Q9R0I6 (XIAP_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 87. History...
Names and origin
|Protein names||Recommended name:|
E3 ubiquitin-protein ligase XIAP
Baculoviral IAP repeat-containing protein 4
IAP homolog A
Inhibitor of apoptosis protein 3
X-linked inhibitor of apoptosis protein
Short name=X-linked IAP
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||496 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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 By similarity.
Monomer, and homodimer. Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with TAB1/MAP3K7IP1 and AIFM1. Interaction with SMAC hinders binding of TAB1/MAP3K7IP1 and AIFM1. Interacts with TCF25 and COMMD1. Interacts with SEPT4 isoform 6, but not with other SEPT4 isoforms. Interacts with RIP1, RIP2, RIP3, RIP4, CCS and USP19. Interacts (via BIR 2 domain and BIR 3 domain) with HAX1 (via C-terminus) and this interaction blocks ubiquitination of XIAP/BIRC4. Interacts with the monomeric form of BIRC5/survivin By similarity. Interacts with TLE3 and TCF7L2/TCF4 By similarity.
The first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization. The second BIR domain is sufficient to inhibit caspase-3 and caspase-7, while the third BIR is involved in caspase-9 inhibition. The interactions with DIABLO/SMAC and PRSS25 are mediated by the second and third BIR domains By similarity.
S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase activity By similarity.
Autoubiquitinated and degraded by the proteasome in apoptotic cells By similarity.
Phosphorylation by PKB/AKT protects XIAP against ubiquitination and protects the protein against proteasomal degradation By similarity.
Belongs to the IAP family.
Contains 3 BIR repeats.
Contains 1 RING-type zinc finger.
Ubl conjugation pathway
Wnt signaling pathway
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||Wnt receptor signaling pathway|
Inferred from electronic annotation. Source: UniProtKB-KWnegative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Inferred from electronic annotation. Source: Comparanegative regulation of neuron apoptotic process
|Cellular_component||cytosolnucleusperinuclear region of cytoplasmprotein complex|
|Molecular_function||ubiquitin-protein ligase activity|
Inferred from sequence or structural similarity. Source: UniProtKBzinc ion binding
Inferred from electronic annotation. Source: InterPro
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 496||496||E3 ubiquitin-protein ligase XIAP||PRO_0000122354|
|Repeat||26 – 93||68||BIR 1|
|Repeat||163 – 230||68||BIR 2|
|Repeat||264 – 329||66||BIR 3|
|Zinc finger||449 – 484||36||RING-type|
|Region||141 – 149||9||Interaction with caspase-7 By similarity|
|Metal binding||299||1||Zinc By similarity|
|Metal binding||302||1||Zinc By similarity|
|Metal binding||319||1||Zinc By similarity|
|Metal binding||326||1||Zinc By similarity|
Amino acid modifications
|Modified residue||87||1||Phosphoserine; by PKB By similarity|
|Modified residue||449||1||S-nitrosocysteine By similarity|
|Cross-link||321||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Cross-link||327||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|AB033366 mRNA. Translation: BAA85304.1.|
|RefSeq||NP_071567.1. NM_022231.2. |
3D structure databases
|SMR||Q9R0I6. Positions 20-99, 124-240, 242-354, 430-496. |
Protein-protein interaction databases
Protein family/group databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000009336; ENSRNOP00000009336; ENSRNOG00000006967. |
|UCSC||RGD:620692. rat. |
|RGD||620692. Xiap. |
Gene expression databases
|GermOnline||ENSRNOG00000006967. Rattus norvegicus. |
Family and domain databases
|Gene3D||1.10.1170.10. 4 hits. |
|InterPro||IPR001370. BIR. |
|Pfam||PF00653. BIR. 3 hits. |
|SMART||SM00238. BIR. 3 hits. |
SM00184. RING. 1 hit.
|PROSITE||PS01282. BIR_REPEAT_1. 3 hits. |
PS50143. BIR_REPEAT_2. 3 hits.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
|Accession||Primary (citable) accession number: Q9R0I6|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families