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

• E3 ubiquitin ligase protein,
  • ubiquitin conjugation, 3rd step
• methylation-dependent transcriptional regulation
  • binds methylated CpG containing oligonucleotides
• binds to inverted 5'-CCAAT-3' box 2 in the TOP2A promoter, activates TOP2A expression
• G1/S transition
• DNA repair
• chromosomal stability
• interactions: histones H3, H1, H2B, HDAC1, UHRF1BP1
• phosphorylation on Ser enhances DNA-binding activity
• ubiquitination leads to proteasomal degradation
• 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

More general terms

• E3 ubiquitin ligase
• ring finger protein
• phosphoprotein

Component of

• UHRF2/CDK2/CCNE1 complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=29128
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:29128
• OMIM: https://mirror.omim.org/entry/607990
• UniProt: http://www.uniprot.org/uniprot/Q96T88.html