XIAP
XIAP (X-linked inhibitor of apoptosis, also known as BIRC4, API3, hILP and ILP-1) is a multi-functional member of the IAP family. It inhibits caspases directly and acts as an E3 ubiquitin-protein ligase that shapes NF-kappa-B signalling and innate immunity. Browse Assay Genie's current range of XIAP research reagents below, or read on for the biology behind the target.
XIAP regulates not only caspases and apoptosis but also inflammatory signalling, immunity, copper homeostasis, mitogenic kinase signalling, cell proliferation, invasion and metastasis. As a direct caspase inhibitor, it binds the active site pocket of CASP3 and CASP7 and obstructs substrate entry, and it inactivates CASP9 by holding it in a monomeric, inactive state. It can also act in the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation.
As an E3 ubiquitin-protein ligase, XIAP regulates NF-kappa-B signalling. Its substrates include RIPK1, RIPK2, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS, PTEN and BIRC5/survivin. In innate immunity it mediates 'Lys-63'-linked polyubiquitination of RIPK2 downstream of NOD1 and NOD2, converting RIPK2 into a scaffold that activates NF-kappa-B and MAP kinase signalling and promotes recruitment of the LUBAC complex. Not every ubiquitination event leads to degradation: modification of CCS enhances its chaperone activity towards SOD1, while MAP3K2 and AIFM1 are not degraded. XIAP also promotes proteasomal degradation of COMMD1 and BCL2, suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8, and positively regulates Wnt signalling by ubiquitinating TLE family proteins and AES.
The XIAP gene belongs to the baculoviral IAP repeat-containing family, whose conserved baculovirus IAP repeat motif is necessary for anti-apoptotic function. NCBI describes binding to TRAF1 and TRAF2 and inhibition of apoptosis induced by menadione. Mutations in the gene cause X-linked lymphoproliferative syndrome. Alternate splicing yields multiple transcript variants, and pseudogenes lie on chromosomes 2 and 11.
XIAP directly inhibits CASP3, CASP7 and CASP9, making it a central point of control for studying how cells resist programmed cell death.
XIAP ubiquitinates RIPK2 downstream of NOD1 and NOD2, linking it to NF-kappa-B and MAP kinase activation in innate immunity.
XIAP influences proliferation, invasion and metastasis, and suppresses ripoptosome formation, a complex able to kill cancer cells.
As an E3 ligase acting on targets such as TLE proteins, COMMD1 and BCL2, XIAP connects ubiquitination to Wnt signalling and copper homeostasis.
XIAP suppresses apoptosis by binding the active sites of caspase-3 and caspase-7 and keeping caspase-9 inactive. It also works as an E3 ubiquitin-protein ligase, regulating NF-kappa-B signalling, innate immunity, copper homeostasis and Wnt signalling through substrates such as RIPK1, RIPK2 and TLE proteins.
XIAP is also known as BIRC4 (baculoviral IAP repeat-containing 4), API3, hILP and ILP-1. UniProt names the protein E3 ubiquitin-protein ligase XIAP. NCBI notes that alternate splicing produces multiple transcript variants, so check the datasheet of any product for its validated reactivity.
Mutations in the XIAP gene cause X-linked lymphoproliferative syndrome. The protein also regulates cell invasion and metastasis. Mouse and rat each have an ortholog named Xiap, so the protein can be studied in common rodent models.
Caspases, RIPK kinases, other IAP family members and ubiquitination substrates connected to XIAP biology.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P98170; product specifications from Assay Genie datasheets.