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Plays a regulatory role in the Toll-like signaling pathway by determining the strength of LPS-induced signaling and gene expression (PubMed:18455983). Inhibits TCR-mediated T-cell activation and negatively regulate T-cell function to prevent hyperresponsiveness (By similarity). Also inhibits autolysosome formation via negatively modulating MTOR activation by interacting with RAC1 and promoting the disassociation of the RAC1-MTOR complex (PubMed:34524845). Plays an essential role in NK-cell biology by acting as a checkpoint and displaying an expression pattern correlating with NK-cell maturation process and by negatively regulating NK-cell maturation and antitumor immunity (By similarity). Mechanistically, suppresses IL-15-triggered mTOR activity in NK-cells (PubMed:34524845)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q6P589"}],"value":"May interact with CASP8; however, such result is unclear since could not reproduce the interaction with CASP8. 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Up-regulated in the spinal cord of mice with experimental autoimmune encephalomyelitis. Constitutively expressed by macrophages, B and T-lymphocytes at various developmental stages"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18455983"}],"value":"By TNF in fibroblasts"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding (By similarity)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q6P589"}],"value":"Phosphorylated by TAK1/MAP3K7; this phosphorylation triggers association with BTRC and subsequent ubiquitination and degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q6P589"}],"value":"Ubiquitinated in a BTRC-depdent manner; leading to degradation mediated through the proteasome pathway"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18455983"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34524845"}],"value":"When infected with lymphocytic choriomeningitis virus (LCMV), TIPE2-deficient mice exhibit significantly enhanced CD4(+) and CD8(+) T-cell immune responses compared with WT mice (PubMed:18455983). TIPE2-deficient NK-cells exhibit enhanced activation, cytotoxicity, and IFN-gamma production upon stimulation and enhanced response to IL-15 for maturation (PubMed:34524845)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the TNFAIP8 family. 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