CDT1 chromatin licensing and DNA replication factor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDT1provided by HGNC
Official Full Name: chromatin licensing and DNA replication factor 1provided by HGNC
Primary source: HGNC:HGNC:24576
See related: Ensembl:ENSG00000167513 MIM:605525; AllianceGenome:HGNC:24576
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DUP; RIS2
Summary: 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]
Expression: Biased expression in bone marrow (RPKM 13.5), placenta (RPKM 2.5) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q24.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (88803789..88809258)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (94874309..94879778)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (88870197..88875666)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The proliferation of atypical hepatocytes and CDT1 expression in noncancerous tissue are associated with the postoperative recurrence of hepatocellular carcinoma.
Title: The proliferation of atypical hepatocytes and CDT1 expression in noncancerous tissue are associated with the postoperative recurrence of hepatocellular carcinoma.
Long non-coding RNA-PCGEM1 contributes to prostate cancer progression by sponging microRNA miR-129-5p to enhance chromatin licensing and DNA replication factor 1 expression.
Title: Long non-coding RNA-PCGEM1 contributes to prostate cancer progression by sponging microRNA miR-129-5p to enhance chromatin licensing and DNA replication factor 1 expression.
Elevated expression of CDT1 in childhood acute lymphoblastic leukemia promotes cell proliferation, invasion and migration through activation of EMT.
Title: Elevated expression of CDT1 in childhood acute lymphoblastic leukemia promotes cell proliferation, invasion and migration through activation of EMT.
Successful pregnancies in an adult with Meier-Gorlin syndrome harboring biallelic CDT1 variants.
Title: Successful pregnancies in an adult with Meier-Gorlin syndrome harboring biallelic CDT1 variants.
SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors.
Title: SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors.
Cdt1 mutations found in humans afflicted with Meier-Gorlin syndrome result in either Cdt1/minichromosome maintenance protein binding or cyclin/CDK binding defects
Title: Cdt1 variants reveal unanticipated aspects of interactions with cyclin/CDK and MCM important for normal genome replication.
Mitotic kinase Aurora B interacts with and phosphorylates Cdt1. Aurora B-phosphomimetic Cdt1 exhibited attenuated MT binding, and its cellular expression induced defective kinetochore-microtubule attachments with a concomitant delay in mitotic progression.
Title: Cdt1 stabilizes kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism.
The deletion of the entire C-terminal region of Cdt2 decreased its polyubiquitination activity towards Cdt1, resulting in decreased Cdt1 degradation.
Title: A DNA-binding domain in the C-terminal region of Cdt2 enhances the DNA synthesis-coupled CRL4Cdt2 ubiquitin ligase activity for Cdt1.
Results show that both Cdc6 and Cdt1, when expressed in a high level, alone or in combination, were significantly associated with poorer survival in the breast cancer patient cohort. In line with this finding, the expression of Cdc6 and Cdt1 was upregulated in breast cancer cells compared to normal breast epithelial cells. Expression of Cdc6 and Cdt1 was significantly higher in ER negative breast cancer.
Title: The prognostic significance of Cdc6 and Cdt1 in breast cancer.
CDT1, MCM7, and NUDT1 were shown to be up-regulated in hepatocellular carcinoma tissues and provide a more accurate diagnosis than alpha-fetal protein alone.
Title: Five Novel Oncogenic Signatures Could Be Utilized as AFP-Related Diagnostic Biomarkers for Hepatocellular Carcinoma Based on Next-Generation Sequencing.

Submit: New GeneRIF Correction See all GeneRIFs (66)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Meier-Gorlin syndrome 4 MedGen: C3151120 OMIM: 613804 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study of hematological and biochemical traits in a Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	Phosphorylation of Chk1 at position Ser345 is required for HIV-1 Vpr-induced G2/M arrest possibly through signaling of DNA re-replication via Cdt1	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables DNA polymerase binding	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA replication checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication checkpoint signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA replication preinitiation complex assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication preinitiation complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in attachment of mitotic spindle microtubules to kinetochore	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of DNA-templated DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chromatin binding	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated DNA replication initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of DNA-templated DNA replication initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of nuclear cell cycle DNA replication	IEA Inferred from Electronic Annotation more info
involved_in response to sorbitol	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in kinetochore	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: DNA replication factor Cdt1

Names: Double parked, Drosophila, homolog of

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028266.1 RefSeqGene

Range

5012..10481

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_030928.4 → NP_112190.2 DNA replication factor Cdt1

See identical proteins and their annotated locations for NP_112190.2

Status: REVIEWED

Source sequence(s)

AB053172, AC092384, BC000137

Consensus CDS

CCDS32510.1

UniProtKB/Swiss-Prot

Q86XX9, Q96CJ5, Q96GK5, Q96H67, Q96HE6, Q9BWM0, Q9H211

Related

ENSP00000301019.4, ENST00000301019.9

Conserved Domains (2) summary

cd08674
Location:168 → 352

Cdt1_m; 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

cd08767
Location:415 → 537

Cdt1_c; The C-terminal fold of replication licensing factor Cdt1 is essential for Cdt1 activity and directly interacts with MCM2-7 helicase