ubiquitin carboxyl-terminal hydrolase 28; deubiquitinating enzyme 28; ubiquitin thiolesterase 28; ubiquitin-specific-processing protease 28 (USP28, KIAA1515)

Function: - deubiquitinase involved in DNA damage response checkpoint & MYC proto-oncogene stability - involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway including CLSPN - role in G2 DNA damage checkpoint, by deubiquitinating CLSPN, & preventing its degradation by the anaphase promoting complex/ cyclosome (APC/C) - in contrast, it does not deubiquitinate PLK1 - specifically deubiquitinates MYC in the nucleoplasm, leading preventing MYC degradation by the proteasome - specifically interacts with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm & counteracts ubiquitination of MYC by the SCF(FBW7) complex - in contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation & explaining the selective MYC degradation in the nucleolus - thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin - degradaded upon nickel ion level or hypoxia exposure - phosphorylated upon DNA damage at Ser-67 & Ser-714, by ATM or ATR - interacts with isoform 1 of FBXW7; - following DNA damage, dissociates from FBXW7 leading to degradation of MYC Structure: - belongs to the peptidase C19 family, USP28 subfamily - contains 1 UIM (ubiquitin-interacting motif) repeat Compartment: nucleus, nucleoplasm Alternative splicing: named isoforms=2 Expression: down-regulated upon hypoxia

General

nuclear protein phosphoprotein ubiquitin C-terminal hydrolase; UCH; ubiquitin thiolesterase; ubiquitin-specific processing protease; deubiquitinating enzyme

Properties

SIZE: entity length = 1077 aa MW = 122 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S67} UIM {97-116} cysteine residue {C171} histidine residue {H600} Ser phosphorylation site {S714}

Database Correlations

OMIM 610748 UniProt Q96RU2 Pfam PF00443 Entrez Gene 57646 Kegg hsa:57646 ENZYME 3.4.19.12

References

UniProt :accession Q96RU2