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Protein

DNA replication factor Cdt1

Gene

CDT1

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

Functioni

Required for both DNA replication and mitosis (PubMed:11125146, PubMed:22581055, PubMed:21856198, PubMed:14993212, PubMed:26842564). DNA replication licensing factor, required for pre-replication complex assembly. Cooperates with CDC6 and the origin recognition complex (ORC) during G1 phase of the cell cycle to promote the loading of the mini-chromosome maintenance (MCM) complex onto DNA to generate pre-replication complexes (pre-RC)(PubMed:14672932). Required also for mitosis by promoting stable kinetochore-microtubule attachments (PubMed:22581055). Potential oncogene (By similarity).By similarity6 Publications

GO - Molecular functioni

  • chromatin binding Source: CAFA
  • DNA binding Source: UniProtKB

GO - Biological processi

  • attachment of mitotic spindle microtubules to kinetochore Source: UniProtKB
  • cell division Source: CAFA
  • chromosome segregation Source: UniProtKB
  • deactivation of mitotic spindle assembly checkpoint Source: CAFA
  • DNA replication checkpoint Source: UniProtKB
  • DNA replication preinitiation complex assembly Source: CAFA
  • G1/S transition of mitotic cell cycle Source: Reactome
  • kinetochore organization Source: CAFA
  • mitotic cell cycle Source: UniProtKB
  • negative regulation of protein localization to kinetochore Source: CAFA
  • positive regulation of chromatin binding Source: CAFA
  • positive regulation of DNA-dependent DNA replication Source: CAFA
  • positive regulation of DNA replication Source: UniProtKB
  • positive regulation of mediator complex assembly Source: CAFA
  • positive regulation of protein complex assembly Source: CAFA
  • positive regulation of protein localization to kinetochore Source: CAFA
  • regulation of chromosome organization Source: CAFA
  • regulation of DNA-dependent DNA replication initiation Source: UniProtKB
  • regulation of DNA replication origin binding Source: CAFA
  • regulation of nuclear cell cycle DNA replication Source: Ensembl
  • regulation of transcription involved in G1/S transition of mitotic cell cycle Source: Reactome
  • response to sorbitol Source: CAFA

Keywordsi

Biological processCell cycle, Cell division, DNA replication, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-539107 Activation of E2F1 target genes at G1/S
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
SIGNORiQ9H211

Protein family/group databases

MoonProtiQ9H211

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

EuPathDBiHostDB:ENSG00000167513.8
HGNCiHGNC:24576 CDT1
MIMi605525 gene
neXtProtiNX_Q9H211

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Kinetochore, 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 dbSNP:rs387906918EnsemblClinVar.1
Natural variantiVAR_065489117Q → H in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs779871947Ensembl.1
Natural variantiVAR_065490453R → W in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs200672589EnsemblClinVar.1
Natural variantiVAR_065491462R → Q in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs387906917EnsemblClinVar.1
Natural variantiVAR_065492468E → K in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs200652608EnsemblClinVar.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 residuei93Phosphoserine; by MAPK81 Publication1
Modified residuei318Phosphoserine; by MAPK8Combined sources1 Publication1
Modified residuei380PhosphoserineCombined sources1
Modified residuei394PhosphoserineCombined sources1

Post-translational modificationi

Two independent E3 ubiquitin ligase complexes, SCF(SKP2) and the DCX(DTL) complex, mediated CDT1 degradation in S phase. Ubiquitinated by the DCX(DTL) 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. Phosphorylation at Thr-29 by CDK2 targets CDT1 for ubiquitination by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation (PubMed:14993212). The interaction with GMNN protects it against ubiquitination. Deubiquitinated by USP37 (PubMed:27296872).6 Publications
Phosphorylation by cyclin A-dependent kinases at Thr-29 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation (PubMed:14993212). Phosphorylated at Thr-29 by MAPK8/JNK1, which blocks replication licensing in response to stress (PubMed:21856198). Binding to GMNN is not affected by phosphorylation.By similarity3 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.2 Publications

Inductioni

Induced by E2F transcription factors (PubMed:14990995).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 binding of the MCM complex to origins of replication (PubMed:11125146, PubMed:14672932, PubMed:14993212, PubMed:15257290). Interacts with CDC6; are mutually dependent on one another for loading MCM complexes onto chromatin (PubMed:14672932). Interacts with PCNA (PubMed:16861906). Interacts with LRWD1 during G1 phase and during mitosis (PubMed:22645314). Interacts with NDC80 subunit of the NDC80 complex; leading to kinetochore localization (PubMed:22581055). Interacts with GRWD1; origin binding of GRWD1 is dependent on CDT1 (PubMed:25990725). Interacts with KAT7 (PubMed:18832067). Interacts with ubiquitin-binding protein FAF1; the interaction is likely to promote CDT1 degradation (PubMed:26842564).11 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi123555, 66 interactors
CORUMiQ9H211
DIPiDIP-31089N
IntActiQ9H211, 28 interactors
MINTiQ9H211
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

InterProiView protein in InterPro
IPR032054 Cdt1_C
IPR014939 CDT1_Gemini-bd-like
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF08839 CDT1, 1 hit
PF16679 CDT1_C, 1 hit
SMARTiView protein in SMART
SM01075 CDT1, 1 hit
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 dbSNP:rs387906918EnsemblClinVar.1
Natural variantiVAR_065489117Q → H in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs779871947Ensembl.1
Natural variantiVAR_029163135A → V. Corresponds to variant dbSNP:rs3218725EnsemblClinVar.1
Natural variantiVAR_029164172R → C. Corresponds to variant dbSNP:rs3218727EnsemblClinVar.1
Natural variantiVAR_054504234C → R4 PublicationsCorresponds to variant dbSNP:rs507329EnsemblClinVar.1
Natural variantiVAR_054505262T → A3 PublicationsCorresponds to variant dbSNP:rs480727EnsemblClinVar.1
Natural variantiVAR_065490453R → W in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs200672589EnsemblClinVar.1
Natural variantiVAR_029165456E → A. Corresponds to variant dbSNP:rs3218729EnsemblClinVar.1
Natural variantiVAR_065491462R → Q in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs387906917EnsemblClinVar.1
Natural variantiVAR_065492468E → K in MGORS4. 1 PublicationCorresponds to variant dbSNP:rs200652608EnsemblClinVar.1
Natural variantiVAR_024408537A → V. Corresponds to variant dbSNP:rs3218721EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiCDT1_HUMAN
AccessioniPrimary (citable) accession number: Q9H211
Secondary accession number(s): Q86XX9
, Q96CJ5, Q96GK5, Q96H67, Q96HE6, Q9BWM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: October 5, 2010
Last modified: May 23, 2018
This is version 144 of the entry and version 3 of the sequence. See 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

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