Baculoviral IAP repeat-containing protein 3
Also known as: API2, BIRC3, MIHC, RNF49
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.
Classification
- Family (Pfam)
- PF00653 BIR, PF00619 CARD, PF21290 UBA_BIRC2-3, PF13920 zf-C3HC4_3
- InterPro
- BIR_rpt, BIRC2-3-like_UBA, CARD, DEATH-like_dom_sf, IAP, Znf_RING
- Functional cluster
- Zinc-Finger & Chromatin Regulatory Proteins
Experimental structures · PDB · 6
A predicted model is available from AlphaFold.
Gene Ontology · 32
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0032991 protein-containing complex
- GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process
- GO:0044877 protein-containing complex binding
- GO:0016740 transferase activity
- GO:0061630 ubiquitin protein ligase activity
- GO:0004842 ubiquitin-protein transferase activity
- GO:0008270 zinc ion binding
- GO:0007249 canonical NF-kappaB signal transduction
- GO:0007166 cell surface receptor signaling pathway
- GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
- GO:0006954 inflammatory response
- GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
- GO:0043066 negative regulation of apoptotic process
- GO:0060546 negative regulation of necroptotic process
- GO:0038061 non-canonical NF-kappaB signal transduction
- GO:0043123 positive regulation of canonical NF-kappaB signal transduction
- GO:0031398 positive regulation of protein ubiquitination
- GO:0042981 regulation of apoptotic process
- GO:0051726 regulation of cell cycle
- GO:0050727 regulation of inflammatory response
- GO:0045088 regulation of innate immune response
- GO:0060544 regulation of necroptotic process
- GO:0070424 regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
- GO:0039535 regulation of RIG-I signaling pathway
- GO:0034121 regulation of toll-like receptor signaling pathway
- GO:0007283 spermatogenesis
- GO:0033209 tumor necrosis factor-mediated signaling pathway
Drugs targeting this protein · 1
- BIRINAPANT inhibitor
Related proteins · sequence + function similarity
- Baculoviral IAP repeat-containing protein 2 0.98
- Inhibitor of apoptosis protein 0.95
- Baculoviral IAP repeat-containing protein 2 0.95
- E3 ubiquitin-protein ligase XIAP 0.94
- Baculoviral IAP repeat-containing protein 3 0.94
- Baculoviral IAP repeat-containing protein 3 0.93
- E3 ubiquitin-protein ligase XIAP 0.93
- Putative inhibitor of apoptosis 0.93
- E3 ubiquitin-protein ligase XIAP 0.93
- E3 ubiquitin-protein ligase XIAP 0.88
- E3 ubiquitin-protein ligase XIAP 0.87
- Baculoviral IAP repeat-containing protein 8 0.81
Co-cited proteins · studied together in the literature
- Baculoviral IAP repeat-containing protein 2 12 shared papers
- E3 ubiquitin-protein ligase XIAP 9 shared papers
- Death-associated inhibitor of apoptosis 2 3 shared papers
- Baculoviral IAP repeat-containing protein 2 1 shared papers
- Tumor necrosis factor alpha-induced protein 8 1 shared papers
- Baculoviral IAP repeat-containing protein 1 2 shared papers
- Kinesin-like protein KIF20A 1 shared papers
- Apolipoprotein L3 1 shared papers
- Stannin 1 shared papers
- E3 ubiquitin-protein ligase XIAP 1 shared papers
- Ubiquitin carboxyl-terminal hydrolase 19 1 shared papers
- Death-associated inhibitor of apoptosis 1 1 shared papers
Literature · 15 cited papers
- IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex. Cell Rep. · 2013
- IAPs: guardians of RIPK1. Cell Death Differ. · 2012
- cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4). PLoS ONE · 2011
- The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2. J. Biol. Chem. · 2011
- Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity. Discov. Med. · 2011
- To fight or die - inhibitor of apoptosis proteins at the crossroad of innate immunity and death. Curr. Opin. Cell Biol. · 2010
- IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat. Rev. Cancer · 2010
- IAPs: more than just inhibitors of apoptosis proteins. Cell Cycle · 2008
- cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. Cancer Res. · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Structure of the MLT gene and molecular characterization of the genomic breakpoint junctions in the t(11;18)(q21;q21) of marginal zone B-cell lymphomas of MALT type. Genes Chromosomes Cancer · 2000
- Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes. Blood · 1999
- … and 3 more in the literature graph