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ubiquitin-like PHD & RING finger domain-containing protein 1; E3 ubiquitin-protein ligase UHRF1; inverted CCAAT box-binding protein of 90 kDa; nuclear protein 95; nuclear zinc finger protein Np95; HuNp95; RING finger protein 106; transcription factor ICBP90; ubiquitin-like-containing PHD & RING finger domains protein 1 (UHRF1, ICBP90, NP95, RNF106)
Function:
1) E3 ubiquitin ligase protein,
- ubiquitin conjugation, 3rd step
2) methylation-dependent transcriptional regulation
- binds methylated CpG containing oligonucleotides
3) binds to inverted 5'-CCAAT-3' box 2 in the TOP2A promoter, activates TOP2A expression
4) G1/S transition
5) DNA repair
6) chromosomal stability
7) interactions: histones H3, H1, H2B, HDAC1, UHRF1BP1
8) phosphorylation on Ser enhances DNA-binding activity
9) ubiquitination leads to proteasomal degradation
10) polyubiquitination stimulated by DNA damage
Structure:
- the RING finger is required for ubiquitin ligase activity
- the YDG domain mediates the interaction with histone H3
- 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:
- expressed in: thymus, bone marrow, testis, lung, heart, fetal thymus, liver, kidney
- up-regulated in proliferating cells (induced by E2F1), down-regulated in quiescent cells
Pathology:
- overexpressed in breast cancer
- down-regulated upon adriamycin-induced DNA damage, TP53/p53 & CDKN1A-dependent
General
phosphoprotein
ring finger protein
E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein
Properties
SIZE: entity length = 793 aa
MW = 90 kD
COMPARTMENT: cell nucleus
MOTIF: Ubiquitin-like {1-78}
MOTIF: Ser phosphorylation site {S76}
Ser phosphorylation site {S91}
Ser phosphorylation site {S287}
Ser phosphorylation site {S298}
Zn finger PHD-type
NAME: Zn finger PHD-type
SITE: 310-366
EFFECTOR-BOUND: Zn+2
Methyl-CpG binding and interaction with HDAC1 {386-575}
YDG {419-582}
Ser phosphorylation site {S639}
Ser phosphorylation site {S707}
RING-finger {724-763}
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
Database Correlations
OMIM 607990
UniProt Q96T88
PFAM correlations
Entrez Gene 29128
Kegg hsa:29128
References
- UniProt :accession Q96T88
- NIEHS-SNPs
http://egp.gs.washington.edu/data/uhrf1/