BIN1

The BIN1 protein, which is encoded by the BIN1 gene, belongs to Myc-interacting protein family which is one of the nucleocytoplasmic adaptor proteins. The BIN1 protein can interact with the functionally critically Myc-box region at the N-terminal of the Myc oncoprotein, with a feature of tumor suppressor. Myc family proteins promote proliferation, growth, and apoptosis and, when deregulated, are profoundly involved in the genesis of an extraordinarily wide range of cancers. Although BIN1 is expressed in many normal cells, its levels were greatly reduced or undetectable in 14/27 carcinoma cell lines and 3/6 primary breast tumours. Deficits were functionally Although BIN1 is expressed in many normal cells, its levels were greatly reduced or undetectable in 14/27 carcinoma cell lines and 3/6 primary breast tumours. Deficits were functionally significant because ectopic expression of BIN1 inhibited the growth of tumour cells lacking endogenous message. We conclude that BIN1 is an MYC-interacting protein with features of a tumour suppressor.

BIN1 Related Areas

Cancer>>Cell Cycle>>Cell Cycle Inhibitor>>BIN1

Signal Transduction>>Translational Regulator>>BIN1

BIN1 Alternative Names

BIN1, AMPH2, AMPHL, DKFZp547F068, MGC10367, SH3P9 [Homo sapiens]

Bin1, ALP-1, Amphl, BRAMP-2, SH3P9 [Mus musculus]

Summaries for BIN1

Entrez Gene summary for BIN1:

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 dynamin, 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.

OMIM - description for BIN1:

BIN1 (AMPH2) is a novel human gene product with features of a tumor suppressor protein (Negorev et al., 1996). It was identified in a 2-hybrid screen for proteins that interact with the MYC oncoprotein (190080). Loss of BIN1 expression appears to be a frequent aberration in human hepatocellular carcinomas.

Wikipedia summary for BIN1:

Myc box-dependent-interacting protein 1 is a protein that in humans is encoded by the BIN1 gene. 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

Human BIN1 Protein General Information

 

• Protein names: Recommended name: Myc box-dependent-interacting protein 1
• Sequence length: 593 AA
• Domain: Coiled coil SH3 domain
• Sequence similarities: Contains 1 BAR domain. Contains 1 SH3 domain.
• Post-translational modification: Phosphorylated by protein kinase C
• Subunit structure: Heterodimer with AMPH. Binds SH3GLB1 By similarity. Interacts (via SH3 domain) with SYNJ1. Interacts (via SH3 domain) with DNM1. Isoform IIA interacts with CLTC. Isoform IIB does not interact with CLTC. Isoform IIC1 does not interact with CLTC. Isoform IIC2 does not interact with CLTC. Interacts with AP2A2. Interacts with AP2B1. Interacts with MYC (via N-terminal transactivation domain); the interaction requires the integrity of the conserved MYC box regions 1 and 2. Interacts with BIN2. Interacts (SH3 domain) with HCV NS5A
• Subcellular location: Isoform BIN1: Nucleus. Isoform IIA: Cytoplasm.
• Tissue specificity: Ubiquitous. Highest expression in the brain and muscle. Isoform IIA is expressed only in the brain where it is concentrated in axon initial segments and nodes of Ranvier. Isoform BIN1 is widely expressed with highest expression in skeletal muscle.
• Involvement in disease: Defects in BIN1 are the cause of centronuclear myopathy type 2 (CNM2) [MIM:255200]. A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.

General information above from UniProt

Function for BIN1 Protein

UniProtKB:

May be involved in regulation of synaptic vesicle endocytosis. May act as a tumor suppressor and inhibits malignant cell transformation.

Genatlas:

• BIN1 is implicated in membrane tubulation and in protein-lipid and protein-protein interactions
• BIN1 inhibits induction of CDKNA1A in early stage of muscle differentiation program
• BIN1 plays a physiological role in striated muscle membrane deformation (for T-tubule biogenesis)
• BIN1 may be involved in regulation of synaptic vesicle endocytosis
• BIN1 may act as a tumor suppressor and inhibiting malignant cell transformation
• BIN1 is involved in negative regulation of progression through cell cycle
• BIN1 plays a role in regulation of endocytosis
• BIN1 plays a role at the surface of the endocytic vesicle that has just been formed and of the future endosomes, in order to regulate intracellular trafficking
• BIN1 displays protein scaffold-like properties and binds with sarcomeric factors important in directing sarcomere protein assembly and myofiber maturation
• BIN1 isoforms expressed in CNS may be involved in synaptic vesicles endocytosis and may interact with dynamin, synaptojanin, endophilin and clathrin
• BIN1 isoforms expressed in muscle and ubiquitously, localize to cytoplasm and nucleus and activate a caspase-independent apoptotic process
• BIN1 plays an important role in cardiac muscle development
• BIN1 appears to function as a metastasis suppressor and chemosensitizer in neuroblastoma, and resistance to anoikis may be an important metastatic mechanism
• BIN1 is involved in tubular invaginations of membranes and is required for the biogenesis of muscle T tubules, which are specialized skeletal muscle membrane structures essential for excitation-contraction coupling

Homology for human BIN1

• homolog to murine Bin1 (95.9pc)
• homolog to rattus Bin1 (95.6pc)

Phenotype Information for BIN1

• Gene/Locus: BIN1, AMPHL
• Phenotype: Myopathy, centronuclear, autosomal recessive

Phenotype Information for BIN1 from OMIM (Online Mendelian Inheritance in Man)