claspin; hclaspin (CLSPN)

Function: - required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing & UV irradiation - adapter protein which binds to BRCA1 & the checkpoint kinase CHEK1 & facilitates the ATR-dependent phosphorylation of both proteins - can also bind specifically to branched DNA structures & may associate with S-phase chromatin following formation of the pre-replication complex - this may indicate a role for this protein as a sensor which monitors the integrity of DNA replication forks - phosphorylated - undergoes ATR-dependent phosphorylation by CHEK1 during activation of DNA replication or damage checkpoints - phosphorylation by CSNK1G1/CK1 promotes CHEK1 binding - ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) during G1 phase, leading to its degradation by the proteasome - ubiquitination is mediated via its interaction with FZR1/CDH1 - following DNA damage, it is deubiquitinated by USP28 in G2 phase, preventing its degradation - interacts (phosphorylation-dependent) with CHEK1 - regulates CLSPN function in checkpoint for DNA damage & replication - interacts with ATR & RAD9A; these interactions are slightly reduced during checkpoint activation - interacts with BRCA1; interaction increases during checkpoint activation - interacts with TIMELESS Structure: - the C-terminus of the protein contains 3 potential CHEK1- binding motifs (CKB motifs) - potential phosphorylation sites within CKB motif 1 & CKB motif 2 are required for interaction with CHEK1 - belongs to the claspin family Compartment: nucleus Alternative splicing: named isoforms=3 Expression: - expression peaks at S-phase & G2 phase of the cell cycle

General

DNA-binding protein phosphoprotein

Properties

SIZE: entity length = 1339 aa MW = 151 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S65} Ser phosphorylation site {S67} Ser phosphorylation site {S75} Ser phosphorylation site {S83} coiled coil {162-196} Ser phosphorylation site {S225} coiled coil {592-681} Ser phosphorylation site {S720} Ser phosphorylation site {S723} Thr phosphorylation site {T724} Ser phosphorylation site {S762} Ser phosphorylation site {S764} Ser phosphorylation site {S808} Ser phosphorylation site {S810} Ser phosphorylation site {S833} Ser phosphorylation site {S839} Ser phosphorylation site {S846} consensus repeat {910-919} SEQUENCE-IS: CKB MOTIF: Thr phosphorylation site {T916} consensus repeat {939-948} SEQUENCE-IS: CKB Ser phosphorylation site {S950} Ser phosphorylation site {S954} Thr phosphorylation site {T955} Ser phosphorylation site {S959} consensus repeat {976-985} SEQUENCE-IS: CKB Ser phosphorylation site {S1012} Ser phosphorylation site {S1018} Ser phosphorylation site {S1020} Ser phosphorylation site {S1156} Thr phosphorylation site {T1287} Ser phosphorylation site {S1289}

Database Correlations

OMIM 605434 UniProt Q9HAW4 Entrez Gene 63967 Kegg hsa:63967

References

UniProt Q9HAW4