A Novel Apoptosis Regulator
Abstract
BAR is a multi-domain protein. A screen for cDNAs encoding suppressors of Bax induced cell death was performed in the yeast S. cerevisiae, resulting in a cDNA containing an open reading frame (ORF) encoding a novel human protein of 450 amino acids (-52 kDa), which we assigned the acronym BAR, for Bi-functional Apoptosis Regulator (Accession number bankit 283835). The predicted BAR protein contains several protein domains, including: (1) an N-terminal zinc-binding RING domain at residues 24-86; (2) a SAM domain at amino acids 180-254; (3) a DED-like domain at 273-345, and (4) a C-terminal hydrophobic transmembrane (TM) domain at 400-428 (Figure 1A, B). The first two assignments have high statistical significance, with PSI-BLAST e. values of e-14 and e-28 respectively, indicating high confidence of the prediction. The DED-Like domain is not recognized by any of the standard sequence analysis programs, and instead was identified by detailed comparison to known DED proteins, as described below. The DED-like domain of BAR was most homologous to the first DED domain of pro-caspases-lO, sharing 21% amino acid sequence identity (39% similarity), respectively, with these proteins (Figure 1C). The BAR DED domain contains 14 of the 21 residues previously recognized to be conserved among DED-family domains based on sequence alignments (28), and 16 of the 19 hydrophobic residues known to be conserved among DED-family domains based on structural considerations (29). A consensus secondary-structure prediction based on PHD (30) and nearest neighbor (31) algorithms suggested the presence of six alpha-helices, consistent with the known structure of other DED- family proteins (29). The SAM domain of BAR shares greatest homology with the human Ephb2 SAM domain (17% identity), and is predicted by FFAS to adopt a four a-helix bundle structure typical of SAM domains (32), with excellent conservation of the signature residues found in other members of this domain family.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA385300
Entities
People
- Hong Zhang
Organizations
- Sanford Burnham Prebys Medical Discovery Institute