Target General Information
Target ID T16769 Target Info
Target Name X-linked inhibitor of apoptosis protein (XIAP)
Synonyms hILP; hIAP3; hIAP-3; Xlinked IAP; X-linked IAP; RING-type E3 ubiquitin transferase XIAP; Inhibitor of apoptosis protein 3; ILP; IAPlike protein; IAP3; IAP-like protein; IAP-3; E3 ubiquitinprotein ligase XIAP; E3 ubiquitin-protein ligase XIAP; Baculoviral IAP repeatcontaining protein 4; Baculoviral IAP repeat-containing protein 4; BIRC4; API3
Target Type Clinical trial Target
Gene Name XIAP
Biochemical Class Acyltransferase
UniProt ID
XIAP_HUMAN 
Target Interacting Proteins
Acid anhydride hydrolases [+] 1 Acid anhydride hydrolases +
Interacting Target Name Ras-related C3 botulinum toxin substrate 1 (RAC1) Literature-reported Target Interacting Protein Info
UniProt ID
RAC1_HUMAN 
Synonyms TC25; Ras-like protein TC25; p21-Rac1; MIG5; Cell migration-inducing gene5 protein; Cell migration-inducing gene 5 protein
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Luminescence [1]
2 Affinity Capture-Western [2]
Acyltransferases [+] 3 Acyltransferases +
Interacting Target Name Cellular inhibitor of apoptosis 1 (BIRC2) Clinical trial Target Interacting Protein Info
UniProt ID
BIRC2_HUMAN 
Synonyms TNFR2-TRAF-signaling complex protein 2; TNFR2TRAFsignaling complex protein 2; RNF48; RING-type E3 ubiquitin transferase BIRC2; RING finger protein 48; MIHB; Inhibitor of apoptosis protein 2; IAP2; IAP homolog B; hIAP-2; hIAP2; C-IAP1; CIAP1; Baculoviral IAP repeat-containing protein 2; Baculoviral IAP repeatcontaining protein 2; API1
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [4]
Interacting Target Name Melanoma inhibitor of apoptosis protein (ML-IAP) Patented-recorded Target Interacting Protein Info
UniProt ID
BIRC7_HUMAN 
Synonyms UNQ5800/PRO19607/PRO21344; RNF50; RING-type E3 ubiquitin transferase BIRC7; RING finger protein 50; MLIAP; Livin; Kidney inhibitor of apoptosis protein; KIAP; Baculoviral IAP repeat-containing protein 7
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [5]
Interacting Target Name TNF receptor-associated factor 6 (TRAF6) Literature-reported Target Interacting Protein Info
UniProt ID
TRAF6_HUMAN 
Synonyms RNF85; RING-type E3 ubiquitin transferase TRAF6; RING finger protein 85; Interleukin-1 signal transducer; E3 ubiquitin-protein ligase TRAF6
Evidence Score (E-score) 2 Experimental Evidences +
1 Co-localization [6]
2 Yeast two hybrid [7]
Beta-transducin repeats [+] 1 Beta-transducin repeats +
Interacting Protein Name Transducin-like enhancer protein 3 (TLE3) Interacting Protein Interacting Protein Info
UniProt ID
TLE3_HUMAN 
Synonyms ESG; ESG3; GRG3; HsT18976
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [8]
2 Biochemical Activity [8]
Kinases [+] 5 Kinases +
Interacting Target Name Proto-oncogene c-RAF (c-RAF) Clinical trial Target Interacting Protein Info
UniProt ID
RAF1_HUMAN 
Synonyms Raf-1; RAF proto-oncogene serine/threonine-protein kinase; RAF; cRaf
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-Western [9]
2 Biochemical Activity [9]
3 Co-localization [6]
4 Reconstituted Complex [9]
5 Yeast two hybrid [9]
Interacting Protein Name Receptor-interacting protein 2 (RIP2) Interacting Protein Interacting Protein Info
UniProt ID
RIPK2_HUMAN 
Synonyms UNQ277/PRO314/PRO34092; Tyrosine-protein kinase RIPK2; RIP-like-interacting CLARP kinase; RIP-2; RIP2; RICK; Receptor-interacting serine/threonine-protein kinase 2; Receptor-interacting protein 2; CARDIAK; CARD-containing interleukin-1 beta-converting enzyme-associated kinase; CARD-containing IL-1 beta ICE-kinase
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [10]
2 Biochemical Activity [11]
3 Reconstituted Complex [12]
4 Yeast two hybrid [13]
Interacting Target Name RAC-alpha serine/threonine-protein kinase (AKT1) Clinical trial Target Interacting Protein Info
UniProt ID
AKT1_HUMAN 
Synonyms RAC-PK-alpha; RAC; Proto-oncogene c-Akt; Protein kinase B alpha; Protein kinase B; PKB alpha; PKB
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [14]
2 Biochemical Activity [15]
3 Co-localization [6]
Interacting Target Name MAPK/ERK kinase kinase 2 (MAP3K2) Clinical trial Target Interacting Protein Info
UniProt ID
M3K2_HUMAN 
Synonyms Mitogen-activated protein kinase kinase kinase 2; MEKK2; MEKK 2; MEK kinase 2; MAPKKK2
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [16]
2 Biochemical Activity [16]
3 Reconstituted Complex [17]
Interacting Target Name Glycogen synthase kinase-3 beta (GSK-3B) Clinical trial Target Interacting Protein Info
UniProt ID
GSK3B_HUMAN 
Synonyms Serine/threonine-protein kinase GSK3B; GSK-3 beta
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [18]
2 Biochemical Activity [19]
Oxidoreductases [+] 1 Oxidoreductases +
Interacting Protein Name Programmed cell death protein 8 (AIFM1) Interacting Protein Interacting Protein Info
UniProt ID
AIFM1_HUMAN 
Synonyms AIF; CMT2D; CMTX4; COWCK; COXPD6; NADMR; NAMSD; PDCD8
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [20]
2 Biochemical Activity [21]
Peptidases [+] 5 Peptidases +
Interacting Target Name Caspase-9 (CASP9) Clinical trial Target Interacting Protein Info
UniProt ID
CASP9_HUMAN 
Synonyms MCH6; ICE-like apoptotic protease 6; ICE-LAP6; CASP-9; Apoptotic protease-activating factor 3; Apoptotic protease Mch-6; Apoptotic protease activating factor 3; APAF-3
Evidence Score (E-score) 7 Experimental Evidences +
1 Affinity Capture-Western [22]
2 Biochemical Activity [23]
3 Co-crystal Structure [24]
4 Co-localization [6]
5 Far Western [25]
6 Reconstituted Complex [26]
7 Yeast two hybrid [27]
Interacting Target Name Caspase-3 (CASP3) Clinical trial Target Interacting Protein Info
UniProt ID
CASP3_HUMAN 
Synonyms Yama protein; SREBP cleavage activity 1; SCA-1; Protein Yama; Cysteine protease CPP32; CPP-32; CPP32; Caspase 3; CASP-3; Apopain
Evidence Score (E-score) 6 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [28]
3 Biochemical Activity [29]
4 Co-crystal Structure [30]
5 Co-localization [6]
6 Reconstituted Complex [31]
Interacting Target Name Caspase-7 (CASP7) Clinical trial Target Interacting Protein Info
UniProt ID
CASP7_HUMAN 
Synonyms MCH3; ICE-like apoptotic protease 3; ICE-LAP3; CMH-1; CASP-7; Apoptotic protease Mch-3
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [32]
2 Co-crystal Structure [33]
3 Reconstituted Complex [31]
Interacting Protein Name High temperature requirement protein A2 (HTRA2) Interacting Protein Interacting Protein Info
UniProt ID
HTRA2_HUMAN 
Synonyms OMI; PARK13; PRSS25
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-MS [34]
2 Affinity Capture-Western [34]
3 Reconstituted Complex [35]
Interacting Target Name Caspase-10 (CASP10) Patented-recorded Target Interacting Protein Info
UniProt ID
CASPA_HUMAN 
Synonyms MCH4; ICE-like apoptotic protease 4; FLICE2; FAS-associated death domain protein interleukin-1B-converting enzyme 2; Caspase-10 subunit p23/17; Caspase-10 subunit p12; CASP-10; Apoptotic protease Mch-4
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [36]
2 Yeast two hybrid [13]
Ubiquitin related proteins [+] 6 Ubiquitin related proteins +
Interacting Target Name Ubiquitin-protein ligase E3 Mdm2 (MDM2) Clinical trial Target Interacting Protein Info
UniProt ID
MDM2_HUMAN 
Synonyms RING-type E3 ubiquitin transferase Mdm2; P53-binding protein Mdm2; Oncoprotein Mdm2; MDM2 protein; Hdm2; E3 ubiquitin-protein ligase Mdm2; Double minute 2 protein
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [37]
2 Protein-peptide [38]
3 Reconstituted Complex [39]
Interacting Protein Name Ubiquitin-conjugating enzyme E2 D1 (UBE2D1) Interacting Protein Interacting Protein Info
UniProt ID
UB2D1_HUMAN 
Synonyms E2(17)KB1; SFT; UBC4/5; UBCH5; UBCH5A
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [40]
2 Reconstituted Complex [23]
3 Yeast two hybrid [41]
Interacting Protein Name Ubiquitin-conjugating enzyme E2 D2 (UBE2D2) Interacting Protein Interacting Protein Info
UniProt ID
UB2D2_HUMAN 
Synonyms E2(17)KB2; PUBC1; UBC4; UBC4/5; UBCH4; UBCH5B
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [40]
2 Reconstituted Complex [42]
3 Yeast two hybrid [41]
Interacting Protein Name Ubiquitin-conjugating enzyme E2 D3 (UBE2D3) Interacting Protein Interacting Protein Info
UniProt ID
UB2D3_HUMAN 
Synonyms E2(17)KB3; UBC4/5; UBCH5C
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [40]
2 Reconstituted Complex [43]
3 Yeast two hybrid [41]
Interacting Target Name Polyubiquitin-C (UBC) Patented-recorded Target Interacting Protein Info
UniProt ID
UBC_HUMAN 
Synonyms HMG20; ubiquitin C
Evidence Score (E-score) 2 Experimental Evidences +
1 Co-crystal Structure [44]
2 Reconstituted Complex [45]
Interacting Protein Name Ubiquitin-conjugating enzyme E2 E1 (UBE2E1) Interacting Protein Interacting Protein Info
UniProt ID
UB2E1_HUMAN 
Synonyms UBCH6
Evidence Score (E-score) 2 Experimental Evidences +
1 Reconstituted Complex [46]
2 Yeast two hybrid [41]
Other proteins [+] 5 Other proteins +
Interacting Target Name Direct IAP-binding protein with low pI (DIABLO) Literature-reported Target Interacting Protein Info
UniProt ID
DBLOH_HUMAN 
Synonyms Smac protein; Smac; Second mitochondria-derived activator of caspase; Direct IAP binding protein with low pI; Diablo homolog, mitochondrial
Evidence Score (E-score) 7 Experimental Evidences +
1 Affinity Capture-MS [47]
2 Affinity Capture-Western [47]
3 Biochemical Activity [48]
4 Co-crystal Structure [49]
5 Far Western [50]
6 Protein-peptide [51]
7 Reconstituted Complex [49]
Interacting Protein Name XIAP-associated factor 1 (XAF1) Interacting Protein Interacting Protein Info
UniProt ID
XAF1_HUMAN 
Synonyms BIRC4BP; HSXIAPAF1; XIAPAF1
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [52]
2 Biochemical Activity [53]
3 Co-localization [52]
4 Yeast two hybrid [52]
Interacting Target Name Apoptosis inhibitor survivin (BIRC5) Clinical trial Target Interacting Protein Info
UniProt ID
BIRC5_HUMAN 
Synonyms Survivin; IAP4; Baculoviral IAP repeat-containing protein 5; Apoptosis inhibitor survivin; Apoptosis inhibitor 4; API4
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [54]
2 Reconstituted Complex [55]
Interacting Protein Name Apoptosis regulatory protein Siva (SIVA1) Interacting Protein Interacting Protein Info
UniProt ID
SIVA_HUMAN 
Synonyms CD27BP; SIVA; Siva.1; Siva.2
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [56]
2 Yeast two hybrid [56]
Interacting Protein Name TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 (TAB1) Interacting Protein Interacting Protein Info
UniProt ID
TAB1_HUMAN 
Synonyms 3.Tab1; MAP3K7IP1
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [57]
2 Yeast two hybrid [57]
References
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REF 2 IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation. EMBO J. 2012 Jan 4;31(1):14-28.
REF 3 Architecture of the human interactome defines protein communities and disease networks. Nature. 2017 May 25;545(7655):505-509.
REF 4 Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance. Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16182-7.
REF 5 Role of melanoma inhibitor of apoptosis (ML-IAP) protein, a member of the baculoviral IAP repeat (BIR) domain family, in the regulation of C-RAF kinase and cell migration. J Biol Chem. 2012 Aug 17;287(34):28445-55.
REF 6 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. J Proteome Res. 2014 Dec 5;13(12):5339-46.
REF 7 Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks. Mol Cell Proteomics. 2012 Jul;11(7):M111.016162.
REF 8 XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling. Mol Cell. 2012 Mar 9;45(5):619-28.
REF 9 Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase. Int J Oncol. 2006 Oct;29(4):861-7.
REF 10 Small molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling. EMBO J. 2018 Sep 3;37(17). pii: e99372.
REF 11 Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling. EMBO Mol Med. 2013 Aug;5(8):1278-95.
REF 12 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;6(9):e22356.
REF 13 A proteome-scale map of the human interactome network. Cell. 2014 Nov 20;159(5):1212-1226.
REF 14 Caffeic acid phenethyl ester suppresses melanoma tumor growth by inhibiting PI3K/AKT/XIAP pathway. Carcinogenesis. 2013 Sep;34(9):2061-70.
REF 15 Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem. 2004 Feb 13;279(7):5405-12.
REF 16 XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2. Cell Signal. 2008 Nov;20(11):2107-12.
REF 17 Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1. EMBO J. 2014 Aug 18;33(16):1784-801.
REF 18 XIAP associates with GSK3 and inhibits the promotion of intrinsic apoptotic signaling by GSK3. Cell Signal. 2009 Dec;21(12):1857-65.
REF 19 Phosphorylation of XIAP at threonine 180 controls its activity in Wnt signaling. J Cell Sci. 2018 May 22;131(10). pii: jcs210575.
REF 20 Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP. Mol Cell Biol. 2008 Jan;28(1):237-47.
REF 21 Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation. Biochemistry. 2011 Dec 27;50(51):11084-96.
REF 22 IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J. 1998 Apr 15;17(8):2215-23.
REF 23 X-linked inhibitor of apoptosis functions as ubiquitin ligase toward mature caspase-9 and cytosolic Smac/DIABLO. J Biochem. 2005 Feb;137(2):125-32.
REF 24 Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell. 2003 Feb;11(2):519-27.
REF 25 Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9. J Biol Chem. 2004 Sep 24;279(39):40622-8.
REF 26 IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell. 2007 Nov 16;131(4):669-81.
REF 27 Towards a proteome-scale map of the human protein-protein interaction network. Nature. 2005 Oct 20;437(7062):1173-8.
REF 28 Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell. 2004 Jun 18;14(6):801-11.
REF 29 Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12815-9.
REF 30 XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J. 2005 Feb 9;24(3):645-55.
REF 31 X-linked IAP is a direct inhibitor of cell-death proteases. Nature. 1997 Jul 17;388(6639):300-4.
REF 32 IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. Nat Cell Biol. 2005 Jan;7(1):70-7.
REF 33 Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell. 2001 Mar 9;104(5):781-90.
REF 34 A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell. 2001 Sep;8(3):613-21.
REF 35 The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ. 2002 Jan;9(1):20-6.
REF 36 Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6170-5.
REF 37 XIAP inhibits autophagy via XIAP-Mdm2-p53 signalling. EMBO J. 2013 Aug 14;32(16):2204-16.
REF 38 Inhibition of MDM2 homodimerization by XIAP IRES stabilizes MDM2, influencing cancer cell survival. Mol Cancer. 2015 Mar 26;14:65.
REF 39 Regulation of XIAP translation and induction by MDM2 following irradiation. Cancer Cell. 2009 May 5;15(5):363-75.
REF 40 Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO. J Biol Chem. 2003 Mar 21;278(12):10055-60.
REF 41 c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 2010 Dec 15;29(24):4198-209.
REF 42 Regulation of ubiquitin transfer by XIAP, a dimeric RING E3 ligase. Biochem J. 2013 Mar 15;450(3):629-38.
REF 43 X-linked Inhibitor of Apoptosis Protein promotes the degradation of its antagonist, the pro-apoptotic ARTS protein. Int J Biochem Cell Biol. 2012 Mar;44(3):489-95.
REF 44 Structural analysis of the UBA domain of X-linked inhibitor of apoptosis protein reveals different surfaces for ubiquitin-binding and self-association. PLoS One. 2011;6(12):e28511.
REF 45 IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis. Nat Cell Biol. 2008 Nov;10(11):1309-17.
REF 46 Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Genome Res. 2009 Oct;19(10):1905-11.
REF 47 Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 2000 Jul 7;102(1):43-53.
REF 48 Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol. 2004 Sep;6(9):849-60.
REF 49 Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature. 2000 Dec 21-28;408(6815):1004-8.
REF 50 Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein. J Biol Chem. 2003 Dec 26;278(52):52660-72.
REF 51 The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides of SMAC and caspase-9. Acta Crystallogr D Biol Crystallogr. 2009 Jan;65(Pt 1):58-66.
REF 52 Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol. 2001 Feb;3(2):128-33.
REF 53 Domain organization of XAF1 and the identification and characterization of XIAP(RING) -binding domain of XAF1. Protein Sci. 2012 Oct;21(10):1418-28.
REF 54 Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex. J Biol Chem. 2007 Sep 7;282(36):26202-9.
REF 55 An IAP-IAP complex inhibits apoptosis. J Biol Chem. 2004 Aug 13;279(33):34087-90.
REF 56 Siva1 is a XIAP-interacting protein that balances NFkappaB and JNK signalling to promote apoptosis. J Cell Sci. 2009 Aug 1;122(Pt 15):2651-61.
REF 57 XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway. EMBO J. 1999 Jan 4;18(1):179-87.

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