1.A.20 The BCL2/Adenovirus E1B-interacting Protein 3 (BNip3) Family
BNip3 is a prominent representative of apoptotic Bcl-2 proteins with rather unique properties initiating an atypical programmed cell death pathway resembling both necrosis and apoptosis. Many Bcl-2 family proteins modulate the permeability state of the outer mitochondrial membrane by forming homo- and hetero-oligomers. The structure and dynamics of the homodimeric transmembrane domain of BNip3 have been investigated (Bocharov et al., 2007). The right-handed parallel helix-helix structure of the domain with a hydrogen bond-rich His-Ser node in the middle of the membrane, accessibility of the node for water, and continuous hydrophilic track across the membrane suggest that the domain can provide an ion-conducting pathway through the membrane. Incorporation of the BNip3 transmembrane domain into an artificial lipid bilayer resulted in a pH-dependent conductivity increase. Necrosis-like cell death induced by BNip3 may be related to this activity. Sequence similarity with Bcl-2 family members was not detected.
Humans and other animals (Drosophila, Caenorhabditis) as well as lower eukaryotes (Dictyostelium, Trypanosoma, Cryptospondium, Paramecium) encode several BNIP3 paralogues including the human NIP3L which induces apoptosis by interacting with viral and cellular anti-apoptosis proteins. May function as a tumor suppressor. Inhibits apptosis by BNIP3. It interacts with BNIP3 and STEAP3. Common domains are also found in other proteins such as adenylate cyclases and clumping factor B of Staphylococcus aureus (345 aas; CAL50888) which contains six repeats similar to residues 49-115 in BNIP3.
The reaction catalyzed by BNip3 is:
Small molecules (out) small molecules (in)
NIP3L (NIP3-like protein X; Adenovirus E1B 19kDa-binding protein B5).
NIP3L of Homo sapiens (O60238)
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 homologue of 215 aas and 1 C-terminal TMS.
BCL2 of Aquila chrysaetos canadensis
BCL2/Adenovirus E1B interacting protein, NIP3
NIP3 of Caenorhabditis elegans (Q09969)
NIP2-like protein of 195 aas and 1 C-terminal TMS
NIP3 of Trichinella spiralis (Trichina worm)