UniProtKB - Q62210 (BIRC2_MOUSE)
Protein
Baculoviral IAP repeat-containing protein 2
Gene
Birc2
Organism
Mus musculus (Mouse)
Status
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, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. 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. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.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 EC:2.3.2.27
Activity regulationi
The CARD domain inhibits the activation of E3 ubiquitin ligase activity by preventing RING domain dimerization and E2 ubiquitin donor binding and activation. The CARD domain-mediated autoinhibition of the E3 ubiquitin-protein ligase activity suppresses cell proliferation and migration. USP19 regulates the stability of BIRC2/c-IAP1 by preventing its ubiquitination (By similarity).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 299 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 302 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 319 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 326 | ZincPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 565 – 600 | RING-typePROSITE-ProRule annotationAdd BLAST | 36 |
GO - Molecular functioni
- chaperone binding Source: MGI
- cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: GO_Central
- FBXO family protein binding Source: MGI
- identical protein binding Source: MGI
- protein N-terminus binding Source: MGI
- transcription coactivator activity Source: UniProtKB
- transferase activity Source: MGI
- ubiquitin binding Source: MGI
- ubiquitin protein ligase activity Source: GO_Central
- ubiquitin-protein transferase activity Source: UniProtKB
- zinc ion binding Source: UniProtKB
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 apoptotic process Source: MGI
- negative regulation of necroptotic process Source: MGI
- negative regulation of ripoptosome assembly involved in necroptotic process Source: MGI
- placenta development Source: MGI
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
- positive regulation of protein K48-linked ubiquitination Source: UniProtKB
- positive regulation of protein K63-linked ubiquitination Source: UniProtKB
- positive regulation of protein monoubiquitination Source: MGI
- positive regulation of protein polyubiquitination Source: MGI
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
- protein heterooligomerization Source: MGI
- protein polyubiquitination Source: UniProtKB
- regulation of apoptotic process Source: MGI
- regulation of cell cycle Source: UniProtKB
- regulation of necroptotic process Source: MGI
- regulation of NIK/NF-kappaB signaling Source: MGI
- regulation of reactive oxygen species metabolic process Source: MGI
- response to cAMP Source: Ensembl
- response to ethanol Source: Ensembl
- response to hypoxia Source: MGI
Keywordsi
Molecular function | Activator, Transferase |
Biological process | Apoptosis, Transcription, Transcription regulation, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-111465 Apoptotic cleavage of cellular proteins R-MMU-168638 NOD1/2 Signaling Pathway R-MMU-5213460 RIPK1-mediated regulated necrosis R-MMU-5357905 Regulation of TNFR1 signaling R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway R-MMU-5668541 TNFR2 non-canonical NF-kB pathway R-MMU-5675482 Regulation of necroptotic cell death R-MMU-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway R-MMU-5689880 Ub-specific processing proteases R-MMU-937041 IKK complex recruitment mediated by RIP1 |
Protein family/group databases
MEROPSi | I32.007 |
Names & Taxonomyi
Protein namesi | Recommended name: Baculoviral IAP repeat-containing protein 2 (EC:2.3.2.271 Publication)Alternative name(s): Cellular inhibitor of apoptosis 1 Short name: C-IAP11 Publication Inhibitor of apoptosis protein 21 Publication Short name: mIAP21 Publication RING-type E3 ubiquitin transferase BIRC2Curated |
Gene namesi | Name:Birc2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1197009 Birc2 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Cytoplasm By similarity
Note: Agents that induce either the extrinsic or intrinsic apoptotic pathways promote its redistribution from the nuclear compartment to the cytoplasmic compartment. Associated with the midbody in telophase cells, and found diffusely in the nucleus of interphase cells (By similarity).By similarity
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- CD40 receptor complex Source: BHF-UCL
- cytoplasmic side of plasma membrane Source: BHF-UCL
Other locations
- cytoplasm Source: MGI
- membrane raft Source: MGI
- protein-containing complex Source: MGI
- XY body Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000122348 | 1 – 612 | Baculoviral IAP repeat-containing protein 2Add BLAST | 612 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 143 | Omega-N-methylarginineCombined sources | 1 | |
Modified residuei | 153 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.By similarity
Keywords - PTMi
Methylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q62210 |
MaxQBi | Q62210 |
PaxDbi | Q62210 |
PRIDEi | Q62210 |
PTM databases
iPTMneti | Q62210 |
PhosphoSitePlusi | Q62210 |
Expressioni
Tissue specificityi
Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.
Gene expression databases
Bgeei | ENSMUSG00000057367 Expressed in 294 organ(s), highest expression level in blood |
ExpressionAtlasi | Q62210 baseline and differential |
Genevisiblei | Q62210 MM |
Interactioni
Subunit structurei
Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with CASP9. Interacts (via BIR domains) with TRAF2; the interaction is required for IKBKE ubiquitination. Interacts with E2F1, RIPK1, RIPK2, RIPK3, RIPK4, BIRC5/survivin and USP19 (By similarity). Interacts with HSP90AB1 (By similarity).By similarity
GO - Molecular functioni
- chaperone binding Source: MGI
- FBXO family protein binding Source: MGI
- identical protein binding Source: MGI
- protein N-terminus binding Source: MGI
- ubiquitin binding Source: MGI
Protein-protein interaction databases
BioGridi | 198148, 6 interactors |
CORUMi | Q62210 |
IntActi | Q62210, 3 interactors |
MINTi | Q62210 |
STRINGi | 10090.ENSMUSP00000091422 |
Structurei
3D structure databases
ProteinModelPortali | Q62210 |
SMRi | Q62210 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 46 – 113 | BIR 1Add BLAST | 68 | |
Repeati | 177 – 243 | BIR 2Add BLAST | 67 | |
Repeati | 262 – 329 | BIR 3Add BLAST | 68 | |
Domaini | 447 – 537 | CARDPROSITE-ProRule annotationAdd BLAST | 91 |
Domaini
The BIR domains mediate nuclear localization.By similarity
The CARD domain is necessary to stabilize the protein and inhibit the activation of E3 ubiquitin-protein ligase activity of BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin donor binding and activation.By similarity
Sequence similaritiesi
Belongs to the IAP family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 565 – 600 | RING-typePROSITE-ProRule annotationAdd BLAST | 36 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1101 Eukaryota ENOG410YPNM LUCA |
GeneTreei | ENSGT00940000154175 |
HOGENOMi | HOG000232059 |
HOVERGENi | HBG004848 |
InParanoidi | Q62210 |
KOi | K16060 |
OMAi | YFCGVEI |
OrthoDBi | 1340284at2759 |
PhylomeDBi | Q62210 |
TreeFami | TF105356 |
Family and domain databases
CDDi | cd00022 BIR, 3 hits |
InterProi | View protein in InterPro IPR001370 BIR_rpt IPR001315 CARD IPR011029 DEATH-like_dom_sf IPR001841 Znf_RING |
Pfami | View protein in Pfam PF00653 BIR, 3 hits PF00619 CARD, 1 hit |
SMARTi | View protein in SMART SM00238 BIR, 3 hits SM00114 CARD, 1 hit SM00184 RING, 1 hit |
SUPFAMi | SSF47986 SSF47986, 1 hit |
PROSITEi | View protein in PROSITE PS01282 BIR_REPEAT_1, 3 hits PS50143 BIR_REPEAT_2, 3 hits PS50209 CARD, 1 hit PS50089 ZF_RING_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q62210-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MDKTVSQRLG QGTLHQKLKR IMEKSTILSN WTKESEEKMK FDFSCELYRM
60 70 80 90 100
STYSAFPRGV PVSERSLARA GFYYTGVNDK VKCFCCGLML DNWKQGDSPV
110 120 130 140 150
EKHRQFYPSC SFVQTLLSAS LQSPSKNMSP VKSRFAHSSP LERGGIHSNL
160 170 180 190 200
CSSPLNSRAV EDFSSRMDPC SYAMSTEEAR FLTYSMWPLS FLSPAELARA
210 220 230 240 250
GFYYIGPGDR VACFACGGKL SNWEPKDDAM SEHRRHFPHC PFLENTSETQ
260 270 280 290 300
RFSISNLSMQ THSARLRTFL YWPPSVPVQP EQLASAGFYY VDRNDDVKCF
310 320 330 340 350
CCDGGLRCWE PGDDPWIEHA KWFPRCEFLI RMKGQEFVDE IQARYPHLLE
360 370 380 390 400
QLLSTSDTPG EENADPTETV VHFGPGESSE DVVMMSTPVV KAALEMGFSR
410 420 430 440 450
SLVRQTVQRQ ILATGENYRT VNDIVSVLLN AEDERREEEK ERQTEEMASG
460 470 480 490 500
DLSLIRKNRM ALFQQLTHVL PILDNLLEAS VITKQEHDII RQKTQIPLQA
510 520 530 540 550
RELIDTVLVK GNAAANIFKN SLKEIDSTLY ENLFVEKNMK YIPTEDVSGL
560 570 580 590 600
SLEEQLRRLQ EERTCKVCMD REVSIVFIPC GHLVVCQECA PSLRKCPICR
610
GTIKGTVRTF LS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketF6X8Q0 | F6X8Q0_MOUSE | Baculoviral IAP repeat-containing p... | Birc2 | 125 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 380 | E → K in AAC53532 (PubMed:9441758).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L49433 mRNA Translation: AAC42078.1 U88909 mRNA Translation: AAC53532.1 BC145985 mRNA Translation: AAI45986.1 |
CCDSi | CCDS22811.1 |
RefSeqi | NP_001278432.1, NM_001291503.1 NP_031491.2, NM_007465.3 XP_017168599.1, XM_017313110.1 |
UniGenei | Mm.335659 Mm.400826 |
Genome annotation databases
Ensembli | ENSMUST00000074246; ENSMUSP00000091422; ENSMUSG00000057367 ENSMUST00000190341; ENSMUSP00000140049; ENSMUSG00000057367 |
GeneIDi | 11797 |
KEGGi | mmu:11797 |
UCSCi | uc009ocz.2 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L49433 mRNA Translation: AAC42078.1 U88909 mRNA Translation: AAC53532.1 BC145985 mRNA Translation: AAI45986.1 |
CCDSi | CCDS22811.1 |
RefSeqi | NP_001278432.1, NM_001291503.1 NP_031491.2, NM_007465.3 XP_017168599.1, XM_017313110.1 |
UniGenei | Mm.335659 Mm.400826 |
3D structure databases
ProteinModelPortali | Q62210 |
SMRi | Q62210 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 198148, 6 interactors |
CORUMi | Q62210 |
IntActi | Q62210, 3 interactors |
MINTi | Q62210 |
STRINGi | 10090.ENSMUSP00000091422 |
Protein family/group databases
MEROPSi | I32.007 |
PTM databases
iPTMneti | Q62210 |
PhosphoSitePlusi | Q62210 |
Proteomic databases
EPDi | Q62210 |
MaxQBi | Q62210 |
PaxDbi | Q62210 |
PRIDEi | Q62210 |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENSMUST00000074246; ENSMUSP00000091422; ENSMUSG00000057367 ENSMUST00000190341; ENSMUSP00000140049; ENSMUSG00000057367 |
GeneIDi | 11797 |
KEGGi | mmu:11797 |
UCSCi | uc009ocz.2 mouse |
Organism-specific databases
CTDi | 329 |
MGIi | MGI:1197009 Birc2 |
Phylogenomic databases
eggNOGi | KOG1101 Eukaryota ENOG410YPNM LUCA |
GeneTreei | ENSGT00940000154175 |
HOGENOMi | HOG000232059 |
HOVERGENi | HBG004848 |
InParanoidi | Q62210 |
KOi | K16060 |
OMAi | YFCGVEI |
OrthoDBi | 1340284at2759 |
PhylomeDBi | Q62210 |
TreeFami | TF105356 |
Enzyme and pathway databases
Reactomei | R-MMU-111465 Apoptotic cleavage of cellular proteins R-MMU-168638 NOD1/2 Signaling Pathway R-MMU-5213460 RIPK1-mediated regulated necrosis R-MMU-5357905 Regulation of TNFR1 signaling R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway R-MMU-5668541 TNFR2 non-canonical NF-kB pathway R-MMU-5675482 Regulation of necroptotic cell death R-MMU-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway R-MMU-5689880 Ub-specific processing proteases R-MMU-937041 IKK complex recruitment mediated by RIP1 |
Miscellaneous databases
ChiTaRSi | Birc2 mouse |
PROi | PR:Q62210 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000057367 Expressed in 294 organ(s), highest expression level in blood |
ExpressionAtlasi | Q62210 baseline and differential |
Genevisiblei | Q62210 MM |
Family and domain databases
CDDi | cd00022 BIR, 3 hits |
InterProi | View protein in InterPro IPR001370 BIR_rpt IPR001315 CARD IPR011029 DEATH-like_dom_sf IPR001841 Znf_RING |
Pfami | View protein in Pfam PF00653 BIR, 3 hits PF00619 CARD, 1 hit |
SMARTi | View protein in SMART SM00238 BIR, 3 hits SM00114 CARD, 1 hit SM00184 RING, 1 hit |
SUPFAMi | SSF47986 SSF47986, 1 hit |
PROSITEi | View protein in PROSITE PS01282 BIR_REPEAT_1, 3 hits PS50143 BIR_REPEAT_2, 3 hits PS50209 CARD, 1 hit PS50089 ZF_RING_2, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | BIRC2_MOUSE | |
Accessioni | Q62210Primary (citable) accession number: Q62210 Secondary accession number(s): A6H6S7, O08864 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1996 | |
Last modified: | February 13, 2019 | |
This is version 172 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot