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.[5][6][7]
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.[8]
Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process.[8]
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.[8]
Clinical significance
In humans, mutations in BIN1 have been associated with skeletal myopathies including centronuclear
myopathy causing muscle weakness[7] and myotonic dystrophy causing progressive muscle wasting, myotonia, cataracts, and heart conduction defects.[9] An association has also been found between BIN1 mutations and Alzheimer's disease.[9] Knockdown of BIN1 produces a cardiomyopathy phenotype in zebrafish,[10] and in sheep BIN1 may be responsible for the loss of T-tubules seen in heart failure.[11]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
S2CID21484402.
^
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.
S2CID16861439.
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.
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.
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.[5][6][7]
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.[8]
Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process.[8]
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.[8]
Clinical significance
In humans, mutations in BIN1 have been associated with skeletal myopathies including centronuclear
myopathy causing muscle weakness[7] and myotonic dystrophy causing progressive muscle wasting, myotonia, cataracts, and heart conduction defects.[9] An association has also been found between BIN1 mutations and Alzheimer's disease.[9] Knockdown of BIN1 produces a cardiomyopathy phenotype in zebrafish,[10] and in sheep BIN1 may be responsible for the loss of T-tubules seen in heart failure.[11]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
S2CID21484402.
^
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.
S2CID16861439.
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.
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.