CLSPN_XENLA
ID CLSPN_XENLA Reviewed; 1285 AA.
AC Q9DF50;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Claspin;
DE AltName: Full=xClaspin;
GN Name=clspn;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP INTERACTION WITH CHEK1, DOMAIN CKBD, AND PHOSPHORYLATION.
RX PubMed=11090622; DOI=10.1016/s1097-2765(05)00092-4;
RA Kumagai A., Dunphy W.G.;
RT "Claspin, a novel protein required for the activation of Chk1 during a DNA
RT replication checkpoint response in Xenopus egg extracts.";
RL Mol. Cell 6:839-849(2000).
RN [2]
RP SEQUENCE REVISION.
RA Kumagai A., Dunphy W.G.;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=12897072; DOI=10.1074/jbc.m307144200;
RA Yanow S.K., Gold D.A., Yoo H.Y., Dunphy W.G.;
RT "Xenopus Drf1, a regulator of Cdc7, displays checkpoint-dependent
RT accumulation on chromatin during an S-phase arrest.";
RL J. Biol. Chem. 278:41083-41092(2003).
RN [4]
RP INTERACTION WITH CHEK1.
RX PubMed=12963733; DOI=10.1074/jbc.m304551200;
RA Jeong S.-Y., Kumagai A., Lee J., Dunphy W.G.;
RT "Phosphorylated claspin interacts with a phosphate-binding site in the
RT kinase domain of Chk1 during ATR-mediated activation.";
RL J. Biol. Chem. 278:46782-46788(2003).
RN [5]
RP FUNCTION, ASSOCIATION WITH CHROMATIN, AND PHOSPHORYLATION.
RX PubMed=12620222; DOI=10.1016/s1097-2765(03)00045-5;
RA Lee J., Kumagai A., Dunphy W.G.;
RT "Claspin, a Chk1-regulatory protein, monitors DNA replication on chromatin
RT independently of RPA, ATR, and Rad17.";
RL Mol. Cell 11:329-340(2003).
RN [6]
RP FUNCTION, INTERACTION WITH CHEK1, DOMAIN CKBD, AND PHOSPHORYLATION AT
RP SER-864 AND SER-895.
RX PubMed=12545175; DOI=10.1038/ncb921;
RA Kumagai A., Dunphy W.G.;
RT "Repeated phosphopeptide motifs in claspin mediate the regulated binding of
RT Chk1.";
RL Nat. Cell Biol. 5:161-165(2003).
RN [7]
RP FUNCTION, INTERACTION WITH PLK1, AND PHOSPHORYLATION AT THR-906 AND
RP SER-934.
RX PubMed=15163406; DOI=10.1016/s0092-8674(04)00417-9;
RA Yoo H.Y., Kumagai A., Shevchenko A., Shevchenko A., Dunphy W.G.;
RT "Adaptation of a DNA replication checkpoint response depends upon
RT inactivation of claspin by the Polo-like kinase.";
RL Cell 117:575-588(2004).
RN [8]
RP FUNCTION.
RX PubMed=15371427; DOI=10.1074/jbc.m408353200;
RA Kumagai A., Kim S.-M., Dunphy W.G.;
RT "Claspin and the activated form of ATR-ATRIP collaborate in the activation
RT of Chk1.";
RL J. Biol. Chem. 279:49599-49608(2004).
CC -!- FUNCTION: Required for checkpoint mediated cell cycle arrest in
CC response to inhibition of DNA replication or to DNA damage induced by
CC UV irradiation. Adapter protein which binds to the checkpoint kinase
CC chek1 and facilitates the phosphorylation and activation of this kinase
CC by the ATR-TREX1/ATRIP kinase complex. Also associates with chromatin
CC during S-phase, and this requires the pre-replication complex (pre-RC),
CC cdc45 and cdk2. This may indicate a role for this protein as a sensor
CC which monitors the integrity of DNA replication forks.
CC {ECO:0000269|PubMed:11090622, ECO:0000269|PubMed:12545175,
CC ECO:0000269|PubMed:12620222, ECO:0000269|PubMed:12897072,
CC ECO:0000269|PubMed:15163406, ECO:0000269|PubMed:15371427}.
CC -!- SUBUNIT: Interacts with both chek1 and plk1/plx1 when phosphorylated.
CC {ECO:0000269|PubMed:11090622, ECO:0000269|PubMed:12545175,
CC ECO:0000269|PubMed:12963733, ECO:0000269|PubMed:15163406}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- DOMAIN: The CHEK1-binding domain (CKBD) contains 2 potential CHEK1-
CC binding motifs (CKB motifs). Phosphorylation sites within CKB motif 1
CC and CKB motif 2 are required for interaction with CHEK1.
CC {ECO:0000269|PubMed:11090622, ECO:0000269|PubMed:12545175}.
CC -!- PTM: Phosphorylated. Phosphorylation at Ser-864, Ser-895 and Thr-906
CC occurs during checkpoint activation and requires the ATR kinase.
CC Phosphorylation at Ser-864 within CKB motif 1 and Ser-895 within CKB
CC motif 2 promotes interaction with the catalytic domain of chek1 and
CC subsequent activation of the kinase. Phosphorylation at Thr-906 creates
CC a binding site for the Polo-box domain of the plk1/plx1 kinase, which
CC subsequently phosphorylates Ser-934. Phosphorylation of Ser-934 is
CC required for chek1 inactivation during checkpoint adaptation, the
CC process whereby a prolonged cell cycle arrest is alleviated without
CC prior removal of the checkpoint-inducing DNA lesion. Checkpoint
CC adaptation may promote cellular proliferation when non-lethal DNA
CC damage cannot be repaired in a timely manner.
CC {ECO:0000269|PubMed:11090622, ECO:0000269|PubMed:12545175,
CC ECO:0000269|PubMed:12620222, ECO:0000269|PubMed:15163406}.
CC -!- SIMILARITY: Belongs to the claspin family. {ECO:0000305}.
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DR EMBL; AF297867; AAG24516.2; -; mRNA.
DR RefSeq; NP_001082041.1; NM_001088572.1.
DR AlphaFoldDB; Q9DF50; -.
DR SMR; Q9DF50; -.
DR BioGRID; 99527; 4.
DR iPTMnet; Q9DF50; -.
DR GeneID; 398192; -.
DR KEGG; xla:398192; -.
DR CTD; 398192; -.
DR Xenbase; XB-GENE-6251915; clspn.S.
DR OrthoDB; 132723at2759; -.
DR Proteomes; UP000186698; Chromosome 2S.
DR Bgee; 398192; Expressed in egg cell and 15 other tissues.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR InterPro; IPR024146; Claspin.
DR PANTHER; PTHR14396; PTHR14396; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Coiled coil; DNA damage; DNA repair; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1285
FT /note="Claspin"
FT /id="PRO_0000089877"
FT REPEAT 858..867
FT /note="CKB motif 1"
FT REPEAT 889..898
FT /note="CKB motif 2"
FT REGION 67..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 600..659
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 770..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 847..903
FT /note="CKBD"
FT REGION 878..920
FT /note="Interaction with PLK1"
FT /evidence="ECO:0000269|PubMed:15163406"
FT REGION 904..1038
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1130..1192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1222..1285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 222..248
FT /evidence="ECO:0000255"
FT COILED 957..995
FT /evidence="ECO:0000255"
FT COMPBIAS 67..120
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..135
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..190
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 603..653
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 770..787
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 961..983
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 984..1003
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1004..1038
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1222..1240
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12545175"
FT MOD_RES 895
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12545175"
FT MOD_RES 906
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:15163406"
FT MOD_RES 934
FT /note="Phosphoserine; by PLK1"
FT /evidence="ECO:0000269|PubMed:15163406"
SQ SEQUENCE 1285 AA; 145982 MW; A302479768FDBA7D CRC64;
MAALCEEEQV FLEPEDISLK IVETDSDSGQ GSCEMADQNK LLGCVEDKDT DDEILVRKKS
KKKEVLVDSD SDEELEMRNF ADNVKGHSDN EENEETMSAY REKPRKIRSA VLDSDNSDHE
LDVQISTSQN AAEIPESEHD SLEKETHTVK PKTSKSLKKQ TDTNKEEIVK NKSKRKIPKE
KIKRRTKQKS KAVAEARPNL NDSGCLLTDG DLFDNGVENE MDSNEEEDSL EAIRAKMKSK
LNSHSAENFE DFELDTEGNQ ESPEKRKERK AARLGKEAMK QMHSETQRLI RESSVSLPYH
LPEPKTIHDF FKRRPRPLCQ GNAMQLIKST KYQPCTEEKK KPNEEICAEV PEFDYVSKED
LEISPEQPLL NTQCSHAAVL CVVQNDARTE GLSKSTEAVV TGQMNDHEDA FSDSNIVHEQ
ETVGLITVTE TFQTPFIPQP ESVVCEQIQN DVVEMQRMPE QPTHKPKLSK LEKLKALGVD
LSIKPRLCPD DGSFVNLDEP KPNKEFEALK ERFLKHTLQK SKPRTERKVN LNIIRKETTA
DGKEELKADV VPIVMATEKP DKSIYQKPGE KLQVLKVKLQ EAMKIRRSEE RLKRQALYKL
DNEDGFEDDE EEEEMTEESE DDGDGNAETA DYPGGEDEEE VGDAEDDNDE DDTVNDRLLG
NVPEIVIPLP RPVTTDSSLM LFKDNSSKLG DSLPDESGCK RSSRLEYEED SLLPQLKENS
HNSSFELISS MIPSYQPCNK TTRVVINSNN LGFRSPSPVH FKTSFLSSAS KSSGKMSEPS
LPVEDSQDLY NASPEPKASY LCAGRNSQFQ FSLEDDTQSQ LLDADGFLNV GRHKSSSAKH
RLALDTMDEN AMDANMDELL DLCSGQFKES LSGTSQAAES DAKKQPMDEL LELCSGKFVS
QADCSTQDSS ASAKDRSTAV KKDISDEVAT VSSSFLTERE QEEDEEEEFG EFKLLPCDDS
ESENEEQNEE EEEEEDAKDD EDEEEILQKQ QKRKLRLNDF MEDEAELSGS DVGSGDEYEG
DDDEYEEEAI DEDLPSDEEL QDQVNKIHMK VTMDEDQRQL RFYQERYLAD GDLHSDGPGR
TRKFRWKHLD DASQVDMFRR DSELEEVDGE NEETEETELK WRKERFEREQ WLREQPQGSR
DNNEEEEEDI GEDSQFMKLA KKVTAKALQR KVSTETNEPK KPGPRNPYEV IRPFSLPKLR
TGSLLSKPKE VLQKLAAVSD LNPNAPRNSR NFVFQTVSPG KKEETTDKPR SKVRKNIAVA
MPSPKRFKRD STPTVKSRSI FQLLE
