Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

BIRC2 (Q13490) - Overview - Molecular Target Synopsis

Protein


BIRC2, Baculoviral IAP repeat-containing protein 2
Enzyme Classification 2.3.2.27
UniProt Q13490

Also Known as BIRC2_HUMAN, BIRC2, API1, MIHB, RNF48

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. 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. Interacts with HSP90AB1 (PubMed:25486457). Interacts with UBXN1 (PubMed:25681446).

2L9M
STRUCTURE OF CIAP1 CARD
RCSB/PDB
Inspect Structure
See all 3D Structures for BIRC2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: BIRC2 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: BIRC2 is active in the following subcellular-locations: CD40 receptor complex, cytoplasm, cytoplasmic side of plasma membrane, cytosol, membrane raft, nucleus, XY body.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project BIRC2 has gain in 15 cell-lines, loss in 7 cell-lines and no signal in 982 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_268, EKVX, SF_295

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SF268, HCC1576, Ca Ski

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, IMR-90

(see details)

3D Structures


For BIRC2 there are:
20 structures (39 chains) solved
12 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


BIRC2 has been screened with 546 compounds (734 bioactivities), 350 compounds have bioactivities that show binding affinity of <= 500nM (465 bioactivities). (see details)