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FAM105A/OTULINL is a pseudodebuiquitinase of the OTU-class that localizes to the ER membrane
- Source :
- Structure
- Publication Year :
- 2019
-
Abstract
- Summary Pseudoenzymes have been identified across a diverse range of enzyme classes and fulfill important cellular functions. Examples of pseudoenzymes exist within ubiquitin conjugating and deubiquitinase (DUB) protein families. Here we characterize FAM105A/OTULINL, the only putative pseudodeubiquitinase of the ovarian tumor protease (OTU domain) family in humans. The crystal structure of FAM105A revealed that the OTU domain possesses structural deficiencies in both active site and substrate-binding infrastructure predicted to impair normal DUB function. We confirmed the absence of catalytic function against all ubiquitin linkages and an inability of FAM105A to bind ubiquitin compared with catalytically active FAM105B/OTULIN. FAM105A co-localized with KDEL markers and Lamin B1 at the endoplasmic reticulum (ER) and nuclear envelope, respectively. Accordingly, the FAM105A interactome exhibited significant enrichment in proteins localized to the ER/outer nuclear, Golgi and vesicular membranes. In light of undetectable deubiquitinase activity, we posit that FAM105A/OTULINL functions through its ability to mediate protein-protein interactions.
- Subjects :
- Models, Molecular
Protein family
KDEL
Crystallography, X-Ray
Endoplasmic Reticulum
Article
Deubiquitinating enzyme
03 medical and health sciences
symbols.namesake
Mice
Ubiquitin
Protein Domains
Structural Biology
Catalytic Domain
Cell Line, Tumor
Endopeptidases
Animals
Humans
Amino Acid Sequence
Molecular Biology
030304 developmental biology
0303 health sciences
biology
Deubiquitinating Enzymes
Sequence Homology, Amino Acid
Chemistry
Endoplasmic reticulum
030302 biochemistry & molecular biology
Intracellular Membranes
Golgi apparatus
Subcellular localization
Cell biology
HEK293 Cells
Ubiquitin-Conjugating Enzymes
biology.protein
symbols
Lamin
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Structure
- Accession number :
- edsair.doi.dedup.....1fc17ba8f82e858957b02499184a702e