ubiquitin carboxyl-terminal hydrolase 5; deubiquitinating enzyme 5; isopeptidase T; ubiquitin thiolesterase 5; ubiquitin-specific-processing protease 5 (USP5, ISOT)

Function

• cleaves linear & branched multiubiquitin polymers with a marked preference for branched polymers
• role in unanchored Lys-48-linked polyubiquitin disassembly
• binds linear & Lys-63-linked polyubiquitin with a lower affinity
• knock-down of USP5 causes the accumulation of p53/TP53 & an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition
• thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
• interacts with TRIML1 (putative)

Cofactor: binds 1 Zn+2

Structure

• the UBP-type Zn+2 finger domain interacts selectively with an unmodified C-terminus of the proximal ubiquitin
• the UBP-type Zn+2 finger domain crystallizes as a dimer linked by a disulfide bond between the Cys-195 residues of both molecules, but there is no evidence that the full-length USP5 exists as a dimer
• both UBA domains are involved in polyubiquitin recognition
• belongs to the peptidase C19 family
• contains 2 UBA domains
• contains 1 UBP-type Zn+2 finger

Alternative splicing

named isoforms=2

More general terms

• ubiquitin C-terminal hydrolase
• zinc finger protein
• phosphoprotein

Additional terms

• ubiquitin (UBCEP2, UBB, UBC)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8078
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8078
• OMIM: https://mirror.omim.org/entry/601447
• UniProt: http://www.uniprot.org/uniprot/P45974.html