BIRC2

Domain

The BIR domains mediate nuclear localization.

The CARD domain is necessary to stabilize the protein and inhibit the activation of E3 ubiquitin-protein ligase activity of BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin donor binding and activation.

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, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. 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. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.

Post-translational modifications

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

Upon stimulation of death receptors, including TNFRSF10B, recruited to receptors and cleaved by caspases. Proteolytic fragments remain associated with the receptors. This cleavage presumably inactivates the protein.

Sequence Similarities

Belongs to the IAP family.

Tissue Specificity

Present in many fetal and adult tissues. Mainly expressed in adult skeletal muscle, thymus, testis, ovary, and pancreas, low or absent in brain and peripheral blood leukocytes.

Cellular localization

• Cytoplasm
• Nucleus
• Agents that induce either the extrinsic or intrinsic apoptotic pathways promote its redistribution from the nuclear compartment to the cytoplasmic compartment. Associated with the midbody in telophase cells, and found diffusely in the nucleus of interphase cells.

Alternative names

API1, MIHB, RNF48, BIRC2, Baculoviral IAP repeat-containing protein 2, Cellular inhibitor of apoptosis 1, IAP homolog B, Inhibitor of apoptosis protein 2, RING finger protein 48, RING-type E3 ubiquitin transferase BIRC2, TNFR2-TRAF-signaling complex protein 2, C-IAP1, hIAP-2, hIAP2

Database links

swissprot:Q13490 entrezGene:329 omim:601712 swissprot:Q13489