SNCAIP explained

Synphilin-1 is a protein that in humans is encoded by the SNCAIP gene.^{[1] [2]} SNCAIP stands for "synuclein, alpha interacting protein" and can be signified by SNCAP_HUMAN, synphilin 1, synuclein, alpha interacting protein (synphilin), and SYPH1.

Function

This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. A mutation in this gene has been associated with Parkinson's disease. Alternatively spliced transcript variants encoding different isoforms of this gene have been described, but their full-length nature has yet to be determined.

The SNCAIP gene provides instructions for making a protein called synphilin-1 and a slightly different version of this protein called synphilin-1A. These proteins are produced in the brain. They are usually located in specialized structures called presynaptic terminals, found at the tips of nerve cells. In nerve cells, synphilin-1 and synphilin-1A interact with another protein called alpha-synuclein. The functions of synphilin-1 and synphilin-1A, however, are unknown.

Interactions

SNCAIP has been shown to interact with:

• Alpha-synuclein^{[3] [4] [5]} and
• Parkin (ligase).^[6]

Further reading

• Krüger R . The role of synphilin-1 in synaptic function and protein degradation . Cell Tissue Res. . 318 . 1 . 195–9 . 2005 . 15322916 . 10.1007/s00441-004-0953-z . 12186058 .
• Engelender S, Wanner T, Kleiderlein JJ, Wakabayashi K, Tsuji S, Takahashi H, Ashworth R, Margolis RL, Ross CA . Organization of the human synphilin-1 gene, a candidate for Parkinson's disease . Mamm. Genome . 11 . 9 . 763–6 . 2000 . 10967135 . 10.1007/s003350010123 . 22420090 .
• Kawamata H, McLean PJ, Sharma N, Hyman BT . Interaction of alpha-synuclein and synphilin-1: effect of Parkinson's disease-associated mutations . J. Neurochem. . 77 . 3 . 929–34 . 2001 . 11331421 . 10.1046/j.1471-4159.2001.00301.x . 83885937 . free .
• Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM . Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease . Nat. Med. . 7 . 10 . 1144–50 . 2001 . 11590439 . 10.1038/nm1001-1144 . 12487644 .
• Ribeiro CS, Carneiro K, Ross CA, Menezes JR, Engelender S . Synphilin-1 is developmentally localized to synaptic terminals, and its association with synaptic vesicles is modulated by alpha-synuclein . J. Biol. Chem. . 277 . 26 . 23927–33 . 2002 . 11956199 . 10.1074/jbc.M201115200 . free .
• O'Farrell C, Pickford F, Vink L, McGowan E, Cookson MR . Sequence conservation between mouse and human synphilin-1 . Neurosci. Lett. . 322 . 1 . 9–12 . 2002 . 11958831 . 10.1016/S0304-3940(02)00068-X . 9654263 .
• Neystat M, Rzhetskaya M, Kholodilov N, Burke RE . Analysis of synphilin-1 and synuclein interactions by yeast two-hybrid beta-galactosidase liquid assay . Neurosci. Lett. . 325 . 2 . 119–23 . 2002 . 12044636 . 10.1016/S0304-3940(02)00253-7 . 11517781 .
• Junn E, Lee SS, Suhr UT, Mouradian MM . Parkin accumulation in aggresomes due to proteasome impairment . J. Biol. Chem. . 277 . 49 . 47870–7 . 2003 . 12364339 . 10.1074/jbc.M203159200 . free .
• Ihara M, Tomimoto H, Kitayama H, Morioka Y, Akiguchi I, Shibasaki H, Noda M, Kinoshita M . Association of the cytoskeletal GTP-binding protein Sept4/H5 with cytoplasmic inclusions found in Parkinson's disease and other synucleinopathies . J. Biol. Chem. . 278 . 26 . 24095–102 . 2003 . 12695511 . 10.1074/jbc.M301352200 . free .
• Ito T, Niwa J, Hishikawa N, Ishigaki S, Doyu M, Sobue G . Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1 . J. Biol. Chem. . 278 . 31 . 29106–14 . 2003 . 12750386 . 10.1074/jbc.M302763200 . free .
• Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, Cookson MR, Hernandez D, Farrer MJ, Kachergus J, Engelender S, Ross CA, Berger K, Schöls L, Schulz JB, Riess O, Krüger R . Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease . Hum. Mol. Genet. . 12 . 11 . 1223–31 . 2004 . 12761037 . 10.1093/hmg/ddg134 . free .
• Scherzer CR, Jensen RV, Gullans SR, Feany MB . Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson's disease . Hum. Mol. Genet. . 12 . 19 . 2457–66 . 2004 . 12915459 . 10.1093/hmg/ddg265 . free .
• Nagano Y, Yamashita H, Takahashi T, Kishida S, Nakamura T, Iseki E, Hattori N, Mizuno Y, Kikuchi A, Matsumoto M . Siah-1 facilitates ubiquitination and degradation of synphilin-1 . J. Biol. Chem. . 278 . 51 . 51504–14 . 2004 . 14506261 . 10.1074/jbc.M306347200 . free .
• Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM . Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective . J. Biol. Chem. . 279 . 6 . 4625–31 . 2004 . 14627698 . 10.1074/jbc.M310994200 . free .
• Lee G, Tanaka M, Park K, Lee SS, Kim YM, Junn E, Lee SH, Mouradian MM . Casein kinase II-mediated phosphorylation regulates alpha-synuclein/synphilin-1 interaction and inclusion body formation . J. Biol. Chem. . 279 . 8 . 6834–9 . 2004 . 14645218 . 10.1074/jbc.M312760200 . free .
• Chung KK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, Dawson VL, Dawson TM . S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function . Science . 304 . 5675 . 1328–31 . 2004 . 15105460 . 10.1126/science.1093891 . 86854030 .

Notes and References

1. Engelender S, Kaminsky Z, Guo X, Sharp AH, Amaravi RK, Kleiderlein JJ, Margolis RL, Troncoso JC, Lanahan AA, Worley PF, Dawson VL, Dawson TM, Ross CA . Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions . Nat Genet . 22 . 1 . 110–4 . May 1999 . 10319874 . 10.1038/8820 . 2611127 .
2. Web site: Entrez Gene: SNCAIP synuclein, alpha interacting protein (synphilin).
3. Neystat M, Rzhetskaya M, Kholodilov N, Burke RE . Analysis of synphilin-1 and synuclein interactions by yeast two-hybrid beta-galactosidase liquid assay . Neurosci. Lett. . 325 . 2 . 119–23 . June 2002 . 12044636 . 10.1016/s0304-3940(02)00253-7. 11517781 .
4. Nagano Y, Yamashita H, Nakamura T, Takahashi T, Kondo E, Nakamura S . Lack of binding observed between human alpha-synuclein and Bcl-2 protein family . Neurosci. Lett. . 316 . 2 . 103–7 . Dec 2001 . 11742726 . 10.1016/s0304-3940(01)02330-8. 54363210 .
5. Kawamata H, McLean PJ, Sharma N, Hyman BT . Interaction of alpha-synuclein and synphilin-1: effect of Parkinson's disease-associated mutations . J. Neurochem. . 77 . 3 . 929–34 . May 2001 . 11331421 . 10.1046/j.1471-4159.2001.00301.x. 83885937 . free .
6. Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM . Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease . Nat. Med. . 7 . 10 . 1144–50 . October 2001 . 11590439 . 10.1038/nm1001-1144 . 12487644 .