ubiquitin-like PHD & RING finger domain-containing protein 2; E3 ubiquitin-protein ligase UHRF2; EC=6.3.2.-; Np95/ICBP90-like RING finger protein; Np95-like RING finger protein; nuclear protein 97; nuclear zinc finger protein Np97; RING finger protein 107; ubiquitin-like-containing PHD & RING finger domains protein 2 (UHRF2, NIRF, RNF107)
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Function
- E3 ubiquitin ligase protein
- ubiquitin conjugation, 3rd step
- ubiquitinates cyclins, CCND1 & CCNE1 (phosphorylation independent) & induces G1 arrest
- G1/S transition
- overexpression causes G1 phase cell arrest
- binds methylated CpG containing oligonucleotides
- interacts with PCNP, HDAC1, inactive CDK2
- ubiquitinates PCNP leading to its degradation by the proteasome
- component of UHRF2/CDK2/CCNE1 complex
- may be autoubiquitinated, leading to proteasomal degradation
- phosphorylation may be mediated by CDK2
- component of a complex at least composed of UHRF2, CDK2 & CCNE1
- interaction with CCNE1 ubiquitinates CCNE1
- interaction with CCND1 biquitinates CCND1
- interacts with p53/TP53 & RB1
Structure
- contains 1 PHD-type Zn+2 finger
- contains 2 RING-type Zn+2 fingers
- contains 1 ubiquitin-like domain
- contains 1 YDG domain
Compartment
Expression
- up-regulated in proliferating non tumor cells
- down-regulated by growth arrest & differentiation
Pathology
- chromosomal deletion involving UHRF2 is found in multiple kinds of malignancies including
- brain cancer
- breast cancer
- stomach cancer
- kidney cancer
- hematopoietic malignancy
- lung cancer