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FLASH GENE
Symbol CDC6 contributors: mct/npt/pgu - updated : 10-09-2014
HGNC name CDC6 cell division cycle 6 homolog (S. cerevisiae)
HGNC id 1744
Corresponding disease
MGORS5 Meier-Gorlin syndrome 5
Location 17q21.2      Physical location : 38.444.145 - 38.459.413
Synonym name
  • CDC6-related protein
  • CDC18 (cell division cycle 18, S.pombe, homolog)-like
  • Synonym symbol(s) CDC18L, HsCDC18, p62(cdc6), HsCDC6
    DNA
    TYPE functioning gene
    STRUCTURE 15.27 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • MYOD1 can occupy an E-box within the promoter of CDC6 and this association, along with E2F3A, is required for its activity
  • MAPPING cloned Y linked N status provisional
    Map cen - D17S800 - CDC6 - IGFBP4 - KRT10 - CDC27 - SLC4A1 - D17S930 - qter
    Authors Gene Map (98)
    Physical map
    CAB2 17q21.2 CAB2 protein ERBB2 17q11.2-q12 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) MGC14832 GRB7 17q11.2-q12 growth factor receptor-bound protein 7 ZNFN1A3 17q11.2 zinc finger protein, subfamily 1A, 3 (Aiolos) ZPBP2 17q21.2 zona pellucida binding protein 2 GSDML 17q21.2 gasdermin-like ORMDL3 17q12 ORM1-like 3 (S. cerevisiae) LOC342669 17q21.2 similar to leucine-rich repeat domain-containing protein GSDM 17q21.2 gasdermin PSMD3 17q21.1 proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 CSF3 17q11.2-q12 colony stimulating factor 3 (granulocyte) TRAP100 THRA 17q11.2 thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian) NR1D1 17q11.2 nuclear receptor subfamily 1, group D, member 1 MLN51 17q12-q21.3 nuclear receptor subfamily 1, group D, member 1 LOC339287 17q21.2 hypothetical protein LOC339287 Link-GEFII 17q21.2 Link guanine nucleotide exchange factor II WIRE 17q21.2 WIRE protein CDC6 17q21.3 CDC6 cell division cycle 6 homolog (S. cerevisiae) RARA 17q12 retinoic acid receptor, alpha GJC1 17q21.1 gap junction protein, chi 1, 31.9kDa (connexin 31.9) LOC390791 17 similar to peptidyl-Pro cis trans isomerase TOP2A 17q21.31 topoisomerase (DNA) II alpha 170kDa IGFBP4 17q12 insulin-like growth factor binding protein 4 CTEN 17q21.2 C-terminal tensin-like LOC284134 17q21.2 hypothetical LOC284134 CCR7 17q21.1 chemokine (C-C motif) receptor 7 SMARCE1 17q21.1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 MGC45562 17q21.2 hypothetical protein MGC45562 KRT24 17q11.2 keratin 24 KRT25B 17q21.2 keratin 25B KRT25A 17q21.2 keratin 25A KRT25C 17q21.2 keratin 25C KRT25D 17q21.2 keratin 25C MGC21518 17q21.2 hypothetical protein MGC21518 KRT12 17q21.1 keratin 12 (Meesmann corneal dystrophy)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3053 62.6 560 - 1998 9566895
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly
    Digestiveesophagus   moderately
     mouthtongue  highly
    Reproductivefemale systemuteruscervix highly
    Respiratoryrespiratory tractlarynx   
    Urinarybladder   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion lymph
    at STAGE
    physiological period embryo, pregnancy
    Text selectively, in proliferating but not quiescent cell, embryonic kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • putative cyclin-dependent kinase phosphorylation sites
  • a potential leucine zipper
  • a nucleotide binding ATPase domain and destruction boxes
  • a Walker B motif and C-terminal region that are essential for CDH1 transcriptional suppression
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to rattus Cdc6
    ortholog to murine Cdc6
    intraspecies homolog to ORC1
    Homologene
    FAMILY
  • CDC6/cdc18 family
  • CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text localized in cell nucleus during cell cycle G1, but translocated to the cytoplasm at the start of S phase (regulated by phosphorylation by CDKs)
    basic FUNCTION
  • required for the initiation of DNA replication regulated by p53 through CDC6 protein stability
  • acting as a regulator at the early steps of DNA replication
  • substrate for the APC/C complex
  • CDC6 stabilization by cyclin E promotes pre-RC assembly
  • participating in checkpoint controls that ensure DNA replication is completed before mitosis is initiated
  • plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme
  • also plays important roles in the activation and maintenance of the checkpoint mechanisms that coordinate S phase and mitosis
  • essential for DNA replication and its deregulation is involved in carcinogenesis
  • with CDT1 are destabilized by rereplication-induced DNA damage
  • essential to promote the assembly of pre-replicative complexes in the early G1 phase of the cell cycle, a process requiring tight regulation to ensure that proper origin licensing occurs once per cell cycle
  • acts as a molecular switch at the CDH1 locus, linking transcriptional repression to activation of replication
  • role in spindle formation in addition to its role as a DNA replication factor
  • during the G(1)-S transition, is essential for chromosomal replication is activated by the E2F transcriptional factor
  • is an AAA+ ATPase with three functions, all working for life
  • CELLULAR PROCESS cell cycle, checkpoint
    nucleotide, replication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of pre-replication complex
  • CUL4B-CDK2-CDC6 cascade in the regulation of DNA replication licensing
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • DNA replication proteins PCNA and ORC1
  • cyclin A CDK2
  • TTC4 is a nucleoplasmic protein which interacts with HSP90AA1 and HSPA4, and also with the replication protein CDC6
  • interacting with KAT2A (KAT2A-mediated acetylation and site-specific phosphorylation of CDC6 are both necessary for the relocalization of the protein to the cell cytoplasm in the S phase, as well as to regulate its stability)
  • interacting with CDK2 (CDK2 may promote the formation of active ATR complexes in at least two ways: via the phosphorylation of TREX1 and by the stabilization of CDC6)
  • function for MYOD1 in regulating CDC6 that is vital to endowing chromatin with the capability of replicating DNA
  • ATR can have a central role in inhibiting the initiation of DNA replication by the regulation of CDC6 by CDH1
  • strong correlation between increased CDC6 expression and reduced CDH1 levels
  • activates CDKN1B-bound CDK2 protein only after the bound CDKN1B protein undergoes C-terminal phosphorylation
  • CDC6 expression is regulated by lineage-specific transcription factor GATA1
  • CDT1 cooperates with the cell cycle protein CDC6 to promote loading of the minichromosome maintenance helicases (MCM) onto the chromatin-bound origin recognition complex (ORC)
  • CDC6, the licensing factor in replication, was positively regulated by CUL4B and contributed to the loading of MCM2 to chromatin
  • CDC6 and CCNF interact through defined sequence motifs that promote CDC6 ubiquitylation and degradation
  • cell & other
    REGULATION
    activated by MYOD1 (activation of CDC6 by MYOD1 is associated with the expansion of quiescent myogenic satellite cells)
    Other phosphorylated by CDKs, stabilizing it by preventing its association with the APC/C complex
    regulated at the transcriptional level, in response to mitogenic signals through transcriptional control mechanism involving E2F proteins
    ASSOCIATED DISORDERS
    corresponding disease(s) MGORS5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpressed in human cancers
    tumoral     --over  
    in cervix carcinoma in neoplastic progression
    constitutional     --over  
    overexpression in primary cells may promote DNA hyperreplication and induce a senescence response similar to that caused by oncogene activation
    Susceptibility to hepatocellular carcinoma (HCC)
    Variant & Polymorphism other -515A>G polymorphism may affect the CDC6 promoter binding affinity with nuclear protein(s) and in turn its expression, which consequently modulates the individual susceptibility to HCC
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS