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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)
Function:
1) E3 ubiquitin ligase protein
- ubiquitin conjugation, 3rd step
- ubiquitinates cyclins, CCND1 & CCNE1 (phosphorylation independent) & induces G1 arrest
2) G1/S transition
- overexpression causes G1 phase cell arrest
3) binds methylated CpG containing oligonucleotides
4) interacts with PCNP, HDAC1, inactive CDK2
- ubiquitinates PCNP leading to its degradation by the proteasome
5) component of UHRF2/CDK2/CCNE1 complex
6) may be autoubiquitinated, leading to proteasomal degradation
7) phosphorylation may be mediated by CDK2
8) component of a complex at least composed of UHRF2, CDK2 & CCNE1
- interaction with CCNE1 ubiquitinates CCNE1
9) interaction with CCND1 biquitinates CCND1
10) 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: nucleus
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
General
nuclear protein
phosphoprotein
ring finger protein
E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein
Properties
SIZE: entity length = 802 aa
MW = 90 kD
COMPARTMENT: cell nucleus
MOTIF: Ubiquitin-like {1-78}
histone H3 interaction {117-311}
MOTIF: PCNP interaction {194-288}
Zn finger PHD-type
NAME: Zn finger PHD-type
SITE: 344-395
EFFECTOR-BOUND: Zn+2
domain {414-644}
MOTIF: YDG {448-612}
Ser phosphorylation site {S667}
cysteine residue {C704}
MODIFICATION: cysteine residue {CINTERCHAIN}
RING-finger {733-772}
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
Database Correlations
UniProt Q96PU4
PFAM correlations
Entrez Gene 115426
Kegg hsa:115426
References
UniProt :accession Q96PU4
Component-of
UHRF2/CDK2/CCNE1 complex