Function: Interacts with zinc finger protein A20/TNFAIP3 and inhibits TNF-induced NF-kappa-B-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal; however, binding to A20/TNFAIP3 seems not to be required for this function
By similarity. Inhibits NF-kappa-B activation by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcricption. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosohorylation by SRC-family kinases. Interacts with HIV-1 matrix protein and is packaged into virions and overexpression can inhibit viral replication. May regulate matrix nuclear localization, both nuclear import of PIC (Preintegration complex) and export of GAG polyprotein and viral genomic RNA during virion production. In case of infection, promotes association of IKBKG with Shigella flexneri E3 ubiquitin-protein ligase ipah9.8 p which in turn promotes polyubiquitination of IKBKG leading to its proteasome-dependent degradation and thus is perturbing NF-kappa-B activation during bacterial infection. Ref.12 Ref.13 Ref.15 Ref.19
Subunit structure: Interacts with TNFAIP3 and IKBKG; facilitates TNFAIP3-mediated de-ubiquitination of NEMO/IKBKG. Interacts with HIV-1 matrix protein. Interacts with Shigella flexneri ipah9.8; the interaction promotes polyubiquitination of IKBKG. Interacts with polyubiquitin. Interacts with MAPK1, SELPLG and PIK3CD. Interacts with IKBKG (polyubiquitinated). Interacts with IRAK1 (polyubiquitinated). Interacts with MYD88; the interaction is indicative for participation in an activated TLR-signaling complex
By similarity. Ref.12 Ref.13 Ref.15 Ref.19
Subcellular location: Cytoplasm. Nucleus. Note: Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner.
Tissue specificity: Ubiquitous. Strongly expressed in peripheral blood lymphocytes, spleen and skeletal muscle, and is weakly expressed in the brain.
Post-translational modification: Phosphorylation at Tyr-552 by SRC-family kinases recruits phosphoinositide-3-kinase (PI3K) PIK3CD:p85 heterodimer which results in integrin activation and leukocyte adhesion to activated endothelium during inflammation.
Sequence caution: The sequence AAB41438.1 differs from that shown. Reason: Frameshift at positions 152 and 154.
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