BIN1

BIN1 Full Name

bridging integrator 1

BIN1 Introduction

BIN1 (Bridging integrator 1), also known as amphiphysin 2, is a multifunctional adapter protein involved in membrane remodeling, endocytosis, and the regulation of gene expression. The gene encoding BIN1 is located on human chromosome 2q14.3 and produces multiple alternatively spliced isoforms, with the protein size ranging from approximately 50 to 80 kDa depending on the isoform. BIN1 is expressed in various human tissues, with particularly high levels in the brain, heart, skeletal muscle, and testis. The protein belongs to the amphiphysin family and contains an N-terminal BAR (Bin/amphiphysin/Rvs) domain that mediates membrane curvature sensing and generation, as well as a C-terminal SH3 (Src homology 3) domain that binds to proline-rich sequences in various partner proteins. BIN1 has been implicated in diverse cellular processes, including clathrin-mediated endocytosis, synaptic vesicle recycling, T-tubule biogenesis in muscle cells, and transcriptional repression in the nucleus. Dysregulation of BIN1 has been linked to several human diseases, including centronuclear myopathy (myopathy type 2), Alzheimer's disease, and various cancers.

Figure 1. Strcuture of BIN1.

Structural Domains and Isoform Diversity
BIN1 shares the characteristic domain architecture of the amphiphysin family. The N-terminal BAR domain (approximately 230 amino acids) forms a crescent-shaped dimer that binds to and induces membrane curvature. The BAR domain contains positively charged residues that interact with negatively charged phospholipids, allowing the protein to sense and generate membrane invaginations. The C-terminal SH3 domain (approximately 60 amino acids) recognizes and binds to proline-rich motifs (typically PXXP sequences) in various partner proteins, including dynamin, synaptojanin, and myotubularin. Between the BAR and SH3 domains, BIN1 contains a proline-rich region (PRR) that can be alternatively spliced. Multiple alternatively spliced exons generate a large number of BIN1 isoforms with distinct tissue distributions and functions. In muscle, a muscle-specific isoform (including exon 11, which encodes a phosphoinositide-binding domain) is expressed. In the brain, isoforms lacking certain exons are predominant. In cancer cells, alternative splicing often shifts toward isoforms that promote proliferation and invasion. This isoform diversity allows BIN1 to perform cell-type-specific functions.

Role in Endocytosis and Membrane Trafficking
BIN1 is a critical regulator of clathrin-mediated endocytosis, the process by which cells internalize plasma membrane proteins and extracellular ligands. Together with its close homolog amphiphysin 1 (AMPH1), BIN1 participates in the formation and scission of clathrin-coated vesicles. The BAR domain of BIN1 binds to and stabilizes the curved neck of invaginating vesicles, while the SH3 domain recruits dynamin, a GTPase that mediates vesicle scission. BIN1 also interacts with other endocytic proteins, including synaptojanin (a phosphoinositide phosphatase) and endophilin. In neurons, BIN1 is involved in synaptic vesicle recycling at presynaptic terminals, ensuring the availability of synaptic vesicles for neurotransmitter release. In non-neuronal cells, BIN1 regulates the endocytosis of various receptors, including the transferrin receptor, the epidermal growth factor receptor (EGFR), and integrins. Disruption of BIN1 function impairs endocytosis, leading to defects in receptor internalization, signal transduction, and nutrient uptake.

Alternate Names for BIN1

BIN1; bridging integrator 1; AMPHL; myc box-dependent-interacting protein 1; AMPH2; amphiphysin II; SH3P9; amphiphysin-like protein; box dependant MYC interacting protein 1; box-dependent myc-interacting protein 1; MGC10367; DKFZp547F068;