Human Gene CDC6 (uc002huj.1) Description and Page Index
  Description: Homo sapiens cell division cycle 6 (CDC6), mRNA.
RefSeq Summary (NM_001254): The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in cell nucleus during cell cyle G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during cell cyle is regulated through its phosphorylation by Cdks. Transcription of this protein was reported to be regulated in response to mitogenic signals through transcriptional control mechanism involving E2F proteins. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. 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 :: SRR1803617.4610.1, AK313620.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000209728.9/ ENSP00000209728.4 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr17:38,444,146-38,459,413 Size: 15,268 Total Exon Count: 12 Strand: +
Coding Region
   Position: hg19 chr17:38,445,673-38,458,253 Size: 12,581 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr17:38,444,146-38,459,413)mRNA (may differ from genome)Protein (560 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Cell division control protein 6 homolog; AltName: Full=CDC6-related protein; AltName: Full=Cdc18-related protein; Short=HsCdc18; AltName: Full=p62(cdc6); Short=HsCDC6;
FUNCTION: Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
SUBUNIT: Interacts with PCNA, ORC1L, cyclin-CDK and HUWE1.
INTERACTION: Q9H211:CDT1; NbExp=3; IntAct=EBI-374862, EBI-456953;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The protein is nuclear in G1 and cytoplasmic in S-phase cells.
DISEASE: Defects in CDC6 are the cause of Meier-Gorlin syndrome type 5 (MGORS5) [MIM:613805]. MGORS5 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 CDC6/cdc18 family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CDC6
CDC HuGE Published Literature: CDC6
Positive Disease Associations: Carcinoma, Hepatocellular|Liver Neoplasms , Pulmonary Disease, Chronic Obstructive
Related Studies:
  1. Carcinoma, Hepatocellular|Liver Neoplasms
    Xing-Dong Xiong , et al. Mutation research 2008 643(1-2):70-4, A novel functional polymorphism in the Cdc6 promoter is associated with the risk for hepatocellular carcinoma., Mutation research 2008 643(1-2):70-4. [PubMed 18640135]
  2. Pulmonary Disease, Chronic Obstructive
    Noriaki Takabatake , et al. Biochemical and biophysical research communications 2009 381(4):554-9, A novel polymorphism in CDC6 is associated with the decline in lung function of ex-smokers in COPD., Biochemical and biophysical research communications 2009 381(4):554-9. [PubMed 19233139]

-  MalaCards Disease Associations
  MalaCards Gene Search: CDC6
Diseases sorted by gene-association score: meier-gorlin syndrome 5* (1379), meier-gorlin syndrome 1* (150), cervical intraepithelial neoplasia (7), warsaw breakage syndrome (4), growth hormone deficiency, isolated, type ia (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D000082 Acetaminophen
  • D001564 Benzo(a)pyrene
  • D004958 Estradiol
  • D005472 Fluorouracil
  • D013749 Tetrachlorodibenzodioxin
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C010914 2,4-diaminotoluene
  • C548651 2-(1'H-indolo-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • C093973 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 13.38 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 52.18 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -79.50210-0.379 Picture PostScript Text
3' UTR -323.131160-0.279 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003593 - AAA+_ATPase
IPR015163 - Cdc6_C_dom
IPR016314 - Cell_div_Cdc6/18
IPR011991 - WHTH_trsnscrt_rep_DNA-bd

Pfam Domains:
PF00004 - ATPase family associated with various cellular activities (AAA)
PF09079 - CDC6, C terminal winged helix domain
PF13191 - AAA ATPase domain
PF13401 - AAA domain

SCOP Domains:
46785 - "Winged helix" DNA-binding domain
52540 - P-loop containing nucleoside triphosphate hydrolases

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray

- X-ray

ModBase Predicted Comparative 3D Structure on Q99741
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene Details  Gene DetailsGene DetailsGene Details
Gene Sorter  Gene SorterGene SorterGene Sorter
  Protein SequenceProtein SequenceProtein SequenceProtein Sequence

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0019900 kinase binding

Biological Process:
GO:0000076 DNA replication checkpoint
GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity
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:0006270 DNA replication initiation
GO:0007049 cell cycle
GO:0007089 traversing start control point of mitotic cell cycle
GO:0008156 negative regulation of DNA replication
GO:0008285 negative regulation of cell proliferation
GO:0030071 regulation of mitotic metaphase/anaphase transition
GO:0032467 positive regulation of cytokinesis
GO:0045737 positive regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0048146 positive regulation of fibroblast proliferation
GO:0051301 cell division
GO:0051984 positive regulation of chromosome segregation
GO:1904117 cellular response to vasopressin
GO:1904385 cellular response to angiotensin

Cellular Component:
GO:0000922 spindle pole
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0051233 spindle midzone
GO:0005730 nucleolus

-  Descriptions from all associated GenBank mRNAs
  LF209326 - JP 2014500723-A/16829: Polycomb-Associated Non-Coding RNAs.
AK313620 - Homo sapiens cDNA, FLJ94190, highly similar to Homo sapiens CDC6 cell division cycle 6 homolog (S. cerevisiae)(CDC6), mRNA.
LF327701 - JP 2014500723-A/135204: Polycomb-Associated Non-Coding RNAs.
U77949 - Human Cdc6-related protein (HsCDC6) mRNA, complete cds.
BC025232 - Homo sapiens cell division cycle 6 homolog (S. cerevisiae), mRNA (cDNA clone MGC:39078 IMAGE:5457941), complete cds.
JD255008 - Sequence 236032 from Patent EP1572962.
AF022109 - Homo sapiens HsCdc18p (HsCdc18) mRNA, complete cds.
JD489537 - Sequence 470561 from Patent EP1572962.
LF213262 - JP 2014500723-A/20765: Polycomb-Associated Non-Coding RNAs.
JD282428 - Sequence 263452 from Patent EP1572962.
AB590418 - Synthetic construct DNA, clone: pFN21AE1344, Homo sapiens CDC6 gene for cell division cycle 6 homolog, without stop codon, in Flexi system.
DQ892840 - Synthetic construct clone IMAGE:100005470; FLH190190.01X; RZPDo839F0775D CDC6 cell division cycle 6 homolog (S. cerevisiae) (CDC6) gene, encodes complete protein.
DQ896087 - Synthetic construct Homo sapiens clone IMAGE:100010547; FLH190186.01L; RZPDo839F0765D CDC6 cell division cycle 6 homolog (S. cerevisiae) (CDC6) gene, encodes complete protein.
LF327703 - JP 2014500723-A/135206: Polycomb-Associated Non-Coding RNAs.
LF379210 - JP 2014500723-A/186713: Polycomb-Associated Non-Coding RNAs.
LF379209 - JP 2014500723-A/186712: Polycomb-Associated Non-Coding RNAs.
LF327705 - JP 2014500723-A/135208: Polycomb-Associated Non-Coding RNAs.
LF327706 - JP 2014500723-A/135209: Polycomb-Associated Non-Coding RNAs.
LF327710 - JP 2014500723-A/135213: Polycomb-Associated Non-Coding RNAs.
LF327711 - JP 2014500723-A/135214: Polycomb-Associated Non-Coding RNAs.
LF379208 - JP 2014500723-A/186711: Polycomb-Associated Non-Coding RNAs.
LF327712 - JP 2014500723-A/135215: Polycomb-Associated Non-Coding RNAs.
JD064196 - Sequence 45220 from Patent EP1572962.
JD239031 - Sequence 220055 from Patent EP1572962.
JD285256 - Sequence 266280 from Patent EP1572962.
JD127406 - Sequence 108430 from Patent EP1572962.
LF327713 - JP 2014500723-A/135216: Polycomb-Associated Non-Coding RNAs.
LF379207 - JP 2014500723-A/186710: Polycomb-Associated Non-Coding RNAs.
JD566895 - Sequence 547919 from Patent EP1572962.
JD291647 - Sequence 272671 from Patent EP1572962.
JD140220 - Sequence 121244 from Patent EP1572962.
JD541215 - Sequence 522239 from Patent EP1572962.
JD259554 - Sequence 240578 from Patent EP1572962.
JD271433 - Sequence 252457 from Patent EP1572962.
JD489752 - Sequence 470776 from Patent EP1572962.
JD342380 - Sequence 323404 from Patent EP1572962.
JD254583 - Sequence 235607 from Patent EP1572962.
JD133873 - Sequence 114897 from Patent EP1572962.
JD432341 - Sequence 413365 from Patent EP1572962.
JD476959 - Sequence 457983 from Patent EP1572962.
JD397972 - Sequence 378996 from Patent EP1572962.
JD509621 - Sequence 490645 from Patent EP1572962.
JD241926 - Sequence 222950 from Patent EP1572962.
JD302919 - Sequence 283943 from Patent EP1572962.
JD361233 - Sequence 342257 from Patent EP1572962.
JD309432 - Sequence 290456 from Patent EP1572962.
MA563278 - JP 2018138019-A/135204: Polycomb-Associated Non-Coding RNAs.
MA563280 - JP 2018138019-A/135206: Polycomb-Associated Non-Coding RNAs.
MA563282 - JP 2018138019-A/135208: Polycomb-Associated Non-Coding RNAs.
MA563283 - JP 2018138019-A/135209: Polycomb-Associated Non-Coding RNAs.
MA563287 - JP 2018138019-A/135213: Polycomb-Associated Non-Coding RNAs.
MA563288 - JP 2018138019-A/135214: Polycomb-Associated Non-Coding RNAs.
MA563289 - JP 2018138019-A/135215: Polycomb-Associated Non-Coding RNAs.
MA563290 - JP 2018138019-A/135216: Polycomb-Associated Non-Coding RNAs.
MA444903 - JP 2018138019-A/16829: Polycomb-Associated Non-Coding RNAs.
MA448839 - JP 2018138019-A/20765: Polycomb-Associated Non-Coding RNAs.
MA614787 - JP 2018138019-A/186713: Polycomb-Associated Non-Coding RNAs.
MA614786 - JP 2018138019-A/186712: Polycomb-Associated Non-Coding RNAs.
MA614785 - JP 2018138019-A/186711: Polycomb-Associated Non-Coding RNAs.
MA614784 - JP 2018138019-A/186710: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle

BioCarta from NCI Cancer Genome Anatomy Project
h_mcmPathway - CDK Regulation of DNA Replication

Reactome (by CSHL, EBI, and GO)

Protein Q99741 (Reactome details) participates in the following event(s):

R-HSA-68688 CDC6 association with ORC:origin complexes mediated by MCM8
R-HSA-69005 Cdc6 protein is phosphorylated by CDK
R-HSA-69015 Cytoplasmic phosphorylated Cdc6 is ubiquitinated by the anaphase-promoting complex
R-HSA-69006 Phosphorylated Cdc6 is exported from the nucleus
R-HSA-68826 Free CDT1 associates with CDC6:ORC:origin complexes
R-HSA-68944 Orc1 is phosphorylated by cyclin A/CDK2
R-HSA-68849 Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC)
R-HSA-68919 Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7
R-HSA-68918 CDK and DDK associate with the Mcm10:pre-replicative complex
R-HSA-68940 Cdt1 is displaced from the pre-replicative complex.
R-HSA-68917 Cdc45 associates with the pre-replicative complex at the origin
R-HSA-68916 DNA Replication Factor A (RPA) associates with the pre-replicative complex at the origin
R-HSA-176318 Loading of claspin onto DNA during replication origin firing
R-HSA-176298 Activation of claspin
R-HSA-68689 CDC6 association with the ORC:origin complex
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex
R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex
R-HSA-68949 Orc1 removal from chromatin
R-HSA-68867 Assembly of the pre-replicative complex
R-HSA-69052 Switching of origins to a post-replicative state
R-HSA-69205 G1/S-Specific Transcription
R-HSA-1538133 G0 and Early G1
R-HSA-69002 DNA Replication Pre-Initiation
R-HSA-69239 Synthesis of DNA
R-HSA-69206 G1/S Transition
R-HSA-453279 Mitotic G1-G1/S phases
R-HSA-68962 Activation of the pre-replicative complex
R-HSA-68874 M/G1 Transition
R-HSA-69242 S Phase
R-HSA-69306 DNA Replication
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-69481 G2/M Checkpoints
R-HSA-69620 Cell Cycle Checkpoints

-  Other Names for This Gene
  Alternate Gene Symbols: CDC18L, CDC6_HUMAN, NM_001254, NP_001245, Q8TB30, Q99741
UCSC ID: uc002huj.1
RefSeq Accession: NM_001254
Protein: Q99741 (aka CDC6_HUMAN)
CCDS: CCDS11365.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_001254.3
exon count: 12CDS single in 3' UTR: no RNA size: 3053
ORF size: 1683CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3563.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.