chromosome segregation Source: MGI
    6. DNA ligation Source: Ensembl
    7. DNA topological change Source: MGI
    8. DNA unwinding involved in DNA replication Source: RefGenome
    9. embryonic cleavage Source: MGI
    10. hematopoietic progenitor cell differentiation Source: MGI
    11. mitotic DNA integrity checkpoint Source: RefGenome
    12. mitotic recombination Source: RefGenome
    13. positive regulation of apoptotic process Source: Ensembl
    14. positive regulation of single stranded viral RNA replication via double stranded DNA intermediate Source: Ensembl
    15. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    16. resolution of meiotic recombination intermediates Source: RefGenome
    17. sister chromatid segregation Source: RefGenome

    Keywords - Molecular functioni

    Isomerase, Topoisomerase

    Keywords - Ligandi

    ATP-binding, DNA-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_199110. G0 and Early G1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA topoisomerase 2-alpha (EC:5.99.1.3)
    Alternative name(s):
    DNA topoisomerase II, alpha isozyme
    Gene namesi
    Name:Top2a
    Synonyms:Top-2, Top2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:98790. Top2a.

    Subcellular locationi

    GO - Cellular componenti

    1. centriole Source: Ensembl
    2. condensed chromosome Source: MGI
    3. DNA topoisomerase complex (ATP-hydrolyzing) Source: RefGenome
    4. nuclear chromosome Source: Ensembl
    5. nucleolus Source: MGI
    6. nucleoplasm Source: Ensembl
    7. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 15281528DNA topoisomerase 2-alphaPRO_0000145364Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei4 – 41PhosphoserineBy similarity
    Modified residuei281 – 2811PhosphothreonineBy similarity
    Modified residuei1105 – 11051Phosphoserine; by CK1By similarity
    Modified residuei1211 – 12111PhosphoserineBy similarity
    Modified residuei1291 – 12911PhosphoserineBy similarity
    Modified residuei1293 – 12931PhosphoserineBy similarity
    Modified residuei1295 – 12951PhosphoserineBy similarity
    Modified residuei1298 – 12981PhosphoserineBy similarity
    Modified residuei1328 – 13281PhosphoserineBy similarity
    Modified residuei1333 – 13331PhosphoserineBy similarity
    Modified residuei1370 – 13701PhosphoserineBy similarity
    Modified residuei1373 – 13731PhosphoserineBy similarity
    Modified residuei1384 – 13841PhosphoserineBy similarity
    Modified residuei1418 – 14181N6-acetyllysine1 Publication
    Modified residuei1438 – 14381N6-acetyllysine1 Publication
    Modified residuei1465 – 14651PhosphoserineBy similarity
    Modified residuei1467 – 14671PhosphoserineBy similarity
    Modified residuei1470 – 14701PhosphoserineBy similarity
    Modified residuei1472 – 14721PhosphoserineBy similarity
    Modified residuei1521 – 15211PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1105 by CSNK1D/CK1 promotes DNA cleavable complex formation By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiQ01320.
    PRIDEiQ01320.

    PTM databases

    PhosphoSiteiQ01320.

    Expressioni

    Gene expression databases

    ArrayExpressiQ01320.
    BgeeiQ01320.
    CleanExiMM_TOP2A.
    GenevestigatoriQ01320.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation By similarity.By similarity

    Protein-protein interaction databases

    DIPiDIP-40621N.
    IntActiQ01320. 8 interactions.
    MINTiMINT-1712967.

    Structurei

    3D structure databases

    ProteinModelPortaliQ01320.
    SMRiQ01320. Positions 28-404, 433-1187.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini454 – 571118ToprimPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni341 – 3433Interaction with DNABy similarity
    Regioni989 – 99810Interaction with DNABy similarity

    Sequence similaritiesi

    Belongs to the type II topoisomerase family.Curated
    Contains 1 Toprim domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0187.
    GeneTreeiENSGT00390000016222.
    HOGENOMiHOG000216693.
    HOVERGENiHBG052998.
    InParanoidiQ01320.
    KOiK03164.
    OMAiSRWEVCL.
    OrthoDBiEOG73JKTM.
    TreeFamiTF105282.

    Family and domain databases

    Gene3Di1.10.268.10. 1 hit.
    3.30.1360.40. 1 hit.
    3.30.230.10. 1 hit.
    3.30.565.10. 1 hit.
    3.40.50.670. 1 hit.
    3.90.199.10. 1 hit.
    InterProiIPR024946. Arg_repress_C-like.
    IPR012542. DTHCT.
    IPR003594. HATPase_ATP-bd.
    IPR020568. Ribosomal_S5_D2-typ_fold.
    IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
    IPR028466. Top2a.
    IPR001241. Topo_IIA.
    IPR002205. Topo_IIA_A/C.
    IPR013758. Topo_IIA_A/C_ab.
    IPR013757. Topo_IIA_A_a.
    IPR013506. Topo_IIA_bsu_dom2.
    IPR013759. Topo_IIA_cen_dom.
    IPR013760. Topo_IIA_like_dom.
    IPR018522. TopoIIA_CS.
    IPR006171. Toprim_domain.
    [Graphical view]
    PANTHERiPTHR10169:SF33. PTHR10169:SF33. 1 hit.
    PfamiPF00204. DNA_gyraseB. 1 hit.
    PF00521. DNA_topoisoIV. 1 hit.
    PF08070. DTHCT. 1 hit.
    PF02518. HATPase_c. 1 hit.
    PF01751. Toprim. 1 hit.
    [Graphical view]
    PRINTSiPR00418. TPI2FAMILY.
    SMARTiSM00387. HATPase_c. 1 hit.
    SM00433. TOP2c. 1 hit.
    SM00434. TOP4c. 1 hit.
    [Graphical view]
    SUPFAMiSSF54211. SSF54211. 1 hit.
    SSF55874. SSF55874. 1 hit.
    SSF56719. SSF56719. 1 hit.
    PROSITEiPS00177. TOPOISOMERASE_II. 1 hit.
    PS50880. TOPRIM. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q01320-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELSPLQPVN ENMLMNKKKN EDGKKRLSIE RIYQKKTQLE HILLRPDTYI     50
    GSVELVTQQM WVYDEDVGIN YREVTFVPGL YKIFDEILVN AADNKQRDPK 100
    MSCIRVTIDP ENNVISIWNN GKGIPVVEHK VEKIYVPALI FGQLLTSSNY 150
    DDDEKKVTGG RNGYGAKLCN IFSTKFTVET ASREYKKMFK QTWMDNMGRA 200
    GDMELKPFSG EDYTCITFQP DLSKFKMQSL DKDIVALMVR RAYDIAGSTK 250
    DVKVFLNGNS LPVKGFRSYV DLYLKDKVDE TGNSLKVIHE QVNPRWEVCL 300
    TMSERGFQQI SFVNSIATSK GGRHVDYVAD QIVSKLVDVV KKKNKGGVAV 350
    KAHQVKNHMW IFVNALIENP TFDSQTKENM TLQAKSFGST CQLSEKFIKA 400
    AIGCGIVESI LNWVKFKAQI QLNKKCSAVK HTKIKGIPKL DDANDAGSRN 450
    STECTLILTE GDSAKTLAVS GLGVVGRDKY GVFPLRGKIL NVREASHKQI 500
    MENAEINNII KIVGLQYKKN YEDEDSLKTL RYGKIMIMTD QDQDGSHIKG 550
    LLINFIHHNW PSLLRHRFLE EFITPIVKVS KNKQEIAFYS LPEFEEWKSS 600
    TPNHKKWKVK YYKGLGTSTS KEAKEYFADM KRHRIQFKYS GPEDDAAISL 650
    AFSKKQVDDR KEWLTNFMED RRQRKLLGLP EDYLYGQSTS YLTYNDFINK 700
    ELILFSNSDN ERSIPSMVDG LKPGQRKVLF TCFKRNDKRE VKVAQLAGSV 750
    AEMSSYHHGE MSLMMTIINL AQNFVGSNNL NLLQPIGQFG TRLHGGKDSA 800
    SPRYIFTMLS PLARLLFPPK DDHTLRFLYD DNQRVEPEWY IPIIPMVLIN 850
    GAEGIGTGWS CKIPNFDVRE VVNNIRRLLD GEEPLPMLPS YKNFKGTIEE 900
    LASNQYVING EVAILDSTTI EISELPIRTW TQTYKEQVLE PMLNGTEKTP 950
    SLITDYREYH TDTTVKFVIK MTEEKLAEAE RVGLHKVFKL QSSLTCNSMV 1000
    LFDHVGCLKK YDTVLDILRD FFELRLKYYG LRKEWLLGML GAESSKLNNQ 1050
    ARFILEKIDG KIVIENKPKK ELIKVLIQRG YDSDPVKAWK EAQQKVPDEE 1100
    ENEESDTETS TSDSAAEAGP TFNYLLDMPL WYLTKEKKDE LCKQRNEKEQ 1150
    ELNTLKQKSP SDLWKEDLAV FIEELEVVEA KEKQDEQVGL PGKAGKAKGK 1200
    KAQMCADVLP SPRGKRVIPQ VTVEMKAEAE KKIRKKIKSE NVEGTPAEDG 1250
    AEPGSLRQRI EKKQKKEPGA KKQTTLPFKP VKKGRKKNPW SDSESDVSSN 1300
    ESNVDVPPRQ KEQRSAAAKA KFTVDLDSDE DFSGLDEKDE DEDFLPLDAT 1350
    PPKAKIPPKN TKKALKTQGS SMSVVDLESD VKDSVPASPG VPAADFPAET 1400
    EQSKPSKKTV GVKKTATKSQ SSVSTAGTKK RAAPKGTKSD SALSARVSEK 1450
    PAPAKAKNSR KRKPSSSDSS DSDFERAISK GATSKKAKGE EQDFPVDLED 1500
    TIAPRAKSDR ARKPIKYLEE SDDDDDLF 1528
    Length:1,528
    Mass (Da):172,790
    Last modified:December 14, 2011 - v2
    Checksum:i63CBF8F649D103C7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti184 – 1841E → A in BAA02076. (PubMed:1331984)Curated
    Sequence conflicti260 – 2601S → M in BAA02076. (PubMed:1331984)Curated
    Sequence conflicti640 – 6401S → P in BAA02076. (PubMed:1331984)Curated
    Sequence conflicti841 – 8411I → N in BAA02076. (PubMed:1331984)Curated
    Sequence conflicti844 – 8452IP → NT in BAA02076. (PubMed:1331984)Curated
    Sequence conflicti1316 – 13161A → R in BAA02076. (PubMed:1331984)Curated
    Sequence conflicti1316 – 13161A → R in AAC52135. (PubMed:8261398)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D12513 mRNA. Translation: BAA02076.1.
    AL591067 Genomic DNA. No translation available.
    U01915 mRNA. Translation: AAC52135.1.
    CCDSiCCDS25370.1.
    PIRiJS0703.
    RefSeqiNP_035753.2. NM_011623.2.
    XP_006533216.1. XM_006533153.1.
    UniGeneiMm.4237.

    Genome annotation databases

    EnsembliENSMUST00000068031; ENSMUSP00000068896; ENSMUSG00000020914.
    GeneIDi21973.
    KEGGimmu:21973.
    UCSCiuc007lid.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D12513 mRNA. Translation: BAA02076.1 .
    AL591067 Genomic DNA. No translation available.
    U01915 mRNA. Translation: AAC52135.1 .
    CCDSi CCDS25370.1.
    PIRi JS0703.
    RefSeqi NP_035753.2. NM_011623.2.
    XP_006533216.1. XM_006533153.1.
    UniGenei Mm.4237.

    3D structure databases

    ProteinModelPortali Q01320.
    SMRi Q01320. Positions 28-404, 433-1187.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-40621N.
    IntActi Q01320. 8 interactions.
    MINTi MINT-1712967.

    Chemistry

    BindingDBi Q01320.
    ChEMBLi CHEMBL3586.
    GuidetoPHARMACOLOGYi 2637.

    PTM databases

    PhosphoSitei Q01320.

    Proteomic databases

    PaxDbi Q01320.
    PRIDEi Q01320.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000068031 ; ENSMUSP00000068896 ; ENSMUSG00000020914 .
    GeneIDi 21973.
    KEGGi mmu:21973.
    UCSCi uc007lid.1. mouse.

    Organism-specific databases

    CTDi 7153.
    MGIi MGI:98790. Top2a.

    Phylogenomic databases

    eggNOGi COG0187.
    GeneTreei ENSGT00390000016222.
    HOGENOMi HOG000216693.
    HOVERGENi HBG052998.
    InParanoidi Q01320.
    KOi K03164.
    OMAi SRWEVCL.
    OrthoDBi EOG73JKTM.
    TreeFami TF105282.

    Enzyme and pathway databases

    Reactomei REACT_199110. G0 and Early G1.

    Miscellaneous databases

    ChiTaRSi TOP2A. mouse.
    NextBioi 301670.
    PROi Q01320.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q01320.
    Bgeei Q01320.
    CleanExi MM_TOP2A.
    Genevestigatori Q01320.

    Family and domain databases

    Gene3Di 1.10.268.10. 1 hit.
    3.30.1360.40. 1 hit.
    3.30.230.10. 1 hit.
    3.30.565.10. 1 hit.
    3.40.50.670. 1 hit.
    3.90.199.10. 1 hit.
    InterProi IPR024946. Arg_repress_C-like.
    IPR012542. DTHCT.
    IPR003594. HATPase_ATP-bd.
    IPR020568. Ribosomal_S5_D2-typ_fold.
    IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
    IPR028466. Top2a.
    IPR001241. Topo_IIA.
    IPR002205. Topo_IIA_A/C.
    IPR013758. Topo_IIA_A/C_ab.
    IPR013757. Topo_IIA_A_a.
    IPR013506. Topo_IIA_bsu_dom2.
    IPR013759. Topo_IIA_cen_dom.
    IPR013760. Topo_IIA_like_dom.
    IPR018522. TopoIIA_CS.
    IPR006171. Toprim_domain.
    [Graphical view ]
    PANTHERi PTHR10169:SF33. PTHR10169:SF33. 1 hit.
    Pfami PF00204. DNA_gyraseB. 1 hit.
    PF00521. DNA_topoisoIV. 1 hit.
    PF08070. DTHCT. 1 hit.
    PF02518. HATPase_c. 1 hit.
    PF01751. Toprim. 1 hit.
    [Graphical view ]
    PRINTSi PR00418. TPI2FAMILY.
    SMARTi SM00387. HATPase_c. 1 hit.
    SM00433. TOP2c. 1 hit.
    SM00434. TOP4c. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54211. SSF54211. 1 hit.
    SSF55874. SSF55874. 1 hit.
    SSF56719. SSF56719. 1 hit.
    PROSITEi PS00177. TOPOISOMERASE_II. 1 hit.
    PS50880. TOPRIM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of cDNA encoding the mouse DNA topoisomerase II that can complement the budding yeast top2 mutation."
      Adachi N., Miyaike M., Ikeda H., Kikuchi A.
      Nucleic Acids Res. 20:5297-5303(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin-resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding topoisomerase IIalpha and the retinoic acid receptor alpha locus."
      McPherson J., Brown G.A., Goldenberg G.J.
      Cancer Res. 53:5885-5889(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1254-1528.
      Tissue: Lymphoma.
    4. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1418 AND LYS-1438, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiTOP2A_MOUSE
    AccessioniPrimary (citable) accession number: Q01320
    Secondary accession number(s): E9PX08
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: December 14, 2011
    Last modified: October 1, 2014
    This is version 144 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3