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Sep. 10, 2014:
A total of 174 experimentally verified S-nitrosylation sites on 94 S-nitrosylated proteins from individualized human colorectal cancer tissues using a label-free quantitation strategy.

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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 :
( If your security settings prevent Jmol from running, please register http://140.138.144.145/ as a safe location in your Java settings. )

Protein disease:
Disease database Database Entry Disease information
HPRD02094Lymphoproliferative syndrome, X-linked, 2
Network with metabolic pathway:
Kegg map ID Pathway Link
map04064NF-kappa B signaling pathway
map04210Apoptosis
map05145Toxoplasmosis
map05222Small cell lung cancer
map04510Focal adhesion
map05166HTLV-I infection
map05200Pathways in cancer
map04120Ubiquitin mediated proteolysis
Graphical Visualization of S-nitrosylation Sites:
Overview of Protein S-nitrosylation Sites with Functional and Structural Information

3D Structure Databases:
3D structure databases
EntryMethodResolution (A)ChainPositionsView
1C9Q NMR - A124-240Link
1F9X NMR - A241-356Link
1G3F NMR - A241-356Link
1G73 X-ray 2.00 A C/D238-358Link
1I3O X-ray 2.70 A E/F124-240Link
1I4O X-ray 2.40 A C/D120-260Link
1I51 X-ray 2.45 A E/F124-240Link
1KMC X-ray 2.90 A C/D124-242Link
1NW9 X-ray 2.40 A A253-350Link
1TFQ NMR - A241-356Link
1TFT NMR - A241-356Link
2ECG NMR - A430-497Link
2JK7 X-ray 2.82 A A241-356Link
2KNA NMR - A357-449Link
2OPY X-ray 2.80 A A249-354Link
2OPZ X-ray 3.00 A A/B/C/D249-357Link
2POI X-ray 1.80 A A10-99Link
2POP X-ray 3.10 A B/D10-100Link
2QRA X-ray 2.50 A A/B/C/D10-99Link
2VSL X-ray 2.10 A A250-345Link
3CLX X-ray 2.70 A A/B/C/D241-356Link
3CM2 X-ray 2.50 A A/B/C/D/E/F/G/H/I/J241-356Link
3CM7 X-ray 3.10 A A/B/C/D241-356Link
3EYL X-ray 3.00 A A/B241-356Link
3G76 X-ray 3.00 A A/B/C/D/E/F/G/H241-356Link
3HL5 X-ray 1.80 A A/B256-346Link
3UW4 X-ray 1.79 A A338-348Link
3UW5 X-ray 1.71 A A/B296-348Link
4EC4 X-ray 3.30 A A/B/C/D/E/F/G/J/K/L241-356Link
4HY0 X-ray 2.84 A A/B/C/D/E/F/G/H238-357Link
4IC2 X-ray 2.20 A A/B429-497Link
4IC3 X-ray 1.78 A A/B429-497Link
4J3Y X-ray 1.45 A A/C152-236Link
4J44 X-ray 1.30 A A/C152-236Link
4J45 X-ray 1.48 A A/C152-236Link
4J46 X-ray 1.42 A A/C152-236Link
4J47 X-ray 1.35 A A/C152-236Link
4J48 X-ray 2.10 A A/C152-236Link
4KJU X-ray 1.60 A A/C152-236Link
4KJV X-ray 1.70 A A/C152-236Link

The S-nitrosylation sites of XIAP_HUMAN

No. Position S-nitrosylated Peptide Secondary Structure of S-nitrosylated Peptide Solvent Accessibility of nitrosylated Site Substrate Motifs PubMed ID Experiment
112TFNSFEGSKT C VPADINKEEE   3.87%HC0922178444-
212TFNSFEGSKT C VPADINKEEE   3.87%HC0919273858-
390VGRHRKVSPN C RFINGFYLEN   4.22%HC1122178444-
490VGRHRKVSPN C RFINGFYLEN   4.22%HC1119273858-
5213CGGKLKNWEP C DRAWSEHRRH   3.61%HC1122178444-
6213CGGKLKNWEP C DRAWSEHRRH   3.61%HC1119273858-
7300YALGEGDKVK C FHCGGGLTDW   2.93%HC0222178444-
8300YALGEGDKVK C FHCGGGLTDW   2.93%HC0219273858-
9303GEGDKVKCFH C GGGLTDWKPS   2.44%HC0222178444-
10303GEGDKVKCFH C GGGLTDWKPS   2.44%HC0219273858-
11327WEQHAKWYPG C KYLLEQKGQE   1.95%HC0122178444-
12327WEQHAKWYPG C KYLLEQKGQE   1.95%HC0119273858-
13351NIHLTHSLEE C LVRTTEKTPS   2.88%HC0622178444-
14351NIHLTHSLEE C LVRTTEKTPS   2.88%HC0619273858-