Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Snca. (This text reflects annotations as of Wednesday, January 23, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of September 9, 2008. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Four alternatively spliced transcripts encoding two different isoforms have been identified for this gene. [provided by RefSeq, Mar 2009]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Snca
  • participates in the following biological processes:
    • positive regulation of neurotransmitter secretion ^[18]
    • regulation of acyl-CoA biosynthetic process ^[11]
  • performs the following molecular functions:
    • arachidonic acid binding ^[11]
    • histone binding ^[16]
    • identical protein binding ^[22]
  • is located in the following cellular components:
    • cytoplasm ^{[20, 26]}
    • cytoskeleton ^[8]
    • cytosol ^[4]
    • nucleus ^[16]
    • plasma membrane ^[20]
    • synapse ^[14]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Snca
  • participates in the following biological processes:
    • cellular membrane organization ^[24]
    • cellular response to oxidative stress ^[15]
    • dopamine biosynthetic process ^[1]
    • fatty acid metabolic process ^{[3, 24]}
    • long-term synaptic potentiation ^[13]
    • microglial cell activation ^[2]
    • mitochondrial ATP synthesis coupled electron transport ^[9]
    • mitochondrial membrane organization ^[9]
    • neutral lipid metabolic process ^[3]
    • phospholipid metabolic process ^{[9, 10, 11]}
    • positive regulation of peptidyl-serine phosphorylation ^[21]
    • positive regulation of synaptic transmission ^[19]
    • regulation of acyl-CoA biosynthetic process ^[25]
    • regulation of excitatory postsynaptic membrane potential ^[17]
    • regulation of glutamate secretion ^[13]
    • regulation of locomotion ^[1]
    • regulation of long-term neuronal synaptic plasticity ^[18]
    • regulation of macrophage activation ^[2]
    • regulation of neuronal synaptic plasticity ^[17]
    • regulation of neurotransmitter secretion ^{[1, 5, 18]}
    • response to drug ^[1]
    • synaptic transmission, dopaminergic ^{[1, 5]}
    • synaptic vesicle endocytosis ^[4]
    • synaptic vesicle transport ^[5]
• Researchers have inferred, based on genetic interactions, that the gene product of Snca
  • participates in the following biological processes:
    • adult locomotory behavior based on interactions with Sncg ^[23]
    • dopamine metabolic process based on interactions with Sncb ^[7]
    • negative regulation of neuron apoptotic process based on interactions with Dnajc5 ^[6]
    • regulation of dopamine secretion based on interactions with Sncg ^[23]
    • regulation of neurotransmitter secretion based on interactions with Sncg ^[23]
    • synapse organization based on interactions with Sncb, Sncg ^[12]
    • synaptic transmission based on interactions with Sncb, Sncg ^[12]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Snca:
  • participates in the following biological processes:
    • activation of cysteine-type endopeptidase activity involved in apoptotic process
    • behavioral response to cocaine
    • cellular response to copper ion
    • negative regulation of apoptotic process
    • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
    • negative regulation of dopamine metabolic process
    • negative regulation of dopamine uptake involved in synaptic transmission
    • negative regulation of exocytosis
    • negative regulation of histone acetylation
    • negative regulation of microtubule polymerization
    • negative regulation of monooxygenase activity
    • negative regulation of neuron apoptotic process
    • negative regulation of norepinephrine uptake
    • negative regulation of platelet-derived growth factor receptor signaling pathway
    • negative regulation of protein phosphorylation
    • negative regulation of serotonin uptake
    • negative regulation of thrombin receptor signaling pathway
    • negative regulation of transporter activity
    • oxidation-reduction process
    • positive regulation of endocytosis
    • positive regulation of inositol phosphate biosynthetic process
    • positive regulation of protein serine/threonine kinase activity
    • positive regulation of receptor recycling
    • positive regulation of release of sequestered calcium ion into cytosol
    • protein destabilization
    • receptor internalization
    • regulation of phospholipase activity
    • response to interferon-gamma
    • response to interleukin-1
    • response to iron(II) ion
    • response to lipopolysaccharide
    • response to magnesium ion
  • performs the following molecular functions:
    • alpha-tubulin binding
    • beta-tubulin binding
    • calcium ion binding
    • copper ion binding
    • cysteine-type endopeptidase inhibitor activity involved in apoptotic process
    • dynein binding
    • enzyme binding
    • ferrous iron binding
    • histone binding
    • Hsp70 protein binding
    • identical protein binding
    • kinesin binding
    • magnesium ion binding
    • microtubule binding
    • oxidoreductase activity
    • phospholipase binding
    • phospholipid binding
    • phosphoprotein binding
    • protein domain specific binding
    • protein N-terminus binding
    • tau protein binding
    • zinc ion binding
  • is located in the following cellular components:
    • actin cytoskeleton
    • axon
    • axon terminus
    • cell cortex
    • cytoplasm
    • cytoplasmic vesicle membrane
    • cytosol
    • fibril
    • Golgi apparatus
    • growth cone
    • inclusion body
    • intracellular membrane-bounded organelle
    • mitochondrion
    • nuclear outer membrane
    • nucleus
    • perinuclear region of cytoplasm
    • plasma membrane
    • ribosome
    • rough endoplasmic reticulum
    • synaptic vesicle
    • terminal button

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Snca indicates that it:
  • performs the following molecular functions:
    • metal ion binding

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References

1. Abeliovich A et al. (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron, 25:239-52. (PubMed:10707987)
2. Austin SA et al. (2006) Alpha-synuclein expression modulates microglial activation phenotype. J Neurosci, 26:10558-63. (PubMed:17035541)
3. Barcelo-Coblijn G et al. (2007) Brain neutral lipids mass is increased in alpha-synuclein gene-ablated mice. J Neurochem, 101:132-41. (PubMed:17250686)
4. Ben Gedalya T et al. (2009) Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic, 10:218-34. (PubMed:18980610)
5. Cabin DE et al. (2002) Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci, 22:8797-807. (PubMed:12388586)
6. Chandra S et al. (2005) Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell, 123:383-96. (PubMed:16269331)
7. Chandra S et al. (2004) Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc Natl Acad Sci U S A, 101:14966-71. (PubMed:15465911)
8. Duka T et al. (2006) Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. FASEB J, 20:2302-12. (PubMed:17077307)
9. Ellis CE et al. (2005) Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol, 25:10190-201. (PubMed:16260631)
10. Golovko MY et al. (2005) Alpha-synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding. Biochemistry, 44:8251-9. (PubMed:15938614)
11. Golovko MY et al. (2006) Acyl-CoA synthetase activity links wild-type but not mutant alpha-synuclein to brain arachidonate metabolism. Biochemistry, 45:6956-66. (PubMed:16734431)
12. Greten-Harrison B et al. (2010) alphabetagamma-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Proc Natl Acad Sci U S A, 107:19573-8. (PubMed:20974939)
13. Gureviciene I et al. (2007) Role of alpha-synuclein in synaptic glutamate release. Neurobiol Dis, 28:83-9. (PubMed:17689254)
14. Kahle PJ et al. (2000) Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brain J Neurosci, 20:6365-73. (PubMed:10964942)
15. Klivenyi P et al. (2006) Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol Dis, 21:541-8. (PubMed:16298531)
16. Kontopoulos E et al. (2006) Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet, 15:3012-23. (PubMed:16959795)
17. Liu S et al. (2007) Alpha-synuclein involvement in hippocampal synaptic plasticity: role of NO, cGMP, cGK and CaMKII. Eur J Neurosci, 25:3583-96. (PubMed:17610578)
18. Liu S et al. (2004) alpha-Synuclein produces a long-lasting increase in neurotransmitter release. EMBO J, 23:4506-16. (PubMed:15510220)
19. Martin ED et al. (2004) Stressor-related impairment of synaptic transmission in hippocampal slices from alpha-synuclein knockout mice. Eur J Neurosci, 20:3085-91. (PubMed:15579163)
20. Nakai M et al. (2007) Expression of alpha-synuclein, a presynaptic protein implicated in Parkinson's disease, in erythropoietic lineage. Biochem Biophys Res Commun, 358:104-10. (PubMed:17475220)
21. Qureshi HY et al. (2011) Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and {alpha}-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro. J Biol Chem, 286:5055-68. (PubMed:21127069)
22. Rochet JC et al. (2000) Inhibition of fibrillization and accumulation of prefibrillar oligomers in mixtures of human and mouse alpha-synuclein. Biochemistry, 39:10619-26. (PubMed:10978144)
23. Senior SL et al. (2008) Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein. Eur J Neurosci, 27:947-57. (PubMed:18333965)
24. Sharon R et al. (2003) Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alpha-synucleinopathies. J Biol Chem, 278:49874-81. (PubMed:14507911)
25. Stanic AK et al. (2006) Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus. Proc Natl Acad Sci U S A, 103:7018-23. (PubMed:16636270)
26. Tong Y et al. (2010) Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of {alpha}-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A, 107:9879-84. (PubMed:20457918)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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