SNCAIP

Synuclein, alpha interacting protein
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsSNCAIP ; SYPH1; Sph1
External IDsOMIM: 603779 MGI: 1915097 HomoloGene: 3987 GeneCards: SNCAIP Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez962767847
EnsemblENSG00000064692ENSMUSG00000024534
UniProtQ9Y6H5Q99ME3
RefSeq (mRNA)NM_001242935NM_001199151
RefSeq (protein)NP_001229864NP_001186080
Location (UCSC)Chr 5:
121.65 – 121.8 Mb		Chr 18:
52.77 – 52.92 Mb
PubMed search

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.[2]

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:

References

  1. ↑ 1.0 1.1 Engelender S, Kaminsky Z, Guo X, Sharp AH, Amaravi RK, Kleiderlein JJ et al. (May 1999). "Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions". Nat Genet 22 (1): 110–4. doi:10.1038/8820. PMID 10319874.
  2. ↑ 2.0 2.1 "Entrez Gene: SNCAIP synuclein, alpha interacting protein (synphilin)".
  3. ↑ Neystat M, Rzhetskaya M, Kholodilov N, Burke RE (June 2002). "Analysis of synphilin-1 and synuclein interactions by yeast two-hybrid beta-galactosidase liquid assay". Neurosci. Lett. 325 (2): 119–23. doi:10.1016/s0304-3940(02)00253-7. PMID 12044636.
  4. ↑ Nagano Y, Yamashita H, Nakamura T, Takahashi T, Kondo E, Nakamura S (Dec 2001). "Lack of binding observed between human alpha-synuclein and Bcl-2 protein family". Neurosci. Lett. 316 (2): 103–7. doi:10.1016/s0304-3940(01)02330-8. PMID 11742726.
  5. ↑ Kawamata H, McLean PJ, Sharma N, Hyman BT (May 2001). "Interaction of alpha-synuclein and synphilin-1: effect of Parkinson's disease-associated mutations". J. Neurochem. 77 (3): 929–34. doi:10.1046/j.1471-4159.2001.00301.x. PMID 11331421.
  6. ↑ Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J et al. (October 2001). "Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease". Nat. Med. 7 (10): 1144–50. doi:10.1038/nm1001-1144. PMID 11590439.

Further reading

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