| Tbio | Ubiquitin thioesterase otulin |
Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:27523608, PubMed:27559085, PubMed:24726323, PubMed:24726327). Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:24726323, PubMed:24726327). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex (PubMed:23746843, PubMed:23806334). Required for homeostasis of the LUBAC complex by restricting autoubiquination of the LUBAC complex subunit RNF31 (PubMed:24726323). Some results have suggested that OTULIN function is restricted to homeostasis of the LUBAC complex, because it is not stably associated with TNF or NOD2 receptor signaling complexes (RSCs) (PubMed:26670046). However, further report have shown that it plays active roles in receptor signaling (PubMed:26997266, PubMed:27523608). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a key role in innate immune response by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling (PubMed:23806334).
This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]
This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]
Comments
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| AUTOINFLAMMATION, PANNICULITIS, AND DERMATOSIS SYNDROME | 1 | 0.0 | 0.0 |
| Disease | Target Count | P-value |
|---|---|---|
| ovarian cancer | 8520 | 8.9e-09 |
| tuberculosis | 2010 | 9.6e-08 |
| oligodendroglioma | 2850 | 2.9e-03 |
| astrocytic glioma | 2597 | 3.4e-03 |
| intraductal papillary-mucinous adenoma (IPMA) | 2955 | 5.6e-03 |
| intraductal papillary-mucinous carcinoma (IPMC) | 2989 | 5.7e-03 |
| ependymoma | 4679 | 8.2e-03 |
| interstitial cystitis | 2312 | 3.1e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Otulipenia | 2 | 6.236 | 3.1 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Panniculitis | 9 | 3.05 | 1.5 |
| Disease | log2 FC | p |
|---|---|---|
| astrocytic glioma | 1.100 | 3.4e-03 |
| ependymoma | 1.200 | 8.2e-03 |
| interstitial cystitis | 1.100 | 3.1e-02 |
| intraductal papillary-mucinous adenoma (... | 1.400 | 5.6e-03 |
| intraductal papillary-mucinous carcinoma... | 1.100 | 5.7e-03 |
| oligodendroglioma | 1.100 | 2.9e-03 |
| ovarian cancer | -1.500 | 8.9e-09 |
| tuberculosis | -1.500 | 9.6e-08 |
MSRGTMPQPEAWPGASCAETPAREAAATARDGGKAAASGQPRPEMQCPAEHEEDMYRAADEIEKEKELLI 1 - 70 HERGASEPRLSVAPEMDIMDYCKKEWRGNTQKATCMKMGYEEVSQKFTSIRRVRGDNYCALRATLFQAMS 71 - 140 QAVGLPPWLQDPELMLLPEKLISKYNWIKQWKLGLKFDGKNEDLVDKIKESLTLLRKKWAGLAEMRTAEA 141 - 210 RQIACDELFTNEAEEYSLYEAVKFLMLNRAIELYNDKEKGKEVPFFSVLLFARDTSNDPGQLLRNHLNQV 211 - 280 GHTGGLEQVEMFLLAYAVRHTIQVYRLSKYNTEEFITVYPTDPPKDWPVVTLIAEDDRHYNIPVRVCEET 281 - 350 SL 351 - 352 //
