Human Gene CDT1 (uc002flu.3) Description and Page Index
Description: Homo sapiens chromatin licensing and DNA replication factor 1 (CDT1), mRNA. RefSeq Summary (NM_030928): The protein encoded by this gene is involved in the formation of the pre-replication complex that is necessary for DNA replication. The encoded protein can bind geminin, which prevents replication and may function to prevent this protein from initiating replication at inappropriate origins. Phosphorylation of this protein by cyclin A-dependent kinases results in degradation of the protein. [provided by RefSeq, Mar 2011]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AB053172.1, SRR1163655.442740.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000301019.9/ ENSP00000301019.4 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END## Transcript (Including UTRs) Position: hg19 chr16:88,870,186-88,875,666 Size: 5,481 Total Exon Count: 10 Strand: + Coding Region Position: hg19 chr16:88,870,240-88,874,686 Size: 4,447 Coding Exon Count: 10
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;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): CDT1 CDC HuGE Published Literature: CDT1
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