Baculoviral IAP repeat-containing protein 2

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.

Classification

Family (Pfam)

PF00653 BIR, PF00619 CARD, PF21290 UBA_BIRC2-3, PF13920 zf-C3HC4_3

InterPro

BIR_rpt, BIRC2-3-like_UBA, BIRC2/BIRC3_UBA, CARD, DEATH-like_dom_sf, IAP, Znf_RING

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 28

• 1QBH NMR
• 2L9M NMR
• 3D9T X-ray 1.50A
• 3D9U X-ray 2.30A
• 3M1D X-ray 2.00A
• 3MUP X-ray 2.60A
• 3OZ1 X-ray 3.00A
• 3T6P X-ray 1.90A
• 3UW4 X-ray 1.79A
• 4EB9 X-ray 2.60A
• 4HY4 X-ray 1.25A
• 4HY5 X-ray 1.75A
• … and 16 more

A predicted model is available from AlphaFold.

Gene Ontology · 51

• GO:0035631 CD40 receptor complex
• GO:0005737 cytoplasm
• GO:0009898 cytoplasmic side of plasma membrane
• GO:0005829 cytosol
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0001741 XY body
• GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process
• GO:0098770 FBXO family protein binding
• GO:0042802 identical protein binding
• GO:0044877 protein-containing complex binding
• GO:0051087 protein-folding chaperone binding
• GO:0003713 transcription coactivator activity
• GO:0016740 transferase activity
• GO:0043130 ubiquitin binding
• 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:0006351 DNA-templated transcription
• 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:0070266 necroptotic process
• 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:1902524 positive regulation of protein K48-linked ubiquitination
• GO:1902523 positive regulation of protein K63-linked ubiquitination
• GO:1902527 positive regulation of protein monoubiquitination
• GO:0031398 positive regulation of protein ubiquitination
• GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
• GO:0000209 protein polyubiquitination
• GO:0042981 regulation of apoptotic process
• GO:0051726 regulation of cell cycle
• GO:0045595 regulation of cell differentiation
• GO:0042127 regulation of cell population proliferation
• 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:1904975 response to bleomycin
• GO:0051591 response to cAMP
• GO:0045471 response to ethanol
• GO:0001666 response to hypoxia
• 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 3 0.98
• Inhibitor of apoptosis protein 0.96
• Baculoviral IAP repeat-containing protein 2 0.96
• Baculoviral IAP repeat-containing protein 3 0.94
• Putative inhibitor of apoptosis 0.93
• Baculoviral IAP repeat-containing protein 3 0.93
• E3 ubiquitin-protein ligase XIAP 0.92
• E3 ubiquitin-protein ligase XIAP 0.91
• E3 ubiquitin-protein ligase XIAP 0.91
• E3 ubiquitin-protein ligase XIAP 0.89
• E3 ubiquitin-protein ligase XIAP 0.89
• Baculoviral IAP repeat-containing protein 8 0.81

Co-cited proteins · studied together in the literature

• Baculoviral IAP repeat-containing protein 3 12 shared papers
• Max dimerization protein 1 1 shared papers
• E3 ubiquitin-protein ligase XIAP 10 shared papers
• UBX domain-containing protein 1 1 shared papers
• Death-associated inhibitor of apoptosis 2 3 shared papers
• Diablo IAP-binding mitochondrial protein 1 shared papers
• Baculoviral IAP repeat-containing protein 2 1 shared papers
• Transcription factor E2F1 1 shared papers
• Death-associated inhibitor of apoptosis 1 2 shared papers
• Baculoviral IAP repeat-containing protein 1 2 shared papers
• Heat shock protein HSP 90-beta 1 shared papers
• E3 ubiquitin-protein ligase XIAP 1 shared papers

Literature · 26 cited papers

• Ubiquitin-associated domain-containing ubiquitin regulatory X (UBX) protein UBXN1 is a negative regulator of nuclear factor kappaB (NF-kappaB) signaling. J. Biol. Chem. · 2015
• Middle domain of human Hsp90 isoforms differentially binds Aha1 in human cells and alters Hsp90 activity in yeast. Biochim. Biophys. Acta · 2015
• 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
• Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription. J. Biol. Chem. · 2011
• CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration. Mol. Cell · 2011
• Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity. Discov. Med. · 2011
• Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. Mol. Cell · 2010
• 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
• … and 14 more in the literature graph