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FLASH GENE
Symbol CLSPN contributors: mct - updated : 30-10-2015
HGNC name claspin
HGNC id 19715
Location 1p34.3      Physical location : 36.197.712 - 36.235.551
Synonym name claspin homolog (Xenopus laevis)
Synonym symbol(s) CLASPIN, MGC131612, MGC131613, MGC131615, Hu-Claspin
DNA
TYPE functioning gene
STRUCTURE 37.84 kb     25 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
motif repetitive sequence
text structure
  • promoter is directly regulated by REL (IKBKB and IKBKG control REL recruitment to the Claspin promoter)
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC113444 1p34.3 hypothetical protein BC011880 SAPAP3 1p35.3-p34.1 SAP90/PSD-95-associated protein 3 LOC388617 1 LOC388617 MGC14276 1p34.3 hypothetical protein MGC14276 ZNF258 1p34.2 zinc finger protein 258 LOC388618 1 similar to RIKEN cDNA 9330177P20 FLJ23151 1p34.3 hypothetical protein FLJ23151 SFPQ 1pter-p32.3 splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated) ZNF262 1p34-p32 zinc finger protein 262 LOC388619 1 similar to ribosomal protein L5; 60S ribosomal protein L5 PKD1-like 1p34.2 polycystic kidney disease 1-like NCDN 1p34.3 neurochondrin MGC49007 PSMB2 1p34.2 proteasome (prosome, macropain) subunit, beta type, 2 FLJ38984 1p34.3 hypothetical protein FLJ38984 CLSPN 1p34.2 claspin homolog (Xenopus laevis) EIF2C4 1p34.3 eukaryotic translation initiation factor 2C, 4 EIF2C1 1p35-p34 eukaryotic translation initiation factor 2C, 1 EIF2C3 1p34.3 eukaryotic translation initiation factor 2C, 3 LOC388620 1 similar to implantation-associated protein TEKT2 1p35.3-p34.1 tektin 2 (testicular) ADPRHL2 1p34.3 ADP-ribosylhydrolase like 2 COL8A2 1p34.3-p32.3 collagen, type VIII, alpha 2 TRAPPC3 1p34.2 trafficking protein particle complex 3 FLJ10350 1p34.3 hypothetical protein FLJ10350 TRAP150 FLJ22938 1p34.3 hypothetical protein FLJ22938 FLJ10647 1p34.3 hypothetical protein FLJ10647 MGC4796 1p34.3 Ser/Thr-like kinase LSM10 1p34.3 U7 snRNP-specific Sm-like protein LSM10 NOR1 1p34.3 oxidored-nitro domain-containing protein MRPS15 1p35-p34.1 mitochondrial ribosomal protein S15 CSF3R 1p34.2-p34.1 colony stimulating factor 3 receptor (granulocyte)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 8484 - 1339 - 2008 18077083
    24 - 8292 - 1275 - 2008 18077083
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Nervousbrain    
    Reproductivefemale systembreastmammary gland highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, S, G2
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus of Claspin binds to the replicative helicase co-factor CDC45, the Timeless protein and a branched, replication fork-like DNA structure
  • ser/thr rich domain and repeats
  • a CHEK1-activating domain (CKAD), undergoing phosphorylation on multiple conserved sites
  • C terminus associates with DNA polymerase epsilon and RAD17-Replication Factor C (RFC)
  • HOMOLOGY
    intraspecies homolog to MRC1
    Homologene
    FAMILY
  • claspin family
  • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • mediating phosphorylation and activation of checkpoint protein kinases
  • may have a function in S phase cells
  • playing a potentially critical role in replication checkpoint control in cells
  • involved in monitoring of replication and sensoring of DNA damage and cooperates with CHEK1 and BRCA1
  • required for the inducible FANCD2 mono-ubiquitination
  • required for resistance to mulptiple forms of genotoxic stress including UV,IR and hydroxyurea
  • works as an adaptator bringing CHEK1, ATR and RAD9 together
  • is involved in the pathway that prevents the premature chromatin condensation
  • is required for cell survival
  • functioning at late stages of CHEK1 activation following DNA damage
  • having an antiapoptotic activity and is degraded by two different pathways during apoptosis
  • is not only necessary for the propagation of the DNA-damage signal, but its destruction by the ubiquitin-proteosome pathway is required to allow the cell to continue the cell cycle allowing checkpoint recovery
  • mediator of the ATR-dependent DNA replication checkpoint in human cells and also promotes DNA replication fork progression and stability
  • multiple protein-DNA and protein-protein interactions may be important for CLSPN function during DNA replication and DNA replication checkpoint signaling
  • can plays a critical role in DNA replication in the absence of exogenous stress
  • CELLULAR PROCESS cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with BRCA1 to regulating BRCA1 phosphorylation
  • WDHD1-CLSPN-TIPIN-TIMELESS complex, which coordinate DNA unwinding with polymerase alpha-, delta-, and epsilon- dependent DNA polymerization are constituents of the Replisome
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with RAD9 and ATR
  • CHEK1-interacting protein that participates in the DNA replication checkpoint
  • interacts with CDC7 (CDC7 is potentially required for activation of the ATR-CHEK1 checkpoint pathway through regulation of Claspin)
  • acts synergistically with damaged DNA to increase phosphorylation of CHEK1 by ATR
  • RAD9A-mediated Claspin localization is a vital step during checkpoint activation
  • RAD9A, RAD9B plays a role in locating Claspin to sites of DNA damage, facilitating its role during the CHEK1-mediated checkpoint response
  • mediates the phosphorylation and activation of CHEK1 by ATR
  • TIMELESS associates with S phase replication checkpoint proteins CLSPN and TIPIN , and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites
  • interacts with many factors involved in checkpoint regulation and replication fork machinery, including ATR, ATM, CHEK1, Tim, MCM4, MCM10, CDC45, CDC7K, DNA polymerases
  • in the presence of BRCA1, HERC2 interacts with CLSPN, a protein essential for G(2)-M checkpoint activation and replication fork stability
  • Claspin and RAD17 are reportedly involved in the DNA damage-induced phosphorylation of CHEK1, a hallmark of checkpoint activation
  • function of HERC2/USP20 in coordinating CHEK1 activation by modulating CLSPN stability, which ultimately promotes genome stability and suppresses tumor growth
  • USP20 is a positive regulator of CLSPN and suppresses the malignant characteristics of gastric cancer cells
  • cell & other
    REGULATION
    inhibited by by the proteasome-mediated degradation pathway and CHEK1 is required to maintain Claspin stability
    Phosphorylated by CSNK1G1, that phosphorylates the CHEK1-activating domain of Claspin
    Other phosphorylation in response to replication stress is required for its association with CHEK1
    regulated by cell cycle
    regulated by ATR in response to DNA damage
    levels are controlled by proteasomal degradation, and this is regulated by PLK1
    cleavage by caspases, and proteasome-dependent degradation under apoptotic conditions, resulting in a reduction of the levels of both full-length claspin and its cleavage products
    REL directly controls Claspin gene transcription
    IKK complex(IKBKG, IKBKB) can regulate Claspin levels by controlling its mRNA expression
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS