Family C101
Summary for family C101
| Family type peptidase | C101.001 - OTULIN peptidase (Homo sapiens), MEROPS Accession MER0491756 (peptidase unit: 1-352) |
| Content of family | Family 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 type | Cysteine |
| Active site residues | D126 C129 H339 N341 |
| Active site | Active 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 specificities | The 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 structure | The 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. |
| Clan | CA |
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Distribution of family
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Protozoa |
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Fungi |
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Plants |
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Animals |
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Viruses |
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| Biological functions | The 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 C101 | Sequences: | 349 |
| Identifiers: | 2 |
| Identifiers with PDB entries: | 2 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
