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SPO11_MOUSE
ID   SPO11_MOUSE             Reviewed;         396 AA.
AC   Q9WTK8; Q8VIH6; Q9QUK2; Q9QY57; Q9QZS1;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   23-APR-2003, sequence version 2.
DT   03-AUG-2022, entry version 169.
DE   RecName: Full=Meiotic recombination protein SPO11;
DE            EC=5.6.2.2 {ECO:0000305};
GN   Name=Spo11;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RC   STRAIN=BALB/cJ; TISSUE=Spermatocyte;
RX   PubMed=10622720; DOI=10.1016/s0014-5793(99)01546-x;
RA   Shannon M., Richardson L., Christian A., Handel M.A., Thelen M.P.;
RT   "Differential gene expression of mammalian SPO11/TOP6A homologs during
RT   meiosis.";
RL   FEBS Lett. 462:329-334(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC   STRAIN=BALB/cJ; TISSUE=Testis;
RX   PubMed=10534401; DOI=10.1006/geno.1999.5955;
RA   Romanienko P.J., Camerini-Otero R.D.;
RT   "Cloning, characterization, and localization of mouse and human SPO11.";
RL   Genomics 61:156-169(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 4 AND 5).
RC   STRAIN=129/SvJ; TISSUE=Testis;
RX   PubMed=10534402; DOI=10.1006/geno.1999.5956;
RA   Keeney S., Baudat F., Angeles M., Zhou Z.-H., Copeland N.G., Jenkins N.A.,
RA   Manova K., Jasin M.;
RT   "A mouse homolog of the Saccharomyces cerevisiae meiotic recombination DNA
RT   transesterase Spo11p.";
RL   Genomics 61:170-182(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RC   TISSUE=Testis;
RX   PubMed=10855504; DOI=10.1007/s004120050421;
RA   Metzler-Guillemain C., de Massy B.;
RT   "Identification and characterization of an SPO11 homolog in the mouse.";
RL   Chromosoma 109:133-138(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE OF 45-93.
RC   STRAIN=BALB/cJ; TISSUE=Thymus;
RA   Tokuyama H., Tokuyama Y.;
RL   Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   FUNCTION (ISOFORM 1), FUNCTION (ISOFORM 4), AND TISSUE SPECIFICITY (ISOFORM
RP   1).
RX   PubMed=21330546; DOI=10.1126/science.1195774;
RA   Kauppi L., Barchi M., Baudat F., Romanienko P.J., Keeney S., Jasin M.;
RT   "Distinct properties of the XY pseudoautosomal region crucial for male
RT   meiosis.";
RL   Science 331:916-920(2011).
RN   [7]
RP   FUNCTION.
RX   PubMed=22346761; DOI=10.1371/journal.pgen.1002485;
RA   Fukuda T., Pratto F., Schimenti J.C., Turner J.M., Camerini-Otero R.D.,
RA   Hoeoeg C.;
RT   "Phosphorylation of chromosome core components may serve as axis marks for
RT   the status of chromosomal events during mammalian meiosis.";
RL   PLoS Genet. 8:E1002485-E1002485(2012).
RN   [8]
RP   INTERACTION WITH TOP6BL (ISOFORM 1).
RX   PubMed=26917764; DOI=10.1126/science.aad5309;
RA   Robert T., Nore A., Brun C., Maffre C., Crimi B., Bourbon H.M.,
RA   de Massy B.;
RT   "The TopoVIB-Like protein family is required for meiotic DNA double-strand
RT   break formation.";
RL   Science 351:943-949(2016).
CC   -!- FUNCTION: [Isoform 1]: Component of a topoisomerase 6 complex
CC       specifically required for meiotic recombination. Together with TOP6BL,
CC       mediates DNA cleavage that forms the double-strand breaks (DSB) that
CC       initiate meiotic recombination (PubMed:26917764). The complex promotes
CC       relaxation of negative and positive supercoiled DNA and DNA
CC       decatenation through cleavage and ligation cycles. Essential for the
CC       phosphorylation of SMC3, HORMAD1 and HORMAD2 (PubMed:22346761).
CC       {ECO:0000269|PubMed:22346761, ECO:0000269|PubMed:26917764}.
CC   -!- FUNCTION: [Isoform 4]: In contrast to isoform 1, does not mediate DNA
CC       cleavage that forms the double-strand breaks (DSB) that initiate
CC       meiotic recombination. {ECO:0000269|PubMed:22346761}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP-dependent breakage, passage and rejoining of double-
CC         stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000305};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q57815};
CC   -!- SUBUNIT: [Isoform 1]: Heterotetramer of SPO11 and 2 TOP6BL chains
CC       (Probable). Interacts with TOP6BL (PubMed:26917764).
CC       {ECO:0000269|PubMed:26917764, ECO:0000305}.
CC   -!- SUBUNIT: [Isoform 4]: Does not interact with TOP6BL (PubMed:26917764).
CC       {ECO:0000269|PubMed:26917764}.
CC   -!- INTERACTION:
CC       Q9WTK8-1; J3QMY9: Top6bl; NbExp=6; IntAct=EBI-16201014, EBI-16200997;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1; Synonyms=Spo11beta {ECO:0000303|PubMed:21330546}, Beta
CC       {ECO:0000303|PubMed:21330546};
CC         IsoId=Q9WTK8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9WTK8-2; Sequence=VSP_007200;
CC       Name=3;
CC         IsoId=Q9WTK8-3; Sequence=VSP_007197, VSP_007198, VSP_007199;
CC       Name=4; Synonyms=Spo11alpha {ECO:0000303|PubMed:21330546}, Alpha
CC       {ECO:0000303|PubMed:21330546};
CC         IsoId=Q9WTK8-4; Sequence=VSP_007197, VSP_007198;
CC       Name=5;
CC         IsoId=Q9WTK8-5; Sequence=VSP_007197, VSP_007198, VSP_007200;
CC   -!- TISSUE SPECIFICITY: High levels are found only in the testis where
CC       expression is restricted primarily to meiotic germ cells. Not expressed
CC       in spermatogonia. Highest levels are found in pachytene spermatocytes.
CC       Very low levels are found in thymus, brain and oocytes of embryonic
CC       ovary. Not detected in adult ovary (PubMed:10622720, PubMed:10855504).
CC       Isoform 1: Expressed early in meiosis, when most double-strand breaks
CC       (DSB) are formed (PubMed:21330546). {ECO:0000269|PubMed:10534401,
CC       ECO:0000269|PubMed:10622720, ECO:0000269|PubMed:10855504,
CC       ECO:0000269|PubMed:21330546}.
CC   -!- DEVELOPMENTAL STAGE: Not detected at day 7 postpartum (dpp). Levels are
CC       low at 12 dpp but increase by 17 dpp. High levels are maintained
CC       throughout the remainder of testis development.
CC       {ECO:0000269|PubMed:10622720, ECO:0000269|PubMed:10855504}.
CC   -!- SIMILARITY: Belongs to the TOP6A family. {ECO:0000305}.
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DR   EMBL; AF126400; AAD49561.1; -; mRNA.
DR   EMBL; AF149309; AAD44811.1; -; mRNA.
DR   EMBL; AF169386; AAD52563.1; -; mRNA.
DR   EMBL; AF163053; AAD43588.1; -; mRNA.
DR   EMBL; AF163052; AAD43591.1; -; Genomic_DNA.
DR   EMBL; AF163049; AAD43591.1; JOINED; Genomic_DNA.
DR   EMBL; AF163051; AAD43591.1; JOINED; Genomic_DNA.
DR   EMBL; AF163052; AAD43592.1; -; Genomic_DNA.
DR   EMBL; AF163049; AAD43592.1; JOINED; Genomic_DNA.
DR   EMBL; AF163051; AAD43592.1; JOINED; Genomic_DNA.
DR   EMBL; AF163054; AAD43589.1; -; mRNA.
DR   EMBL; AF165313; AAF87090.1; -; mRNA.
DR   EMBL; AF167439; AAF87094.1; -; mRNA.
DR   EMBL; AF173848; AAF87096.1; -; mRNA.
DR   EMBL; AF443910; AAL32063.1; -; Genomic_DNA.
DR   CCDS; CCDS17137.1; -. [Q9WTK8-1]
DR   CCDS; CCDS50811.1; -. [Q9WTK8-3]
DR   CCDS; CCDS50812.1; -. [Q9WTK8-4]
DR   RefSeq; NP_001077428.1; NM_001083959.1. [Q9WTK8-3]
DR   RefSeq; NP_001077429.1; NM_001083960.1. [Q9WTK8-4]
DR   RefSeq; NP_001292363.1; NM_001305434.1. [Q9WTK8-5]
DR   RefSeq; NP_036176.1; NM_012046.2. [Q9WTK8-1]
DR   AlphaFoldDB; Q9WTK8; -.
DR   SMR; Q9WTK8; -.
DR   BioGRID; 205092; 1.
DR   DIP; DIP-62006N; -.
DR   IntAct; Q9WTK8; 1.
DR   STRING; 10090.ENSMUSP00000059056; -.
DR   iPTMnet; Q9WTK8; -.
DR   PhosphoSitePlus; Q9WTK8; -.
DR   PaxDb; Q9WTK8; -.
DR   PRIDE; Q9WTK8; -.
DR   ProteomicsDB; 258598; -. [Q9WTK8-1]
DR   ProteomicsDB; 258599; -. [Q9WTK8-2]
DR   ProteomicsDB; 258600; -. [Q9WTK8-3]
DR   ProteomicsDB; 258601; -. [Q9WTK8-4]
DR   ProteomicsDB; 258602; -. [Q9WTK8-5]
DR   Antibodypedia; 28951; 201 antibodies from 28 providers.
DR   DNASU; 26972; -.
DR   Ensembl; ENSMUST00000050442; ENSMUSP00000059056; ENSMUSG00000005883. [Q9WTK8-1]
DR   Ensembl; ENSMUST00000109125; ENSMUSP00000104753; ENSMUSG00000005883. [Q9WTK8-4]
DR   Ensembl; ENSMUST00000109126; ENSMUSP00000104754; ENSMUSG00000005883. [Q9WTK8-3]
DR   GeneID; 26972; -.
DR   KEGG; mmu:26972; -.
DR   UCSC; uc008odd.1; mouse. [Q9WTK8-1]
DR   UCSC; uc008ode.1; mouse. [Q9WTK8-4]
DR   UCSC; uc008odf.1; mouse. [Q9WTK8-3]
DR   UCSC; uc012ckq.1; mouse. [Q9WTK8-5]
DR   CTD; 23626; -.
DR   MGI; MGI:1349669; Spo11.
DR   VEuPathDB; HostDB:ENSMUSG00000005883; -.
DR   eggNOG; KOG2795; Eukaryota.
DR   GeneTree; ENSGT00390000001787; -.
DR   HOGENOM; CLU_037229_1_1_1; -.
DR   InParanoid; Q9WTK8; -.
DR   OMA; NWGEARF; -.
DR   OrthoDB; 1272299at2759; -.
DR   PhylomeDB; Q9WTK8; -.
DR   TreeFam; TF314157; -.
DR   BioGRID-ORCS; 26972; 2 hits in 73 CRISPR screens.
DR   PRO; PR:Q9WTK8; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q9WTK8; protein.
DR   Bgee; ENSMUSG00000005883; Expressed in spermatocyte and 29 other tissues.
DR   Genevisible; Q9WTK8; MM.
DR   GO; GO:0000781; C:chromosome, telomeric region; IDA:MGI.
DR   GO; GO:0000228; C:nuclear chromosome; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR   GO; GO:0003918; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity; IEA:UniProtKB-EC.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; IGI:MGI.
DR   GO; GO:0007129; P:homologous chromosome pairing at meiosis; IMP:MGI.
DR   GO; GO:0007141; P:male meiosis I; IMP:MGI.
DR   GO; GO:0042138; P:meiotic DNA double-strand break formation; IBA:GO_Central.
DR   GO; GO:0000706; P:meiotic DNA double-strand break processing; IBA:GO_Central.
DR   GO; GO:0045141; P:meiotic telomere clustering; IMP:MGI.
DR   GO; GO:0048477; P:oogenesis; IMP:MGI.
DR   GO; GO:0001541; P:ovarian follicle development; IMP:MGI.
DR   GO; GO:0034502; P:protein localization to chromosome; IMP:MGI.
DR   GO; GO:0007131; P:reciprocal meiotic recombination; IMP:MGI.
DR   GO; GO:0007286; P:spermatid development; IMP:MGI.
DR   GO; GO:0007130; P:synaptonemal complex assembly; IMP:MGI.
DR   CDD; cd00223; TOPRIM_TopoIIB_SPO; 1.
DR   Gene3D; 1.10.10.10; -; 1.
DR   InterPro; IPR004084; Meiosis_Spo11.
DR   InterPro; IPR013048; Meiotic_Spo11.
DR   InterPro; IPR002815; Spo11/TopoVI_A.
DR   InterPro; IPR013049; Spo11/TopoVI_A_N.
DR   InterPro; IPR036078; Spo11/TopoVI_A_sf.
DR   InterPro; IPR034136; TOPRIM_Topo6A/Spo11.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   PANTHER; PTHR10848; PTHR10848; 1.
DR   Pfam; PF03533; SPO11_like; 1.
DR   Pfam; PF04406; TP6A_N; 1.
DR   PRINTS; PR01551; SPO11HOMOLOG.
DR   PRINTS; PR01550; TOP6AFAMILY.
DR   SUPFAM; SSF56726; SSF56726; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; DNA-binding; Hydrolase; Isomerase; Magnesium;
KW   Meiosis; Metal-binding; Nucleus; Reference proteome.
FT   CHAIN           1..396
FT                   /note="Meiotic recombination protein SPO11"
FT                   /id="PRO_0000145475"
FT   ACT_SITE        138
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q9M4A2"
FT   BINDING         224
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q57815"
FT   BINDING         277
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:Q57815"
FT   VAR_SEQ         44..81
FT                   /note="Missing (in isoform 3, isoform 4 and isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:10534402,
FT                   ECO:0000303|PubMed:10622720, ECO:0000303|PubMed:10855504"
FT                   /id="VSP_007197"
FT   VAR_SEQ         82
FT                   /note="M -> R (in isoform 3, isoform 4 and isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:10534402,
FT                   ECO:0000303|PubMed:10622720, ECO:0000303|PubMed:10855504"
FT                   /id="VSP_007198"
FT   VAR_SEQ         134
FT                   /note="R -> RSNAHSVLTLHLHR (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10622720,
FT                   ECO:0000303|PubMed:10855504"
FT                   /id="VSP_007199"
FT   VAR_SEQ         213..216
FT                   /note="Missing (in isoform 2 and isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:10534401,
FT                   ECO:0000303|PubMed:10534402"
FT                   /id="VSP_007200"
SQ   SEQUENCE   396 AA;  44570 MW;  F4B9723C02844A5E CRC64;
     MAFAPMGPEA SFFDALDRHR ASLLAMVKRG AGETPAGATR VASSSEVLTA IENIIQDIIK
     SLARNEVPAF TIDNRSSWEN IMFDDSVGLR MIPQCTTRKI RSDSPKSVKK FALILKVLSM
     IYKLIQSDTY ATKRDIYYTD SQLFGNQAAV DSAIDDISCM LKVPRRSLHV LSTSKGLIAG
     NLRYMEEDGT RVQCTCSATA TAVPTNIQGM QHLITDAKFL LIVEKDATFQ RLLDDNFCSR
     MSPCIMVTGK GVPDLNTRLL VKKLWDTFHI PVFTLVDADP YGIEIMCIYK YGSMSMSFEA
     HNLTIPTIRW LGLLPSDIQR LNIPKDSLIP LTKHDQMKLD SILKRPYITY QPLWKKELEM
     MADSKMKAEI QALTLLSSDY LSRVYLPNKL RFGGWI
 
 
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