2QBY,2V1U


Conserved Protein Domain Family
Cdc6_C

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cd08768: Cdc6_C 
Click on image for an interactive view with Cn3D
Winged-helix domain of essential DNA replication protein Cell division control protein (Cdc6), which mediates DNA binding.
This model characterizes the winged-helix, C-terminal domain of the Cell division control protein (Cdc6_C). Cdc6 (also known as Cell division cycle 6 or Cdc18) functions as a regulator at the early stages of DNA replication, by helping to recruit and load the Minichromosome Maintenance Complex (MCM) onto DNA and may have additional roles in the control of mitotic entry. Precise duplication of chromosomal DNA is required for genomic stability during replication. Cdc6 has an essential role in DNA replication and irregular expression of Cdc6 may lead to genomic instability. Cdc6 over-expression is observed in many cancerous lesions. DNA replication begins when an origin recognition complex (ORC) binds to a replication origin site on the chromatin. Studies indicate that Cdc6 interacts with ORC through the Orc1 subunit, and that this association increases the specificity of the ORC-origins interaction. Further studies suggest that hydrolysis of Cdc6-bound ATP promotes the association of the replication licensing factor Cdt1 with origins through an interaction with Orc6 and this in turn promotes the loading of MCM2-7 helicase onto chromatin. The MCM2-7 complex promotes the unwinding of DNA origins, and the binding of additional factors to initiate the DNA replication. S-Cdk (S-phase cyclin and cyclin-dependent kinase complex) prevents rereplication by causing the Cdc6 protein to dissociate from ORC and prevents the Cdc6 and MCM proteins from reassembling at any origin. By phosphorylating Cdc6, S-Cdk also triggers Cdc6's ubiquitination. The Cdc6 protein is composed of three domains, an N-terminal AAA+ domain with Walker A and B, and Sensor-1 and -2 motifs. The central region contains a conserved nucleotide binding/ATPase domain and is a member of the ATPase superfamily. The C-terminal domain (Cdc6_C) is a conserved winged-helix domain that possibly mediates protein-protein interactions or direct DNA interactions. Cdc6 is conserved in eukaryotes, and related genes are found in Archaea. The winged helix fold structure of Cdc6_C is similar to the structures of other eukaryotic replication initiators without apparent sequence similarity.
Statistics
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PSSM-Id: 176573
View PSSM: cd08768
Aligned: 60 rows
Threshold Bit Score: 58.0163
Threshold Setting Gi: 267528
Created: 23-Nov-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
DNA binding
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:DNA binding site [nucleic acid binding site]
Evidence:
  • Structure:Archaeal, Sulfolobus solfataricus Cdc6/Orc1 C-terminal winged helix domain binds DNA at 4.0 A.
    View structure with Cn3D
  • Comment: DNA binding of Cdc6 is mediated principally by the C-terminal winged helix domain.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                 #                    ##                 # #      ###   
2QBY_B       283 PFHYKLALRSLIese--------dvMSAHKMYTDLCNkfkqKPLSYRRFSDIISELDMFGIVKIRIINRGraggVKKYAL 354  Sulfolobus sol...
Q94CM2       411 PQHQQIIVCSAAkafrgs-kkdrtiAELNKLYLEICKssmiTPAGITEFSNMCTVLNDQGILKLSLARDDk---LKRVSL 486  thale cress
Q01BC5       711 PQMQQLVLCSAAklfhsvgtvetttGTLHDRYVVVCKtagvKELSQGEFYNMCTALEDHALVKVGKSGNDr---MRKLKL 787  Ostreococcus t...
Q28YI8       839 SRLEQIFLQAVAaevtrtgveestfMGVYTQVETIAAfmgvSLPPPGRALRLCAKLGAERLIISEHSRNDl---FQKILL 915  Drosophila pse...
Q7PPI6       782 SRLEQLFLQAVTaevtrtgieecnfLGVYSQFESLAAfsgiIVPNPGRAMAICARLAASRLLICECGKSDi---YQKILL 858  Anopheles gamb...
Q7ZYW6       820 SVQGQLLLRAVIaefrrlgleeatfQQVFVQHQALCRveglQPVSVSEGLLVCQRLGSCRLLLLEGSRLDl---FLRIRL 896  zebrafish
Q58DC8       773 SVLEQSFLRAILaefrrsgleeatfQQVYIQHVALCRmeglPYPTMSETMAVCSRLGACRLLLVEPSRNDv---LRRVRL 849  cattle
P70049       796 SLMEQTFLRAVIaefrrsgleeatfQQIYRQHVALCRieglQPPQMSETMAVCHRLGASRLLLVESSRNDl---HLRVRI 872  African clawed...
Q5ZMC5       768 SLHEQIFFKAILaefrrvgveeatvQQVYRQHIALCRmegmQSPTVSDILAICARLGACRLLLLESSSKYl---HMRVRL 844  chicken
XP_001625060 332 SMFEGLLMKAVLaefkrsgveeaafSEVYCQLGNLCRleglTPPSTTEASIITSRLGATRLLLVEPGRLDq---QRRIRL 408  starlet sea an...
Feature 1               
2QBY_B       355 VEDKEKV 361  Sulfolobus solfataricus
Q94CM2       487 RVDEADI 493  thale cress
Q01BC5       788 QVKYDDV 794  Ostreococcus tauri
Q28YI8       916 NVSADDI 922  Drosophila pseudoobscura
Q7PPI6       859 NISTDDV 865  Anopheles gambiae str. PEST
Q7ZYW6       897 NVSQDDV 903  zebrafish
Q58DC8       850 NVSQDDV 856  cattle
P70049       873 NVSQDDI 879  African clawed frog
Q5ZMC5       845 NISQDDV 851  chicken
XP_001625060 409 NVNQDDV 415  starlet sea anemone

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