Family C101


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

Summary for family C101

Family type peptidaseC101.001 - OTULIN peptidase (Homo sapiens), MEROPS Accession MER0491756 (peptidase unit: 1-352)
Content of familyFamily C101 contains deubiquitinases
History Identifier created: MEROPS 9.9 (23 August 2013)
Linear ubiquitination is a process by which ubiquitin is linked to a protein (including ubiquitin) via Met1. A special linear ubiquitin chain assembly complex known as LUBIC exists, which is an E3 ligase consisting of the components HOIL-1L, HOIP and SHARPIN, and nuclear factor KappaB (NF-kappaB) signalling is regulated. NF-kappaB signalling is essential for infammatory and immune responses (Tokunaga, 2013). The FAM105B isopeptidase (C101.001) has been identified as a deubiquitinase that is specific for Met1 linkages (Keusekotten et al., 2013).
Catalytic typeCysteine
Active site residuesD126 C129 H339 N341 
Active siteActive site residues have been identified from the tertiary structure of human FAM105B isopeptidase: Asp126, Cys129, His339, Asn341 (Rivkin et al., 2013). However, His339 and Asn341 are poorly conserved.
Activities and specificitiesThe FAM105B isopeptidase cleaves linear ubiquitin linkages (Rivkin et al., 2013). The proximal ubiquitin in the substrate is required for activation of the catalytic triad, and mutation of ubiquitin Glu16 inhibits activity. This mechanism of activation is an example of substrate-assisted catalysis (Keusekotten et al., 2013).
Molecular structureThe tertiary structure has been determined for the FAM105B isopeptidase and shows a papain-like fold (Rivkin et al., 2013). Consequently, family C101 is included in clan CA.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses -  
Biological functionsThe sprouting of new blood vessels from existing ones during angiogenesis is controlled by a complex series of signalling events, including the Wnt pathway. The FAM105B isopeptidase is expressed in Wnt-responsive endothelial cells and interacts with the proteins disheveled 2 and HOIP. HOIP is a key component of the linear ubiquitin assembly process, and interaction with FAM105B leads to reduction in linear ubiquitination and activation of NF-kappaB-dependent transcription (Rivkin et al., 2013). Impairment of linear ubiquitination leads to muliple disorders, including autoinflammation, immunodeficiency, dermatitis, B cell lymphoma and Parkinson"s disease (Tokunaga, 2013).
Statistics for family C101Sequences:349
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
OTULIN peptidaseC101.001Yes
family C101 non-peptidase homologuesC101.UNW-
family C101 unassigned peptidasesunassigned-