TNIP1

TNIP1 is an A20-binding protein which plays a role in autoimmunity and tissue homeostasis through the regulation of nuclear factor kappa-B activation. Mutations in TNIP1 have been associated with psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus.

Full Name

TNFAIP3 Interacting Protein 1

Function

Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression 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 transcription. 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 phosphorylation 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.

Biological Process

Biological Process cellular response to lipopolysaccharide Source:GO_Central1 Publication
Biological Process defense response Source:ProtInc1 Publication
Biological Process glycoprotein biosynthetic process Source:UniProtKB1 Publication
Biological Process inflammatory response Source:UniProtKB-KW
Biological Process leukocyte cell-cell adhesion Source:UniProtKB1 Publication
Biological Process MyD88-dependent toll-like receptor signaling pathway Source:UniProtKB
Biological Process negative regulation of ERK1 and ERK2 cascade Source:UniProtKB1 Publication
Biological Process negative regulation of I-kappaB kinase/NF-kappaB signaling Source:UniProtKB1 Publication
Biological Process negative regulation of viral genome replication Source:UniProtKB1 Publication
Biological Process positive regulation of inflammatory response Source:UniProtKB
Biological Process positive regulation of protein deubiquitination Source:UniProtKB1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:UniProtKB
Biological Process regulation of transcription by RNA polymerase II Source:GO_Central1 Publication
Biological Process translation Source:ProtInc1 Publication

Cellular Location

Cytoplasm
Nucleus
Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner.

PTM

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.