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 27-MAR-2024, entry version 175. DE RecName: Full=Claspin {ECO:0000305}; DE Short=hClaspin; GN Name=CLSPN {ECO:0000312|HGNC:HGNC:19715}; 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 FUNCTION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-841; ASP-1031; RP ASP-1072; ASP-1085 AND ASP-1158. RX PubMed=16123041; DOI=10.1074/jbc.m506460200; RA Clarke C.A., Bennett L.N., Clarke P.R.; RT "Cleavage of claspin by caspase-7 during apoptosis inhibits the Chk1 RT pathway."; RL J. Biol. Chem. 280:35337-35345(2005). RN [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] RP FUNCTION, INTERACTION WITH CDC7 AND MCM2-7 COMPLEX, DOMAIN, SUBCELLULAR RP LOCATION, INTERACTION WITH CDC7 AND PCNA, SUBUNIT, MUTAGENESIS OF RP 311-ASN--PHE-318, AND PHOSPHORYLATION BY CDC7. RX PubMed=27401717; DOI=10.1038/ncomms12135; RA Yang C.C., Suzuki M., Yamakawa S., Uno S., Ishii A., Yamazaki S., RA Fukatsu R., Fujisawa R., Sakimura K., Tsurimoto T., Masai H.; RT "Claspin recruits Cdc7 kinase for initiation of DNA replication in human RT cells."; RL Nat. Commun. 7:12135-12135(2016). RN [25] RP FUNCTION, AND INTERACTION WITH TIMELESS. RX PubMed=35585232; DOI=10.1038/s41586-022-04759-1; RA Baris Y., Taylor M.R.G., Aria V., Yeeles J.T.P.; RT "Fast and efficient DNA replication with purified human proteins."; RL Nature 606:204-210(2022). RN [26] {ECO:0007744|PDB:7PFO} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN REPLISOME, SUBUNIT, RP AND FUNCTION. RX PubMed=34694004; DOI=10.15252/embj.2021108819; RA Jones M.L., Baris Y., Taylor M.R.G., Yeeles J.T.P.; RT "Structure of a human replisome shows the organisation and interactions of RT a DNA replication machine."; RL EMBO J. 40:e108819-e108819(2021). RN [27] {ECO:0007744|PDB:7PLO} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN REPLISOME, AND RP SUBUNIT. RX PubMed=34700328; DOI=10.1038/s41586-021-04145-3; RA Jenkyn-Bedford M., Jones M.L., Baris Y., Labib K.P.M., Cannone G., RA Yeeles J.T.P., Deegan T.D.; RT "A conserved mechanism for regulating replisome disassembly in RT eukaryotes."; RL Nature 600:743-747(2021). RN [28] 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 [29] 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 (PubMed:12766152, PubMed:15190204, CC PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 CC and the checkpoint kinase CHEK1 and facilitates the ATR-dependent CC phosphorylation of both proteins (PubMed:12766152, PubMed:15707391, CC PubMed:15096610, PubMed:16123041). Also required to maintain normal CC rates of replication fork progression during unperturbed DNA CC replication. Binds directly to DNA, with particular affinity for CC branched or forked molecules and interacts with multiple protein CC components of the replisome such as the MCM2-7 complex and TIMELESS CC (PubMed:15226314, PubMed:35585232, PubMed:34694004). Important for CC initiation of DNA replication, recruits kinase CDC7 to phosphorylate CC MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, CC ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, CC ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, CC ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, CC ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. CC -!- SUBUNIT: Interacts (phosphorylation-dependent) with CHEK1; regulates CC CLSPN function in checkpoint for DNA damage and replication CC (PubMed:12766152, PubMed:15707391, PubMed:16963448). Interacts with ATR CC and RAD9A and these interactions are slightly reduced during checkpoint CC activation (PubMed:12766152). Interacts with BRCA1 and this interaction CC increases during checkpoint activation (PubMed:15096610). Interacts CC with TIMELESS; the interaction is required for leading-strand CC replication (PubMed:17141802, PubMed:35585232, PubMed:34700328, CC PubMed:34694004). Associates with the MCM2-7 complex and other CC replisome factors (PubMed:34700328, PubMed:34694004, PubMed:27401717). CC Interacts (via the acidic patch) with CDC7; the interaction is required CC for phosphorylation of MCM proteins and CLASPIN by CDC7 CC (PubMed:27401717). Interacts with PCNA (PubMed:27401717). Interacts CC with FZR1 (PubMed:18662541). {ECO:0000269|PubMed:12766152, CC ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15707391, CC ECO:0000269|PubMed:16963448, ECO:0000269|PubMed:17141802, CC ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:27401717, CC ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, CC ECO:0000269|PubMed:35585232}. 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 -!- 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 -!- DOMAIN: The acidic patch region is required for normal DNA replication. CC Interacts with the N-terminal segments and inhibits binding to DNA and CC PCNA. Mediates the interaction with the kinase CDC7 as well as some CC replisome factors and DNA polymerases. {ECO:0000269|PubMed:27401717}. 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 (PubMed:12766152, CC PubMed:15096610, PubMed:16963448, PubMed:21680713). Phosphorylated by CC CDC7 during DNA replication, phosphorylation inhibits interaction CC between the acidic patch and N-terminal segments leading to increased CC binding to DNA and PCNA (PubMed:27401717). CC {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, CC ECO:0000269|PubMed:16963448, ECO:0000269|PubMed:21680713, CC ECO:0000269|PubMed:27401717}. 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 -!- PTM: Proteolytically cleaved by caspase-7 (CASP7) in response to CC apoptosis, leading to its inactivation. {ECO:0000269|PubMed:16123041}. 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="https://atlasgeneticsoncology.org/gene/40105/CLSPN"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8B9D; EM; 3.40 A; Q=1-1339. DR PDBsum; 7AKO; -. DR PDBsum; 7PFO; -. DR PDBsum; 7PLO; -. DR PDBsum; 8B9D; -. DR AlphaFoldDB; Q9HAW4; -. DR EMDB; EMD-13375; -. DR EMDB; EMD-13494; -. DR SMR; Q9HAW4; -. DR BioGRID; 122015; 100. DR ELM; Q9HAW4; -. DR IntAct; Q9HAW4; 23. DR MINT; Q9HAW4; -. DR STRING; 9606.ENSP00000312995; -. DR GlyGen; Q9HAW4; 3 sites, 1 O-linked glycan (3 sites). 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; 9606-ENSP00000312995; -. DR PeptideAtlas; Q9HAW4; -. DR ProteomicsDB; 81451; -. [Q9HAW4-1] DR ProteomicsDB; 81452; -. [Q9HAW4-2] DR ProteomicsDB; 81453; -. [Q9HAW4-3] DR Pumba; Q9HAW4; -. DR Antibodypedia; 17335; 119 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 AGR; HGNC:19715; -. 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; 2919866at2759; -. 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; 572 hits in 1167 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 male germ line stem cell (sensu Vertebrata) in testis and 113 other cell types or tissues. DR ExpressionAtlas; Q9HAW4; baseline and differential. 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:UniProtKB. 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; CLASPIN; 1. DR PANTHER; PTHR14396:SF10; CLASPIN; 1. DR Genevisible; Q9HAW4; HS. 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 988..1086 FT /note="Acidic patch" FT /evidence="ECO:0000269|PubMed:27401717" 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 MOTIF 311..318 FT /note="PCNA-interacting protein (PIP)" FT /evidence="ECO:0000269|PubMed:27401717" 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 SITE 1072..1073 FT /note="Cleavage; by caspase-7" FT /evidence="ECO:0000269|PubMed:16123041" 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 311..318 FT /note="NKTIHDFF->AKTAHDAA: Strongly decreases interaction FT with PCNA." FT /evidence="ECO:0000269|PubMed:27401717" FT MUTAGEN 841 FT /note="D->A: Does not affect cleavage by caspase-7 FT (CASP7)." FT /evidence="ECO:0000269|PubMed:16123041" 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 MUTAGEN 1031 FT /note="D->A: Does not affect cleavage by caspase-7 FT (CASP7)." FT /evidence="ECO:0000269|PubMed:16123041" FT MUTAGEN 1072 FT /note="D->A: Abolished cleavage by caspase-7 (CASP7)." FT /evidence="ECO:0000269|PubMed:16123041" FT MUTAGEN 1085 FT /note="D->A: Does not affect cleavage by caspase-7 FT (CASP7)." FT /evidence="ECO:0000269|PubMed:16123041" FT MUTAGEN 1158 FT /note="D->A: Does not affect cleavage by caspase-7 FT (CASP7)." FT /evidence="ECO:0000269|PubMed:16123041" 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 //