Reviewed, UniProtKB/Swiss-Prot Q9HAW4 (CLSPN_HUMAN)

Names and origin

Protein names

Recommended name:
    Claspin
Alternative name(s):
    hClaspin
    Hu-Claspin

Gene names

Name:

CLSPN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1332 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation. Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins. Can also bind specifically to branched DNA structures and may associate with S-phase chromatin following formation of the pre-replication complex (pre-RC). This may indicate a role for this protein as a sensor which monitors the integrity of DNA replication forks.
Subunit structure	Interacts with CHEK1 when phosphorylated. Interacts with ATR and RAD9A and these interactions are slightly reduced during checkpoint activation. Interacts with BRCA1 and this interaction increases during checkpoint activation. Interacts with TIMELESS.
Subcellular location	Nucleus.
Induction	Expression peaks at S/G2 phases of the cell cycle.
Domain	The C-terminus of the protein contains 3 potential CHEK1-binding motifs (CKB motifs). Potential phosphorylation sites within CKB motif 1 and CKB motif 2 are required for interaction with CHEK1.
Post-translational modification	Phosphorylated during activation of DNA replication or DNA damage checkpoints. This requires ATR.
Sequence caution	AAH38991.1 sequence differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. AAH62215.1 sequence differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. CAH73807.1 sequence differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Chromosomal protein Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat
Ligand	DNA-binding
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA replication Inferred from Experiment. Source: Reactome
Cellular component	nucleoplasm Ref.6 Ref.8 Inferred from Experiment. Source: Reactome
Molecular function	protein binding Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHEK1	O14757	4	EBI-1369377,EBI-974488

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 1332	1332	Claspin
Regions
	Repeat	910 – 919	10	CKB motif 1
	Repeat	939 – 948	10	CKB motif 2
	Repeat	976 – 985	10	CKB motif 3
	Coiled coil	162 – 196	35	Potential
	Coiled coil	592 – 681	90	Potential
Amino acid modifications
	Modified residue	65	1	Phosphoserine
	Modified residue	67	1	Phosphoserine
	Modified residue	75	1	Phosphoserine
	Modified residue	762	1	Phosphoserine
	Modified residue	764	1	Phosphoserine
	Modified residue	833	1	Phosphoserine
	Modified residue	839	1	Phosphoserine
	Modified residue	846	1	Phosphoserine
	Modified residue	950	1	Phosphoserine
	Modified residue	1287	1	Phosphothreonine
	Modified residue	1289	1	Phosphoserine
Natural variations
	Natural variant	439	1	H → R in a breast cancer sample; somatic mutation.
	Natural variant	525	1	N → S: dbSNP rs7537203.
Experimental info
	Mutagenesis	916	1	T → A: Impairs interaction with CHEK1
	Mutagenesis	945	1	S → A: Impairs interaction with CHEK1
	Mutagenesis	982	1	S → A: No effect on interaction with CHEK1
	Sequence conflict	628	1	F → S in AAG24515. Ref.1
	Sequence conflict	664	1	E → G in AAG24515. Ref.1
	Sequence conflict	738	1	F → S in AAG24515. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9HAW4-1 [UniParc]. Last modified August 30, 2005. Version 2. Checksum: 6FF64D7891BB7484	FASTA	1,332	150,368
	10 20 30 40 50 60 MTGEVGSEVH LEINDPNVIS QEEADSPSDS GQGSYETIGP LSEGDSDEEI FVSKKLKNRK 70 80 90 100 110 120 VLQDSDSETE DTNASPEKTT YDSAEEENKE NLYAGKNTKI KRIYKTVADS DESYMEKSLY 130 140 150 160 170 180 QENLEAQVKP CLELSLQSGN STDFTTDRKS SKKHIHDKEG TAGKAKVKSK RRLEKEERKM 190 200 210 220 230 240 EKIRQLKKKE TKNQEDDVEQ PFNDSGCLLV DKDLFETGLE DENNSPLEDE ESLESIRAAV 250 260 270 280 290 300 KNKVKKHKKK EPSLESGVHS FEEGSELSKG TTRKERKAAR LSKEALKQLH SETQRLIRES 310 320 330 340 350 360 ALNLPYHMPE NKTIHDFFKR KPRPTCHGNA MALLKSSKYQ SSHHKEIIDT ANTTEMNSDH 370 380 390 400 410 420 HSKGSEQTTG AENEVETNAL PVVSKETQII TGSDESCRKD LVKNEELEIQ EKQKQSDIRP 430 440 450 460 470 480 SPGDSSVLQQ ESNFLGNNHS EECQVGGLVA FEPHALEGEG PQNPEETDEK VEEPEQQNKS 490 500 510 520 530 540 SAVGPPEKVR RFTLDRLKQL GVDVSIKPRL GADEDSFVIL EPETNRELEA LKQRFWKHAN 550 560 570 580 590 600 PAAKPRAGQT VNVNVIVKDM GTDGKEELKA DVVPVTLAPK KLDGASHTKP GEKLQVLKAK 610 620 630 640 650 660 LQEAMKLRRF EERQKRQALF KLDNEDGFEE EEEEEEEMTD ESEEDGEEKV EKEEKEEELE 670 680 690 700 710 720 EEEEKEEEEE EEGNQETAEF LLSSEEIETK DEKEMDKENN DGSSEIGKAV GFLSVPKSLS 730 740 750 760 770 780 SDSTLLLFKD SSSKMGYFPT EEKSETDENS GKQPSKLDED DSCSLLTKES SHNSSFELIG 790 800 810 820 830 840 STIPSYQPCN RQTGRGTSFF PTAGGFRSPS PGLFRASLVS SASKSSGKLS EPSLPIEDSQ 850 860 870 880 890 900 DLYNASPEPK TLFLGAGDFQ FCLEDDTQSQ LLDADGFLNV RNHRNQYQAL KPRLPLASMD 910 920 930 940 950 960 ENAMDANMDE LLDLCTGKFT SQAEKHLPRK SDKKENMEEL LNLCSGKFTS QDASTPASSE 970 980 990 1000 1010 1020 LNKQEKESSM GDPMEEALAL CSGSFPTDKE EEDEEEEFGD FRLVSNDNEF DSDEDEHSDS 1030 1040 1050 1060 1070 1080 GNDLALEDHE DDDEEELLKR SEKLKRQMRL RKYLEDEAEV SGSDVGSEDE YDGEEIDEYE 1090 1100 1110 1120 1130 1140 EDVIDEVLPS DEELQSQIKK IHMKTMLDDD KRQLRLYQER YLADGDLHSD GPGRMRKFRW 1150 1160 1170 1180 1190 1200 KNIDDASQMD LFHRDSDDDQ TEEQLDESEA RWRKERIERE QWLRDMAQQG KITAEEEEEI 1210 1220 1230 1240 1250 1260 GEDSQFMILA KKVTAKALQK NASRPMVIQE SKSLLRNPFE AIRPGSAQQV KTGSLLNQPK 1270 1280 1290 1300 1310 1320 AVLQKLAALS DHNPSAPRNS RNFVFHTLSP VKAEAAKESS KSQKIPEKDS DWLTWSGAPI 1330 PGFFRLSFDP HG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts." Kumagai A., Dunphy W.G. Mol. Cell 6:839-849(2000) [PubMed: 11090622] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-690. Tissue: Skin.
[4]	"Human claspin is required for replication checkpoint control." Chini C.C.S., Chen J. J. Biol. Chem. 278:30057-30062(2003) [PubMed: 12766152] [Abstract] Cited for: FUNCTION, INTERACTION WITH CHEK1; ATR AND RAD9A, SUBCELLULAR LOCATION, INDUCTION, PHOSPHORYLATION.
[5]	"ATR, claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage." Sorensen C.S., Syljuasen R.G., Lukas J., Bartek J. Cell Cycle 3:941-945(2004) [PubMed: 15190204] [Abstract] Cited for: FUNCTION.
[6]	"Human claspin is a ring-shaped DNA-binding protein with high affinity to branched DNA structures." Sar F., Lindsey-Boltz L.A., Subramanian D., Croteau D.L., Hutsell S.Q., Griffith J.D., Sancar A. J. Biol. Chem. 279:39289-39295(2004) [PubMed: 15226314] [Abstract] Cited for: FUNCTION.
[7]	"Human claspin works with BRCA1 to both positively and negatively regulate cell proliferation." Lin S.-Y., Li K., Stewart G.S., Elledge S.J. Proc. Natl. Acad. Sci. U.S.A. 101:6484-6489(2004) [PubMed: 15096610] [Abstract] Cited for: FUNCTION, INTERACTION WITH BRCA1, PHOSPHORYLATION BY ATR.
[8]	"DNA-dependent phosphorylation of Chk1 and claspin in a human cell-free system." Clarke C.A.L., Clarke P.R. Biochem. J. 388:705-712(2005) [PubMed: 15707391] [Abstract] Cited for: FUNCTION, INTERACTION WITH CHEK1, MUTAGENESIS OF THR-916; SER-945 AND SER-982.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-67; SER-75; SER-762; SER-764; THR-1287 AND SER-1289, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors." Gotter A.L., Suppa C., Emanuel B.S. J. Mol. Biol. 366:36-52(2007) [PubMed: 17141802] [Abstract] Cited for: INTERACTION WITH TIMELESS.
[11]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-833; SER-839; SER-846 AND SER-950, MASS SPECTROMETRY.
[12]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-439.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF297866 mRNA. Translation: AAG24515.1. AL354864 Genomic DNA. Translation: CAH73807.1. Sequence problems. BC038991 mRNA. Translation: AAH38991.1. Sequence problems. BC062215 mRNA. Translation: AAH62215.1. Sequence problems.
RefSeq	NP_071394.2.
UniGene	Hs.175613
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HAW4.
PTM databases
PhosphoSite	Q9HAW4.
Genome annotation databases
Ensembl	ENSG00000092853. Homo sapiens. [Contig view]
GeneID	63967.
KEGG	hsa:63967.
Organism-specific databases
HGNC	HGNC:19715. CLSPN.
MIM	605434. gene.
PharmGKB	PA134920757.
GenAtlas	Search...
GeneCards	Search...
GeneLynx	Search...
Phylogenomic databases
HOVERGEN	Q9HAW4.
Enzyme and pathway databases
Reactome	REACT_1538. Cell Cycle Checkpoints.
Gene expression databases
ArrayExpress	Q9HAW4.
CleanEx	HS_CLSPN.
GermOnline	ENSG00000092853. Homo sapiens.
Family and domain databases
ProDom	Q9HAW4. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

CLSPN_HUMAN

Accession

Primary (citable) accession number: Q9HAW4
Secondary accession number(s): Q5VYG0, Q6P6H5, Q8IWI1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	August 30, 2005
Last modified:	July 22, 2008
This is version 46 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)