Alternative titles; symbols
HGNC Approved Gene Symbol: SH3GLB1
Cytogenetic location: 1p22.3 Genomic coordinates (GRCh38): 1:86,704,576-86,748,184 (from NCBI)
Using BAX (600040) as bait in a yeast 2-hybrid screen of a skeletal muscle cDNA library, Pierrat et al. (2001) cloned SH3GLB1. The deduced 362-amino acid protein contains an N-terminal domain, a central coiled-coil region, and a C-terminal SH3 domain. SH3GLB1 shares 65% amino acid identity with SH3GLB2 (609288). Northern blot analysis detected a major 1.9-kb transcript and a minor 1.7-kb transcript in most tissues examined, with higher levels in heart, placenta, and skeletal muscle. Osteosarcoma and HeLa cells transfected with SH3GLB1 expressed the protein in the cytoplasm, but it was excluded from the nucleus.
Cuddeback et al. (2001) cloned SH3GLB1, which they called BIF1, using BAX as bait in a yeast 2-hybrid screen of a brain cDNA library. The deduced protein contains 365 amino acids. Northern blot analysis revealed abundant expression in heart, skeletal muscle, kidney, and placenta. Transcripts of 1.5, 2.0, and 6.0 kb were detected. Fluorescence-tagged SH3GLB1 showed a cytoplasmic distribution, and a proportion of the protein associated with mitochondria.
Modregger et al. (2003) cloned several variants of mouse Sh3glb1, which they called endophilin B1. The deduced proteins range from 365 to 386 residues in length. The N-terminal domain of endophilin B1 shares highest similarity with the lipid-binding and -modifying (LBM) domain of class A endophilins (see SH3GL2; 604465), which mediates lysophosphatidic acid (LPA) acyltransferase activity, liposome binding, and tubulation. Northern blot analysis detected transcripts of 2.6, 5.0, 6.5, and 8.0 kb that were generated by alternative splicing and the use of alternate polyadenylation signals. Two brain-specific transcripts, designated endophilins B1b and B1c, differ in the 3-prime exon 6 splice site. The ubiquitously expressed transcript, endophilin B1a, lacks exons 6 and 7. Western blot analysis detected a 40-kD protein in most mouse tissues, a 42-kD protein in brain only, and a 43-kD protein in lung and spleen only. Confocal microscopy detected epitope-tagged endophilin B1b in a reticular pattern throughout the cytoplasm. Endophilin B1b associated with membranes in fractionated mouse brain homogenates.
Using SH3GLB1 truncation mutants, Pierrat et al. (2001) determined that the first 42 N-terminal amino acids of SH3GLB1, and not the SH3 domain, were required for its interaction with BAX, and a point mutation at val5 of SH3GLB1 abrogated the interaction. SH3GLB1 could form homodimers and heterodimers with SH3GLB2. Mutation analysis indicated that the coiled-coil region between amino acids 153 and 183 was required for homo- and heterodimer formation. SH3GLB1 overexpression in HeLa and human embryonic kidney cells had a general weak protective effect (5 to 10%) against cell death induced by BAX overexpression, FAS ligand (TNFSF6; 134638), and chemical agents.
By yeast 2-hybrid analysis, Cuddeback et al. (2001) confirmed a direct interaction between SH3GLB1 and BAX. Immunoprecipitation analysis detected an endogenous interaction between Sh3glb1 and Bax in a mouse hematopoietic cell line. Induction of apoptosis by interleukin-3 (IL3; 147740) withdrawal increased the association of Bax with Sh3glb1, and this was accompanied by a conformational change in the Bax protein. Overexpression of Sh3glb1 promoted Bax conformational change, caspase activation, and apoptotic cell death in mouse hematopoietic cells following IL3 deprivation.
Modregger et al. (2003) found that immobilized mouse endophilin B1 bound dynamin (see 602378), huntingtin (HTT; 613004), and 2 amphiphysins (see 600418) in mouse brain detergent extracts. It did not bind synaptojanin-1 (SYNJ1; 604297). Yeast 2-hybrid analysis confirmed that endophilin B1b interacts with dynamin and huntingtin, and the SH3 domain of endophilin B1b was sufficient for these interactions. Endophilin B1b also interacted with itself, and this self-interaction required the N-terminal LBM domain and the coiled-coil region. Endophilin B1b expressed in mouse fibroblasts bound palmitoyl-CoA.
Gallop et al. (2005) found that the LPA acyltransferase, or LPAAT, activity associated with endophilin (e.g., Modregger et al., 2003) is a contaminant of the purification procedure and could also be found associated with the pleckstrin homology domain of dynamin.
Karbowski et al. (2004) found that knockdown of endophilin B1 in HeLa cells by RNA interference led to changes in mitochondrial shape, formation of vesicular structures continuous with mitochondria, and a separation of the outer and inner mitochondrial membrane compartments. Overexpression of endophilin B1 lacking the N-terminal LBM domain caused similar changes. Endophilin B1 translocated to mitochondria during synchronous remodeling of the mitochondrial network during apoptosis. Double knockdown of endophilin B1 and DRP1 (DNM1L; 602462) led to a mitochondrial phenotype identical to that of DRP1 single knockdown. Karbowski et al. (2004) concluded that endophilin B1 is required for the maintenance of mitochondria and that DRP1 acts upstream of endophilin B1.
Modregger et al. (2003) determined that the SH3GLB1 gene contains 11 exons.
By genomic sequence analysis, Modregger et al. (2003) mapped the SH3GLB1 gene to chromosome 1p31.1-p22.2.
Kim et al. (2008) detected only 1 somatic mutation in the BIF1 gene among 284 human cancer tissues of various origin. They concluded that BIF1 mutation is rare in cancers.
Cuddeback, S. M., Yamaguchi, H., Komatsu, K., Miyashita, T., Yamada, M., Wu, C., Singh, S., Wang, H.-G. Molecular cloning and characterization of Bif-1: a novel Src homology 3 domain-containing protein that associates with Bax. J. Biol. Chem. 276: 20559-20565, 2001. [PubMed: 11259440] [Full Text: https://doi.org/10.1074/jbc.M101527200]
Gallop, J. L., Butler, P. J. G., McMahon, H. T. Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 438: 675-678, 2005. [PubMed: 16319893] [Full Text: https://doi.org/10.1038/nature04136]
Karbowski, M., Jeong, S.-Y., Youle, R. J. Endophilin B1 is required for the maintenance of mitochondrial morphology. J. Cell Biol. 166: 1027-1039, 2004. [PubMed: 15452144] [Full Text: https://doi.org/10.1083/jcb.200407046]
Kim, M. S., Yoo, N. J., Lee, S. H. Somatic mutation of pro-cell death Bif-1 gene is rare in common human cancers. (Letter) APMIS 116: 939-940, 2008. [PubMed: 19132989] [Full Text: https://doi.org/10.1111/j.1600-0463.2008.01091.x]
Modregger, J., Schmidt, A. A., Ritter, B., Huttner, W. B., Plomann, M. Characterization of endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl transferase with properties distinct from endophilin A1. J. Biol. Chem. 278: 4160-4167, 2003. [PubMed: 12456676] [Full Text: https://doi.org/10.1074/jbc.M208568200]
Pierrat, B., Simonen, M., Cueto, M., Mestan, J., Ferrigno, P., Heim, J. SH3GLB, a new endophilin-related protein family featuring an SH3 domain. Genomics 71: 222-234, 2001. [PubMed: 11161816] [Full Text: https://doi.org/10.1006/geno.2000.6378]