UHRF2

This gene encodes a nuclear protein which is involved in cell-cycle regulation. The encoded protein is a ubiquitin-ligase capable of ubiquinating PCNP (PEST-containing nuclear protein), and together they may play a role in tumorigenesis. [provided by RefSeq]

Full Name

ubiquitin-like with PHD and ring finger domains 2

Function

E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair (PubMed:15178429, PubMed:29506131, PubMed:27743347, PubMed:23404503).
Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:27129234, PubMed:24813944).
This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (By similarity).
Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby inducing G1 arrest (PubMed:15178429, PubMed:15361834, PubMed:21952639).
Ubiquitinates also PCNP leading to its degradation by the proteasome (PubMed:14741369, PubMed:12176013).
Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteosomal degradation (PubMed:29923055).
Promotes also DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation (PubMed:30335751).
Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (PubMed:33848395).

Biological Process

Biological Process cell cycle Source:UniProtKB-KW
Biological Process cell differentiation Source:HGNC-UCL1 Publication
Biological Process maintenance of DNA methylation Source:GO_Central1 Publication
Biological Process protein autoubiquitination Source:HGNC-UCL1 Publication
Biological Process protein ubiquitination Source:HGNC-UCL1 Publication
Biological Process regulation of cell cycle Source:UniProtKB1 Publication

Cellular Location

Nucleus
Chromosome
Enriched at genomic loci that are enriched for 5-hydroxymethylcytosine (5hmC).

Involvement in disease

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.

PTM

May be autoubiquitinated; which may lead to proteasomal degradation.
Phosphorylated. Phosphorylation may be mediated by CDK2.
Autosumoylated.