UniProt Accession

 XIAP_MOUSE; Q60989; A2BGY6; O08865 

Genbank Protein ID

 U36842; U88990; BX530028; CH466570; CH466570; BC138528; BC145861 

Genbank Nucleotide ID

 AAC52594.1; AAB58376.1; CAM17468.1; EDL29039.1; EDL29040.1; AAI38529.1; AAI45862.1 

Protein Name

 E3 ubiquitin-protein ligase XIAP 

Protein Synonyms/Alias

 Baculoviral IAP repeat-containing protein 4; IAP homolog A; Inhibitor of apoptosis protein 3; IAP-3; mIAP-3; mIAP3; X-linked inhibitor of apoptosis protein; X-linked IAP 

Gene Name

 Xiap 

Gene Synonyms/Alias

 Aipa; Api3; Birc4; Miha 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
19	FVLADTNKDEEFVEE	ubiquitination	[1]
31	VEEFNRLKTFANFPS	ubiquitination	[1]
168	CSEEARLKSFQNWPD	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional Description

 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. 

Sequence Annotation

 REPEAT 26 93 BIR 1.
 REPEAT 163 230 BIR 2.
 REPEAT 264 329 BIR 3.
 ZN_FING 449 484 RING-type.
 REGION 141 149 Interaction with caspase-7 (By
 METAL 299 299 Zinc (By similarity).
 METAL 302 302 Zinc (By similarity).
 METAL 319 319 Zinc (By similarity).
 METAL 326 326 Zinc (By similarity).
 MOD_RES 87 87 Phosphoserine; by PKB (By similarity).
 MOD_RES 449 449 S-nitrosocysteine (By similarity).
 CROSSLNK 321 321 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 327 327 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 Apoptosis; Complete proteome; Cytoplasm; Isopeptide bond; Ligase; Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; S-nitrosylation; Ubl conjugation; Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 496 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:MGI.
 GO:0005829; C:cytosol; IEA:Compara.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0043234; C:protein complex; IEA:Compara.
 GO:0004842; F:ubiquitin-protein ligase activity; ISS:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:1990001; P:inhibition of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
 GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0051402; P:neuron apoptotic process; IMP:MGI.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 

Interpro

 IPR001370; BIR.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD. 

Pfam

 PF00653; BIR 

SMART

 SM00238; BIR
 SM00184; RING 

PROSITE

 PS01282; BIR_REPEAT_1
 PS50143; BIR_REPEAT_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS