2WVR,2ZXX


Conserved Protein Domain Family
Cdt1_m

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cd08674: Cdt1_m 
Click on image for an interactive view with Cn3D
The middle winged helix fold of replication licensing factor Cdt1 binds geminin to inhibit binding of the MCM complex to origins of replication and DNA
Cdt1 is a replication licensing factor in eukaryotes that recruits the Minichromosome Maintenance Complex (MCM2-7) to the origin recognition complex (ORC). The Cdt1 protein is divided into three regions based on sequence comparison and biochemical analyses: the N-terminal region (Cdt1_n) binds DNA in a sequence-, strand-, and conformation-independent manner; the middle winged helix fold (Cdt1_m) binds geminin to inhibit both binding of the MCM complex to origins of replication and DNA; and the C-terminal region (Cdt1_c) is essential for Cdt1 activity and directly interacts with the MCM2-7 helicase. Precise duplication of chromosomal DNA is required for genomic stability during replication. Assembly of replication factors to start DNA replication in eukaryotes must occur only once per cell cycle. To form a pre-replicative complex on replication origins in the G phase, ORC first binds origin DNA and triggers the binding of Cdc6 and Cdt1. These two factors recruit a putative replicative helicase and the MCM2-7. The MCM2-7 complex promotes the unwinding of DNA origins, and the binding of additional factors to initiate the DNA replication in S-phase. Cdt1 is present during G1 and early S phase of the cell cycle and degraded during the late S, G2, and M phases. The winged helix fold structure of Cdt1_m is similar to the structures of Cdt1_c and other archaeal homologues of the eukaryotic replication initiator, without apparent sequence similarity.
Statistics
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PSSM-Id: 176571
View PSSM: cd08674
Aligned: 33 rows
Threshold Bit Score: 124.73
Threshold Setting Gi: 262110770
Created: 23-Nov-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Cdt1-GemininCdt1-Geminin
Conserved site includes 19 residues -Click on image for an interactive view with Cn3D
Feature 1:Cdt1-Geminin permissive interaction site
Evidence:
  • Comment:Inhibition of Cdt1 by Geminin is essential to prevent DNA rereplication.
  • Comment:The Cdt1-Geminin complex can exist in two distinct forms, a permissive heterotrimer and an inhibitory heterohexamer. The transition between the heterotrimer and the heterohexamer has been postulated to represent a molecular switch between licensing-competent and licensing-defective states.
  • Structure:2WVR; Human Cdt1-geminin permissive heterotrimer interaction at 4.0A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1         ## ##  #### #                                                                  
2WVR_C       168 PAYQRFHALAQPGLPGLVLPYKYQVLAEMFRSMDTIVGMLHNRSETPTFAKVQRGVQDMMRRRFEERNVGQIKTVYPASY 247 human
EEH54095      93 ATTATAVPAPARWHSSLPLPPKYEVLDDAFVALAQIGPLLRKRGQASTADNVCENVEATTRRRCTLKTLREVEGVLPGTV 172 Micromonas pusi...
CAH65885     113 QLGVGPAPVRSPVKRRAKLPESYEMLCEFFNCFESSTRLLRMKGSKASFPNICASIQHLSERRFTYSHLAQLKYIMPEVI 192 Indian rice
XP_002532371  90 WPEESTGGEKSNKQPEEKIPEGYEILSEFFDCLDSTIRLMRLKGSMPTLTNISPKIECLTDRRFDHGHLAQMKYILPEAI 169 castor bean
XP_001768172  57 SDTPDEVYLSLPKKTPAHLPEKFALLESFYEGVEAAVSLLGIRCQLCTFQAVCATVEATTKRRFLQKHLAQIKHILPEAV 136 Physcomitrella ...
NP_180685     93 SSSPSKRKSSNKNAEKEKLPEKYENLGKFFEALDNSMLLSKLRGSKPTFSNISKQIEHLTERRFCYSHLAQIKHILPEAI 172 thale cress
NP_191031     28 TVKRQIFSSSPKPESVIKLPERFEILEEFFNGLDTAIRLLKLKGSSTTYANICPKIEYLTNRIFSYDHLAQMKHIYPEAI 107 thale cress
CAN63578     135 PQKTSEPLHANFKEKEINLPDKYKTIAEFFDRMNCSLRLLGLRKKPTTFQNICTQVEILTKRKFSYRHLAQIKYILPEVV 214 wine grape
ACN25476      94 NGSVSPSSSQSLFSESIELLDKHKDLLSLFNRMESSIRLLHLRKKMATFNNIATQVEILTKRKLLYSHLAQMKHLFPEAI 173 maize
XP_002305692  50 TPAKTNEPLHAKFRGELEILERHKTIVELFDSMNCSLRLLVMRKKSPTFQNISAQVEVLTQRKFSYGHLARIKYLLPEAI 129 black cottonwood
Feature 1                                                                                        
2WVR_C       248 RFRQERsvptfkdgtRRSDYQLTIEPLLEQeadg-----aapQLTASRLLQRRQIFSQKLVEHVKEHHKAFLasls---- 318 human
EEH54095     173 GLSTRApvhd-ggalDPRRVRVDVEEGAPGarapgagagasrKTGSGWFDDRRKKFRAALLELVGAHHDAFVagldddgg 251 Micromonas pusi...
CAH65885     193 VINKILlrde-ttccMKPDLQVNLLVDAVEgv--------akQKGETGYSALRRIFRQRLVDYFRDHPEGHDipeh---- 259 Indian rice
XP_002532371 170 EITRVLvfde-rsscMKPDLHVSLNVDAIEcd--------vnLKSESKNLHLRKVFRARLEDFYKAHPEGDEipke---- 236 castor bean
XP_001768172 137 DLEYVRlydq-esytRKWELKIALLPMPAEetepirdgkctsKKPKIESVQRRRVFHTRLARFAVTHSEDDDipah---- 211 Physcomitrella ...
NP_180685    173 EIKRVLihde-ttccMKPDLHVTLNADAVEyn--------dkSKSESKKIALRKVFRARLADFVKAHPQGDEvpe----- 238 thale cress
NP_191031    108 ELKRVLkfve-dtccMKPRLHIKLNTDAIVve---------dTICGTKYMELRKVFHSKLVDFRKAHPKDEIpke----- 172 thale cress
CAN63578     215 QXDYILihdv-kslcMKPDMKISLLFDVIEg-----------HQEKSTFMALRQVFAYRLLDFFNXHPEGCDipeai--- 279 wine grape
ACN25476     174 QIKRILvhde-kslcMYADMEITLLMDVVEc----------tSPDQSPSMTICEAFYSKLLSFLDAHHKGADipe----- 237 maize
XP_002305692 130 QMDKILvhdk-kslcMKSDMKIGVLFDVVEg-----------HDEESDFIALRQVFASRLVDYFIKHPEIDYws------ 191 black cottonwood
Feature 1                    #   ######## #                        
2WVR_C       319 --------pamvVPEDQLTRWHPRFNVDe--------vPDIEPAALPQPP 352 human
EEH54095     252 gggggggggvevDDDGVVTSWHPKYDPTtapdppaarvVGAESAVVGVDP 301 Micromonas pusilla CCMP1545
CAH65885     260 ---------elpHPFGPTRSSAPQAIQEdi-------pKTVSALPLSSAT 293 Indian rice
XP_002532371 237 ---------llpEPFNRSKLDLSSGTTKp--------sTSLSIIETPAGT 269 castor bean
XP_001768172 212 ---------pmpERPFNGNSTFKRGFTDmp------vaMTCIPMGINITA 246 Physcomitrella patens subsp. patens
NP_180685    239 ---------eplPEPFNRRKPVENSNVEvk-------rVSSLMEEMASIP 272 thale cress
NP_191031    173 ---------llpEPFNSPQRDSYSGIVSv--------gLGEPKLEVGGFD 205 thale cress
CAN63578     280 --------lpepFNQRTQNIIPKSLPVDss-------iESQPTSEVELLA 314 wine grape
ACN25476     238 ----------aiLPELFNSKPREKLYLEa--------vHNGYAAESPLQG 269 maize
XP_002305692 192 ----------akYGTDLLLDKLWLLYMEpk------mrKYTGACDIPQAI 225 black cottonwood

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