Myc box-dependent-interacting protein 1, also known as Bridging Integrator-1 and Amphiphysin-2 is a protein that in humans is encoded by the BIN1gene.
This gene encodes several isoforms of a nucleocytoplasmic adaptor protein, one of which was initially identified as a MYC-interacting protein with features of a tumor suppressor.
Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynanim, synaptojanin, endophilin, and clathrin.
Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process.
Studies in mouse suggest that this gene plays an important role in cardiac muscle development. Alternate splicing of the gene results in ten transcript variants encoding different isoforms. Aberrant splice variants expressed in tumor cell lines have also been described.
In humans, mutations in BIN1 have been associated with skeletal myopathies including centronuclear myopathy causing muscle weakness and myotonic dystrophy causing progressive muscle wasting, myotonia, cataracts, and heart conduction defects. An association has also been found between BIN1 mutations and Alzheimer's disease. Knockdown of BIN1 produces a cardiomyopathy phenotype in zebrafish, and in sheep BIN1 may be responsible for the loss of T-tubules seen in heart failure.
^Negorev D, Riethman H, Wechsler-Reya R, Sakamuro D, Prendergast GC, Simon D (January 1997). "The Bin1 gene localizes to human chromosome 2q14 by PCR analysis of somatic cell hybrids and fluorescence in situ hybridization". Genomics. 33 (2): 329–31. doi:10.1006/geno.1996.0205. PMID8725406.
^Sakamuro D, Elliott KJ, Wechsler-Reya R, Prendergast GC (October 1996). "BIN1 is a novel MYC-interacting protein with features of a tumour suppressor". Nat Genet. 14 (1): 69–77. doi:10.1038/ng0996-69. PMID8782822.
^ abNicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM, Biancalana V, Oldfors A, Mandel JL, Laporte J (August 2007). "Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy". Nat Genet. 39 (9): 1134–9. doi:10.1038/ng2086. PMID17676042.
^Leprince, Corinne; Le Scolan Erwan; Meunier Brigitte; Fraisier Vincent; Brandon Nathalie; De Gunzburg Jean; Camonis Jacques (May 2003). "Sorting nexin 4 and amphiphysin 2, a new partnership between endocytosis and intracellular trafficking". J. Cell Sci. 116 (Pt 10): 1937–48. doi:10.1242/jcs.00403. ISSN0021-9533. PMID12668730.
Leprince C, Romero F, Cussac D, et al. (1997). "A new member of the amphiphysin family connecting endocytosis and signal transduction pathways". J. Biol. Chem. 272 (24): 15101–5. doi:10.1074/jbc.272.24.15101. PMID9182529.
Ramjaun AR, Micheva KD, Bouchelet I, McPherson PS (1997). "Identification and characterization of a nerve terminal-enriched amphiphysin isoform". J. Biol. Chem. 272 (26): 16700–6. doi:10.1074/jbc.272.26.16700. PMID9195986.
Tsutsui K, Maeda Y, Tsutsui K, et al. (1997). "cDNA cloning of a novel amphiphysin isoform and tissue-specific expression of its multiple splice variants". Biochem. Biophys. Res. Commun. 236 (1): 178–83. doi:10.1006/bbrc.1997.6927. PMID9223448.
Micheva KD, Kay BK, McPherson PS (1997). "Synaptojanin forms two separate complexes in the nerve terminal. Interactions with endophilin and amphiphysin". J. Biol. Chem. 272 (43): 27239–45. doi:10.1074/jbc.272.43.27239. PMID9341169.
Wechsler-Reya R, Sakamuro D, Zhang J, et al. (1998). "Structural analysis of the human BIN1 gene. Evidence for tissue-specific transcriptional regulation and alternate RNA splicing". J. Biol. Chem. 272 (50): 31453–8. doi:10.1074/jbc.272.50.31453. PMID9395479.
Ramjaun AR, McPherson PS (1998). "Multiple amphiphysin II splice variants display differential clathrin binding: identification of two distinct clathrin-binding sites". J. Neurochem. 70 (6): 2369–76. doi:10.1046/j.1471-4159.1998.70062369.x. PMID9603201.
Mao NC, Steingrimsson E, DuHadaway J, et al. (1999). "The murine Bin1 gene functions early in myogenesis and defines a new region of synteny between mouse chromosome 18 and human chromosome 2". Genomics. 56 (1): 51–8. doi:10.1006/geno.1998.5709. PMID10036185.
Wixler V, Laplantine E, Geerts D, et al. (1999). "Identification of novel interaction partners for the conserved membrane proximal region of alpha-integrin cytoplasmic domains". FEBS Lett. 445 (2–3): 351–5. doi:10.1016/S0014-5793(99)00151-9. PMID10094488.
Ramjaun AR, Philie J, de Heuvel E, McPherson PS (1999). "The N terminus of amphiphysin II mediates dimerization and plasma membrane targeting". J. Biol. Chem. 274 (28): 19785–91. doi:10.1074/jbc.274.28.19785. PMID10391921.