CDT1_HUMAN
ID CDT1_HUMAN Reviewed; 546 AA.
AC Q9H211; Q86XX9; Q96CJ5; Q96GK5; Q96H67; Q96HE6; Q9BWM0;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=DNA replication factor Cdt1;
DE AltName: Full=Double parked homolog;
DE Short=DUP;
GN Name=CDT1 {ECO:0000312|EMBL:AAG45181.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAG45181.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR
RP LOCATION, INTERACTION WITH GMNN, AND VARIANTS ARG-234 AND ALA-262.
RX PubMed=11125146; DOI=10.1126/science.290.5500.2309;
RA Wohlschlegel J.A., Dwyer B.T., Dhar S.K., Cvetic C., Walter J.C., Dutta A.;
RT "Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.";
RL Science 290:2309-2312(2000).
RN [2] {ECO:0000312|EMBL:BAB61878.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-234 AND ALA-262.
RX PubMed=10766248; DOI=10.1038/35007110;
RA Nishitani H., Lygerou Z., Nishimoto T., Nurse P.;
RT "The Cdt1 protein is required to license DNA for replication in fission
RT yeast.";
RL Nature 404:625-628(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4] {ECO:0000312|EMBL:AAH14202.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-234 AND ALA-262.
RC TISSUE=Brain {ECO:0000312|EMBL:AAH08860.2},
RC Cervix {ECO:0000312|EMBL:AAH00137.2}, Eye {ECO:0000312|EMBL:AAH08676.1},
RC Kidney {ECO:0000312|EMBL:AAH14202.2}, Liver {ECO:0000312|EMBL:AAH49205.1},
RC and Uterus {ECO:0000312|EMBL:AAH09410.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-546, AND VARIANT ARG-234.
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INDUCTION.
RX PubMed=14990995; DOI=10.1038/sj.onc.1207488;
RA Yoshida K., Inoue I.;
RT "Regulation of Geminin and Cdt1 expression by E2F transcription factors.";
RL Oncogene 23:3802-3812(2004).
RN [7]
RP INTERACTION WITH KAT7.
RX PubMed=18832067; DOI=10.1101/gad.1674108;
RA Miotto B., Struhl K.;
RT "HBO1 histone acetylase is a coactivator of the replication licensing
RT factor Cdt1.";
RL Genes Dev. 22:2633-2638(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP PHOSPHORYLATION AT THR-29; SER-93 AND SER-318 BY MAPK8/JNK1, AND FUNCTION.
RX PubMed=21856198; DOI=10.1016/j.molcel.2011.06.021;
RA Miotto B., Struhl K.;
RT "JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone
RT acetylase and blocks replication licensing in response to stress.";
RL Mol. Cell 44:62-71(2011).
RN [11]
RP UBIQUITINATION, AND INTERACTION WITH GMNN.
RX PubMed=15257290; DOI=10.1038/sj.emboj.7600314;
RA Ballabeni A., Melixetian M., Zamponi R., Masiero L., Marinoni F., Helin K.;
RT "Human geminin promotes pre-RC formation and DNA replication by stabilizing
RT CDT1 in mitosis.";
RL EMBO J. 23:3122-3132(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH MCM2; GMNN AND CDC6.
RX PubMed=14672932; DOI=10.1074/jbc.m311933200;
RA Cook J.G., Chasse D.A.D., Nevins J.R.;
RT "The regulated association of Cdt1 with minichromosome maintenance proteins
RT and Cdc6 in mammalian cells.";
RL J. Biol. Chem. 279:9625-9633(2004).
RN [13]
RP FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF 68-ARG--LEU-70, AND INTERACTION
RP WITH SKP2; GMNN AND CYCLIN A-DEPENDENT KINASES.
RX PubMed=14993212; DOI=10.1074/jbc.m313175200;
RA Sugimoto N., Tatsumi Y., Tsurumi T., Matsukage A., Kiyono T., Nishitani H.,
RA Fujita M.;
RT "Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates
RT its function without affecting geminin binding.";
RL J. Biol. Chem. 279:19691-19697(2004).
RN [14]
RP UBIQUITINATION, AND INTERACTION WITH PCNA.
RX PubMed=16861906; DOI=10.4161/cc.5.15.3149;
RA Higa L.A., Banks D., Wu M., Kobayashi R., Sun H., Zhang H.;
RT "L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates
RT CDT1 proteolysis in response to DNA damage.";
RL Cell Cycle 5:1675-1680(2006).
RN [15]
RP UBIQUITINATION.
RX PubMed=17085480; DOI=10.1101/gad.1482106;
RA Sansam C.L., Shepard J.L., Lai K., Ianari A., Danielian P.S., Amsterdam A.,
RA Hopkins N., Lees J.A.;
RT "DTL/CDT2 is essential for both CDT1 regulation and the early G2/M
RT checkpoint.";
RL Genes Dev. 20:3117-3129(2006).
RN [16]
RP UBIQUITINATION.
RX PubMed=16949367; DOI=10.1016/j.molcel.2006.08.010;
RA Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.;
RT "A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is
RT required for S phase destruction of the replication factor Cdt1.";
RL Mol. Cell 23:709-721(2006).
RN [17]
RP INTERACTION WITH GMNN, AND MUTAGENESIS OF TYR-170.
RX PubMed=21543332; DOI=10.1074/jbc.m110.207688;
RA Pefani D.E., Dimaki M., Spella M., Karantzelis N., Mitsiki E., Kyrousi C.,
RA Symeonidou I.E., Perrakis A., Taraviras S., Lygerou Z.;
RT "Idas, a novel phylogenetically conserved geminin-related protein, binds to
RT geminin and is required for cell cycle progression.";
RL J. Biol. Chem. 286:23234-23246(2011).
RN [18]
RP INTERACTION WITH LRWD1, AND PHOSPHORYLATION DURING MITOSIS.
RX PubMed=22645314; DOI=10.1128/mcb.00362-12;
RA Shen Z., Chakraborty A., Jain A., Giri S., Ha T., Prasanth K.V.,
RA Prasanth S.G.;
RT "Dynamic association of ORCA with prereplicative complex components
RT regulates DNA replication initiation.";
RL Mol. Cell. Biol. 32:3107-3120(2012).
RN [19]
RP FUNCTION IN MITOSIS, SUBCELLULAR LOCATION, AND INTERACTION WITH NDC80.
RX PubMed=22581055; DOI=10.1038/ncb2489;
RA Varma D., Chandrasekaran S., Sundin L.J., Reidy K.T., Wan X., Chasse D.A.,
RA Nevis K.R., DeLuca J.G., Salmon E.D., Cook J.G.;
RT "Recruitment of the human Cdt1 replication licensing protein by the loop
RT domain of Hec1 is required for stable kinetochore-microtubule attachment.";
RL Nat. Cell Biol. 14:593-603(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31 AND SER-380, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP INTERACTION WITH GRWD1.
RX PubMed=25990725; DOI=10.1093/nar/gkv509;
RA Sugimoto N., Maehara K., Yoshida K., Yasukouchi S., Osano S., Watanabe S.,
RA Aizawa M., Yugawa T., Kiyono T., Kurumizaka H., Ohkawa Y., Fujita M.;
RT "Cdt1-binding protein GRWD1 is a novel histone-binding protein that
RT facilitates MCM loading through its influence on chromatin architecture.";
RL Nucleic Acids Res. 43:5898-5911(2015).
RN [22]
RP DEUBIQUITINATION BY USP37, AND DEVELOPMENTAL STAGE.
RX PubMed=27296872; DOI=10.1016/j.molonc.2016.05.008;
RA Hernandez-Perez S., Cabrera E., Amoedo H., Rodriguez-Acebes S.,
RA Koundrioukoff S., Debatisse M., Mendez J., Freire R.;
RT "USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.";
RL Mol. Oncol. 10:1196-1206(2016).
RN [23]
RP FUNCTION, INTERACTION WITH FAF1, AND SUBCELLULAR LOCATION.
RX PubMed=26842564; DOI=10.1038/ncomms10612;
RA Franz A., Pirson P.A., Pilger D., Halder S., Achuthankutty D., Kashkar H.,
RA Ramadan K., Hoppe T.;
RT "Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard
RT DNA replication fork progression.";
RL Nat. Commun. 7:10612-10612(2016).
RN [24]
RP VARIANTS MGORS4 THR-66; HIS-117; TRP-453 AND GLN-462.
RX PubMed=21358632; DOI=10.1038/ng.775;
RA Bicknell L.S., Bongers E.M., Leitch A., Brown S., Schoots J., Harley M.E.,
RA Aftimos S., Al-Aama J.Y., Bober M., Brown P.A., van Bokhoven H., Dean J.,
RA Edrees A.Y., Feingold M., Fryer A., Hoefsloot L.H., Kau N., Knoers N.V.,
RA Mackenzie J., Opitz J.M., Sarda P., Ross A., Temple I.K., Toutain A.,
RA Wise C.A., Wright M., Jackson A.P.;
RT "Mutations in the pre-replication complex cause Meier-Gorlin syndrome.";
RL Nat. Genet. 43:356-359(2011).
RN [25]
RP VARIANT MGORS4 LYS-468.
RX PubMed=21358631; DOI=10.1038/ng.777;
RA Guernsey D.L., Matsuoka M., Jiang H., Evans S., Macgillivray C.,
RA Nightingale M., Perry S., Ferguson M., LeBlanc M., Paquette J., Patry L.,
RA Rideout A.L., Thomas A., Orr A., McMaster C.R., Michaud J.L., Deal C.,
RA Langlois S., Superneau D.W., Parkash S., Ludman M., Skidmore D.L.,
RA Samuels M.E.;
RT "Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin
RT syndrome.";
RL Nat. Genet. 43:360-364(2011).
CC -!- FUNCTION: Required for both DNA replication and mitosis
CC (PubMed:11125146, PubMed:22581055, PubMed:21856198, PubMed:14993212,
CC PubMed:26842564). DNA replication licensing factor, required for pre-
CC replication complex assembly. Cooperates with CDC6 and the origin
CC recognition complex (ORC) during G1 phase of the cell cycle to promote
CC the loading of the mini-chromosome maintenance (MCM) complex onto DNA
CC to generate pre-replication complexes (pre-RC)(PubMed:14672932).
CC Required also for mitosis by promoting stable kinetochore-microtubule
CC attachments (PubMed:22581055). Potential oncogene (By similarity).
CC {ECO:0000250|UniProtKB:Q8R4E9, ECO:0000269|PubMed:11125146,
CC ECO:0000269|PubMed:14672932, ECO:0000269|PubMed:14993212,
CC ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22581055,
CC ECO:0000269|PubMed:26842564}.
CC -!- SUBUNIT: Interacts with GMNN; the interaction inhibits binding of the
CC MCM complex to origins of replication (PubMed:11125146,
CC PubMed:14672932, PubMed:14993212, PubMed:15257290). Interacts with MCM6
CC (By similarity). Interacts with CDC6; are mutually dependent on one
CC another for loading MCM complexes onto chromatin (PubMed:14672932).
CC Interacts with PCNA (PubMed:16861906). Interacts with LRWD1 during G1
CC phase and during mitosis (PubMed:22645314). Interacts with NDC80
CC subunit of the NDC80 complex; leading to kinetochore localization
CC (PubMed:22581055). Interacts with GRWD1; origin binding of GRWD1 is
CC dependent on CDT1 (PubMed:25990725). Interacts with KAT7
CC (PubMed:18832067). Interacts with ubiquitin-binding protein FAF1; the
CC interaction is likely to promote CDT1 degradation (PubMed:26842564).
CC {ECO:0000250|UniProtKB:Q8R4E9, ECO:0000269|PubMed:11125146,
CC ECO:0000269|PubMed:14672932, ECO:0000269|PubMed:14993212,
CC ECO:0000269|PubMed:15257290, ECO:0000269|PubMed:16861906,
CC ECO:0000269|PubMed:18832067, ECO:0000269|PubMed:21543332,
CC ECO:0000269|PubMed:22581055, ECO:0000269|PubMed:22645314,
CC ECO:0000269|PubMed:25990725, ECO:0000269|PubMed:26842564}.
CC -!- INTERACTION:
CC Q9H211; Q99741: CDC6; NbExp=3; IntAct=EBI-456953, EBI-374862;
CC Q9H211; O75496: GMNN; NbExp=21; IntAct=EBI-456953, EBI-371669;
CC Q9H211; Q14566: MCM6; NbExp=4; IntAct=EBI-456953, EBI-374900;
CC Q9H211; O14777: NDC80; NbExp=7; IntAct=EBI-456953, EBI-715849;
CC Q9H211; P12004: PCNA; NbExp=2; IntAct=EBI-456953, EBI-358311;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11125146,
CC ECO:0000269|PubMed:26842564}. Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:22581055}. Note=Transiently localizes to
CC kinetochores during prometaphase and metaphase.
CC {ECO:0000269|PubMed:22581055}.
CC -!- DEVELOPMENTAL STAGE: Present during G1 and early S phase of the cell
CC cycle. Degraded during the late S, G2, and M phases.
CC {ECO:0000269|PubMed:11125146, ECO:0000269|PubMed:27296872}.
CC -!- INDUCTION: Induced by E2F transcription factors (PubMed:14990995).
CC {ECO:0000269|PubMed:14990995}.
CC -!- DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA
CC and the recruitment of the DCX(DTL) complex: while the PIP-box
CC interacts with PCNA, the presence of the K+4 submotif, recruits the
CC DCX(DTL) complex, leading to its ubiquitination.
CC {ECO:0000250|UniProtKB:Q9I9A7}.
CC -!- PTM: Two independent E3 ubiquitin ligase complexes, SCF(SKP2) and the
CC DCX(DTL) complex, mediated CDT1 degradation in S phase. Ubiquitinated
CC by the DCX(DTL) complex, in response to DNA damage, leading to its
CC degradation. Ubiquitination by the DCX(DTL) complex is necessary to
CC ensure proper cell cycle regulation and is PCNA-dependent: interacts
CC with PCNA via its PIP-box, while the presence of the containing the
CC 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to
CC its degradation. Phosphorylation at Thr-29 by CDK2 targets CDT1 for
CC ubiquitination by SCF(SKP2) E3 ubiquitin ligase and subsequent
CC degradation (PubMed:14993212). The interaction with GMNN protects it
CC against ubiquitination. Deubiquitinated by USP37 (PubMed:27296872).
CC {ECO:0000269|PubMed:14993212, ECO:0000269|PubMed:15257290,
CC ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367,
CC ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:27296872}.
CC -!- PTM: Phosphorylation by cyclin A-dependent kinases at Thr-29 targets
CC CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent
CC degradation (PubMed:14993212). Phosphorylated at Thr-29 by MAPK8/JNK1,
CC which blocks replication licensing in response to stress
CC (PubMed:21856198). Binding to GMNN is not affected by phosphorylation.
CC {ECO:0000250|UniProtKB:Q8R4E9, ECO:0000269|PubMed:14993212,
CC ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22645314}.
CC -!- DISEASE: Meier-Gorlin syndrome 4 (MGORS4) [MIM:613804]: A syndrome
CC characterized by bilateral microtia, aplasia/hypoplasia of the
CC patellae, and severe intrauterine and postnatal growth retardation with
CC short stature and poor weight gain. Additional clinical findings
CC include anomalies of cranial sutures, microcephaly, apparently low-set
CC and simple ears, microstomia, full lips, highly arched or cleft palate,
CC micrognathia, genitourinary tract anomalies, and various skeletal
CC anomalies. While almost all cases have primordial dwarfism with
CC substantial prenatal and postnatal growth retardation, not all cases
CC have microcephaly, and microtia and absent/hypoplastic patella are
CC absent in some. Despite the presence of microcephaly, intellect is
CC usually normal. {ECO:0000269|PubMed:21358631,
CC ECO:0000269|PubMed:21358632}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Cdt1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AF070552; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDT1ID44175ch16q24.html";
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DR EMBL; AF321125; AAG45181.1; -; mRNA.
DR EMBL; AB053172; BAB61878.1; -; mRNA.
DR EMBL; AC092384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000137; AAH00137.2; -; mRNA.
DR EMBL; BC008676; AAH08676.1; -; mRNA.
DR EMBL; BC008860; AAH08860.2; -; mRNA.
DR EMBL; BC009410; AAH09410.1; -; mRNA.
DR EMBL; BC014202; AAH14202.2; -; mRNA.
DR EMBL; BC049205; AAH49205.1; -; mRNA.
DR EMBL; AF070552; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS32510.1; -.
DR RefSeq; NP_112190.2; NM_030928.3.
DR PDB; 2LE8; NMR; -; B=413-440.
DR PDB; 2WVR; X-ray; 3.30 A; C=1-546.
DR PDB; 6QCG; X-ray; 3.40 A; G/H/I/J/K/L=1-14.
DR PDBsum; 2LE8; -.
DR PDBsum; 2WVR; -.
DR PDBsum; 6QCG; -.
DR AlphaFoldDB; Q9H211; -.
DR BMRB; Q9H211; -.
DR SASBDB; Q9H211; -.
DR SMR; Q9H211; -.
DR BioGRID; 123555; 74.
DR ComplexPortal; CPX-659; CDT1-Geminin complex.
DR CORUM; Q9H211; -.
DR DIP; DIP-31089N; -.
DR IntAct; Q9H211; 31.
DR MINT; Q9H211; -.
DR STRING; 9606.ENSP00000301019; -.
DR MoonProt; Q9H211; -.
DR iPTMnet; Q9H211; -.
DR PhosphoSitePlus; Q9H211; -.
DR BioMuta; CDT1; -.
DR DMDM; 308153620; -.
DR EPD; Q9H211; -.
DR jPOST; Q9H211; -.
DR MassIVE; Q9H211; -.
DR MaxQB; Q9H211; -.
DR PaxDb; Q9H211; -.
DR PeptideAtlas; Q9H211; -.
DR PRIDE; Q9H211; -.
DR ProteomicsDB; 80471; -.
DR Antibodypedia; 1905; 220 antibodies from 36 providers.
DR DNASU; 81620; -.
DR Ensembl; ENST00000301019.9; ENSP00000301019.4; ENSG00000167513.9.
DR GeneID; 81620; -.
DR KEGG; hsa:81620; -.
DR MANE-Select; ENST00000301019.9; ENSP00000301019.4; NM_030928.4; NP_112190.2.
DR UCSC; uc002flu.4; human.
DR CTD; 81620; -.
DR DisGeNET; 81620; -.
DR GeneCards; CDT1; -.
DR HGNC; HGNC:24576; CDT1.
DR HPA; ENSG00000167513; Tissue enriched (bone).
DR MalaCards; CDT1; -.
DR MIM; 605525; gene.
DR MIM; 613804; phenotype.
DR neXtProt; NX_Q9H211; -.
DR OpenTargets; ENSG00000167513; -.
DR Orphanet; 2554; Ear-patella-short stature syndrome.
DR PharmGKB; PA145008572; -.
DR VEuPathDB; HostDB:ENSG00000167513; -.
DR eggNOG; KOG4762; Eukaryota.
DR GeneTree; ENSGT00390000012337; -.
DR HOGENOM; CLU_023373_1_0_1; -.
DR InParanoid; Q9H211; -.
DR OMA; DRVKEHH; -.
DR OrthoDB; 648388at2759; -.
DR PhylomeDB; Q9H211; -.
DR TreeFam; TF101159; -.
DR PathwayCommons; Q9H211; -.
DR Reactome; R-HSA-68867; Assembly of the pre-replicative complex.
DR Reactome; R-HSA-68949; Orc1 removal from chromatin.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR Reactome; R-HSA-69052; Switching of origins to a post-replicative state.
DR Reactome; R-HSA-69205; G1/S-Specific Transcription.
DR SignaLink; Q9H211; -.
DR SIGNOR; Q9H211; -.
DR BioGRID-ORCS; 81620; 786 hits in 1089 CRISPR screens.
DR ChiTaRS; CDT1; human.
DR EvolutionaryTrace; Q9H211; -.
DR GeneWiki; DNA_replication_factor_CDT1; -.
DR GenomeRNAi; 81620; -.
DR Pharos; Q9H211; Tbio.
DR PRO; PR:Q9H211; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9H211; protein.
DR Bgee; ENSG00000167513; Expressed in mucosa of paranasal sinus and 133 other tissues.
DR ExpressionAtlas; Q9H211; baseline and differential.
DR Genevisible; Q9H211; HS.
DR GO; GO:0000776; C:kinetochore; IDA:CAFA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:CAFA.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0070182; F:DNA polymerase binding; IBA:GO_Central.
DR GO; GO:0051315; P:attachment of mitotic spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IMP:CAFA.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:1902426; P:deactivation of mitotic spindle assembly checkpoint; IMP:CAFA.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0071163; P:DNA replication preinitiation complex assembly; IDA:CAFA.
DR GO; GO:0051383; P:kinetochore organization; IMP:CAFA.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:ComplexPortal.
DR GO; GO:2000104; P:negative regulation of DNA-templated DNA replication; IDA:ComplexPortal.
DR GO; GO:1905341; P:negative regulation of protein localization to kinetochore; IMP:CAFA.
DR GO; GO:0035563; P:positive regulation of chromatin binding; IDA:CAFA.
DR GO; GO:0045740; P:positive regulation of DNA replication; IMP:UniProtKB.
DR GO; GO:2000105; P:positive regulation of DNA-templated DNA replication; IDA:CAFA.
DR GO; GO:1905342; P:positive regulation of protein localization to kinetochore; IMP:CAFA.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IMP:CAFA.
DR GO; GO:0033044; P:regulation of chromosome organization; IMP:CAFA.
DR GO; GO:1902595; P:regulation of DNA replication origin binding; IDA:CAFA.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IDA:UniProtKB.
DR GO; GO:0033262; P:regulation of nuclear cell cycle DNA replication; IEA:Ensembl.
DR GO; GO:0072708; P:response to sorbitol; IDA:CAFA.
DR CDD; cd08767; Cdt1_c; 1.
DR CDD; cd08674; Cdt1_m; 1.
DR DisProt; DP01193; -.
DR Gene3D; 1.10.10.1420; -; 1.
DR InterPro; IPR045173; Cdt1.
DR InterPro; IPR032054; Cdt1_C.
DR InterPro; IPR038090; Cdt1_C_WH_dom_sf.
DR InterPro; IPR014939; CDT1_Gemini-bd-like.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR28637; PTHR28637; 1.
DR Pfam; PF08839; CDT1; 1.
DR Pfam; PF16679; CDT1_C; 1.
DR SMART; SM01075; CDT1; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Centromere; Chromosome;
KW Disease variant; DNA replication; Dwarfism; Kinetochore; Mitosis; Nucleus;
KW Phosphoprotein; Proto-oncogene; Reference proteome; Ubl conjugation.
FT CHAIN 1..546
FT /note="DNA replication factor Cdt1"
FT /id="PRO_0000191619"
FT REGION 1..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..190
FT /note="Interaction with GMNN"
FT REGION 383..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 451..546
FT /note="Interaction with LRWD1"
FT /evidence="ECO:0000269|PubMed:22645314"
FT MOTIF 1..23
FT /note="PIP-box K+4 motif"
FT MOTIF 68..70
FT /note="Cyclin-binding motif"
FT COMPBIAS 393..410
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 29
FT /note="Phosphothreonine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:21856198"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 93
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:21856198"
FT MOD_RES 318
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:21856198,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT 66
FT /note="A -> T (in MGORS4; dbSNP:rs387906918)"
FT /evidence="ECO:0000269|PubMed:21358632"
FT /id="VAR_065488"
FT VARIANT 117
FT /note="Q -> H (in MGORS4; dbSNP:rs779871947)"
FT /evidence="ECO:0000269|PubMed:21358632"
FT /id="VAR_065489"
FT VARIANT 135
FT /note="A -> V (in dbSNP:rs3218725)"
FT /id="VAR_029163"
FT VARIANT 172
FT /note="R -> C (in dbSNP:rs3218727)"
FT /id="VAR_029164"
FT VARIANT 234
FT /note="C -> R (in dbSNP:rs507329)"
FT /evidence="ECO:0000269|PubMed:10766248,
FT ECO:0000269|PubMed:11125146, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.5"
FT /id="VAR_054504"
FT VARIANT 262
FT /note="T -> A (in dbSNP:rs480727)"
FT /evidence="ECO:0000269|PubMed:10766248,
FT ECO:0000269|PubMed:11125146, ECO:0000269|PubMed:15489334"
FT /id="VAR_054505"
FT VARIANT 453
FT /note="R -> W (in MGORS4; dbSNP:rs200672589)"
FT /evidence="ECO:0000269|PubMed:21358632"
FT /id="VAR_065490"
FT VARIANT 456
FT /note="E -> A (in dbSNP:rs3218729)"
FT /id="VAR_029165"
FT VARIANT 462
FT /note="R -> Q (in MGORS4; dbSNP:rs387906917)"
FT /evidence="ECO:0000269|PubMed:21358632"
FT /id="VAR_065491"
FT VARIANT 468
FT /note="E -> K (in MGORS4; dbSNP:rs200652608)"
FT /evidence="ECO:0000269|PubMed:21358631"
FT /id="VAR_065492"
FT VARIANT 537
FT /note="A -> V (in dbSNP:rs3218721)"
FT /id="VAR_024408"
FT MUTAGEN 68..70
FT /note="RRL->AAA: Abolishes binding of cyclin A-dependent
FT protein kinases."
FT /evidence="ECO:0000269|PubMed:14993212"
FT MUTAGEN 170
FT /note="Y->A: Alters interaction with GMNN."
FT /evidence="ECO:0000269|PubMed:21543332"
FT CONFLICT 494
FT /note="E -> K (in Ref. 4; AAH49205)"
FT /evidence="ECO:0000305"
FT TURN 6..9
FT /evidence="ECO:0007829|PDB:6QCG"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 174..177
FT /evidence="ECO:0007829|PDB:2WVR"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 188..209
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 216..227
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 233..242
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:2WVR"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:2WVR"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 288..314
FT /evidence="ECO:0007829|PDB:2WVR"
FT TURN 315..319
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:2WVR"
FT HELIX 420..423
FT /evidence="ECO:0007829|PDB:2LE8"
FT HELIX 425..435
FT /evidence="ECO:0007829|PDB:2LE8"
SQ SEQUENCE 546 AA; 60390 MW; 8179D0330C135FB7 CRC64;
MEQRRVTDFF ARRRPGPPRI APPKLACRTP SPARPALRAP ASATSGSRKR ARPPAAPGRD
QARPPARRRL RLSVDEVSSP STPEAPDIPA CPSPGQKIKK STPAAGQPPH LTSAQDQDTI
SELASCLQRA RELGARVRAL KASAQDAGES CTPEAEGRPE EPCGEKAPAY QRFHALAQPG
LPGLVLPYKY QVLAEMFRSM DTIVGMLHNR SETPTFAKVQ RGVQDMMRRR FEECNVGQIK
TVYPASYRFR QERSVPTFKD GTRRSDYQLT IEPLLEQEAD GAAPQLTASR LLQRRQIFSQ
KLVEHVKEHH KAFLASLSPA MVVPEDQLTR WHPRFNVDEV PDIEPAALPQ PPATEKLTTA
QEVLARARNL ISPRMEKALS QLALRSAAPS SPGSPRPALP ATPPATPPAA SPSALKGVSQ
DLLERIRAKE AQKQLAQMTR CPEQEQRLQR LERLPELARV LRSVFVSERK PALSMEVACA
RMVGSCCTIM SPGEMEKHLL LLSELLPDWL SLHRIRTDTY VKLDKAADLA HITARLAHQT
RAEEGL
