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Q9R0I6 (XIAP_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase XIAP
EC=6.3.2.-
Alternative name(s):
Baculoviral IAP repeat-containing protein 4
IAP homolog A
Inhibitor of apoptosis protein 3
Short name=IAP-3
Short name=rIAP-3
Short name=rIAP3
X-linked inhibitor of apoptosis protein
Short name=X-linked IAP
Gene names
Name:Xiap
Synonyms:Api3, Birc4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length496 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 By similarity.

Subunit structure

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.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: TLE3 promotes its nuclear localization By similarity.

Domain

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.

Post-translational modification

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.

Sequence similarities

Belongs to the IAP family.

Contains 3 BIR repeats.

Contains 1 RING-type zinc finger.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 496496E3 ubiquitin-protein ligase XIAP
PRO_0000122354

Regions

Repeat26 – 9368BIR 1
Repeat163 – 23068BIR 2
Repeat264 – 32966BIR 3
Zinc finger449 – 48436RING-type
Region141 – 1499Interaction with caspase-7 By similarity

Sites

Metal binding2991Zinc By similarity
Metal binding3021Zinc By similarity
Metal binding3191Zinc By similarity
Metal binding3261Zinc By similarity

Amino acid modifications

Modified residue871Phosphoserine; by PKB By similarity
Modified residue4491S-nitrosocysteine By similarity
Cross-link321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link327Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9R0I6 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: E250E3C77461A469

FASTA49656,073
        10         20         30         40         50         60 
MTFNSFEGSR TVVPADTNKD EEFVEEFNRL KTFANFPSSS PVSASTLARA GFLYTGEGDT 

        70         80         90        100        110        120 
VQCFSCHAAV DRWQYGDSAV GRHRRISPNC RFINGFYFEN GATQSTSPGI QNGQYKSENC 

       130        140        150        160        170        180 
VGNRNHFALD RPSETHADYL LRTGQVVDIS DTIYPRNPAM CSEEARLKTF QNWPDYAHLS 

       190        200        210        220        230        240 
PRELASAGLY YTGIDDQVQC FCCGGKLKNW EPCDRAWSEH RRHFPNCFFV LGRNVNVRSE 

       250        260        270        280        290        300 
SGVSSDRNFP NSTNSPRNPA MAEYDARIVT FGTWLYSVNK EQLARAGFYA LGEGDKVKCF 

       310        320        330        340        350        360 
HCGGGLTDWK PSEDPWEQHA KWYPGCKYLL DEKGQEYINN IHLTHSLGES VVRTAEKTPS 

       370        380        390        400        410        420 
VTKKIDDTIF QNPMVQEAIR MGFNFKDIKK TMEEKLQTSG SNYLSLEVLI ADLVSAQKDN 

       430        440        450        460        470        480 
SQDESSQTSL QKDISTEEQL RRLQEEKLCK ICMDRNIAIV FVPCGHLVTC KQCAEAVDKC 

       490 
PMCCTVITFK QKIFMS

« Hide

References

[1]"Rattus norvegicus X-linked inhibitor of apoptosis (riap3) mRNA."
Saito N.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AB033366 mRNA. Translation: BAA85304.1.
IPIIPI00569380.
RefSeqNP_071567.1. NM_022231.2.
UniGeneRn.91239.

3D structure databases

ProteinModelPortalQ9R0I6.
SMRQ9R0I6. Positions 20-99, 124-240, 242-354, 430-496.
ModBaseSearch...

Protein-protein interaction databases

MINTMINT-2839635.

Protein family/group databases

MEROPSI32.004.

PTM databases

PhosphoSiteQ9R0I6.

Proteomic databases

PaxDbQ9R0I6.
PRIDEQ9R0I6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000009336; ENSRNOP00000009336; ENSRNOG00000006967.
GeneID63879.
KEGGrno:63879.
UCSCRGD:620692. rat.

Organism-specific databases

CTD331.
RGD620692. Xiap.

Phylogenomic databases

eggNOGNOG243347.
GeneTreeENSGT00500000044782.
HOGENOMHOG000232059.
HOVERGENHBG004848.
KOK04725.
OrthoDBEOG45TCMX.

Gene expression databases

ArrayExpressQ9R0I6.
GenevestigatorQ9R0I6.
GermOnlineENSRNOG00000006967. Rattus norvegicus.

Family and domain databases

Gene3D1.10.1170.10. 4 hits.
InterProIPR001370. BIR.
IPR001841. Znf_RING.
[Graphical view]
PfamPF00653. BIR. 3 hits.
[Graphical view]
SMARTSM00238. BIR. 3 hits.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio612496.

Entry information

Entry nameXIAP_RAT
AccessionPrimary (citable) accession number: Q9R0I6
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: May 1, 2000
Last modified: April 3, 2013
This is version 87 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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