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FLASH GENE

Symbol

BIN1

contributors: mct/pgu - updated : 23-01-2014

HGNC name	bridging integrator 1
HGNC id	1052

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CNM3 centronuclear myopathy 3
Location	2q14.3      Physical location : 127.805.606 - 127.864.864
Synonym name	BAR adaptor gene 1
	box-dependent myc-interacting protein 1
	amphiphysin 2
	amphiphysin-like
Synonym symbol(s)	AMPHL, SH3P9, AMPH2, DKFZp547F068, MGC10367

DNA

TYPE	functioning gene
STRUCTURE	59.26 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	cytosine-phosphate-guanine/HTF
text structure	no TATA box, housekeeping, CpG rich

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	missplicing results in expression of an inactive form of BIN1 lacking phosphatidylinositol 5-phosphate-binding and membrane-tubulating activities (PMID: 21623381)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_139347 16 splicing 2412 NP_647597 56.4 518 - 2011 21623381 lacking three in-frame exons in the coding region compared to variant 1 variant 5 - IIb binding dynamin, synaptojanin and endophilin isoform 5 NM_139345 16 splicing 2376 NP_647595 55 506 - 2011 21623381 lacking three in-frame exons in the coding region compared to variant 1 variant 3 - IIc1 binding dynamin and synaptojanin isoform 3 NM_139350 14 splicing 2165 NP_647600 48.1 439 ubiquitously expressed 2011 21623381 excluding MBD lacking five in-frame exons in the coding region compared to variant 1 variant 9 - IIB, BIN1-10 isoform 9 NM_139351 13 splicing 2075 NP_647601 45.4 409 ubiquitously expressed 2011 21623381 lacking six in-frame exons in the coding region compared to variant 1 variant 10 - BIN1-10-13 isoform 10 NM_139346 16 splicing 2333 NP_647596 54.8 497 - 2011 21623381 lacking four in-frame exons and having an additional in-frame exon in the coding region compared to variant 1 variant 4 - BIN1+12A isoform 4 NM_139348 15 splicing 2289 NP_647598 52.9 482 - 2011 21623381 lacking four in-frame exons in the coding region compared to variant 1 variant 6 - II2 isoform 6 NM_139343 19 splicing 2637 NP_647593 64.6 593 . brain specific (nerve terminals) . cytoplasmic 2011 21623381 excluding MBD binding dynamin, synaptojanin, and clathrin variant 1 - IIa, S11R3-a isoform 1 NM_139349 15 splicing 2283 NP_647599 51.6 475 brain specific 2011 21623381 lacking three in-frame exons in the coding region compared to variant 1 variant 7 - IIc2, S1/R3-c binding dynamin and synaptojanin isoform 7 NM_004305 15 splicing 2210 NP_004296 50.1 454 . expressed in muscle . localized to the nucleus 2011 21623381 lacking five in-frame exons and having an additional in-frame exon in the coding region compared to variant 1 variant 8 - BIN1 isoform 8 NM_139344 18 splicing 2508 NP_647594 59.8 550 - 2011 21623381 lacking an in-frame exon in the coding region compared to variant 1 variant 2 - IId, S1/R3-6 binding dynamin, synaptojanin, and clathrin isoform 2

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately Digestive salivary gland       predominantly   stomach       moderately Lymphoid/Immune spleen       moderately   tonsils       highly Nervous brain       highly   nerve       highly Reproductive female system uterus cervix   moderately Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal BAR (Bin1, Amphiphysin, Rv167) domain, a specialized domain that is associated with t-tubule development in skeletal muscle and involved in tethering the dihydropyridine receptors (DHPR) to the t-tubule
	a nuclear localization signal (NLS)
	two unique sequences (1, 2)
	a MYC interaction domain (MYC-binding domain MBD), a MYC-independent effector domain (MID) for cancer suppression
	a C terminal SH3 domain (lacking in the alternative form), mediating interactions with numerous proteins such as synaptojanin and dynamin, important for sarcomeric protein organization in skeletal muscle

conjugated

PhosphoP

mono polymer

heteromer , dimer

HOMOLOGY

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

Homologene

FAMILY

CATEGORY

adaptor , regulatory , tumor suppressor , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytoskeleton
	intracellular,nucleus
text	transverse (T) tubules
	isoform BIN1 localizes to nucleus, IIA in cytoplasm
	IIA, only in brain, concentrated in axon initial segments and Nodes of Ranvier

basic FUNCTION	implicated in membrane tubulation and in protein-lipid and protein-protein interactions
	inhibiting induction of CDKNA1A in early stage of muscle differentiation program
	playing a physiological role in striated muscle membrane deformation (for T-tubule biogenesis)
	may be involved in regulation of synaptic vesicle endocytosis
	may act as a tumor suppressor and inhibiting malignant cell transformation
	involved in negative regulation of progression through cell cycle
	playing a role in regulation of endocytosis
	playing 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
	displays protein scaffold-like properties and binds with sarcomeric factors important in directing sarcomere protein assembly and myofiber maturation
	isoforms expressed in CNS may be involved in synaptic vesicles endocytosis and may interact with dynamin, synaptojanin, endophilin and clathrin
	isoforms expressed in muscle and ubiquitously, localize to cytoplasm and nucleus and activate a caspase-independent apoptotic process
	plays an important role in cardiac muscle development
	appears to function as a metastasis suppressor and chemosensitizer in neuroblastoma, and resistance to anoikis may be an important metastatic mechanism
	functions to initiate T-tubule genesis in skeletal muscle cells
	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
	nucleocytoplasmic adaptor protein with tumor suppressor properties
	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
	potential role of BIN1 in skeletal muscle contractility and pathology of myopathy
	might play an important role in tumor growth, cell motility and invasion

CELLULAR PROCESS	cell cycle, progression
	cell life, differentiation
	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

development , endocytosis transport

text	cell differentiation in skeletal muscle

PATHWAY

metabolism

signaling

a component	heterodimer with AMPH
	forming a complex with both actin and myosin filaments and CDK5

INTERACTION

DNA

RNA

small molecule

protein	actin
	SH3GLB1
	SYNJ1 through its SH3 domain
	DNM1 through its SH3 domain
	clathrin through a region outside of the SH3 domain
	AP2A2
	N-terminal transactivation domain of MYC in a manner requiring the integrity of the conserved MYC box regions 1 and 2
	interacting with BIN2
	CACNA1C targeting to BIN1 is functionally important to cardiac calcium signaling
	MBNL1 binds the BIN1 pre-mRNA and regulates its alternative splicing
	can interact with MYC oncoprotein in cancer
	EGFR activation also promotes RIN1 interaction with BIN1, a membrane bending protein
	MTM1 is a novel binding partner of BIN1, endogenously in skeletal muscle
	role for WASL in BIN1-dependent nuclear positioning and triad organization and in centronuclear myopathy (CNM) and myotonic dystrophy pathophysiology

cell & other

REGULATION

activated by

transactivated by MYOD

Other

phosphorylated by PKC

ASSOCIATED DISORDERS

corresponding disease(s)

CNM3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         prostate and breast carcinomas tumoral     --low   in primary hepatocellular carcinoma tumor tissues

Susceptibility

to familial late-onset Alzheimer disease

Variant & Polymorphism SNP	SNPs in BIN1, in association with APOE epsilon4 homozygotes associated to familial late-onset Alzheimer disease

Candidate gene
Marker	could serve as a marker for metastatic potential and chemosensitivity (
	novel prognostic marker in hepatocellular carcinoma
Therapy target
	System Type Disorder Pubmed immunology inflammatory   novel therapeutic target for IBD treatment

ANIMAL & CELL MODELS

Bin1 splicing alteration in mice is sufficient to promote T tubule alterations and muscle weakness, a predominant feature of myotonic dystrophy