UniProt functional annotation for Q96PU4



	UniProt functional annotation for Q96PU4

UniProt code: Q96PU4.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131. {ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:14741369, ECO:0000269|PubMed:15178429, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:23404503}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Pathway: Protein modification; protein ubiquitination.

Subunit: Homodimer; disulfide-linked. Binds methylated CpG containing oligonucleotides. Interacts with H3: the interaction has a preference for the 'Lys-9' trimethylated form of H3 (H3K9me3) (By similarity). Interacts with PCNP, HDAC1 and CDK2 (inactive form). Component of a complex at least composed of UHRF2, CDK2 and CCNE1. Interacts directly with CCNE1; the interaction ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation. Interacts with CCND1; the interaction ubiquitinates CCND1 and appears independent of CCND1 phosphorylation. Interacts with p53/TP53 and RB1. Interacts with UBE2I. {ECO:0000250, ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:14741369, ECO:0000269|PubMed:15178429, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:23404503, ECO:0000269|Ref.15, ECO:0000269|Ref.16}.

Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358, ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:23404503}. Note=Enriched at pericentric heterochromatin (PH). This localization is dependent on the interaction with H3K9me3 (By similarity). {ECO:0000250}.

Induction: Up-regulated in proliferating fetal lung fibroblasts and in U-937 myeloid leukemia cells. Down-regulated in these cells by growth arrest and differentiation. In other cell types which cannot leave the cell cycle, such as tumoral HT-1080 and Hep-G2, levels are consistently up-regulated. {ECO:0000269|PubMed:12176013}.

Ptm: May be autoubiquitinated; which may lead to proteasomal degradation. {ECO:0000269|PubMed:14741369}.

Ptm: Phosphorylated. Phosphorylation may be mediated by CDK2. {ECO:0000269|PubMed:15178429}.

Ptm: Autosumoylated.

Disease: Note=Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131. {ECO:0000269\|PubMed:12176013, ECO:0000269\|PubMed:14741369, ECO:0000269\|PubMed:15178429, ECO:0000269\|PubMed:15361834, ECO:0000269\|PubMed:21952639, ECO:0000269\|PubMed:23404503}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Homodimer; disulfide-linked. Binds methylated CpG containing oligonucleotides. Interacts with H3: the interaction has a preference for the 'Lys-9' trimethylated form of H3 (H3K9me3) (By similarity). Interacts with PCNP, HDAC1 and CDK2 (inactive form). Component of a complex at least composed of UHRF2, CDK2 and CCNE1. Interacts directly with CCNE1; the interaction ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation. Interacts with CCND1; the interaction ubiquitinates CCND1 and appears independent of CCND1 phosphorylation. Interacts with p53/TP53 and RB1. Interacts with UBE2I. {ECO:0000250, ECO:0000269\|PubMed:12176013, ECO:0000269\|PubMed:14741369, ECO:0000269\|PubMed:15178429, ECO:0000269\|PubMed:15361834, ECO:0000269\|PubMed:21952639, ECO:0000269\|PubMed:23404503, ECO:0000269\|Ref.15, ECO:0000269\|Ref.16}.
Subcellular location:		Nucleus {ECO:0000255\|PROSITE-ProRule:PRU00358, ECO:0000269\|PubMed:12176013, ECO:0000269\|PubMed:23404503}. Note=Enriched at pericentric heterochromatin (PH). This localization is dependent on the interaction with H3K9me3 (By similarity). {ECO:0000250}.
Induction:		Up-regulated in proliferating fetal lung fibroblasts and in U-937 myeloid leukemia cells. Down-regulated in these cells by growth arrest and differentiation. In other cell types which cannot leave the cell cycle, such as tumoral HT-1080 and Hep-G2, levels are consistently up-regulated. {ECO:0000269\|PubMed:12176013}.
Ptm:		May be autoubiquitinated; which may lead to proteasomal degradation. {ECO:0000269\|PubMed:14741369}.
Ptm:		Phosphorylated. Phosphorylation may be mediated by CDK2. {ECO:0000269\|PubMed:15178429}.
Ptm:		Autosumoylated.
Disease:		Note=Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.