Reviewed, UniProtKB/Swiss-Prot Q9H211 (CDT1_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA replication factor Cdt1
Alternative name(s):
    Double parked homolog
      Short name=DUP

Gene names

Name:

CDT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	546 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Ref.1 Ref.8 Ref.9 UniProtKB Q8R4E9
Subunit structure	Interaction with GMNN inhibits both binding of the MCM complex to origins of replication and DNA-binding activity. Ref.1 Ref.8 UniProtKB Q8R4E9
Subcellular location	Nucleus. Ref.1
Developmental stage	Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases. Ref.1
Post-translational modification	Ubiquitinated, leading to its subsequent degradation. The interaction with GMNN protects it against ubiquitination. Ref.6 Phosphorylated by cyclin A-dependent kinases which results in the binding of CDT1 to the F-box protein SKP2 and subsequent degradation. Binding to GMNN is not affected by phosphorylation. Ref.9 Ref.7 Ref.10
Sequence similarities	Belongs to the Cdt1 family.
Sequence caution	The sequence AF070552 differs from that shown. Reason: Frameshift at positions 278 and 312.

Ontologies

Keywords
Biological process	Cell cycle DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Ligand	DNA-binding
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW DNA replication checkpoint Ref.8 Inferred from direct assay. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleoplasm Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	DNA binding Inferred from sequence or structural similarity. Source: UniProtKB protein binding Ref.1 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC5L	Q99459	1	EBI-456953,EBI-374880
CDC6	Q99741	2	EBI-456953,EBI-374862
GMNN	O75496	5	EBI-456953,EBI-371669
ORC1L	Q13415	1	EBI-456953,EBI-374847
ORC2L	Q13416	1	EBI-456953,EBI-374957

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 546	546	DNA replication factor Cdt1		PRO_0000191619
Regions
	Region	150 – 190	41	Interaction with GMNN
	Motif	68 – 70	3	Cyclin-binding motif Ref.9
Amino acid modifications
	Modified residue	29	1	Phosphothreonine Ref.10
	Modified residue	31	1	Phosphoserine Ref.10
	Modified residue	318	1	Phosphoserine Ref.7
	Modified residue	372	1	Phosphoserine Ref.10
	Modified residue	394	1	Phosphoserine Ref.10
Natural variations
	Natural variant	135	1	A → V: dbSNP rs3218725.		VAR_029163
	Natural variant	172	1	R → C: dbSNP rs3218727.		VAR_029164
	Natural variant	234	1	R → C: dbSNP rs507329. Ref.3		VAR_054504
	Natural variant	262	1	T → A: dbSNP rs480727. Ref.1 Ref.2 Ref.4		VAR_054505
	Natural variant	456	1	E → A: dbSNP rs3218729.		VAR_029165
	Natural variant	537	1	A → V: dbSNP rs3218721.		VAR_024408
Experimental info
	Mutagenesis	68 – 70	3	RRL → AAA: Abolishes binding of cyclin A-dependent protein kinases. Ref.9
	Sequence conflict	494	1	E → K in AAH49205. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9H211-1 [UniParc]. Last modified March 3, 2009. Version 2. Checksum: 7FCDC53716BDEFBC	FASTA	546	60,443
	10 20 30 40 50 60 MEQRRVTDFF ARRRPGPPRI APPKLACRTP SPARPALRAP ASATSGSRKR ARPPAAPGRD 70 80 90 100 110 120 QARPPARRRL RLSVDEVSSP STPEAPDIPA CPSPGQKIKK STPAAGQPPH LTSAQDQDTI 130 140 150 160 170 180 SELASCLQRA RELGARVRAL KASAQDAGES CTPEAEGRPE EPCGEKAPAY QRFHALAQPG 190 200 210 220 230 240 LPGLVLPYKY QVLAEMFRSM DTIVGMLHNR SETPTFAKVQ RGVQDMMRRR FEERNVGQIK 250 260 270 280 290 300 TVYPASYRFR QERSVPTFKD GTRRSDYQLT IEPLLEQEAD GAAPQLTASR LLQRRQIFSQ 310 320 330 340 350 360 KLVEHVKEHH KAFLASLSPA MVVPEDQLTR WHPRFNVDEV PDIEPAALPQ PPATEKLTTA 370 380 390 400 410 420 QEVLARARNL ISPRMEKALS QLALRSAAPS SPGSPRPALP ATPPATPPAA SPSALKGVSQ 430 440 450 460 470 480 DLLERIRAKE AQKQLAQMTR CPEQEQRLQR LERLPELARV LRSVFVSERK PALSMEVACA 490 500 510 520 530 540 RMVGSCCTIM SPGEMEKHLL LLSELLPDWL SLHRIRTDTY VKLDKAADLA HITARLAHQT RAEEGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inhibition of eukaryotic DNA replication by geminin binding to Cdt1." Wohlschlegel J.A., Dwyer B.T., Dhar S.K., Cvetic C., Walter J.C., Dutta A. Science 290:2309-2312(2000) [PubMed: 11125146] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, INTERACTION WITH GMNN, VARIANT ALA-262.
[2]	"The Cdt1 protein is required to license DNA for replication in fission yeast." Nishitani H., Lygerou Z., Nishimoto T., Nurse P. Nature 404:625-628(2000) [PubMed: 10766248] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-262.
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT CYS-234.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-262. Tissue: Brain, Cervix, Eye, Kidney, Liver and Uterus.
[5]	Yu W., Gibbs R.A. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-546. Tissue: Brain.
[6]	"Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis." Ballabeni A., Melixetian M., Zamponi R., Masiero L., Marinoni F., Helin K. EMBO J. 23:3122-3132(2004) [PubMed: 15257290] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH GMNN.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells." Cook J.G., Chasse D.A.D., Nevins J.R. J. Biol. Chem. 279:9625-9633(2004) [PubMed: 14672932] [Abstract] Cited for: FUNCTION, INTERACTION WITH MCM2; GMNN AND CDC6.
[9]	"Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding." Sugimoto N., Tatsumi Y., Tsurumi T., Matsukage A., Kiyono T., Nishitani H., Fujita M. J. Biol. Chem. 279:19691-19697(2004) [PubMed: 14993212] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF 68-ARG--LEU-70, INTERACTION WITH SKP2; GMNN AND CYCLIN A-DEPENDENT KINASES.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-29; SER-31; SER-372 AND SER-394, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00096899.
RefSeq	NP_112190.2.
UniGene	Hs.122908 Hs.28914
3D structure databases
SMR	Q9H211. Positions 166-352.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H211. 10 interactions.
PTM databases
PhosphoSite	Q9H211.
Genome annotation databases
Ensembl	ENSG00000167513. Homo sapiens. [Contig view]
GeneID	81620.
KEGG	hsa:81620.
Organism-specific databases
GeneCards	GC16P087397.
H-InvDB	HIX0013345.
HGNC	HGNC:24576. CDT1.
HPA	HPA017224.
MIM	605525. gene.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9H211.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_383. DNA Replication.
Gene expression databases
Bgee	Q9H211.
CleanEx	HS_CDT1.
GermOnline	ENSG00000167513. Homo sapiens.
Family and domain databases
InterPro	IPR014939. DNA_replication_fac_CDT1-like. [Graphical view]
Pfam	PF08839. CDT1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

CDT1_HUMAN

Accession

Primary (citable) accession number: Q9H211
Secondary accession number(s): Q86XX9 , Q96CJ5, Q96GK5, Q96H67, Q96HE6, Q9BWM0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	March 3, 2009
Last modified:	June 16, 2009
This is version 58 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)