TOB1A_XENLA
ID TOB1A_XENLA Reviewed; 1513 AA.
AC Q800K6; B7ZSK6;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 2.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=DNA topoisomerase 2-binding protein 1-A;
DE AltName: Full=Cut5 protein {ECO:0000303|PubMed:12743046};
DE AltName: Full=DNA topoisomerase II-binding protein 1-A;
DE Short=TopBP1-A;
DE Short=XtopBP {ECO:0000303|PubMed:16530042};
GN Name=topbp1-A; Synonyms=cut5 {ECO:0000312|EMBL:BAC65235.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAC65235.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CDC45, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Oocyte {ECO:0000269|PubMed:12743046};
RX PubMed=12743046; DOI=10.1093/emboj/cdg238;
RA Hashimoto Y., Takisawa H.;
RT "Xenopus Cut5 is essential for a CDK-dependent process in the initiation of
RT DNA replication.";
RL EMBO J. 22:2526-2535(2003).
RN [2] {ECO:0000312|EMBL:AAI70556.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Oocyte {ECO:0000312|EMBL:AAI70556.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=12730133; DOI=10.1101/gad.1070003;
RA Kubota Y., Takase Y., Komori Y., Hashimoto Y., Arata T., Kamimura Y.,
RA Araki H., Takisawa H.;
RT "A novel ring-like complex of Xenopus proteins essential for the initiation
RT of DNA replication.";
RL Genes Dev. 17:1141-1152(2003).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=14525986; DOI=10.1074/jbc.c300418200;
RA Parrilla-Castellar E.R., Karnitz L.M.;
RT "Cut5 is required for the binding of Atr and DNA polymerase alpha to
RT genotoxin-damaged chromatin.";
RL J. Biol. Chem. 278:45507-45511(2003).
RN [5] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15960976; DOI=10.1016/j.cell.2005.05.015;
RA Sangrithi M.N., Bernal J.A., Madine M., Philpott A., Lee J., Dunphy W.G.,
RA Venkitaraman A.R.;
RT "Initiation of DNA replication requires the RECQL4 protein mutated in
RT Rothmund-Thomson syndrome.";
RL Cell 121:887-898(2005).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH ATR, AND MUTAGENESIS OF TRP-1138.
RX PubMed=16530042; DOI=10.1016/j.cell.2005.12.041;
RA Kumagai A., Lee J., Yoo H.Y., Dunphy W.G.;
RT "TopBP1 activates the ATR-ATRIP complex.";
RL Cell 124:943-955(2006).
RN [7] {ECO:0000305}
RP FUNCTION, DOMAIN, PHOSPHORYLATION AT SER-1131, AND MUTAGENESIS OF SER-1131.
RX PubMed=16923121; DOI=10.1111/j.1365-2443.2006.00998.x;
RA Hashimoto Y., Tsujimura T., Sugino A., Takisawa H.;
RT "The phosphorylated C-terminal domain of Xenopus Cut5 directly mediates
RT ATR-dependent activation of Chk1.";
RL Genes Cells 11:993-1007(2006).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=16436514; DOI=10.1091/mbc.e05-09-0865;
RA Lupardus P.J., Cimprich K.A.;
RT "Phosphorylation of Xenopus Rad1 and Hus1 defines a readout for ATR
RT activation that is independent of Claspin and the Rad9 carboxy terminus.";
RL Mol. Biol. Cell 17:1559-1569(2006).
RN [9] {ECO:0000305}
RP INTERACTION WITH RECQL4, AND SUBCELLULAR LOCATION.
RX PubMed=16782873; DOI=10.1128/mcb.02267-05;
RA Matsuno K., Kumano M., Kubota Y., Hashimoto Y., Takisawa H.;
RT "The N-terminal noncatalytic region of Xenopus RecQ4 is required for
RT chromatin binding of DNA polymerase alpha in the initiation of DNA
RT replication.";
RL Mol. Cell. Biol. 26:4843-4852(2006).
RN [10] {ECO:0000305}
RP FUNCTION, INTERACTION WITH TICRR, AND SUBCELLULAR LOCATION.
RX PubMed=20116089; DOI=10.1016/j.cell.2009.12.049;
RA Kumagai A., Shevchenko A., Shevchenko A., Dunphy W.G.;
RT "Treslin collaborates with TopBP1 in triggering the initiation of DNA
RT replication.";
RL Cell 140:349-359(2010).
RN [11] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH GEMC1.
RX PubMed=20383140; DOI=10.1038/ncb2050;
RA Balestrini A., Cosentino C., Errico A., Garner E., Costanzo V.;
RT "GEMC1 is a TopBP1-interacting protein required for chromosomal DNA
RT replication.";
RL Nat. Cell Biol. 12:484-491(2010).
CC -!- FUNCTION: Has dual roles in initiation of DNA replication, and
CC regulation of checkpoint responses. Required for DNA replication
CC initiation but not for the formation of pre-replicative complexes or
CC the elongation stages. Necessary for the loading of replication factors
CC onto chromatin, including gemc1, cdc45, DNA polymerases and components
CC of the GINS complex such as ginsl/sld5. Binds chromatin in both S-phase
CC cyclin-dependent kinase (S-CDK)-independent and S-CDK-dependent modes.
CC Chromatin binding is required for the action of S-CDK, which in turn
CC triggers the formation of preinitiation complexes of DNA replication.
CC Its role in checkpoint activation is independent of the DNA replication
CC role. In response to DNA damage, triggers the recruitment of checkpoint
CC signaling proteins on chromatin, which activate the chek1 signaling
CC pathway and block S-phase progression. Increases the kinase activity of
CC atr to numerous substrates, and is required for the phosphorylation of
CC Rad1. {ECO:0000269|PubMed:12730133, ECO:0000269|PubMed:12743046,
CC ECO:0000269|PubMed:14525986, ECO:0000269|PubMed:15960976,
CC ECO:0000269|PubMed:16436514, ECO:0000269|PubMed:16530042,
CC ECO:0000269|PubMed:16923121, ECO:0000269|PubMed:20116089,
CC ECO:0000269|PubMed:20383140}.
CC -!- SUBUNIT: Interacts with cdc45. Interacts (via BRCT domains) with ticrr;
CC interaction is cdk2-dependent. Interacts with atr in the presence of
CC atrip. Interacts with recql4 (via N-terminus).
CC {ECO:0000269|PubMed:12743046, ECO:0000269|PubMed:16530042,
CC ECO:0000269|PubMed:16782873, ECO:0000269|PubMed:20116089,
CC ECO:0000269|PubMed:20383140}.
CC -!- INTERACTION:
CC Q800K6; D3IUT5: ticrr; NbExp=4; IntAct=EBI-2607374, EBI-2607396;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12743046,
CC ECO:0000269|PubMed:15960976, ECO:0000269|PubMed:16782873,
CC ECO:0000269|PubMed:20116089}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250}. Cytoplasm, cytoskeleton,
CC spindle pole {ECO:0000250}. Chromosome {ECO:0000250}. Note=Associates
CC with chromatin. {ECO:0000269|PubMed:12743046,
CC ECO:0000269|PubMed:15960976, ECO:0000269|PubMed:16782873,
CC ECO:0000269|PubMed:20116089}.
CC -!- DOMAIN: The N-terminal half is sufficient for DNA replication.
CC {ECO:0000269|PubMed:16923121}.
CC -!- PTM: Phosphorylation at 1131 is essential for phosphorylation of chek1,
CC and thus for checkpoint regulation. {ECO:0000269|PubMed:16923121}.
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DR EMBL; AB091779; BAC65235.1; -; mRNA.
DR EMBL; BC170556; AAI70556.1; -; mRNA.
DR EMBL; BC170557; AAI70557.1; -; mRNA.
DR RefSeq; NP_001082568.1; NM_001089099.1.
DR AlphaFoldDB; Q800K6; -.
DR SMR; Q800K6; -.
DR BioGRID; 99905; 6.
DR IntAct; Q800K6; 2.
DR iPTMnet; Q800K6; -.
DR GeneID; 398573; -.
DR KEGG; xla:398573; -.
DR CTD; 398573; -.
DR Xenbase; XB-GENE-990641; topbp1.L.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 398573; Expressed in egg cell and 19 other tissues.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; IMP:UniProtKB.
DR GO; GO:0071163; P:DNA replication preinitiation complex assembly; IMP:UniProtKB.
DR GO; GO:0071165; P:GINS complex assembly; IMP:UniProtKB.
DR GO; GO:0035563; P:positive regulation of chromatin binding; IMP:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IMP:UniProtKB.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IMP:UniProtKB.
DR CDD; cd17737; BRCT_TopBP1_rpt1; 1.
DR Gene3D; 3.40.50.10190; -; 9.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR035960; Secretoglobin_sf.
DR InterPro; IPR044737; TopBP1_BRCT_1.
DR Pfam; PF00533; BRCT; 4.
DR Pfam; PF12738; PTCB-BRCT; 2.
DR SMART; SM00292; BRCT; 9.
DR SUPFAM; SSF48201; SSF48201; 1.
DR SUPFAM; SSF52113; SSF52113; 6.
DR PROSITE; PS50172; BRCT; 7.
PE 1: Evidence at protein level;
KW Cell cycle; Chromosome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW DNA replication; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..1513
FT /note="DNA topoisomerase 2-binding protein 1-A"
FT /id="PRO_0000397210"
FT DOMAIN 101..189
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 194..283
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 354..444
FT /note="BRCT 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 530..621
FT /note="BRCT 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 629..726
FT /note="BRCT 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 892..984
FT /note="BRCT 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1253..1344
FT /note="BRCT 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1383..1480
FT /note="BRCT 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 289..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 789..809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1031..1053
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1086..1109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 844..850
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 1508..1511
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 789..803
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1131
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16923121"
FT MUTAGEN 1131
FT /note="S->A: Prevents phosphorylation. Prevents role in
FT checkpoint activation."
FT /evidence="ECO:0000269|PubMed:16923121"
FT MUTAGEN 1131
FT /note="S->E: Phosphomimic. Exhibits minor defects in
FT checkpoint activation."
FT /evidence="ECO:0000269|PubMed:16923121"
FT MUTAGEN 1138
FT /note="W->R: Abolishes activation of kinase activity of atr
FT but no effect on atr binding. Defective in checkpoint
FT regulation. No effect on DNA replication."
FT /evidence="ECO:0000269|PubMed:16530042"
FT CONFLICT 309
FT /note="T -> A (in Ref. 1; BAC65235)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="D -> G (in Ref. 1; BAC65235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1188
FT /note="T -> S (in Ref. 1; BAC65235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1347
FT /note="M -> I (in Ref. 1; BAC65235)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1513 AA; 169288 MW; 31BB4CB37DEF225B CRC64;
MASSENEPFC VKFIKSPENS EYFFKAYEAI KQIQSDESLQ LTEEREALLL KEKDKSLYIC
DPFSGAAFSH LKKLGCRIVG PQVVIFCMEN QRRVPRAEYP VYNMAMADVT ISCTSLDKET
REDVHHYVQI MGGCVYRDLN VSVTHLIAGE VGSKKYLVAA SLEKPILLPS WVKELWEKSN
QRIIRYSDVN MTEYLCPIFR GCTICVTGLS SLDRKEVQRL TALHGGEYTG QLKMNESTHL
IVQEAKGQKY ECARKWNVHC ISVQWFFDSI EKGFCQDETM YKIEPASTIK SVPDTSTPTG
GNSKPNSRTL YDVSQISNIS TSCVNESAFN SAMASRLDPP ADTLENLDIS SLQAPDDLLD
GCRIYLCGFG GRKLDKLRKL INNGGGVRFN QLTGDVTHII VGETDEELKQ FLNKTQHRPY
VLTVKWLLDS FAKGHLQPEE IYFHSSYQQT EMPSPFEPAI NLTANKMSST RDPLNHTRNH
QADEDLLSQY TENNSTLIED EHPKTSNTNS ISQMSMHEDM TTCTSQSGLA DTSTIIEGGL
FSRKQFMVLG FLEEDEACII DIIKKSAGKV LSSQKRAIAD YAVVPLLGCE VESTVGEVVT
NAWLGMCIEQ EKLLDPHSNA LFTPVPFLEG STPLRECVLS VSQFMGAERD SLVYLAGLLG
AKVQEFFVRK ANPKKGMFAS THLVLKDAEG SKYEAAKKWN LPAVTMNWLL QCARTGRKAD
EDSYLVDNVP EEDKDESFIS QTYKPQAIRL SMHAPCHLEN HPEALTKAAV TPLDMNRFKS
KAFQSVISQH NKNPQTSGGE SKVLQREPSL HLDTPSKFLS KDKLFKPSFD VKDALAALET
PGGPNQKNRT QSTPLSEVIG RNLQLAIANS TRQTAAVTAS PQLKAAEKKE FDNSKLLINV
VICVSKKLIK KQGELNGIAA SLGAEYRWCF DESVTHFIYH GRQNDMSREY KSVKERSGIY
IVSEHWLFAC SEQQKRVPEA LYPHTYNPKM SLDISAVQDG SYTASKFSAD TSLQQDENSE
LQLQQNNKFG ETSDDQVKKA AGDGNPQNPS KDVKGALTQT LEMRENFQRQ LQEFMSATSV
VKPRGSVGRA GFDNSPCTPE GARSTRNGRS RVLEALRQSR QAMTDLNTEP SQNEQIIWDD
PTAREERAKL VSNLQWPDSP SQYSEQLQHN MNDAGGNYTP AKESLTDTEI AELEACEFEP
KSAMRTPVIE NNLQSPTKPD HLTPTPQAPS IAFPLANPPV APQPREKPVQ PFSKEETLKE
RRFQLSSLDP QERIDYSQLI EELGGVVIEK QCFDPSCTHI VVGHPLRNEK YLASMAAGKW
VLHRSYLEAC RAAKRFIQEE DYEWGSMSIL SAVTNINPQQ RMLAEAAMRW RKKLQGIKQN
MGIAEGAFSG WKVILNVDQT KEPGFKRLLQ SGGAKVFAGH SSPLFKEASH LFADFSKLKP
DEPRVNVAEA AAQGVNCLKP EYIADYLMKE LPPPMNNYCL PDAIPYVRVT GTGLSRKRKT
SGDVSDVKRS RHY
