Target General Infomation
Target ID
T59479
Former ID
TTDR01410
Target Name
mRNA of Apoptosis-2
Gene Name
BIRC3
Synonyms
API2 (mRNA); Apoptosis inhibitor 2 (mRNA); Baculoviral IAP repeatcontaining protein 3 (mRNA); CIAP2 (mRNA); IAP homolog C (mRNA); IAP1 (mRNA); Inhibitor of apoptosis protein 1 (mRNA); RING finger protein 49 (mRNA); TNFR2TRAFsignaling complex protein 1 (mRNA); hIAP1 (mRNA); BIRC3
Target Type
Research
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 andsuppresses 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.
BioChemical Class
Carbon-nitrogen ligase
Target Validation
T59479
UniProt ID
EC Number
EC 6.3.2.-
Sequence
MNIVENSIFLSNLMKSANTFELKYDLSCELYRMSTYSTFPAGVPVSERSLARAGFYYTGV
NDKVKCFCCGLMLDNWKRGDSPTEKHKKLYPSCRFVQSLNSVNNLEATSQPTFPSSVTNS
THSLLPGTENSGYFRGSYSNSPSNPVNSRANQDFSALMRSSYHCAMNNENARLLTFQTWP
LTFLSPTDLAKAGFYYIGPGDRVACFACGGKLSNWEPKDNAMSEHLRHFPKCPFIENQLQ
DTSRYTVSNLSMQTHAARFKTFFNWPSSVLVNPEQLASAGFYYVGNSDDVKCFCCDGGLR
CWESGDDPWVQHAKWFPRCEYLIRIKGQEFIRQVQASYPHLLEQLLSTSDSPGDENAESS
IIHFEPGEDHSEDAIMMNTPVINAAVEMGFSRSLVKQTVQRKILATGENYRLVNDLVLDL
LNAEDEIREEERERATEEKESNDLLLIRKNRMALFQHLTCVIPILDSLLTAGIINEQEHD
VIKQKTQTSLQARELIDTILVKGNIAATVFRNSLQEAEAVLYEHLFVQQDIKYIPTEDVS
DLPVEEQLRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRSTIKGTVR
TFLS
Inhibitor SM-122 Drug Info [531078]
SM-131 Drug Info [529809]
SM-337 Drug Info [531078]
Pathways
KEGG Pathway NF-kappa B signaling pathway
Ubiquitin mediated proteolysis
Apoptosis
Focal adhesion
NOD-like receptor signaling pathway
TNF signaling pathway
Toxoplasmosis
Pathways in cancer
Transcriptional misregulation in cancer
Small cell lung cancer
NetPath Pathway IL5 Signaling Pathway
IL1 Signaling Pathway
IL2 Signaling Pathway
TNFalpha Signaling Pathway
Notch Signaling Pathway
TCR Signaling Pathway
PANTHER Pathway Apoptosis signaling pathway
CCKR signaling map ST
Pathway Interaction Database CD40/CD40L signaling
FAS (CD95) signaling pathway
TNF receptor signaling pathway
Ceramide signaling pathway
p75(NTR)-mediated signaling
C-MYB transcription factor network
Negative effector of Fas and TNF-alpha
Caspase Cascade in Apoptosis
Reactome NOD1/2 Signaling Pathway
RIPK1-mediated regulated necrosis
Regulation of TNFR1 signaling
TNFR1-induced NFkappaB signaling pathway
TNFR2 non-canonical NF-kB pathway
Regulation of necroptotic cell death
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
IKK complex recruitment mediated by RIP1
WikiPathways Focal Adhesion
Apoptosis
TNF alpha Signaling Pathway
TWEAK Signaling Pathway
Apoptosis Modulation and Signaling
References
Ref 529809J Med Chem. 2008 Dec 11;51(23):7352-5.Design, synthesis, and evaluation of tricyclic, conformationally constrained small-molecule mimetics of second mitochondria-derived activator of caspases.
Ref 531078J Med Chem. 2010 Sep 9;53(17):6361-7.Nonpeptidic and potent small-molecule inhibitors of cIAP-1/2 and XIAP proteins.
Ref 549606US patent application no. 5,958,771, Antisense modulation of cellular inhibitor of Apoptosis-2 expression.

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