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Protein Name: E3 ubiquitin-protein ligase XIAP

UniprotKB/SwissProt ID: XIAP_HUMAN (P98170)

Gene Name: XIAP

Synonyms: API3, BIRC4, IAP3

Organism: Homo sapiens (Human).

Function: Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). 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. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta- catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program.

Other Modifications: View all modification sites in dbPTM

Protein Subcellular Localization: Cytoplasm. Nucleus. Note=TLE3 promotes its nuclear localization.

PDB :
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Graphical Visualization of Ubiquitination Sites:
Overview of Protein Ubiquitination Sites with Functional and Structural Information


The ubiquitination sites of XIAP_HUMAN

No. Position Ubiquitinated Peptide Secondary Structure Solvent Accessibility Substrate Motifs PubMed ID
110NSFEGS K TCVPAD   57.72%21890473
231EEFNRL K TFANFP   38.06%20972266
3116IQNGQY K VENYLG   34.87%21890473
4168SEEARL K SFQNWP   43.61%20972266
5322PWEQHA K WYPGCK   45.17%12747801
6322PWEQHA K WYPGCK   45.17%12747801
7322PWEQHA K WYPGCK   45.17%12747801
8328KWYPGC K YLLEQK   44.86%12747801
9328KWYPGC K YLLEQK   44.86%12747801
10328KWYPGC K YLLEQK   44.86%12747801
11358LVRTTE K TPSLTR   64.74%20972266
12433SQTSLQ K EISTEE   63.41%2190698

The interacting network mediated by proteins: XIAP_HUMAN


Disease:
Disease database Database Entry Disease information
HPRD02094Lymphoproliferative syndrome, X-linked, 2
Metabolic pathway:
Kegg map ID Pathway
map03008Ribosome biogenesis in eukaryotes