UniProt functional annotation for Q8R4E9



	UniProt functional annotation for Q8R4E9

UniProt code: Q8R4E9.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Required for both DNA replication and mitosis. 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). Required also for mitosis by promoting stable kinetochore-microtubule attachments (By similarity). Potential oncogene (PubMed:11850834). {ECO:0000250|UniProtKB:Q9H211, ECO:0000269|PubMed:11850834, ECO:0000269|PubMed:12192004, ECO:0000269|PubMed:14993212}.

Subunit: Interacts with GMNN; inhibits binding of the MCM complex to origins of replication (PubMed:12192004). Interacts with CDC6; are mutually dependent on one another for loading MCM complexes onto chromatin (By similarity). Interacts with PCNA (By similarity). Interacts with LRWD1 during G1 phase and during mitosis (By similarity). Interacts with NDC80 subunit of the NDC80 complex; leading to kinetochore localization (By similarity). Interacts with KAT7 (By similarity). Interacts with ubiquitin-binding protein FAF1; the interaction is likely to promote CDT1 degradation (By similarity). {ECO:0000250|UniProtKB:Q9H211, ECO:0000269|PubMed:12192004}.

Subcellular location: Nucleus {ECO:0000269|PubMed:14993212}. Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:Q9H211}. Note=Transiently localizes to kinetochores during prometaphase and metaphase. {ECO:0000250|UniProtKB:Q9H211}.

Developmental stage: Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases. {ECO:0000269|PubMed:11850834}.

Domain: 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. {ECO:0000250|UniProtKB:Q9I9A7}.

Ptm: 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-28 by CDK2 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation. The interaction with GMNN protects it against ubiquitination. Deubiquitinated by USP37. {ECO:0000250|UniProtKB:Q9H211}.

Ptm: Phosphorylation by cyclin A-dependent kinases at Thr-28 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation. Phosphorylated at Thr-28 by MAPK8/JNK1, which blocks replication licensing in response to stress. Binding to GMNN is not affected by phosphorylation (PubMed:14993212). {ECO:0000250|UniProtKB:Q9H211, ECO:0000269|PubMed:14993212}.

Similarity: Belongs to the Cdt1 family. {ECO:0000305}.

Sequence caution: Sequence=BAC38731.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Required for both DNA replication and mitosis. 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). Required also for mitosis by promoting stable kinetochore-microtubule attachments (By similarity). Potential oncogene (PubMed:11850834). {ECO:0000250\|UniProtKB:Q9H211, ECO:0000269\|PubMed:11850834, ECO:0000269\|PubMed:12192004, ECO:0000269\|PubMed:14993212}.


Subunit:		Interacts with GMNN; inhibits binding of the MCM complex to origins of replication (PubMed:12192004). Interacts with CDC6; are mutually dependent on one another for loading MCM complexes onto chromatin (By similarity). Interacts with PCNA (By similarity). Interacts with LRWD1 during G1 phase and during mitosis (By similarity). Interacts with NDC80 subunit of the NDC80 complex; leading to kinetochore localization (By similarity). Interacts with KAT7 (By similarity). Interacts with ubiquitin-binding protein FAF1; the interaction is likely to promote CDT1 degradation (By similarity). {ECO:0000250\|UniProtKB:Q9H211, ECO:0000269\|PubMed:12192004}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:14993212}. Chromosome, centromere, kinetochore {ECO:0000250\|UniProtKB:Q9H211}. Note=Transiently localizes to kinetochores during prometaphase and metaphase. {ECO:0000250\|UniProtKB:Q9H211}.
Developmental stage:		Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases. {ECO:0000269\|PubMed:11850834}.
Domain:		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. {ECO:0000250\|UniProtKB:Q9I9A7}.
Ptm:		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-28 by CDK2 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation. The interaction with GMNN protects it against ubiquitination. Deubiquitinated by USP37. {ECO:0000250\|UniProtKB:Q9H211}.
Ptm:		Phosphorylation by cyclin A-dependent kinases at Thr-28 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation. Phosphorylated at Thr-28 by MAPK8/JNK1, which blocks replication licensing in response to stress. Binding to GMNN is not affected by phosphorylation (PubMed:14993212). {ECO:0000250\|UniProtKB:Q9H211, ECO:0000269\|PubMed:14993212}.
Similarity:		Belongs to the Cdt1 family. {ECO:0000305}.
Sequence caution:		Sequence=BAC38731.1; Type=Frameshift; Evidence={ECO:0000305};