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PR01550

Identifier
TOP6AFAMILY  [View Relations]  [View Alignment]  
Accession
PR01550
No. of Motifs
6
Creation Date
19-JUN-2001
Title
DNA topoisomerase VI subunit A family signature
Database References
PRINTS; PR01551 SPO11HOMOLOG; PR01552 TPISMRASE6A
INTERPRO; IPR002815 DNA_t
PDB; 1D3Y
SCOP; 1D3Y
CATH; 1D3Y
Literature References
1. NICHOLS, M.D., DEANGELIS, K., KECK, J.L. AND BERGER, J.M.
Structure and function of an archaeal topoisomerase VI subunit with homology
to the meiotic recombination factor Spo11.
EMBO J. 18 6177-6188 (1999). 
 
2. ROMANIENKO, P.J. AND CAMERINI-OTERO, R.D.
Cloning, characterization, and localization of mouse and human SPO11. 
GENOMICS 61 156-169 (1999).  
 
3. SHANNON, M., RICHARDSON, L., CHRISTIAN, A., HANDEL, M.A. AND THELEN, M.P.
Differential gene expression of mammalian SPO11/TOP6A homologs during
meiosis.
FEBS LETT. 462 329-334 (1999). 

Documentation
In all organisms, type II DNA topoisomerases are essential for untangling
chromosomal DNA [1]. The structure of the DNA-binding core of the 
Methanococcus jannaschii DNA topoisomerase VI A subunit has been determined
to 2.0A resolution [1]. The overall structure of the subunit is unique,
demonstrating that archaeal type II enzymes are distinct from other type II
topoisomerases [1]. Nevertheless, the core structure contains a pair of 
domains that are also found in type IA and classic type II topoisomerases
[1]. Such regions may form the basis of a DNA cleavage mechanism shared
among these enzymes [1]. 
 
The core A subunit is a dimer, with a deep groove spanning both protomers
[1]. The dimer architecture is such that DNA is thought to bind in the 
groove, across the A subunit interface, and the monomers are thought to
separate during DNA transport [1]. The A subunit of topoisomerase VI is 
similar to the meiotic recombination factor, Spo11.
 
Spo11 is a meiosis-specific protein in yeast that covalently binds to DNA
double-strand breaks (DSBs) during the early stages of meiosis [2]. These
DSBs initiate homologous recombination, which is required for chromosomal 
segregation and generation of genetic diversity during meiosis [2]. Mouse
and human homologues of Spo11 have been cloned and characterised [2]. The 
proteins are 82% identical and share ~25% identity with other family 
members. Mouse Spo11 has been localised to chromosome 2H4, and human SPO11
to chromosome 20q13.2-q13.3, a region amplified in some breast and ovarian 
tumours [2]. 
 
Similarity between SPO11 and archaebacterial TOP6A proteins points to 
evolutionary specialisation of a DNA-cleavage function for meiotic
recombination [3]. 
 
TOP6AFAMILY is a 6-element fingerprint that provides a signature for the
DNA topoisomerase VI subunit A family. The fingerprint was derived from an 
initial alignment of 12 sequences: the motifs were drawn from short
conserved regions spanning the central portion of the alignment - motif 1
includes an active site tyrosine residue involved in DNA cleavage; and 
motifs 4 and 6 each include conserved metal-binding aspartate residues.
Two iterations on SPTR39_15f were required to reach convergence, at which
point a true set comprising 16 sequences was identified. Several partial 
matches were also found, all of which are family members that fail to make
significant matches with one or more motifs.
Summary Information
  16 codes involving  6 elements
2 codes involving 5 elements
3 codes involving 4 elements
1 codes involving 3 elements
4 codes involving 2 elements
Composite Feature Index
6161616161616
5211222
4103233
3001101
2010142
123456
True Positives
Q9LZ03        Q9M4A2        Q9NQM7        Q9NQM8        
Q9QUK2 Q9QY57 Q9QZS1 Q9V134
RE12_SCHPO SP11_HUMAN SP11_MOUSE SP11_YEAST
TP6A_AERPE TP6A_PYRHO TP6A_SULSH YJ94_CAEEL
True Positive Partials
Codes involving 5 elements
Q9LK56 Q9P4D2
Codes involving 4 elements
O77205 Q9M4A1 Q9P6Y7
Codes involving 3 elements
Q9SH50
Codes involving 2 elements
Q9HR32 TP6A_ARCFU TP6A_METJA TP6A_METTH
Sequence Titles
Q9LZ03      MEIOSIS SPECIFIC-LIKE PROTEIN - Arabidopsis thaliana (Mouse-ear cress). 
Q9M4A2 PUTATIVE TOPOISOMERASE VIA - Arabidopsis thaliana (Mouse-ear cress).
Q9NQM7 DJ481F12.2.1 (SPO11, MEIOTIC PROTEIN COVALENTLY BOUND TO DSB (S. CEREVISIAE)-LIKE (A DNA TRANSESTERASE/TOPOISOMERASE HOMOLOG ISOFORM 1)) - Homo sapiens (Human).
Q9NQM8 DJ481F12.2.2 (SPO11, MEIOTIC PROTEIN COVALENTLY BOUND TO DSB (S.CEREVISIAE)-LIKE (MEIOTIC DNA TRANSESTERASE/TOPOISOMERASE HOMOLOG ISOFORM 2 (HIGH SIMILARITY TO MOUSE VARIANT))) - Homo sapiens (Human).
Q9QUK2 MEIOTIC DNA TRANSESTERASE/TOPOISOMERASE HOMOLOG VARIANT B - Mus musculus (Mouse).
Q9QY57 SPO11 PROTEIN (SPO11B) - Mus musculus (Mouse).
Q9QZS1 SPO11 (SPO11 PROTEIN) - Mus musculus (Mouse).
Q9V134 DNA TOPOISOMERASE VI, SUBUNIT A (TOP6A) - Pyrococcus abyssi.
RE12_SCHPO MEIOTIC RECOMBINATION PROTEIN REC12 - Schizosaccharomyces pombe (Fission yeast).
SP11_HUMAN SPO11 PROTEIN HOMOLOG - Homo sapiens (Human).
SP11_MOUSE SPO11 PROTEIN HOMOLOG - Mus musculus (Mouse).
SP11_YEAST MEIOSIS-SPECIFIC SPORULATION PROTEIN SPO11 - Saccharomyces cerevisiae (Baker's yeast).
TP6A_AERPE TYPE II DNA TOPOISOMERASE VI SUBUNIT A (EC 5.99.1.3) - Aeropyrum pernix.
TP6A_PYRHO TYPE II DNA TOPOISOMERASE VI SUBUNIT A (EC 5.99.1.3) - Pyrococcus horikoshii.
TP6A_SULSH TYPE II DNA TOPOISOMERASE VI SUBUNIT A (EC 5.99.1.3) - Sulfolobus shibatae.
YJ94_CAEEL HYPOTHETICAL 49.2 KDA PROTEIN T05E11.4 IN CHROMOSOME IV - Caenorhabditis elegans.

Q9LK56 DNA TOPOISOMERASE VI, SUBUNIT A - Arabidopsis thaliana (Mouse-ear cress).
Q9P4D2 SPO11 - Coprinus cinereus (Inky cap fungus).

O77205 MEI-W68 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9M4A1 PUTATIVE TOPOISOMERASE VIA - Arabidopsis thaliana (Mouse-ear cress).
Q9P6Y7 MEIOTIC RECOMBINATION PROTEIN REC12 RELATED PROTEIN - Neurospora crassa.

Q9SH50 F22C12.24 - Arabidopsis thaliana (Mouse-ear cress).

Q9HR32 DNA TOPOISOMERASE VI SUBUNIT A - Halobacterium sp. (strain NRC-1).
TP6A_ARCFU TYPE II DNA TOPOISOMERASE VI SUBUNIT A (EC 5.99.1.3) - Archaeoglobus fulgidus.
TP6A_METJA TYPE II DNA TOPOISOMERASE VI SUBUNIT A (EC 5.99.1.3) - Methanococcus jannaschii.
TP6A_METTH TYPE II DNA TOPOISOMERASE VI SUBUNIT A (EC 5.99.1.3) - Methanobacterium thermoautotrophicum.
Scan History
SPTR39_15f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
KRDIYYTDSQLF Q9QUK2 95 95 -
KRDIYYTDSQLF Q9QZS1 133 133 -
KRDIYYTDSQLF SP11_MOUSE 95 95 -
KRDIYYTDSQLF SP11_HUMAN 133 133 -
HRDIYYTDSQLF Q9QY57 108 108 -
IRDLYYKGKHTI TP6A_AERPE 98 98 -
KRDIYYRDVDLF RE12_SCHPO 93 93 -
IRDLYYRGKHSL TP6A_SULSH 101 101 -
KRDIYYMHPSAF Q9M4A2 98 98 -
KRELYYEHKAVY YJ94_CAEEL 114 114 -
LREAYYANKHTV TP6A_PYRHO 103 103 -
VRDIFYSNVELF SP11_YEAST 130 130 -

Motif 2 width=18
Element Seqn Id St Int Rpt
QAAVDSAIDDISCMLKVP Q9QUK2 109 2 -
QAAVDSAIDDISCMLKVP Q9QZS1 147 2 -
QAAVDSAIDDISCMLKVP SP11_MOUSE 109 2 -
QTVVDNIINDISCMLKVS SP11_HUMAN 147 2 -
QAAVDSAIDDISCMLKVP Q9QY57 122 2 -
QKESDSVIQDIEVYTGLF TP6A_AERPE 127 17 -
QTVVDELLGDISNTIGCS RE12_SCHPO 107 2 -
QKESDSVIVDIEVFTSLL TP6A_SULSH 132 19 -
QSIVDRAIGDICILFQCS Q9M4A2 112 2 -
QKYLDSSIKSICELLNES YJ94_CAEEL 128 2 -
QSESDPIIEDLERMLGVL TP6A_PYRHO 125 10 -
QANVVQWLDVIRFNFKLS SP11_YEAST 144 2 -

Motif 3 width=16
Element Seqn Id St Int Rpt
RRSLHVLSTSKGLIAG Q9QUK2 127 0 -
RRSLHVLSTSKGLIAG Q9QZS1 165 0 -
RRSLHVLSTSKGLIAG SP11_MOUSE 127 0 -
RRSLHILSTSKGLIAG SP11_HUMAN 165 0 -
RRSLHVLSTSKGLIAG Q9QY57 140 0 -
REDMLILSKEKGKVVG TP6A_AERPE 145 0 -
RSDLNVEASAKGLVFG RE12_SCHPO 125 0 -
REEMLILSKEKGKVVG TP6A_SULSH 150 0 -
RYNLNVVSVGNGLVMG Q9M4A2 130 0 -
RANLNILSCGRGIIRG YJ94_CAEEL 146 0 -
REEMHITADRRGYIYG TP6A_PYRHO 143 0 -
RKSLNIIPAQKGLVYS SP11_YEAST 163 1 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LLIVEKDATFQRLLDDNF Q9QUK2 178 35 -
LLIVEKDATFQRLLDDNF Q9QZS1 220 39 -
LLIVEKDATFQRLLDDNF SP11_MOUSE 182 39 -
VLIVEKDATFQRLLDDNF SP11_HUMAN 220 39 -
LLIVEKDATFQRLLDDNF Q9QY57 195 39 -
VLVVEKDAVFQQLHRAGF TP6A_AERPE 200 39 -
VLVIEKEAVFQTLTEEAL RE12_SCHPO 175 34 -
VLVVEKDAVFQQLHRAGF TP6A_SULSH 205 39 -
ILVVEKETVFQRLANDMF Q9M4A2 185 39 -
ILVVEKDTTFQKLMDENF YJ94_CAEEL 198 36 -
VLVVETAAMADRLIEEKY TP6A_PYRHO 198 39 -
IVIVEKEAVFTKLVNNYH SP11_YEAST 229 50 -

Motif 5 width=22
Element Seqn Id St Int Rpt
IMVTGKGVPDLNTRLLVKKLWD Q9QUK2 203 7 -
IMVTGKGVPDLNTRLLVKKLWD Q9QZS1 245 7 -
IMVTGKGVPDLNTRLLVKKLWD SP11_MOUSE 207 7 -
IMITGKGVPDLNTRLLVKKLWD SP11_HUMAN 245 7 -
IMVTGKGVPDLNTRLLVKKLWD Q9QY57 220 7 -
LLVTGSGQPDRATRRFVRRLHE TP6A_AERPE 224 6 -
IIVTAKGFPDLMTRKFLVKLAK RE12_SCHPO 196 3 -
ILITSAGQPDRATRRFVRRLNE TP6A_SULSH 229 6 -
IVITGRGYPDVSTRRFLRLLME Q9M4A2 209 6 -
ILATSKGYPDIATRNVLKMLSE YJ94_CAEEL 223 7 -
LIVATQGQASRGVRRLIHRLHY TP6A_PYRHO 222 6 -
MLITGKGFPDFLTRLFLKKLEQ SP11_YEAST 253 6 -

Motif 6 width=17
Element Seqn Id St Int Rpt
DADPYGIEIMCIYKYGS Q9QUK2 235 10 -
DADPYGIEIMCIYKYGS Q9QZS1 277 10 -
DADPYGIEIMCIYKYGS SP11_MOUSE 239 10 -
DADPHGIEIMCIYKYGS SP11_HUMAN 277 10 -
DADPYGIEIMCIYKYGS Q9QY57 252 10 -
DSDPYGWYIYSVYKVGS TP6A_AERPE 256 10 -
DWDPHGLCIYSCFKYGS RE12_SCHPO 229 11 -
DADPYGWYIFSVFRIGS TP6A_SULSH 261 10 -
DCDPYGFEILATYRFGS Q9M4A2 241 10 -
DADPHGIEIYLTYKYGP YJ94_CAEEL 255 10 -
DGDPYGWYIYSTIKRGS TP6A_PYRHO 254 10 -
DADPYGISIALNYTHSN SP11_YEAST 288 13 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
KRDIYYTDSQLF Q9QUK2 95 95 -
KRDIYYTDSQLF Q9QZS1 133 133 -
KRDIYYTDSQLF SP11_MOUSE 95 95 -
KRDIYYTDSQLF Q9NQM7 132 132 -
KRDIYYTDSQLF Q9NQM8 94 94 -
KRDIYYTDSQLF SP11_HUMAN 133 133 -
HRDIYYTDSQLF Q9QY57 108 108 -
IRDLYYKGKHTI TP6A_AERPE 98 98 -
KRDIYYRDVDLF RE12_SCHPO 93 93 -
KRDLFYTDVKLF Q9LZ03 165 165 -
IRDLYYRGKHSL TP6A_SULSH 101 101 -
KRDIYYMHPSAF Q9M4A2 98 98 -
KRELYYEHKAVY YJ94_CAEEL 114 114 -
LREAYYANKHTI Q9V134 103 103 -
LREAYYANKHTV TP6A_PYRHO 103 103 -
VRDIFYSNVELF SP11_YEAST 130 130 -

Motif 2 width=18
Element Seqn Id St Int Rpt
QAAVDSAIDDISCMLKVP Q9QUK2 109 2 -
QAAVDSAIDDISCMLKVP Q9QZS1 147 2 -
QAAVDSAIDDISCMLKVP SP11_MOUSE 109 2 -
QTVVDNIINDISCMLKVS Q9NQM7 146 2 -
QTVVDNIINDISCMLKVS Q9NQM8 108 2 -
QTVVDNIINDISCMLKVS SP11_HUMAN 147 2 -
QAAVDSAIDDISCMLKVP Q9QY57 122 2 -
QKESDSVIQDIEVYTGLF TP6A_AERPE 127 17 -
QTVVDELLGDISNTIGCS RE12_SCHPO 107 2 -
QTQSDAVLDDVSCMLGCT Q9LZ03 179 2 -
QKESDSVIVDIEVFTSLL TP6A_SULSH 132 19 -
QSIVDRAIGDICILFQCS Q9M4A2 112 2 -
QKYLDSSIKSICELLNES YJ94_CAEEL 128 2 -
QSESDPIIEDLERMLGVL Q9V134 125 10 -
QSESDPIIEDLERMLGVL TP6A_PYRHO 125 10 -
QANVVQWLDVIRFNFKLS SP11_YEAST 144 2 -

Motif 3 width=16
Element Seqn Id St Int Rpt
RRSLHVLSTSKGLIAG Q9QUK2 127 0 -
RRSLHVLSTSKGLIAG Q9QZS1 165 0 -
RRSLHVLSTSKGLIAG SP11_MOUSE 127 0 -
RRSLHILSTSKGLIAG Q9NQM7 164 0 -
RRSLHILSTSKGLIAG Q9NQM8 126 0 -
RRSLHILSTSKGLIAG SP11_HUMAN 165 0 -
RRSLHVLSTSKGLIAG Q9QY57 140 0 -
REDMLILSKEKGKVVG TP6A_AERPE 145 0 -
RSDLNVEASAKGLVFG RE12_SCHPO 125 0 -
RSSLNVIAAEKGVVVG Q9LZ03 197 0 -
REEMLILSKEKGKVVG TP6A_SULSH 150 0 -
RYNLNVVSVGNGLVMG Q9M4A2 130 0 -
RANLNILSCGRGIIRG YJ94_CAEEL 146 0 -
REEMHITADRRGYIYG Q9V134 143 0 -
REEMHITADRRGYIYG TP6A_PYRHO 143 0 -
RKSLNIIPAQKGLVYS SP11_YEAST 163 1 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LLIVEKDATFQRLLDDNF Q9QUK2 178 35 -
LLIVEKDATFQRLLDDNF Q9QZS1 220 39 -
LLIVEKDATFQRLLDDNF SP11_MOUSE 182 39 -
VLIVEKDATFQRLLDDNF Q9NQM7 219 39 -
VLIVEKDATFQRLLDDNF Q9NQM8 181 39 -
VLIVEKDATFQRLLDDNF SP11_HUMAN 220 39 -
LLIVEKDATFQRLLDDNF Q9QY57 195 39 -
VLVVEKDAVFQQLHRAGF TP6A_AERPE 200 39 -
VLVIEKEAVFQTLTEEAL RE12_SCHPO 175 34 -
ILLVEKDAAYMRLAEDRF Q9LZ03 252 39 -
VLVVEKDAVFQQLHRAGF TP6A_SULSH 205 39 -
ILVVEKETVFQRLANDMF Q9M4A2 185 39 -
ILVVEKDTTFQKLMDENF YJ94_CAEEL 198 36 -
VLVVETAAMADRLIEEKY Q9V134 198 39 -
VLVVETAAMADRLIEEKY TP6A_PYRHO 198 39 -
IVIVEKEAVFTKLVNNYH SP11_YEAST 229 50 -

Motif 5 width=22
Element Seqn Id St Int Rpt
IMVTGKGVPDLNTRLLVKKLWD Q9QUK2 203 7 -
IMVTGKGVPDLNTRLLVKKLWD Q9QZS1 245 7 -
IMVTGKGVPDLNTRLLVKKLWD SP11_MOUSE 207 7 -
IMITGKGVPDLNTRLLVKKLWD Q9NQM7 244 7 -
IMITGKGVPDLNTRLLVKKLWD Q9NQM8 206 7 -
IMITGKGVPDLNTRLLVKKLWD SP11_HUMAN 245 7 -
IMVTGKGVPDLNTRLLVKKLWD Q9QY57 220 7 -
LLVTGSGQPDRATRRFVRRLHE TP6A_AERPE 224 6 -
IIVTAKGFPDLMTRKFLVKLAK RE12_SCHPO 196 3 -
IIVTAKGQPDVATRLFLRKMKM Q9LZ03 276 6 -
ILITSAGQPDRATRRFVRRLNE TP6A_SULSH 229 6 -
IVITGRGYPDVSTRRFLRLLME Q9M4A2 209 6 -
ILATSKGYPDIATRNVLKMLSE YJ94_CAEEL 223 7 -
LIVATQGQASRGVRRLIHRLHY Q9V134 222 6 -
LIVATQGQASRGVRRLIHRLHY TP6A_PYRHO 222 6 -
MLITGKGFPDFLTRLFLKKLEQ SP11_YEAST 253 6 -

Motif 6 width=17
Element Seqn Id St Int Rpt
DADPYGIEIMCIYKYGS Q9QUK2 235 10 -
DADPYGIEIMCIYKYGS Q9QZS1 277 10 -
DADPYGIEIMCIYKYGS SP11_MOUSE 239 10 -
DADPHGIEIMCIYKYGS Q9NQM7 276 10 -
DADPHGIEIMCIYKYGS Q9NQM8 238 10 -
DADPHGIEIMCIYKYGS SP11_HUMAN 277 10 -
DADPYGIEIMCIYKYGS Q9QY57 252 10 -
DSDPYGWYIYSVYKVGS TP6A_AERPE 256 10 -
DWDPHGLCIYSCFKYGS RE12_SCHPO 229 11 -
DSDPYGLKILSVYGCGS Q9LZ03 308 10 -
DADPYGWYIFSVFRIGS TP6A_SULSH 261 10 -
DCDPYGFEILATYRFGS Q9M4A2 241 10 -
DADPHGIEIYLTYKYGP YJ94_CAEEL 255 10 -
DGDPYGWYIYSTIKQGS Q9V134 254 10 -
DGDPYGWYIYSTIKRGS TP6A_PYRHO 254 10 -
DADPYGISIALNYTHSN SP11_YEAST 288 13 -