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BIN1

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BIN1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBIN1, AMPH2, AMPHL, SH3P9, bridging integrator 1, CNM2
External IDsOMIM: 601248; MGI: 108092; HomoloGene: 113707; GeneCards: BIN1; OMA:BIN1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

274

30948

Ensembl

ENSG00000136717

ENSMUSG00000024381

UniProt

O00499

O08539

RefSeq (mRNA)

NM_001083334
NM_009668
NM_001360876

RefSeq (protein)

NP_001076803
NP_033798
NP_001347805

Location (UCSC)Chr 2: 127.05 – 127.11 MbChr 18: 32.51 – 32.57 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Myc box‑dependent‑interacting protein 1 (BIN1), also known as bridging integrator 1 and amphiphysin‑2, is a protein that in humans is encoded by the BIN1 gene.[5][6][7]

Function

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This gene encodes multiple isoforms of a membrane‑associated adaptor protein that can localize to the cytoplasm and, in some contexts, the nucleus. One isoform was originally identified as a MYC-interacting protein with characteristics of a tumor suppressor.[6] BIN1 plays important roles in membrane curvature, endocytosis, and organization of specialized membrane structures such as transverse (T)‑tubules in striated muscle.[8]

Nervous system

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Isoforms expressed in the central nervous system participate in synaptic vesicle endocytosis and membrane trafficking through interactions with dynamin, endophilin, synaptojanin, and clathrin.[9] Genetic variation at the BIN1 locus has been associated with risk of late‑onset Alzheimer's disease, and neuronal BIN1 isoforms interact with the microtubule‑associated protein tau.[10][11]

Muscle and cellular functions

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Muscle-specific and ubiquitously expressed isoforms are essential for the formation and maintenance of T-tubules and excitation–contraction coupling in skeletal and cardiac muscle.[7][8] Certain nuclear-localized isoforms have been reported to modulate cell cycle progression and to induce an apoptotic or growth‑suppressive response independent of caspase activation in tumor cells.[12]

Development and splicing

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Studies in mice suggest that this gene plays an important role in cardiac muscle development and postnatal maturation of T-tubules.[13] Alternative splicing of BIN1 generates numerous transcript variants encoding distinct isoforms with tissue‑specific expression patterns, and aberrant splice variants that attenuate BIN1 tumor-suppressor activity have been identified in several tumor cell lines and cancers.[14][15]

Clinical significance

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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,[16] and in sheep BIN1 may be responsible for the loss of T-tubules seen in heart failure.[17]

References

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  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000136717 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024381 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ 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): 329–331. doi:10.1006/geno.1996.0205. PMID 8725406.
  6. 1 2 Sakamuro D, Elliott KJ, Wechsler-Reya R, Prendergast GC (October 1996). "BIN1 is a novel MYC-interacting protein with features of a tumour suppressor". Nature Genetics. 14 (1): 69–77. doi:10.1038/ng0996-69. PMID 8782822. S2CID 21484402.
  7. 1 2 3 Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, et al. (August 2007). "Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy". Nature Genetics. 39 (9): 1134–1139. doi:10.1038/ng2086. PMID 17676042. S2CID 16861439.
  8. 1 2 Hong T, Smyth JW, Gao H, Chu KY, Vogan JM, Fong TS, et al. (January 2014). "BIN1 localizes the L-type calcium channel to cardiac T-tubules". PLOS Biology. 12 (2) e1001682. doi:10.1371/journal.pbio.1001682. PMC 3933470. PMID 24586119.
  9. 1 2 3 Prokic I, Cowling BS, Laporte J (May 2014). "Amphiphysin 2 (BIN1) in physiology and diseases". Journal of Molecular Medicine. 92 (5). Berlin, Germany: 453–463. doi:10.1007/s00109-014-1138-1. PMID 24590001. S2CID 14038898.
  10. ↑ Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, et al. (December 2013). "Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease". Nature Genetics. 45 (12): 1452–1458. doi:10.1038/ng.2802. PMC 3896259. PMID 24162737.
  11. ↑ Ramijan K, Ultee E, Willemse J, Zhang Z, Wondergem JA, van der Meij A, et al. (2018). "Structural basis of tau interaction with BIN1 and regulation by tau phosphorylation". Frontiers in Molecular Neuroscience. 11 421. doi:10.3389/fnmol.2018.00421. PMC 6259631. PMID 30514921.
  12. ↑ Elliott K, Sakamuro D, Basu A, Du W, Wunner W, Staller P, et al. (May 1999). "BIN1 functionally interacts with Myc and inhibits cell proliferation via multiple mechanisms". Oncogene. 18 (24): 3564–3573. doi:10.1038/sj.onc.1202707. PMID 10380881.
  13. ↑ Hong T, Yang H, Zhang SS, Cho HC, Kalashnikova M, Sun B, et al. (December 2010). "Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia". Nature Medicine. 16 (12): 1281–1286. doi:10.1038/nm.2250. PMC 3058211. PMID 21076393.
  14. ↑ Ge K, Minhas F, Duhadaway JB, Mao NC, Wilson D, Buccafusca R, et al. (March 2000). "Loss of heterozygosity and tumor suppressor activity of BIN1 in prostate carcinoma". International Journal of Cancer. 87 (3): 241–245. doi:10.1002/1097-0215(20000801)87:3<241::AID-IJC1>3.0.CO;2-I. PMID 10861484.
  15. ↑ Zhu J, Sanborn JZ, Benz S, Szeto C, Hsu F, Kuhn RM, et al. (February 2012). "The association of aberrant alternative splicing with tumor status in human cancer". Molecular Cancer. 11 13. doi:10.1186/1476-4598-11-13. PMC 3311074. PMID 22369237.
  16. ↑ Hong TT, Smyth JW, Chu KY, Vogan JM, Fong TS, Jensen BC, et al. (May 2012). "BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes". Heart Rhythm. 9 (5): 812–820. doi:10.1016/j.hrthm.2011.11.055. PMC 3306544. PMID 22138472.
  17. ↑ Caldwell JL, Smith CE, Taylor RF, Kitmitto A, Eisner DA, Dibb KM, et al. (December 2014). "Dependence of cardiac transverse tubules on the BAR domain protein amphiphysin II (BIN-1)". Circulation Research. 115 (12): 986–996. doi:10.1161/CIRCRESAHA.116.303448. PMC 4274343. PMID 25332206.

Further reading

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