OTU (ovarian tumor) domain of ubiquitin thioesterase otulin family
Otulin family includes otulin and otulinl. Otulin, also called FAM105B, deubiquitinating enzyme otulin, OTU domain-containing deubiquitinase with linear linkage specificity, or ubiquitin thioesterase Gumby, is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response. It acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis. Otulinl, also called FAM105A, is an OTU-class pseudo-deubiquitinase with a disrupted catalytic triad and undetectable cleavage activity for any diubiquitin linkage. It may play a role in endoplasmic reticulum (ER)-organelle communication. Otulin and otulinl belong to the OTU family of cysteine proteases that use a conserved cysteine and histidine, and in some cases an aspartate, as the catalytic dyad (or triad).
Feature 1: putative active site [active site], 4 residue positions
Conserved feature residue pattern:[DE] C H N
Evidence:
Comment:Active site residues have been identified from the tertiary structure of human otulin/FAM105B isopeptidase: Asp126, Cys129, His339, Asn341.
Comment:Although highly similar to the deubiquitinase OTULIN, it lacks the conserved active site Cys at position 139 which is replaced by an Asp residue, and does not show deubiquitinase activity. It does not bind ubiquitin or ubiquitin-like proteins.
Comment:The key residues are conserved in some family members.
Jiyao W et al.(2023). "The conserved domain database in 2023.",