Tchem BIRC2 Baculoviral IAP repeat-containing protein 2

Protein Summary

Description

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. The protein encoded by this gene is a member of a family of proteins that inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. This encoded protein inhibits apoptosis induced by serum deprivation and menadione, a potent inducer of free radicals. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Uniprot Accession IDs

• Q13490
• B4E026
• Q16516
• Q4TTG0

Gene Name

• BIRC2

Ensembl ID

• ENST00000227758
• ENSP00000227758
• ENSG00000110330
• ENST00000530675
• ENSP00000431723
• ENST00000613397
• ENSP00000477613

Symbol

• API1
• MIHB
• RNF48
• API1
• MIHB
• HIAP2
• RNF48
• cIAP1
• Hiap-2
• c-IAP1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
disease perturbation	0.99
chemical	0.95
virus perturbation	0.94
molecular function	0.9

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Protease Inhibitor / Baculoviral Iap Repeat-containing Protein 2

DTO Classes

Protein / Enzyme Modulator / Protease Inhibitor / Baculoviral Iap Repeat-containing Protein 2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 466.19   (req: < 5)

Gene RIFs: 128   (req: <= 3)

Antibodies: 447   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 466.19   (req: >= 5)

Gene RIFs: 128   (req: > 3)

Antibodies: 447   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 46

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 525

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (525)

Explore Active Ligands

1 – 10 of 525

GDC-0152

BIRC2Tchem

pKi : 7.8

birinapant

BIRC2Tchem

pKd : 9

SM-337

BIRC2Tchem

pKi : 8.38

SM-122

BIRC2Tchem

pKi : 8.74

CHEMBL456400

BIRC2Tchem

pKi : 8.72

AT-406

BIRC2Tchem

pKi : 8.72

AZD5582

BIRC2Tchem

pEC50 : 10

LCL161

BIRC2Tchem

pKd : 7.98

CHEMBL2436227,CHEMBL2431755

BIRC2Tchem

pKi : 6

CHEMBL4064619

BIRC2Tchem

pIC50 : 9.49

Protein-Protein Interactions (290)

Explore Interacting Targets

1 – 10 of 290

• See Interactions on String-DB

TRAF2

Tbio

Novelty:  0.00983658

p_int:  1

Score:  0.997

Data Source:  BioPlex,Reactome,STRINGDB

DIABLO

Tbio

Novelty:  0.0007851

p_int:  0.99999986

p_ni:  1.4e-7

Score:  0.998

Data Source:  BioPlex,STRINGDB

TRAF1

Tbio

Novelty:  0.00526776

p_int:  0.99999919

p_ni:  8.1e-7

Score:  0.989

Data Source:  BioPlex,STRINGDB

PDIA5

Tbio

Family:  Enzyme

Novelty:  0.06234465

p_int:  0.999996205

p_ni:  0.000003795

Data Source:  BioPlex

CXCL1

Tbio

Novelty:  0.00059123

p_int:  0.999995556

p_ni:  0.000004444

Score:  0.214

Data Source:  BioPlex,STRINGDB

WDYHV1

Tbio

Family:  Enzyme

Novelty:  0.1844203

p_int:  0.999992331

p_ni:  0.000007668

p_wrong:  1e-9

Data Source:  BioPlex

CXCL3

Tbio

Novelty:  0.01001656

p_int:  0.999967534

p_ni:  0.000032466

Data Source:  BioPlex

LRRN2

Tdark

Novelty:  0.22583761

p_int:  0.999963181

p_ni:  0.000036818

p_wrong:  1e-9

Score:  0.341

Data Source:  BioPlex,STRINGDB

LTBR

Tbio

Novelty:  0.003823

p_int:  0.999936348

p_ni:  0.000063651

p_wrong:  2e-9

Score:  0.959

Data Source:  BioPlex,Reactome,STRINGDB

OSTM1

Tbio

Novelty:  0.03033192

p_int:  0.999928866

p_ni:  0.000071134

Data Source:  BioPlex

Nearest Tclin Targets (2)

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Upstream (2)

1 – 2 of 2

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  3

Common Pathways:  4

1: Focal adhesion

2: TNF signaling pathway

3: Pathways in cancer

4: Apoptosis

TNF

Tclin

Family:  Other

KEGG Distance:  3

Common Pathways:  7

1: TNF signaling pathway

2: Necroptosis

3: NOD-like receptor signaling pathway

4: Toxoplasmosis

more:  3 more common pathways

Pathways (60)

Reactome (30)

KEGG (14)

PathwayCommons (8)

WikiPathways (8)

Apoptosis (R-HSA-109581)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Apoptosis	177 targets	R-HSA-109581
Reactome	Apoptotic cleavage of cellular proteins	38 targets	R-HSA-111465
Reactome	Apoptotic execution phase	52 targets	R-HSA-75153
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Death Receptor Signalling	141 targets	R-HSA-73887

Name	Explore in Pharos	Explore in Source
Apoptosis	177 targets	R-HSA-109581
Apoptotic cleavage of cellular proteins	38 targets	R-HSA-111465
Apoptotic execution phase	52 targets	R-HSA-75153
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Death Receptor Signalling	141 targets	R-HSA-73887

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (53)

Functions (11)

Components (7)

Processes (35)

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1 – 10 of 11

GO Term	Evidence	Assigned by
transferase activity	Inferred from Experiment (EXP)	Reactome
ubiquitin binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
ubiquitin-protein transferase activity	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
chaperone binding	Inferred from Physical Interaction (IPI)	UniProtKB
FBXO family protein binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein N-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
transcription coactivator activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
cysteine-type endopeptidase inhibitor activity involved in apoptotic process	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations ()

No disease associations found

GWAS Traits (4)

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1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
serum non-albumin protein measurement	EFO_0004568	1	2	2		71
matrix metalloproteinase 1 measurement	EFO_0010588	1	1	1		64.4
blood protein measurement	EFO_0007937	1	1	1		10.6
testosterone measurement	EFO_0004908	1	1	1		1.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
serum non-albumin protein measurement	EFO_0004568	2		71
matrix metalloproteinase 1 measurement	EFO_0010588	1		64.4
blood protein measurement	EFO_0007937	1		10.6
testosterone measurement	EFO_0004908	1		1.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Activator
Alternative splicing
Apoptosis
Complete proteome
Cytoplasm
Metal-binding
Nucleus
Polymorphism
Reference proteome

GWAS Trait Find Similar Targets

No Header	No Header
blood protein measurement
matrix metalloproteinase 1 measurement
serum non-albumin protein measurement
testosterone measurement

MGI Phenotype Find Similar Targets

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cellular phenotype
hematopoietic system phenotype
immune system phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	baculoviral IAP repeat containing 2	VGNC:3201	451508
Macaque	baculoviral IAP repeat containing 2		702592
Mouse	baculoviral IAP repeat-containing 2	MGI:1197009	11797
Rat	baculoviral IAP repeat-containing 2	RGD:620690	60371
Dog	baculoviral IAP repeat containing 2	VGNC:38460	479464

Species	Name	OMA	EggNOG	Inparanoid
Chimp	baculoviral IAP repeat containing 2
Macaque	baculoviral IAP repeat containing 2
Mouse	baculoviral IAP repeat-containing 2
Rat	baculoviral IAP repeat-containing 2
Dog	baculoviral IAP repeat containing 2

Publication Statistics

PubMed Score 466.19

PubMed score by year

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PubTator Score 319.44

PubTator score by year

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Related Publications

Text Mined References (183)

GeneRif Annotations (128)

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PMID	Year	Title