Target Information
Target General Infomation | |||||
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Target ID |
T84780
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Former ID |
TTDI02025
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Target Name |
Inhibitor of apoptosis protein 2
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Gene Name |
BIRC2
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Synonyms |
Baculoviral IAP repeatcontaining protein 2; CIAP1; IAP homolog B; IAP2; RING finger protein 48; TNFR2TRAFsignaling complex protein 2; hIAP2; BIRC2
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Target Type |
Clinical Trial
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Disease | Lymphoma [ICD9: 202.8, 208.9; ICD10: C81-C86] | ||||
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.
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BioChemical Class |
Carbon-nitrogen ligase
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UniProt ID | |||||
EC Number |
EC 6.3.2.-
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Sequence |
MHKTASQRLFPGPSYQNIKSIMEDSTILSDWTNSNKQKMKYDFSCELYRMSTYSTFPAGV
PVSERSLARAGFYYTGVNDKVKCFCCGLMLDNWKLGDSPIQKHKQLYPSCSFIQNLVSAS LGSTSKNTSPMRNSFAHSLSPTLEHSSLFSGSYSSLSPNPLNSRAVEDISSSRTNPYSYA MSTEEARFLTYHMWPLTFLSPSELARAGFYYIGPGDRVACFACGGKLSNWEPKDDAMSEH RRHFPNCPFLENSLETLRFSISNLSMQTHAARMRTFMYWPSSVPVQPEQLASAGFYYVGR NDDVKCFCCDGGLRCWESGDDPWVEHAKWFPRCEFLIRMKGQEFVDEIQGRYPHLLEQLL STSDTTGEENADPPIIHFGPGESSSEDAVMMNTPVVKSALEMGFNRDLVKQTVQSKILTT GENYKTVNDIVSALLNAEDEKREEEKEKQAEEMASDDLSLIRKNRMALFQQLTCVLPILD NLLKANVINKQEHDIIKQKTQIPLQARELIDTILVKGNAAANIFKNCLKEIDSTLYKNLF VDKNMKYIPTEDVSGLSLEEQLRRLQEERTCKVCMDKEVSVVFIPCGHLVVCQECAPSLR KCPICRGIIKGTVRTFLS |
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Drugs and Mode of Action | |||||
Pathways | |||||
KEGG Pathway | NF-kappa B signaling pathway | ||||
Ubiquitin mediated proteolysis | |||||
Apoptosis | |||||
Hippo signaling pathway | |||||
Focal adhesion | |||||
NOD-like receptor signaling pathway | |||||
TNF signaling pathway | |||||
Toxoplasmosis | |||||
Pathways in cancer | |||||
Small cell lung cancer | |||||
NetPath Pathway | TCR Signaling Pathway | ||||
PANTHER Pathway | Apoptosis signaling pathway | ||||
CCKR signaling map ST | |||||
Pathway Interaction Database | Canonical NF-kappaB pathway | ||||
CD40/CD40L signaling | |||||
FAS (CD95) signaling pathway | |||||
TNF receptor signaling pathway | |||||
p75(NTR)-mediated signaling | |||||
Reactome | Apoptotic cleavage of cellular proteins | ||||
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 | |||||
Apoptotic execution phase | |||||
Apoptosis Modulation and Signaling | |||||
References | |||||
Ref 529155 | IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell. 2007 Nov 16;131(4):669-81. | ||||
Ref 532581 | Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582). J Med Chem. 2013 Dec 27;56(24):9897-919. | ||||
Ref 532662 | cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1- and RIPK3-dependent manner. Blood. 2014 Apr 17;123(16):2562-72. | ||||
Ref 532682 | Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-?B activation, and is active in patient-derived xenograft models. Mol Cancer Ther. 2014 Apr;13(4):867-79. |
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