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Protein

Baculoviral IAP repeat-containing protein 3

Gene

Birc3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). 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 CASP8.1 Publication

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Enzyme regulationi

USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi290ZincPROSITE-ProRule annotation1
Metal bindingi293ZincPROSITE-ProRule annotation1
Metal bindingi310ZincPROSITE-ProRule annotation1
Metal bindingi317ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri553 – 588RING-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

GO - Biological processi

  • cellular response to tumor necrosis factor Source: MGI
  • inhibition of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
  • necroptotic process Source: UniProtKB
  • negative regulation of necroptotic process Source: UniProtKB
  • negative regulation of phosphorylation Source: UniProtKB
  • negative regulation of reactive oxygen species metabolic process Source: UniProtKB
  • positive regulation of protein polyubiquitination Source: MGI
  • positive regulation of protein ubiquitination Source: MGI
  • regulation of apoptotic process Source: MGI
  • regulation of necroptotic process Source: MGI
  • regulation of NIK/NF-kappaB signaling Source: MGI
  • regulation of toll-like receptor signaling pathway Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Apoptosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiI32.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Baculoviral IAP repeat-containing protein 3 (EC:2.3.2.271 Publication)
Alternative name(s):
Cellular inhibitor of apoptosis 2
Short name:
C-IAP21 Publication
Inhibitor of apoptosis protein 11 Publication
Short name:
mIAP11 Publication
RING-type E3 ubiquitin transferase BIRC3Curated
Gene namesi
Name:Birc3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1197007. Birc3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001223501 – 600Baculoviral IAP repeat-containing protein 3Add BLAST600

Post-translational modificationi

Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiO08863.
PaxDbiO08863.
PRIDEiO08863.

PTM databases

iPTMnetiO08863.
PhosphoSitePlusiO08863.

Expressioni

Gene expression databases

BgeeiENSMUSG00000032000.
CleanExiMM_BIRC2.
MM_BIRC3.

Interactioni

Subunit structurei

Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. The BIR motifs region interacts with TNF receptor associated factors 1 and 2 (TRAF1 and TRAF2) to form a heteromeric complex, which is then recruited to the tumor necrosis factor receptor 2 (TNFR2). Interaction with TRAF2 is required for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts with RIP1, RIP2, RIP3, RIP4 and USP19 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Traf2P394297EBI-642236,EBI-520016

Protein-protein interaction databases

BioGridi198147. 15 interactors.
DIPiDIP-43742N.
IntActiO08863. 3 interactors.
MINTiMINT-1581324.
STRINGi10090.ENSMUSP00000013949.

Structurei

3D structure databases

ProteinModelPortaliO08863.
SMRiO08863.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati27 – 94BIR 1Add BLAST68
Repeati167 – 233BIR 2Add BLAST67
Repeati253 – 320BIR 3Add BLAST68
Domaini436 – 525CARDPROSITE-ProRule annotationAdd BLAST90

Sequence similaritiesi

Belongs to the IAP family.Curated
Contains 3 BIR repeats.PROSITE-ProRule annotation
Contains 1 CARD domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri553 – 588RING-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1101. Eukaryota.
ENOG410YPNM. LUCA.
HOGENOMiHOG000232059.
HOVERGENiHBG004848.
InParanoidiO08863.
KOiK16060.

Family and domain databases

CDDicd00022. BIR. 3 hits.
Gene3Di1.10.1170.10. 4 hits.
1.10.533.10. 1 hit.
InterProiIPR001370. BIR_rpt.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001841. Znf_RING.
[Graphical view]
PfamiPF00653. BIR. 3 hits.
PF00619. CARD. 1 hit.
[Graphical view]
SMARTiSM00238. BIR. 3 hits.
SM00114. CARD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50209. CARD. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08863-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVQDSAFLAK LMKSADTFEL KYDFSCELYR LSTYSAFPRG VPVSERSLAR
60 70 80 90 100
AGFYYTGAND KVKCFCCGLM LDNWKQGDSP MEKHRKLYPS CNFVQTLNPA
110 120 130 140 150
NSLEASPRPS LPSTAMSTMP LSFASSENTG YFSGSYSSFP SDPVNFRANQ
160 170 180 190 200
DCPALSTSPY HFAMNTEKAR LLTYETWPLS FLSPAKLAKA GFYYIGPGDR
210 220 230 240 250
VACFACDGKL SNWERKDDAM SEHQRHFPSC PFLKDLGQSA SRYTVSNLSM
260 270 280 290 300
QTHAARIRTF SNWPSSALVH SQELASAGFY YTGHSDDVKC FCCDGGLRCW
310 320 330 340 350
ESGDDPWVEH AKWFPRCEYL LRIKGQEFVS QVQAGYPHLL EQLLSTSDSP
360 370 380 390 400
EDENADAAIV HFGPGESSED VVMMSTPVVK AALEMGFSRS LVRQTVQWQI
410 420 430 440 450
LATGENYRTV SDLVIGLLDA EDEMREEQME QAAEEEESDD LALIRKNKMV
460 470 480 490 500
LFQHLTCVTP MLYCLLSARA ITEQECNAVK QKPHTLQAST LIDTVLAKGN
510 520 530 540 550
TAATSFRNSL REIDPALYRD IFVQQDIRSL PTDDIAALPM EEQLRKLQEE
560 570 580 590 600
RMCKVCMDRE VSIVFIPCGH LVVCKDCAPS LRKCPICRGT IKGTVRTFLS
Length:600
Mass (Da):67,228
Last modified:July 27, 2011 - v2
Checksum:i2EC9C7B567721382
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti398W → R in AAC53531 (PubMed:9441758).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88908 mRNA. Translation: AAC53531.1.
CT030639 Genomic DNA. No translation available.
RefSeqiNP_031490.2. NM_007464.3.
UniGeneiMm.2026.

Genome annotation databases

GeneIDi11796.
KEGGimmu:11796.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88908 mRNA. Translation: AAC53531.1.
CT030639 Genomic DNA. No translation available.
RefSeqiNP_031490.2. NM_007464.3.
UniGeneiMm.2026.

3D structure databases

ProteinModelPortaliO08863.
SMRiO08863.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198147. 15 interactors.
DIPiDIP-43742N.
IntActiO08863. 3 interactors.
MINTiMINT-1581324.
STRINGi10090.ENSMUSP00000013949.

Protein family/group databases

MEROPSiI32.003.

PTM databases

iPTMnetiO08863.
PhosphoSitePlusiO08863.

Proteomic databases

EPDiO08863.
PaxDbiO08863.
PRIDEiO08863.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi11796.
KEGGimmu:11796.

Organism-specific databases

CTDi330.
MGIiMGI:1197007. Birc3.

Phylogenomic databases

eggNOGiKOG1101. Eukaryota.
ENOG410YPNM. LUCA.
HOGENOMiHOG000232059.
HOVERGENiHBG004848.
InParanoidiO08863.
KOiK16060.

Miscellaneous databases

PROiO08863.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032000.
CleanExiMM_BIRC2.
MM_BIRC3.

Family and domain databases

CDDicd00022. BIR. 3 hits.
Gene3Di1.10.1170.10. 4 hits.
1.10.533.10. 1 hit.
InterProiIPR001370. BIR_rpt.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001841. Znf_RING.
[Graphical view]
PfamiPF00653. BIR. 3 hits.
PF00619. CARD. 1 hit.
[Graphical view]
SMARTiSM00238. BIR. 3 hits.
SM00114. CARD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50209. CARD. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBIRC3_MOUSE
AccessioniPrimary (citable) accession number: O08863
Secondary accession number(s): E9QLX3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.