ID:CDT1_HUMAN DESCRIPTION: RecName: Full=DNA replication factor Cdt1; AltName: Full=Double parked homolog; Short=DUP; FUNCTION: Cooperates with CDC6 to promote the loading of the mini- chromosome maintenance complex onto chromatin to form the pre- replication complex necessary to initiate DNA replication. Binds DNA in a sequence-, strand-, and conformation-independent manner. Potential oncogene. SUBUNIT: Interacts with GMNN; inhibits both binding of the MCM complex to origins of replication and DNA-binding activity. Interacts with PCNA. INTERACTION: Q99741:CDC6; NbExp=3; IntAct=EBI-456953, EBI-374862; O75496:GMNN; NbExp=8; IntAct=EBI-456953, EBI-371669; Q14566:MCM6; NbExp=3; IntAct=EBI-456953, EBI-374900; SUBCELLULAR LOCATION: Nucleus. DEVELOPMENTAL STAGE: Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases. DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination (By similarity). PTM: Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, in response to DNA damage, leading to its degradation. Ubiquitination by the DCX(DTL) complex is necessary to ensure proper cell cycle regulation and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. The interaction with GMNN protects it against ubiquitination. PTM: Phosphorylated by cyclin A-dependent kinases which results in the binding of CDT1 to the F-box protein SKP2 and subsequent degradation. Phosphorylated at Thr-29 by MAPK8/JNK1, which blocks replication licensing in response to stress. Binding to GMNN is not affected by phosphorylation. DISEASE: Defects in CDT1 are the cause of Meier-Gorlin syndrome type 4 (MGORS4) [MIM:613804]. MGORS4 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. SIMILARITY: Belongs to the Cdt1 family. SEQUENCE CAUTION: Sequence=AF070552; Type=Frameshift; Positions=278, 312;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9H211
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000076 DNA replication checkpoint GO:0000082 G1/S transition of mitotic cell cycle GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle GO:0000278 mitotic cell cycle GO:0006260 DNA replication GO:0007049 cell cycle GO:0007059 chromosome segregation GO:0030174 regulation of DNA-dependent DNA replication initiation GO:0031334 positive regulation of protein complex assembly GO:0033044 regulation of chromosome organization GO:0033262 regulation of nuclear cell cycle DNA replication GO:0035563 positive regulation of chromatin binding GO:0045740 positive regulation of DNA replication GO:0051301 cell division GO:0051315 attachment of mitotic spindle microtubules to kinetochore GO:0051383 kinetochore organization GO:0071163 DNA replication preinitiation complex assembly GO:0072708 response to sorbitol GO:1902426 deactivation of mitotic spindle assembly checkpoint GO:1902595 regulation of DNA replication origin binding GO:1905341 negative regulation of protein localization to kinetochore GO:1905342 positive regulation of protein localization to kinetochore GO:2000105 positive regulation of DNA-dependent DNA replication GO:2001178 positive regulation of mediator complex assembly
LF208347 - JP 2014500723-A/15850: Polycomb-Associated Non-Coding RNAs. JD124879 - Sequence 105903 from Patent EP1572962. AB053172 - Homo sapiens hCdt1 mRNA, complete cds. JD129287 - Sequence 110311 from Patent EP1572962. AF321125 - Homo sapiens DNA replication factor (CDT1) mRNA, complete cds. BC000137 - Homo sapiens chromatin licensing and DNA replication factor 1, mRNA (cDNA clone MGC:5282 IMAGE:3048353), complete cds. BC009410 - Homo sapiens chromatin licensing and DNA replication factor 1, mRNA (cDNA clone MGC:10817 IMAGE:3613566), complete cds. JD405442 - Sequence 386466 from Patent EP1572962. BC008860 - Homo sapiens chromatin licensing and DNA replication factor 1, mRNA (cDNA clone IMAGE:4126642), partial cds. BC008676 - Homo sapiens chromatin licensing and DNA replication factor 1, mRNA (cDNA clone IMAGE:3867320), partial cds. BC049205 - Homo sapiens chromatin licensing and DNA replication factor 1, mRNA (cDNA clone IMAGE:4450165), partial cds. LF375147 - JP 2014500723-A/182650: Polycomb-Associated Non-Coding RNAs. AF070552 - Homo sapiens clone 24767 mRNA sequence. BC021126 - Homo sapiens chromatin licensing and DNA replication factor 1, mRNA (cDNA clone IMAGE:4329262), partial cds. LF375149 - JP 2014500723-A/182652: Polycomb-Associated Non-Coding RNAs. BC014202 - Homo sapiens chromatin licensing and DNA replication factor 1, mRNA (cDNA clone IMAGE:4564788), partial cds. LF375150 - JP 2014500723-A/182653: Polycomb-Associated Non-Coding RNAs. LF375151 - JP 2014500723-A/182654: Polycomb-Associated Non-Coding RNAs. JD479607 - Sequence 460631 from Patent EP1572962. JD191719 - Sequence 172743 from Patent EP1572962. JD485027 - Sequence 466051 from Patent EP1572962. JD432812 - Sequence 413836 from Patent EP1572962. JD227400 - Sequence 208424 from Patent EP1572962. DQ578182 - Homo sapiens piRNA piR-46294, complete sequence. JD351471 - Sequence 332495 from Patent EP1572962. JD522433 - Sequence 503457 from Patent EP1572962. JD320268 - Sequence 301292 from Patent EP1572962. JD376320 - Sequence 357344 from Patent EP1572962. JD483024 - Sequence 464048 from Patent EP1572962. JD452152 - Sequence 433176 from Patent EP1572962. JD440917 - Sequence 421941 from Patent EP1572962. JD279319 - Sequence 260343 from Patent EP1572962. JD548733 - Sequence 529757 from Patent EP1572962. JD494935 - Sequence 475959 from Patent EP1572962. JD529140 - Sequence 510164 from Patent EP1572962. JD169227 - Sequence 150251 from Patent EP1572962. JD041255 - Sequence 22279 from Patent EP1572962. JD321013 - Sequence 302037 from Patent EP1572962. JD388132 - Sequence 369156 from Patent EP1572962. JD388133 - Sequence 369157 from Patent EP1572962. JD118304 - Sequence 99328 from Patent EP1572962. JD074483 - Sequence 55507 from Patent EP1572962. JD372227 - Sequence 353251 from Patent EP1572962. JD436514 - Sequence 417538 from Patent EP1572962. JD308866 - Sequence 289890 from Patent EP1572962. JD332203 - Sequence 313227 from Patent EP1572962. JD448160 - Sequence 429184 from Patent EP1572962. JD351534 - Sequence 332558 from Patent EP1572962. JD522710 - Sequence 503734 from Patent EP1572962. JD139765 - Sequence 120789 from Patent EP1572962. JD451467 - Sequence 432491 from Patent EP1572962. JD364477 - Sequence 345501 from Patent EP1572962. JD318863 - Sequence 299887 from Patent EP1572962. JD381550 - Sequence 362574 from Patent EP1572962. JD381551 - Sequence 362575 from Patent EP1572962. JD157910 - Sequence 138934 from Patent EP1572962. JD202183 - Sequence 183207 from Patent EP1572962. JD098511 - Sequence 79535 from Patent EP1572962. JD437192 - Sequence 418216 from Patent EP1572962. JD382083 - Sequence 363107 from Patent EP1572962. MA443924 - JP 2018138019-A/15850: Polycomb-Associated Non-Coding RNAs. MA610724 - JP 2018138019-A/182650: Polycomb-Associated Non-Coding RNAs. MA610726 - JP 2018138019-A/182652: Polycomb-Associated Non-Coding RNAs. MA610727 - JP 2018138019-A/182653: Polycomb-Associated Non-Coding RNAs. MA610728 - JP 2018138019-A/182654: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_mcmPathway - CDK Regulation of DNA Replication
Reactome (by CSHL, EBI, and GO)
Protein Q9H211 (Reactome details) participates in the following event(s):
R-HSA-68826 Free CDT1 associates with CDC6:ORC:origin complexes R-HSA-69299 Cdt1 associates with geminin R-HSA-68940 Cdt1 is displaced from the pre-replicative complex. R-HSA-68712 The geminin component of geminin:Cdt1 complexes is ubiquitinated, releasing Cdt1 R-HSA-68849 Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC) R-HSA-68944 Orc1 is phosphorylated by cyclin A/CDK2 R-HSA-68919 Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7 R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex R-HSA-68962 Activation of the pre-replicative complex R-HSA-539107 Activation of E2F1 target genes at G1/S R-HSA-68867 Assembly of the pre-replicative complex R-HSA-68949 Orc1 removal from chromatin R-HSA-69002 DNA Replication Pre-Initiation R-HSA-69206 G1/S Transition R-HSA-69205 G1/S-Specific Transcription R-HSA-69052 Switching of origins to a post-replicative state R-HSA-68874 M/G1 Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69239 Synthesis of DNA R-HSA-69278 Cell Cycle (Mitotic) R-HSA-69306 DNA Replication R-HSA-69242 S Phase R-HSA-1640170 Cell Cycle
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
