BIRC3

This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]

Full Name

Baculoviral IAP Repeat Containing 3

Function

Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8.

Biological Process

Cell surface receptor signaling pathway Source: ProtInc
I-kappaB kinase/NF-kappaB signaling Source: Reactome
MyD88-independent toll-like receptor signaling pathway Source: Reactome
Negative regulation of apoptotic process Source: GO_Central
Negative regulation of necroptotic process Source: GO_Central
NIK/NF-kappaB signaling Source: UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of protein ubiquitination Source: UniProtKB
Protein deubiquitination Source: Reactome
Regulation of apoptotic process Source: UniProtKB
Regulation of cell cycle Source: GO_Central
Regulation of cysteine-type endopeptidase activity Source: UniProtKB
Regulation of inflammatory response Source: UniProtKB
Regulation of innate immune response Source: UniProtKB
Regulation of necroptotic process Source: UniProtKB
Regulation of nucleotide-binding oligomerization domain containing signaling pathway Source: UniProtKB
Regulation of RIG-I signaling pathway Source: UniProtKB
Regulation of toll-like receptor signaling pathway Source: UniProtKB
Regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Tumor necrosis factor-mediated signaling pathway Source: Reactome

Cellular Location

Cytoplasm; Nucleus

Involvement in disease

A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.

PTM

Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.