Pathway
Metalloprotease DUBs
The JAB1/MPN +/MOV34 (JAMM) domain metalloproteases cleave the isopeptide bond at or near the the attachment point of polyubiquitin and substrate. PSMD14 (RPN11), STAMBP (AMSH), STAMBPL1 (AMSH-LP), and BRCC3 (BRCC36) are highly specific for the K63 poly-Ub linkage, which may be a general characteristic. Two multisubunit complexes represented elsewhere in Reactome contain JAMM DUBs. The proteasome 19S lid complex includes PSMD14, an endopeptidase that cleaves poly-Ub chains from substrates as they are degraded by the proteasome. The COP9-Signalosome contains COPS5 (CSN5), which deconjugates the Ub-like modifier Nedd8, modulating the activity of the SCF E3 ligase.
Continue reading
JAMM DUB catalysis requires nucleophilic attack on the carbonyl carbon of the isopeptide bond by an activated water molecule bound to Zn2+ and a conserved glutamate. A negatively-charged tetrahedral transition state ensues, and a nearby conserved Ser/Thr in the JAMM domains stabilizes the oxyanion. The tetrahedral intermediate then collapses and the Glu serves as a general base donating a proton to the leaving Lys side chain.
What the reference databases state
Statements
31 statements
31 statements · 1 reference database · Subject: Metalloprotease DUBs · Sources: Reactome
- ABRAXAS1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- ABRAXAS2 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- BABAM1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- BABAM2 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- BARD1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- BRCA1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- BRCC3 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- EP300 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC11; H2AC13; H2AC15; H2AC16; H2AC17 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC12 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC14 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
Show the remaining 19
- H2AC18; H2AC19 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC20 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC21 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC25 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC4; H2AC8 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC6 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- H2AC7 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- KAT2B participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- MYSM1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- NLRP3 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- PSMD14 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- RPS27A participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- STAM participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- STAMBP participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- STAMBPL1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- UBA52 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- UBB participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- UBC participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only
- UIMC1 participates in Metalloprotease DUBsProteinReactome R-HSA-5689901Inferred only