CLSPN_HUMAN
ID CLSPN_HUMAN Reviewed; 1339 AA.
AC Q9HAW4; A6NFL4; Q1RMC6; Q2KHM3; Q5VYG0; Q6P6H5; Q8IWI1;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 3.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Claspin;
DE Short=hClaspin;
GN Name=CLSPN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH CHEK1; ATR AND RAD9A, SUBCELLULAR LOCATION,
RP INDUCTION, AND PHOSPHORYLATION.
RX PubMed=12766152; DOI=10.1074/jbc.m301136200;
RA Chini C.C.S., Chen J.;
RT "Human claspin is required for replication checkpoint control.";
RL J. Biol. Chem. 278:30057-30062(2003).
RN [5]
RP FUNCTION.
RX PubMed=15190204;
RA Sorensen C.S., Syljuasen R.G., Lukas J., Bartek J.;
RT "ATR, claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in
RT the absence of DNA damage.";
RL Cell Cycle 3:941-945(2004).
RN [6]
RP FUNCTION.
RX PubMed=15226314; DOI=10.1074/jbc.m405793200;
RA Sar F., Lindsey-Boltz L.A., Subramanian D., Croteau D.L., Hutsell S.Q.,
RA Griffith J.D., Sancar A.;
RT "Human claspin is a ring-shaped DNA-binding protein with high affinity to
RT branched DNA structures.";
RL J. Biol. Chem. 279:39289-39295(2004).
RN [7]
RP FUNCTION, INTERACTION WITH BRCA1, AND PHOSPHORYLATION BY ATR.
RX PubMed=15096610; DOI=10.1073/pnas.0401847101;
RA Lin S.-Y., Li K., Stewart G.S., Elledge S.J.;
RT "Human claspin works with BRCA1 to both positively and negatively regulate
RT cell proliferation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6484-6489(2004).
RN [8]
RP FUNCTION, INTERACTION WITH CHEK1, AND MUTAGENESIS OF THR-916; SER-945 AND
RP SER-982.
RX PubMed=15707391; DOI=10.1042/bj20041966;
RA Clarke C.A.L., Clarke P.R.;
RT "DNA-dependent phosphorylation of Chk1 and claspin in a human cell-free
RT system.";
RL Biochem. J. 388:705-712(2005).
RN [9]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP28.
RX PubMed=16901786; DOI=10.1016/j.cell.2006.06.039;
RA Zhang D., Zaugg K., Mak T.W., Elledge S.J.;
RT "A role for the deubiquitinating enzyme USP28 in control of the DNA-damage
RT response.";
RL Cell 126:529-542(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION AT THR-916 BY CHEK1, AND INTERACTION WITH CHEK1.
RX PubMed=16963448; DOI=10.1074/jbc.m604373200;
RA Chini C.C., Chen J.;
RT "Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1
RT and mediate Claspin function.";
RL J. Biol. Chem. 281:33276-33282(2006).
RN [12]
RP INTERACTION WITH TIMELESS.
RX PubMed=17141802; DOI=10.1016/j.jmb.2006.10.097;
RA Gotter A.L., Suppa C., Emanuel B.S.;
RT "Mammalian TIMELESS and Tipin are evolutionarily conserved replication
RT fork-associated factors.";
RL J. Mol. Biol. 366:36-52(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-833, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [14]
RP UBIQUITINATION BY THE APC/C COMPLEX, DEUBIQUITINATION BY USP28, AND
RP INTERACTION WITH FZR1.
RX PubMed=18662541; DOI=10.1016/j.cell.2008.05.043;
RA Bassermann F., Frescas D., Guardavaccaro D., Busino L., Peschiaroli A.,
RA Pagano M.;
RT "The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response
RT checkpoint.";
RL Cell 134:256-267(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-67; SER-225; SER-720;
RP SER-808; SER-810; SER-846; SER-1012; SER-1018; SER-1020; SER-1156 AND
RP SER-1289, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-839; SER-846; SER-1156 AND
RP SER-1289, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-891, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-67; SER-225; SER-718;
RP SER-723; SER-808; SER-810 AND SER-1289, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION BY CSNK1G1/CK1.
RX PubMed=21680713; DOI=10.1091/mbc.e11-01-0048;
RA Meng Z., Capalbo L., Glover D.M., Dunphy W.G.;
RT "Role for casein kinase 1 in the phosphorylation of Claspin on critical
RT residues necessary for the activation of Chk1.";
RL Mol. Biol. Cell 22:2834-2847(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-67; SER-83 AND
RP SER-225, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-225; SER-260;
RP SER-516; SER-718; SER-720; SER-731; SER-744; SER-762; SER-808; SER-810;
RP SER-846; SER-950; SER-954; SER-958; SER-1156 AND SER-1289, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-439.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Required for checkpoint mediated cell cycle arrest in
CC response to inhibition of DNA replication or to DNA damage induced by
CC both ionizing and UV irradiation. Adapter protein which binds to BRCA1
CC and the checkpoint kinase CHEK1 and facilitates the ATR-dependent
CC phosphorylation of both proteins. Can also bind specifically to
CC branched DNA structures and may associate with S-phase chromatin
CC following formation of the pre-replication complex (pre-RC). This may
CC indicate a role for this protein as a sensor which monitors the
CC integrity of DNA replication forks. {ECO:0000269|PubMed:12766152,
CC ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204,
CC ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391}.
CC -!- SUBUNIT: Interacts (phosphorylation-dependent) with CHEK1; regulates
CC CLSPN function in checkpoint for DNA damage and replication. Interacts
CC with ATR and RAD9A and these interactions are slightly reduced during
CC checkpoint activation. Interacts with BRCA1 and this interaction
CC increases during checkpoint activation. Interacts with TIMELESS.
CC {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610,
CC ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16963448,
CC ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:18662541}.
CC -!- INTERACTION:
CC Q9HAW4; O75419: CDC45; NbExp=4; IntAct=EBI-1369377, EBI-374969;
CC Q9HAW4; P50750: CDK9; NbExp=3; IntAct=EBI-1369377, EBI-1383449;
CC Q9HAW4; O14757: CHEK1; NbExp=5; IntAct=EBI-1369377, EBI-974488;
CC Q9HAW4; Q9UM11: FZR1; NbExp=4; IntAct=EBI-1369377, EBI-724997;
CC Q9HAW4; Q9H492: MAP1LC3A; NbExp=2; IntAct=EBI-1369377, EBI-720768;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12766152}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9HAW4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HAW4-2; Sequence=VSP_036033;
CC Name=3;
CC IsoId=Q9HAW4-3; Sequence=VSP_036034;
CC -!- INDUCTION: Expression peaks at S/G2 phases of the cell cycle.
CC {ECO:0000269|PubMed:12766152}.
CC -!- DOMAIN: The C-terminus of the protein contains 3 potential CHEK1-
CC binding motifs (CKB motifs). Potential phosphorylation sites within CKB
CC motif 1 and CKB motif 2 are required for interaction with CHEK1.
CC -!- PTM: Phosphorylated. Undergoes ATR-dependent phosphorylation by CHEK1
CC during activation of DNA replication or damage checkpoints.
CC Phosphorylation by CSNK1G1/CK1 promotes CHEK1 binding.
CC {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610,
CC ECO:0000269|PubMed:16963448, ECO:0000269|PubMed:21680713}.
CC -!- PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C)
CC during G1 phase, leading to its degradation by the proteasome.
CC Ubiquitination is mediated via its interaction with FZR1/CDH1.
CC Following DNA damage, it is deubiquitinated by USP28 in G2 phase,
CC preventing its degradation. {ECO:0000269|PubMed:16901786,
CC ECO:0000269|PubMed:18662541}.
CC -!- SIMILARITY: Belongs to the claspin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH38991.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH62215.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CLSPNID40105ch1p34.html";
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DR EMBL; AF297866; AAG24515.1; -; mRNA.
DR EMBL; AL354864; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038991; AAH38991.1; ALT_SEQ; mRNA.
DR EMBL; BC062215; AAH62215.1; ALT_SEQ; mRNA.
DR EMBL; BC113116; AAI13117.1; -; mRNA.
DR EMBL; BC115025; AAI15026.1; -; mRNA.
DR EMBL; BC137279; AAI37280.1; -; mRNA.
DR EMBL; BC140789; AAI40790.1; -; mRNA.
DR CCDS; CCDS396.1; -. [Q9HAW4-1]
DR CCDS; CCDS53297.1; -. [Q9HAW4-2]
DR CCDS; CCDS81299.1; -. [Q9HAW4-3]
DR RefSeq; NP_001177410.1; NM_001190481.1. [Q9HAW4-2]
DR RefSeq; NP_001317419.1; NM_001330490.1. [Q9HAW4-3]
DR RefSeq; NP_071394.2; NM_022111.3. [Q9HAW4-1]
DR PDB; 7AKO; X-ray; 1.80 A; C/D=937-952.
DR PDB; 7PFO; EM; 3.20 A; Q=1-1339.
DR PDB; 7PLO; EM; 2.80 A; Q=1-1339.
DR PDBsum; 7AKO; -.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; Q9HAW4; -.
DR SMR; Q9HAW4; -.
DR BioGRID; 122015; 67.
DR ELM; Q9HAW4; -.
DR IntAct; Q9HAW4; 24.
DR MINT; Q9HAW4; -.
DR STRING; 9606.ENSP00000312995; -.
DR iPTMnet; Q9HAW4; -.
DR PhosphoSitePlus; Q9HAW4; -.
DR BioMuta; CLSPN; -.
DR DMDM; 218512100; -.
DR CPTAC; CPTAC-962; -.
DR EPD; Q9HAW4; -.
DR jPOST; Q9HAW4; -.
DR MassIVE; Q9HAW4; -.
DR MaxQB; Q9HAW4; -.
DR PaxDb; Q9HAW4; -.
DR PeptideAtlas; Q9HAW4; -.
DR PRIDE; Q9HAW4; -.
DR ProteomicsDB; 81451; -. [Q9HAW4-1]
DR ProteomicsDB; 81452; -. [Q9HAW4-2]
DR ProteomicsDB; 81453; -. [Q9HAW4-3]
DR Antibodypedia; 17335; 107 antibodies from 30 providers.
DR DNASU; 63967; -.
DR Ensembl; ENST00000251195.9; ENSP00000251195.5; ENSG00000092853.14. [Q9HAW4-3]
DR Ensembl; ENST00000318121.8; ENSP00000312995.3; ENSG00000092853.14. [Q9HAW4-1]
DR Ensembl; ENST00000373220.7; ENSP00000362317.3; ENSG00000092853.14. [Q9HAW4-2]
DR GeneID; 63967; -.
DR KEGG; hsa:63967; -.
DR MANE-Select; ENST00000318121.8; ENSP00000312995.3; NM_022111.4; NP_071394.2.
DR UCSC; uc001bzi.4; human. [Q9HAW4-1]
DR CTD; 63967; -.
DR DisGeNET; 63967; -.
DR GeneCards; CLSPN; -.
DR HGNC; HGNC:19715; CLSPN.
DR HPA; ENSG00000092853; Tissue enhanced (bone marrow, lymphoid tissue, retina, testis).
DR MIM; 605434; gene.
DR neXtProt; NX_Q9HAW4; -.
DR OpenTargets; ENSG00000092853; -.
DR PharmGKB; PA134920757; -.
DR VEuPathDB; HostDB:ENSG00000092853; -.
DR eggNOG; KOG4156; Eukaryota.
DR GeneTree; ENSGT00390000012738; -.
DR InParanoid; Q9HAW4; -.
DR OMA; TEMNGDH; -.
DR OrthoDB; 132723at2759; -.
DR PhylomeDB; Q9HAW4; -.
DR TreeFam; TF328925; -.
DR PathwayCommons; Q9HAW4; -.
DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR SignaLink; Q9HAW4; -.
DR SIGNOR; Q9HAW4; -.
DR BioGRID-ORCS; 63967; 555 hits in 1089 CRISPR screens.
DR ChiTaRS; CLSPN; human.
DR GeneWiki; CLSPN; -.
DR GenomeRNAi; 63967; -.
DR Pharos; Q9HAW4; Tbio.
DR PRO; PR:Q9HAW4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9HAW4; protein.
DR Bgee; ENSG00000092853; Expressed in ganglionic eminence and 111 other tissues.
DR ExpressionAtlas; Q9HAW4; baseline and differential.
DR Genevisible; Q9HAW4; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0010997; F:anaphase-promoting complex binding; IPI:UniProtKB.
DR GO; GO:0000217; F:DNA secondary structure binding; IDA:MGI.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IDA:MGI.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR InterPro; IPR024146; Claspin.
DR PANTHER; PTHR14396; PTHR14396; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Coiled coil;
KW DNA damage; DNA repair; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..1339
FT /note="Claspin"
FT /id="PRO_0000089875"
FT REPEAT 910..919
FT /note="CKB motif 1"
FT REPEAT 939..948
FT /note="CKB motif 2"
FT REPEAT 976..985
FT /note="CKB motif 3"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 618..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 730..774
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 946..973
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 985..1075
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1294..1327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 162..196
FT /evidence="ECO:0000255"
FT COILED 592..681
FT /evidence="ECO:0000255"
FT COMPBIAS 19..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..96
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 146..199
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..285
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..391
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..418
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..440
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..476
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 625..676
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 683..703
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 740..766
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 946..964
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1009..1035
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1036..1059
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1061..1075
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1305..1327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80YR7"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80YR7"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80YR7"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80YR7"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80YR7"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80YR7"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 718
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 723
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 731
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 744
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 762
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 833
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 846
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 891
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 916
FT /note="Phosphothreonine; by CHEK1"
FT /evidence="ECO:0000269|PubMed:16963448"
FT MOD_RES 950
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 954
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 958
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1012
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1018
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1020
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 1289
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 527..590
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036033"
FT VAR_SEQ 1304..1339
FT /note="VKKRGPSFMTSPSPKHLKTDDSTSGLTRSIFKYLES -> KIPEKDSDWLTW
FT SGAPIPGFFRLSFDPHG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11090622"
FT /id="VSP_036034"
FT VARIANT 439
FT /note="H -> R (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035674"
FT VARIANT 525
FT /note="N -> S (in dbSNP:rs7537203)"
FT /id="VAR_023439"
FT VARIANT 892
FT /note="P -> T (in dbSNP:rs34390044)"
FT /id="VAR_050867"
FT VARIANT 1280
FT /note="S -> L (in dbSNP:rs35490896)"
FT /id="VAR_050868"
FT MUTAGEN 916
FT /note="T->A: Impairs interaction with CHEK1."
FT /evidence="ECO:0000269|PubMed:15707391"
FT MUTAGEN 945
FT /note="S->A: Impairs interaction with CHEK1."
FT /evidence="ECO:0000269|PubMed:15707391"
FT MUTAGEN 982
FT /note="S->A: No effect on interaction with CHEK1."
FT /evidence="ECO:0000269|PubMed:15707391"
FT CONFLICT 34
FT /note="S -> G (in Ref. 3; AAI15026)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="G -> E (in Ref. 3; AAI15026)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="F -> S (in Ref. 1; AAG24515)"
FT /evidence="ECO:0000305"
FT CONFLICT 664
FT /note="E -> G (in Ref. 1; AAG24515)"
FT /evidence="ECO:0000305"
FT CONFLICT 738
FT /note="F -> S (in Ref. 1; AAG24515)"
FT /evidence="ECO:0000305"
FT CONFLICT 931..933
FT /note="SDK -> GDE (in Ref. 3; AAI15026)"
FT /evidence="ECO:0000305"
FT HELIX 940..942
FT /evidence="ECO:0007829|PDB:7AKO"
FT HELIX 944..946
FT /evidence="ECO:0007829|PDB:7AKO"
SQ SEQUENCE 1339 AA; 151094 MW; 3F3E392D5915955F CRC64;
MTGEVGSEVH LEINDPNVIS QEEADSPSDS GQGSYETIGP LSEGDSDEEI FVSKKLKNRK
VLQDSDSETE DTNASPEKTT YDSAEEENKE NLYAGKNTKI KRIYKTVADS DESYMEKSLY
QENLEAQVKP CLELSLQSGN STDFTTDRKS SKKHIHDKEG TAGKAKVKSK RRLEKEERKM
EKIRQLKKKE TKNQEDDVEQ PFNDSGCLLV DKDLFETGLE DENNSPLEDE ESLESIRAAV
KNKVKKHKKK EPSLESGVHS FEEGSELSKG TTRKERKAAR LSKEALKQLH SETQRLIRES
ALNLPYHMPE NKTIHDFFKR KPRPTCHGNA MALLKSSKYQ SSHHKEIIDT ANTTEMNSDH
HSKGSEQTTG AENEVETNAL PVVSKETQII TGSDESCRKD LVKNEELEIQ EKQKQSDIRP
SPGDSSVLQQ ESNFLGNNHS EECQVGGLVA FEPHALEGEG PQNPEETDEK VEEPEQQNKS
SAVGPPEKVR RFTLDRLKQL GVDVSIKPRL GADEDSFVIL EPETNRELEA LKQRFWKHAN
PAAKPRAGQT VNVNVIVKDM GTDGKEELKA DVVPVTLAPK KLDGASHTKP GEKLQVLKAK
LQEAMKLRRF EERQKRQALF KLDNEDGFEE EEEEEEEMTD ESEEDGEEKV EKEEKEEELE
EEEEKEEEEE EEGNQETAEF LLSSEEIETK DEKEMDKENN DGSSEIGKAV GFLSVPKSLS
SDSTLLLFKD SSSKMGYFPT EEKSETDENS GKQPSKLDED DSCSLLTKES SHNSSFELIG
STIPSYQPCN RQTGRGTSFF PTAGGFRSPS PGLFRASLVS SASKSSGKLS EPSLPIEDSQ
DLYNASPEPK TLFLGAGDFQ FCLEDDTQSQ LLDADGFLNV RNHRNQYQAL KPRLPLASMD
ENAMDANMDE LLDLCTGKFT SQAEKHLPRK SDKKENMEEL LNLCSGKFTS QDASTPASSE
LNKQEKESSM GDPMEEALAL CSGSFPTDKE EEDEEEEFGD FRLVSNDNEF DSDEDEHSDS
GNDLALEDHE DDDEEELLKR SEKLKRQMRL RKYLEDEAEV SGSDVGSEDE YDGEEIDEYE
EDVIDEVLPS DEELQSQIKK IHMKTMLDDD KRQLRLYQER YLADGDLHSD GPGRMRKFRW
KNIDDASQMD LFHRDSDDDQ TEEQLDESEA RWRKERIERE QWLRDMAQQG KITAEEEEEI
GEDSQFMILA KKVTAKALQK NASRPMVIQE SKSLLRNPFE AIRPGSAQQV KTGSLLNQPK
AVLQKLAALS DHNPSAPRNS RNFVFHTLSP VKAEAAKESS KSQVKKRGPS FMTSPSPKHL
KTDDSTSGLT RSIFKYLES
