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O08863

- BIRC3_MOUSE

UniProt

O08863 - BIRC3_MOUSE

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Protein

Baculoviral IAP repeat-containing protein 3

Gene

Birc3

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi290 – 2901ZincPROSITE-ProRule annotation
Metal bindingi293 – 2931ZincPROSITE-ProRule annotation
Metal bindingi310 – 3101ZincPROSITE-ProRule annotation
Metal bindingi317 – 3171ZincPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri553 – 58836RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. ligase activity Source: UniProtKB-KW
  2. ubiquitin-protein transferase activity Source: Ensembl
  3. zinc ion binding Source: InterPro

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. necroptotic process Source: UniProtKB
  3. negative regulation of necroptotic process Source: UniProtKB
  4. negative regulation of phosphorylation Source: UniProtKB
  5. negative regulation of reactive oxygen species metabolic process Source: UniProtKB
  6. positive regulation of protein ubiquitination Source: Ensembl
  7. protein heterooligomerization Source: Ensembl
  8. regulation of apoptotic process Source: Ensembl
  9. spermatogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Apoptosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_226192. IKK complex recruitment mediated by RIP1.

Protein family/group databases

MEROPSiI32.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Baculoviral IAP repeat-containing protein 3 (EC:6.3.2.-)
Alternative name(s):
Inhibitor of apoptosis protein 1
Short name:
IAP-1
Short name:
mIAP-1
Short name:
mIAP1
Gene namesi
Name:Birc3
Synonyms:Birc2, Iap1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:1197007. Birc3.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. membrane raft Source: Ensembl
  3. nucleus Source: UniProtKB
  4. protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 600600Baculoviral IAP repeat-containing protein 3PRO_0000122350Add
BLAST

Post-translational modificationi

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

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiO08863.
PRIDEiO08863.

PTM databases

PhosphoSiteiO08863.

Expressioni

Gene expression databases

BgeeiO08863.
CleanExiMM_BIRC2.
MM_BIRC3.
ExpressionAtlasiO08863. baseline and differential.
GenevestigatoriO08863.

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. 14 interactions.
DIPiDIP-43742N.
IntActiO08863. 3 interactions.
MINTiMINT-1581324.

Structurei

3D structure databases

ProteinModelPortaliO08863.
SMRiO08863. Positions 24-96, 159-600.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati27 – 9468BIR 1Add
BLAST
Repeati167 – 23367BIR 2Add
BLAST
Repeati253 – 32068BIR 3Add
BLAST
Domaini436 – 52590CARDPROSITE-ProRule annotationAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri553 – 58836RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiNOG243347.
HOGENOMiHOG000232059.
HOVERGENiHBG004848.
InParanoidiO08863.
KOiK16060.

Family and domain databases

Gene3Di1.10.1170.10. 4 hits.
1.10.533.10. 1 hit.
InterProiIPR001370. BIR.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti398 – 3981W → R in AAC53531. (PubMed:9441758)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
U88908 mRNA. Translation: AAC53531.1 .
CT030639 Genomic DNA. No translation available.
RefSeqi NP_031490.2. NM_007464.3.
UniGenei Mm.2026.

3D structure databases

ProteinModelPortali O08863.
SMRi O08863. Positions 24-96, 159-600.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198147. 14 interactions.
DIPi DIP-43742N.
IntActi O08863. 3 interactions.
MINTi MINT-1581324.

Protein family/group databases

MEROPSi I32.003.

PTM databases

PhosphoSitei O08863.

Proteomic databases

PaxDbi O08863.
PRIDEi O08863.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 11796.
KEGGi mmu:11796.

Organism-specific databases

CTDi 330.
MGIi MGI:1197007. Birc3.

Phylogenomic databases

eggNOGi NOG243347.
HOGENOMi HOG000232059.
HOVERGENi HBG004848.
InParanoidi O08863.
KOi K16060.

Enzyme and pathway databases

Reactomei REACT_226192. IKK complex recruitment mediated by RIP1.

Miscellaneous databases

NextBioi 279629.
PROi O08863.
SOURCEi Search...

Gene expression databases

Bgeei O08863.
CleanExi MM_BIRC2.
MM_BIRC3.
ExpressionAtlasi O08863. baseline and differential.
Genevestigatori O08863.

Family and domain databases

Gene3Di 1.10.1170.10. 4 hits.
1.10.533.10. 1 hit.
InterProi IPR001370. BIR.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001841. Znf_RING.
[Graphical view ]
Pfami PF00653. BIR. 3 hits.
PF00619. CARD. 1 hit.
[Graphical view ]
SMARTi SM00238. BIR. 3 hits.
SM00114. CARD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 1 hit.
PROSITEi PS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50209. CARD. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Genomic characterization of the mouse inhibitor of apoptosis protein 1 and 2 genes."
    Liston P., Lefebvre C., Fong W.G., Xuan J.Y., Korneluk R.G.
    Genomics 46:495-503(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation."
    Varfolomeev E., Goncharov T., Fedorova A.V., Dynek J.N., Zobel K., Deshayes K., Fairbrother W.J., Vucic D.
    J. Biol. Chem. 283:24295-24299(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE.

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: October 29, 2014
This is version 125 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

External Data

Dasty 3