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Protein

DNA replication factor Cdt1

Gene

CDT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA replication

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-68827. CDT1 association with the CDC6:ORC:origin complex.
R-HSA-68867. Assembly of the pre-replicative complex.
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-68962. Activation of the pre-replicative complex.
R-HSA-69205. G1/S-Specific Transcription.
R-HSA-69298. Association of licensing factors with the pre-replicative complex.
R-HSA-69300. Removal of licensing factors from origins.
SIGNORiQ9H211.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication factor Cdt1
Alternative name(s):
Double parked homolog
Short name:
DUP
Gene namesi
Name:CDT1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:24576. CDT1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Meier-Gorlin syndrome 4 (MGORS4)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613804
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06548866A → T in MGORS4. 1 PublicationCorresponds to variant rs387906918dbSNPEnsembl.1
Natural variantiVAR_065489117Q → H in MGORS4. 1 PublicationCorresponds to variant rs779871947dbSNPEnsembl.1
Natural variantiVAR_065490453R → W in MGORS4. 1 PublicationCorresponds to variant rs200672589dbSNPEnsembl.1
Natural variantiVAR_065491462R → Q in MGORS4. 1 PublicationCorresponds to variant rs387906917dbSNPEnsembl.1
Natural variantiVAR_065492468E → K in MGORS4. 1 PublicationCorresponds to variant rs200652608dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi68 – 70RRL → AAA: Abolishes binding of cyclin A-dependent protein kinases. 1 Publication3
Mutagenesisi170Y → A: Alters interaction with GMNN. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism, Proto-oncogene

Organism-specific databases

DisGeNETi81620.
MalaCardsiCDT1.
MIMi613804. phenotype.
OpenTargetsiENSG00000167513.
Orphaneti2554. Ear-patella-short stature syndrome.
PharmGKBiPA145008572.

Polymorphism and mutation databases

BioMutaiCDT1.
DMDMi308153620.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001916191 – 546DNA replication factor Cdt1Add BLAST546

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei29Phosphothreonine; by MAPK81 Publication1
Modified residuei31PhosphoserineCombined sources1
Modified residuei318PhosphoserineCombined sources1
Modified residuei380PhosphoserineCombined sources1
Modified residuei394PhosphoserineCombined sources1

Post-translational modificationi

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.4 Publications
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.3 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9H211.
MaxQBiQ9H211.
PaxDbiQ9H211.
PeptideAtlasiQ9H211.
PRIDEiQ9H211.

PTM databases

iPTMnetiQ9H211.
PhosphoSitePlusiQ9H211.

Expressioni

Developmental stagei

Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases.1 Publication

Gene expression databases

BgeeiENSG00000167513.
CleanExiHS_CDT1.
ExpressionAtlasiQ9H211. baseline and differential.
GenevisibleiQ9H211. HS.

Organism-specific databases

HPAiHPA017224.

Interactioni

Subunit structurei

Interacts with GMNN; inhibits both binding of the MCM complex to origins of replication and DNA-binding activity. Interacts with PCNA. Interacts with LRWD1 during G1 phase and during mitosis.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDC6Q997413EBI-456953,EBI-374862
GMNNO7549614EBI-456953,EBI-371669
MCM6Q145664EBI-456953,EBI-374900
PCNAP120042EBI-456953,EBI-358311

Protein-protein interaction databases

BioGridi123555. 65 interactors.
DIPiDIP-31089N.
IntActiQ9H211. 25 interactors.
MINTiMINT-1202336.
STRINGi9606.ENSP00000301019.

Structurei

Secondary structure

1546
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi169 – 172Combined sources4
Helixi174 – 177Combined sources4
Beta strandi180 – 182Combined sources3
Helixi188 – 209Combined sources22
Helixi216 – 227Combined sources12
Helixi233 – 242Combined sources10
Helixi244 – 246Combined sources3
Beta strandi247 – 251Combined sources5
Beta strandi269 – 273Combined sources5
Helixi288 – 314Combined sources27
Turni315 – 319Combined sources5
Helixi325 – 327Combined sources3
Helixi420 – 423Combined sources4
Helixi425 – 435Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LE8NMR-B413-440[»]
2WVRX-ray3.30C1-546[»]
ProteinModelPortaliQ9H211.
SMRiQ9H211.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H211.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni150 – 190Interaction with GMNNAdd BLAST41
Regioni451 – 546Interaction with LRWD11 PublicationAdd BLAST96

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1 – 23PIP-box K+4 motifAdd BLAST23
Motifi68 – 70Cyclin-binding motif3

Domaini

The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment 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

Sequence similaritiesi

Belongs to the Cdt1 family.Curated

Phylogenomic databases

eggNOGiKOG4762. Eukaryota.
ENOG410XT37. LUCA.
GeneTreeiENSGT00390000012337.
HOVERGENiHBG050872.
InParanoidiQ9H211.
KOiK10727.
OMAiGMLHNRS.
OrthoDBiEOG091G07YA.
PhylomeDBiQ9H211.
TreeFamiTF101159.

Family and domain databases

InterProiIPR032054. Cdt1_C.
IPR014939. CDT1_Gemini-bd-like.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF08839. CDT1. 1 hit.
PF16679. CDT1_C. 1 hit.
[Graphical view]
SMARTiSM01075. CDT1. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9H211-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQRRVTDFF ARRRPGPPRI APPKLACRTP SPARPALRAP ASATSGSRKR
60 70 80 90 100
ARPPAAPGRD QARPPARRRL RLSVDEVSSP STPEAPDIPA CPSPGQKIKK
110 120 130 140 150
STPAAGQPPH LTSAQDQDTI SELASCLQRA RELGARVRAL KASAQDAGES
160 170 180 190 200
CTPEAEGRPE EPCGEKAPAY QRFHALAQPG LPGLVLPYKY QVLAEMFRSM
210 220 230 240 250
DTIVGMLHNR SETPTFAKVQ RGVQDMMRRR FEECNVGQIK TVYPASYRFR
260 270 280 290 300
QERSVPTFKD GTRRSDYQLT IEPLLEQEAD GAAPQLTASR LLQRRQIFSQ
310 320 330 340 350
KLVEHVKEHH KAFLASLSPA MVVPEDQLTR WHPRFNVDEV PDIEPAALPQ
360 370 380 390 400
PPATEKLTTA QEVLARARNL ISPRMEKALS QLALRSAAPS SPGSPRPALP
410 420 430 440 450
ATPPATPPAA SPSALKGVSQ DLLERIRAKE AQKQLAQMTR CPEQEQRLQR
460 470 480 490 500
LERLPELARV LRSVFVSERK PALSMEVACA RMVGSCCTIM SPGEMEKHLL
510 520 530 540
LLSELLPDWL SLHRIRTDTY VKLDKAADLA HITARLAHQT RAEEGL
Length:546
Mass (Da):60,390
Last modified:October 5, 2010 - v3
Checksum:i8179D0330C135FB7
GO

Sequence cautioni

The sequence AF070552 differs from that shown. Reason: Frameshift at positions 278 and 312.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti494E → K in AAH49205 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06548866A → T in MGORS4. 1 PublicationCorresponds to variant rs387906918dbSNPEnsembl.1
Natural variantiVAR_065489117Q → H in MGORS4. 1 PublicationCorresponds to variant rs779871947dbSNPEnsembl.1
Natural variantiVAR_029163135A → V.Corresponds to variant rs3218725dbSNPEnsembl.1
Natural variantiVAR_029164172R → C.Corresponds to variant rs3218727dbSNPEnsembl.1
Natural variantiVAR_054504234C → R.4 PublicationsCorresponds to variant rs507329dbSNPEnsembl.1
Natural variantiVAR_054505262T → A.3 PublicationsCorresponds to variant rs480727dbSNPEnsembl.1
Natural variantiVAR_065490453R → W in MGORS4. 1 PublicationCorresponds to variant rs200672589dbSNPEnsembl.1
Natural variantiVAR_029165456E → A.Corresponds to variant rs3218729dbSNPEnsembl.1
Natural variantiVAR_065491462R → Q in MGORS4. 1 PublicationCorresponds to variant rs387906917dbSNPEnsembl.1
Natural variantiVAR_065492468E → K in MGORS4. 1 PublicationCorresponds to variant rs200652608dbSNPEnsembl.1
Natural variantiVAR_024408537A → V.Corresponds to variant rs3218721dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF321125 mRNA. Translation: AAG45181.1.
AB053172 mRNA. Translation: BAB61878.1.
AC092384 Genomic DNA. No translation available.
BC000137 mRNA. Translation: AAH00137.2.
BC008676 mRNA. Translation: AAH08676.1.
BC008860 mRNA. Translation: AAH08860.2.
BC009410 mRNA. Translation: AAH09410.1.
BC014202 mRNA. Translation: AAH14202.2.
BC049205 mRNA. Translation: AAH49205.1.
AF070552 mRNA. No translation available.
CCDSiCCDS32510.1.
RefSeqiNP_112190.2. NM_030928.3.
UniGeneiHs.122908.

Genome annotation databases

EnsembliENST00000301019; ENSP00000301019; ENSG00000167513.
GeneIDi81620.
KEGGihsa:81620.
UCSCiuc002flu.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF321125 mRNA. Translation: AAG45181.1.
AB053172 mRNA. Translation: BAB61878.1.
AC092384 Genomic DNA. No translation available.
BC000137 mRNA. Translation: AAH00137.2.
BC008676 mRNA. Translation: AAH08676.1.
BC008860 mRNA. Translation: AAH08860.2.
BC009410 mRNA. Translation: AAH09410.1.
BC014202 mRNA. Translation: AAH14202.2.
BC049205 mRNA. Translation: AAH49205.1.
AF070552 mRNA. No translation available.
CCDSiCCDS32510.1.
RefSeqiNP_112190.2. NM_030928.3.
UniGeneiHs.122908.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LE8NMR-B413-440[»]
2WVRX-ray3.30C1-546[»]
ProteinModelPortaliQ9H211.
SMRiQ9H211.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123555. 65 interactors.
DIPiDIP-31089N.
IntActiQ9H211. 25 interactors.
MINTiMINT-1202336.
STRINGi9606.ENSP00000301019.

PTM databases

iPTMnetiQ9H211.
PhosphoSitePlusiQ9H211.

Polymorphism and mutation databases

BioMutaiCDT1.
DMDMi308153620.

Proteomic databases

EPDiQ9H211.
MaxQBiQ9H211.
PaxDbiQ9H211.
PeptideAtlasiQ9H211.
PRIDEiQ9H211.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301019; ENSP00000301019; ENSG00000167513.
GeneIDi81620.
KEGGihsa:81620.
UCSCiuc002flu.4. human.

Organism-specific databases

CTDi81620.
DisGeNETi81620.
GeneCardsiCDT1.
H-InvDBHIX0013345.
HGNCiHGNC:24576. CDT1.
HPAiHPA017224.
MalaCardsiCDT1.
MIMi605525. gene.
613804. phenotype.
neXtProtiNX_Q9H211.
OpenTargetsiENSG00000167513.
Orphaneti2554. Ear-patella-short stature syndrome.
PharmGKBiPA145008572.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4762. Eukaryota.
ENOG410XT37. LUCA.
GeneTreeiENSGT00390000012337.
HOVERGENiHBG050872.
InParanoidiQ9H211.
KOiK10727.
OMAiGMLHNRS.
OrthoDBiEOG091G07YA.
PhylomeDBiQ9H211.
TreeFamiTF101159.

Enzyme and pathway databases

ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-68827. CDT1 association with the CDC6:ORC:origin complex.
R-HSA-68867. Assembly of the pre-replicative complex.
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-68962. Activation of the pre-replicative complex.
R-HSA-69205. G1/S-Specific Transcription.
R-HSA-69298. Association of licensing factors with the pre-replicative complex.
R-HSA-69300. Removal of licensing factors from origins.
SIGNORiQ9H211.

Miscellaneous databases

EvolutionaryTraceiQ9H211.
GeneWikiiDNA_replication_factor_CDT1.
GenomeRNAii81620.
PROiQ9H211.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167513.
CleanExiHS_CDT1.
ExpressionAtlasiQ9H211. baseline and differential.
GenevisibleiQ9H211. HS.

Family and domain databases

InterProiIPR032054. Cdt1_C.
IPR014939. CDT1_Gemini-bd-like.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF08839. CDT1. 1 hit.
PF16679. CDT1_C. 1 hit.
[Graphical view]
SMARTiSM01075. CDT1. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCDT1_HUMAN
AccessioniPrimary (citable) accession number: Q9H211
Secondary accession number(s): Q86XX9
, Q96CJ5, Q96GK5, Q96H67, Q96HE6, Q9BWM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: October 5, 2010
Last modified: November 2, 2016
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.