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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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti66 – 661A → T in MGORS4. 1 Publication
Corresponds to variant rs387906918 [ dbSNP | Ensembl ].
VAR_065488
Natural varianti117 – 1171Q → H in MGORS4. 1 Publication
Corresponds to variant rs779871947 [ dbSNP | Ensembl ].
VAR_065489
Natural varianti453 – 4531R → W in MGORS4. 1 Publication
Corresponds to variant rs200672589 [ dbSNP | Ensembl ].
VAR_065490
Natural varianti462 – 4621R → Q in MGORS4. 1 Publication
Corresponds to variant rs387906917 [ dbSNP | Ensembl ].
VAR_065491
Natural varianti468 – 4681E → K in MGORS4. 1 Publication
Corresponds to variant rs200652608 [ dbSNP | Ensembl ].
VAR_065492

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi68 – 703RRL → AAA: Abolishes binding of cyclin A-dependent protein kinases. 1 Publication
Mutagenesisi170 – 1701Y → A: Alters interaction with GMNN. 1 Publication

Keywords - Diseasei

Disease mutation, Dwarfism, Proto-oncogene

Organism-specific databases

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

Polymorphism and mutation databases

BioMutaiCDT1.
DMDMi308153620.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 546546DNA replication factor Cdt1PRO_0000191619Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei29 – 291Phosphothreonine; by MAPK81 Publication
Modified residuei31 – 311PhosphoserineCombined sources
Modified residuei318 – 3181PhosphoserineCombined sources
Modified residuei380 – 3801PhosphoserineCombined sources
Modified residuei394 – 3941PhosphoserineCombined sources

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.
PhosphoSiteiQ9H211.

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 interactions.
DIPiDIP-31089N.
IntActiQ9H211. 25 interactions.
MINTiMINT-1202336.
STRINGi9606.ENSP00000301019.

Structurei

Secondary structure

1
546
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi169 – 1724Combined sources
Helixi174 – 1774Combined sources
Beta strandi180 – 1823Combined sources
Helixi188 – 20922Combined sources
Helixi216 – 22712Combined sources
Helixi233 – 24210Combined sources
Helixi244 – 2463Combined sources
Beta strandi247 – 2515Combined sources
Beta strandi269 – 2735Combined sources
Helixi288 – 31427Combined sources
Turni315 – 3195Combined sources
Helixi325 – 3273Combined sources
Helixi420 – 4234Combined sources
Helixi425 – 43511Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LE8NMR-B413-440[»]
2WVRX-ray3.30C1-546[»]
ProteinModelPortaliQ9H211.
SMRiQ9H211. Positions 167-353, 408-543.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H211.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni150 – 19041Interaction with GMNNAdd
BLAST
Regioni451 – 54696Interaction with LRWD1Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1 – 2323PIP-box K+4 motifAdd
BLAST
Motifi68 – 703Cyclin-binding motif

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti494 – 4941E → K in AAH49205 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti66 – 661A → T in MGORS4. 1 Publication
Corresponds to variant rs387906918 [ dbSNP | Ensembl ].
VAR_065488
Natural varianti117 – 1171Q → H in MGORS4. 1 Publication
Corresponds to variant rs779871947 [ dbSNP | Ensembl ].
VAR_065489
Natural varianti135 – 1351A → V.
Corresponds to variant rs3218725 [ dbSNP | Ensembl ].
VAR_029163
Natural varianti172 – 1721R → C.
Corresponds to variant rs3218727 [ dbSNP | Ensembl ].
VAR_029164
Natural varianti234 – 2341C → R.4 Publications
Corresponds to variant rs507329 [ dbSNP | Ensembl ].
VAR_054504
Natural varianti262 – 2621T → A.3 Publications
Corresponds to variant rs480727 [ dbSNP | Ensembl ].
VAR_054505
Natural varianti453 – 4531R → W in MGORS4. 1 Publication
Corresponds to variant rs200672589 [ dbSNP | Ensembl ].
VAR_065490
Natural varianti456 – 4561E → A.
Corresponds to variant rs3218729 [ dbSNP | Ensembl ].
VAR_029165
Natural varianti462 – 4621R → Q in MGORS4. 1 Publication
Corresponds to variant rs387906917 [ dbSNP | Ensembl ].
VAR_065491
Natural varianti468 – 4681E → K in MGORS4. 1 Publication
Corresponds to variant rs200652608 [ dbSNP | Ensembl ].
VAR_065492
Natural varianti537 – 5371A → V.
Corresponds to variant rs3218721 [ dbSNP | Ensembl ].
VAR_024408

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
EntryMethodResolution (Å)ChainPositionsPDBsum
2LE8NMR-B413-440[»]
2WVRX-ray3.30C1-546[»]
ProteinModelPortaliQ9H211.
SMRiQ9H211. Positions 167-353, 408-543.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ9H211.
PhosphoSiteiQ9H211.

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.
GeneCardsiCDT1.
H-InvDBHIX0013345.
HGNCiHGNC:24576. CDT1.
HPAiHPA017224.
MalaCardsiCDT1.
MIMi605525. gene.
613804. phenotype.
neXtProtiNX_Q9H211.
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: September 7, 2016
This is version 131 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.