Biology:Amphiphysin

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Amphiphysin is a protein that in humans is encoded by the AMPH gene.

Function

This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff person syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined.

Amphiphysin is a brain-enriched protein with an N-terminal lipid interaction, dimerisation and membrane bending BAR domain, a middle clathrin and adaptor binding domain and a C-terminal SH3 domain. In the brain, its primary function is thought to be the recruitment of dynamin to sites of clathrin-mediated endocytosis. There are 2 mammalian amphiphysins with similar overall structure. A ubiquitous splice form of amphiphysin-2 (BIN1) that does not contain clathrin or adaptor interactions is highly expressed in muscle tissue and is involved in the formation and stabilization of the T-tubule network. In other tissues amphiphysin is likely involved in other membrane bending and curvature stabilization events.

Interactions

Amphiphysin has been shown to interact with DNM1, Phospholipase D1, CDK5R1, PLD2, CABIN1 and SH3GL2.

See also

• AP180
• Epsin

Further reading

• "Amphiphysin, a novel protein associated with synaptic vesicles". The EMBO Journal 11 (7): 2521–30. July 1992. doi:10.1002/j.1460-2075.1992.tb05317.x. PMID 1628617. 
• "Primary structure of human amphiphysin, the dominant autoantigen of paraneoplastic stiff-man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14". Human Molecular Genetics 4 (2): 265–8. February 1995. doi:10.1093/hmg/4.2.265. PMID 7757077. 
• "Autoimmunity in stiff-Man syndrome with breast cancer is targeted to the C-terminal region of human amphiphysin, a protein similar to the yeast proteins, Rvs167 and Rvs161". FEBS Letters 351 (1): 73–9. August 1994. doi:10.1016/0014-5793(94)00826-4. PMID 8076697. 
• "A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals". Proceedings of the National Academy of Sciences of the United States of America 93 (1): 331–5. January 1996. doi:10.1073/pnas.93.1.331. PMID 8552632. Bibcode: 1996PNAS...93..331D. 
• "The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence". The Journal of Biological Chemistry 272 (20): 13419–25. May 1997. doi:10.1074/jbc.272.20.13419. PMID 9148966. 
• "Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle". The Journal of Cell Biology 137 (6): 1355–67. June 1997. doi:10.1083/jcb.137.6.1355. PMID 9182667. 
• "Identification and characterization of a nerve terminal-enriched amphiphysin isoform". The Journal of Biological Chemistry 272 (26): 16700–6. June 1997. doi:10.1074/jbc.272.26.16700. PMID 9195986. 
• "Clathrin interacts specifically with amphiphysin and is displaced by dynamin". FEBS Letters 413 (2): 319–22. August 1997. doi:10.1016/S0014-5793(97)00928-9. PMID 9280305. 
• "SH3 domain-dependent interactions of endophilin with amphiphysin". FEBS Letters 414 (2): 308–12. September 1997. doi:10.1016/S0014-5793(97)01016-8. PMID 9315708. 
• "Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis". Molecular Biology of the Cell 8 (10): 2003–15. October 1997. doi:10.1091/mbc.8.10.2003. PMID 9348539. 
• "Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer". Molecular Medicine 4 (1): 29–39. January 1998. doi:10.1007/BF03401727. PMID 9513187. 
• "Multiple amphiphysin II splice variants display differential clathrin binding: identification of two distinct clathrin-binding sites". Journal of Neurochemistry 70 (6): 2369–76. June 1998. doi:10.1046/j.1471-4159.1998.70062369.x. PMID 9603201. 
• "Role of phosphorylation in regulation of the assembly of endocytic coat complexes". Science 281 (5378): 821–4. August 1998. doi:10.1126/science.281.5378.821. PMID 9694653. Bibcode: 1998Sci...281..821S. 
• "The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity". The Journal of Biological Chemistry 274 (45): 32001–7. November 1999. doi:10.1074/jbc.274.45.32001. PMID 10542231. 
• "Tandem arrangement of the clathrin and AP-2 binding domains in amphiphysin 1 and disruption of clathrin coat function by amphiphysin fragments comprising these sites". The Journal of Biological Chemistry 275 (23): 17583–9. June 2000. doi:10.1074/jbc.M910430199. PMID 10748223. 
• "Inhibition of phospholipase D by amphiphysins". The Journal of Biological Chemistry 275 (25): 18751–8. June 2000. doi:10.1074/jbc.M001695200. PMID 10764771. 
• "Specificity of the binding of synapsin I to Src homology 3 domains". The Journal of Biological Chemistry 275 (38): 29857–67. September 2000. doi:10.1074/jbc.M006018200. PMID 10899172. 
• "The calcineurin-binding protein cain is a negative regulator of synaptic vesicle endocytosis". The Journal of Biological Chemistry 275 (44): 34017–20. November 2000. doi:10.1074/jbc.C000429200. PMID 10931822. 
• "Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2". The Journal of Biological Chemistry 276 (11): 8104–10. March 2001. doi:10.1074/jbc.M008932200. PMID 11113134. 
• "Drosophila Amphiphysin is a post-synaptic protein required for normal locomotion but not endocytosis". Traffic 2 (11): 839–50. November 2001. doi:10.1034/j.1600-0854.2001.21113.x. PMID 11733051. 
• "Amphiphysins: raising the BAR for synaptic vesicle recycling and membrane dynamics. Bin-Amphiphysin-Rvsp". Traffic 3 (7): 452–60. July 2002. doi:10.1034/j.1600-0854.2002.30702.x. PMID 12047553.  Review.
• "Drosophila Amphiphysin is implicated in protein localization and membrane morphogenesis but not in synaptic vesicle endocytosis". Development 128 (24): 5005–15. December 2001. doi:10.1242/dev.128.24.5005. PMID 11748137. 
• "Drosophila amphiphysin functions during synaptic Fasciclin II membrane cycling". The Journal of Neuroscience 23 (33): 10710–6. November 2003. doi:10.1523/JNEUROSCI.23-33-10710.2003. PMID 14627656. PMC 6740931. http://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1078&context=neurobiology_pp. 
• "Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis". Nature Cell Biology 1 (1): 33–9. May 1999. doi:10.1038/9004. PMID 10559861. 
• "BAR domains as sensors of membrane curvature: the amphiphysin BAR structure". Science 303 (5657): 495–9. January 2004. doi:10.1126/science.1092586. PMID 14645856. Bibcode: 2004Sci...303..495P. 
• "Amphiphysin is a component of clathrin coats formed during synaptic vesicle recycling at the lamprey giant synapse". Traffic 5 (7): 514–28. July 2004. doi:10.1111/j.1398-9219.2004.00198.x. PMID 15180828. 
• "Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila". Genes & Development 15 (22): 2967–79. November 2001. doi:10.1101/gad.207801. PMID 11711432. 

External links

• Bringing your curves to the bar, amphiphysin home page
• Human AMPH genome location and AMPH gene details page in the UCSC Genome Browser.