ID:SYUA_HUMAN DESCRIPTION: RecName: Full=Alpha-synuclein; AltName: Full=Non-A beta component of AD amyloid; AltName: Full=Non-A4 component of amyloid precursor; Short=NACP; FUNCTION: May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation. SUBUNIT: Soluble monomer which can form filamentous aggregates. Interacts with UCHL1 (By similarity). Interacts with phospholipase D and histones. INTERACTION: Self; NbExp=2; IntAct=EBI-985879, EBI-985879; Q9UI14:RABAC1; NbExp=4; IntAct=EBI-985879, EBI-712367; SUBCELLULAR LOCATION: Cytoplasm. Membrane. Nucleus. Cell junction, synapse. Note=Membrane-bound in dopaminergic neurons. TISSUE SPECIFICITY: Expressed principally in brain but is also expressed in low concentrations in all tissues examined except in liver. Concentrated in presynaptic nerve terminals. DOMAIN: The 'non A-beta component of Alzheimer disease amyloid plaque' domain (NAC domain) is involved in fibrils formation. The middle hydrophobic region forms the core of the filaments. The C- terminus may regulate aggregation and determine the diameter of the filaments. PTM: Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress. PTM: Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers. PTM: Ubiquitinated. The predominant conjugate is the diubiquitinated form (By similarity). DISEASE: Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1. DISEASE: Defects in SNCA are the cause of Parkinson disease type 1 (PARK1) [MIM:168601]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. DISEASE: Defects in SNCA are the cause of Parkinson disease type 4 (PARK4) [MIM:605543]. A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. DISEASE: Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:127750]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease. SIMILARITY: Belongs to the synuclein family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SNCA"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/snca/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P37840
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001774 microglial cell activation GO:0001921 positive regulation of receptor recycling GO:0001933 negative regulation of protein phosphorylation GO:0001956 positive regulation of neurotransmitter secretion GO:0001963 synaptic transmission, dopaminergic GO:0006631 fatty acid metabolic process GO:0006638 neutral lipid metabolic process GO:0006644 phospholipid metabolic process GO:0006915 apoptotic process GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0007006 mitochondrial membrane organization GO:0007268 chemical synaptic transmission GO:0007568 aging GO:0008344 adult locomotory behavior GO:0010040 response to iron(II) ion GO:0010517 regulation of phospholipase activity GO:0010642 negative regulation of platelet-derived growth factor receptor signaling pathway GO:0014048 regulation of glutamate secretion GO:0014059 regulation of dopamine secretion GO:0031115 negative regulation of microtubule polymerization GO:0031623 receptor internalization GO:0031648 protein destabilization GO:0032026 response to magnesium ion GO:0032410 negative regulation of transporter activity GO:0032496 response to lipopolysaccharide GO:0032769 negative regulation of monooxygenase activity GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0034341 response to interferon-gamma GO:0034599 cellular response to oxidative stress GO:0035067 negative regulation of histone acetylation GO:0040012 regulation of locomotion GO:0042220 response to cocaine GO:0042416 dopamine biosynthetic process GO:0042417 dopamine metabolic process GO:0042493 response to drug GO:0042775 mitochondrial ATP synthesis coupled electron transport GO:0043030 regulation of macrophage activation GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043524 negative regulation of neuron apoptotic process GO:0044267 cellular protein metabolic process GO:0044344 cellular response to fibroblast growth factor stimulus GO:0045807 positive regulation of endocytosis GO:0045920 negative regulation of exocytosis GO:0045963 negative regulation of dopamine metabolic process GO:0046928 regulation of neurotransmitter secretion GO:0048148 behavioral response to cocaine GO:0048168 regulation of neuronal synaptic plasticity GO:0048169 regulation of long-term neuronal synaptic plasticity GO:0048488 synaptic vesicle endocytosis GO:0048489 synaptic vesicle transport GO:0050729 positive regulation of inflammatory response GO:0050806 positive regulation of synaptic transmission GO:0050808 synapse organization GO:0050812 regulation of acyl-CoA biosynthetic process GO:0051281 positive regulation of release of sequestered calcium ion into cytosol GO:0051583 dopamine uptake involved in synaptic transmission GO:0051585 negative regulation of dopamine uptake involved in synaptic transmission GO:0051612 negative regulation of serotonin uptake GO:0051622 negative regulation of norepinephrine uptake GO:0055114 oxidation-reduction process GO:0060079 excitatory postsynaptic potential GO:0060291 long-term synaptic potentiation GO:0060732 positive regulation of inositol phosphate biosynthetic process GO:0061024 membrane organization GO:0070495 negative regulation of thrombin-activated receptor signaling pathway GO:0070555 response to interleukin-1 GO:0071280 cellular response to copper ion GO:0071872 cellular response to epinephrine stimulus GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0097435 supramolecular fiber organization GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death GO:1901216 positive regulation of neuron death GO:1902957 negative regulation of mitochondrial electron transport, NADH to ubiquinone GO:1903284 positive regulation of glutathione peroxidase activity GO:1903285 positive regulation of hydrogen peroxide catabolic process GO:1903421 regulation of synaptic vesicle recycling GO:1903426 regulation of reactive oxygen species biosynthetic process GO:1904307 response to desipramine GO:1904715 negative regulation of chaperone-mediated autophagy GO:1905606 regulation of presynapse assembly GO:2000377 regulation of reactive oxygen species metabolic process GO:0055074 calcium ion homeostasis
JN709867 - Homo sapiens alpha-synuclein transcript variant 13 (SNCA) mRNA, complete cds, alternatively spliced. JN709868 - Homo sapiens alpha-synuclein transcript variant 14 (SNCA) mRNA, complete cds, alternatively spliced. JN709869 - Homo sapiens alpha-synuclein transcript variant 15 (SNCA) mRNA, complete cds, alternatively spliced. JN709859 - Homo sapiens alpha-synuclein transcript variant 5 (SNCA) mRNA, complete cds, alternatively spliced. JN709860 - Homo sapiens alpha-synuclein transcript variant 6 (SNCA) mRNA, complete cds, alternatively spliced. JN709861 - Homo sapiens alpha-synuclein transcript variant 7 (SNCA) mRNA, complete cds, alternatively spliced. JN709862 - Homo sapiens alpha-synuclein transcript variant 8 (SNCA) mRNA, complete cds, alternatively spliced. JN709863 - Homo sapiens alpha-synuclein transcript variant 9 (SNCA) mRNA, complete cds, alternatively spliced. JN709864 - Homo sapiens alpha-synuclein transcript variant 10 (SNCA) mRNA, complete cds, alternatively spliced. JN709865 - Homo sapiens alpha-synuclein transcript variant 11 (SNCA) mRNA, complete cds, alternatively spliced. JN709866 - Homo sapiens alpha-synuclein transcript variant 12 (SNCA) mRNA, complete cds, alternatively spliced. BC108275 - Homo sapiens synuclein, alpha (non A4 component of amyloid precursor), mRNA (cDNA clone MGC:110988 IMAGE:6147966), complete cds. CQ824587 - Sequence 14 from Patent WO2004047872. CS236150 - Sequence 14 from Patent WO2005116212. DL076403 - TREATMENT OF NEURODEGENERATIVE DISEASE THROUGH INTRACRANIAL DELIVERY OF siRNA. HV187318 - JP 2006515864-A/14: Treatment of Neurodegenerative Disease Through Intracranial Delivery of siRNA. HV308698 - JP 2010500357-A/14: Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna. L08850 - Human AD amyloid mRNA, complete cds. CQ824596 - Sequence 23 from Patent WO2004047872. CS236159 - Sequence 23 from Patent WO2005116212. D31839 - Homo sapiens alternatively spliced mRNA for NACP (precursor of non-A beta component of Alzheimer's disease amyloid), complete cds. DL076412 - TREATMENT OF NEURODEGENERATIVE DISEASE THROUGH INTRACRANIAL DELIVERY OF siRNA. HV187327 - JP 2006515864-A/23: Treatment of Neurodegenerative Disease Through Intracranial Delivery of siRNA. HV308707 - JP 2010500357-A/23: Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna. BC013293 - Homo sapiens synuclein, alpha (non A4 component of amyloid precursor), mRNA (cDNA clone MGC:3484 IMAGE:3604532), complete cds. AK290169 - Homo sapiens cDNA FLJ76529 complete cds, highly similar to Homo sapiens synuclein, alpha (non A4 component of amyloid precursor) (SNCA), transcript variant NACP140, mRNA. L36674 - Human (clone 2-5) synuclein (NACP) mRNA, complete cds. L36675 - Human (clone 2-4) synuclein (NACP) mRNA, complete cds. CR457058 - Homo sapiens full open reading frame cDNA clone RZPDo834A087D for gene SNCA, synuclein, alpha (non A4 component of amyloid precursor); complete cds, incl. stopcodon. MG016711 - Homo sapiens truncated alpha synuclein isoform 41 mRNA, complete cds, alternatively spliced. AY049786 - Homo sapiens synuclein alpha (SNCA) mRNA, complete cds. DQ892564 - Synthetic construct clone IMAGE:100005194; FLH187583.01X; RZPDo839A12150D synuclein, alpha (non A4 component of amyloid precursor) (SNCA) gene, encodes complete protein. KJ892169 - Synthetic construct Homo sapiens clone ccsbBroadEn_01563 SNCA gene, encodes complete protein. KR710286 - Synthetic construct Homo sapiens clone CCSBHm_00011061 SNCA (SNCA) mRNA, encodes complete protein. KR710287 - Synthetic construct Homo sapiens clone CCSBHm_00011062 SNCA (SNCA) mRNA, encodes complete protein. KR710288 - Synthetic construct Homo sapiens clone CCSBHm_00011063 SNCA (SNCA) mRNA, encodes complete protein. EU176705 - Synthetic construct Homo sapiens clone IMAGE:100011624; FLH263920.01L; RZPDo839D10246D synuclein, alpha (non A4 component of amyloid precursor) (SNCA) gene, encodes complete protein. CR541653 - Homo sapiens full open reading frame cDNA clone RZPDo834A0827D for gene SNCA, synuclein, alpha (non A4 component of amyloid precursor); complete cds, without stopcodon. AB464277 - Synthetic construct DNA, clone: pF1KB8172, Homo sapiens SNCA gene for synuclein, alpha, without stop codon, in Flexi system. JD223628 - Sequence 204652 from Patent EP1572962. JD411189 - Sequence 392213 from Patent EP1572962. JD315733 - Sequence 296757 from Patent EP1572962. JD456354 - Sequence 437378 from Patent EP1572962. JD349085 - Sequence 330109 from Patent EP1572962. JD237831 - Sequence 218855 from Patent EP1572962. JD432998 - Sequence 414022 from Patent EP1572962. JD188406 - Sequence 169430 from Patent EP1572962. JD351287 - Sequence 332311 from Patent EP1572962. JD558562 - Sequence 539586 from Patent EP1572962. HQ830268 - Homo sapiens clone asynex1` synuclein alpha-140 (NACP) mRNA, 5' UTR and partial cds, alternatively spliced. HQ830269 - Homo sapiens clone asynex1`` synuclein alpha-140 (NACP) mRNA, 5' UTR and partial cds, alternatively spliced. HQ830267 - Homo sapiens clone asynex1 synuclein alpha-140 (NACP) mRNA, 5' UTR and partial cds, alternatively spliced. HW581683 - JP 2014513065-A/12: Effective Amounts of (3aR)-1,3a,8-Trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3 b]indol-5-yl Phenylcarbamate and Methods Thereof. JC442373 - Sequence 12 from Patent EP2683242. MA353518 - JP 2018076332-A/12: Effective Amounts of (3aR)-1,3a,8-Trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3 b]indol-5-yl Phenylcarbamate and Methods Thereof.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ParkinsonsPathway - Alpha-synuclein and Parkin-mediated proteolysis in Parkinson's disease h_parkinPathway - Role of Parkin in the Ubiquitin-Proteasomal Pathway
Reactome (by CSHL, EBI, and GO)
Protein P37840 (Reactome details) participates in the following event(s):