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P37840

- SYUA_HUMAN

UniProt

P37840 - SYUA_HUMAN

Protein

Alpha-synuclein

Gene

SNCA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi2 – 21CopperCurated
    Metal bindingi50 – 501CopperCurated

    GO - Molecular functioni

    1. alpha-tubulin binding Source: UniProtKB
    2. calcium ion binding Source: UniProtKB
    3. copper ion binding Source: UniProtKB
    4. cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
    5. dynein binding Source: UniProtKB
    6. ferrous iron binding Source: UniProtKB
    7. histone binding Source: UniProtKB
    8. Hsp70 protein binding Source: UniProtKB
    9. identical protein binding Source: IntAct
    10. kinesin binding Source: UniProtKB
    11. magnesium ion binding Source: UniProtKB
    12. oxidoreductase activity Source: UniProtKB
    13. phospholipid binding Source: Ensembl
    14. phosphoprotein binding Source: BHF-UCL
    15. protein binding Source: UniProtKB
    16. tau protein binding Source: UniProtKB
    17. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
    2. adult locomotory behavior Source: Ensembl
    3. aging Source: Ensembl
    4. behavioral response to cocaine Source: Ensembl
    5. cellular response to copper ion Source: UniProtKB
    6. cellular response to epinephrine stimulus Source: UniProtKB
    7. cellular response to fibroblast growth factor stimulus Source: Ensembl
    8. cellular response to oxidative stress Source: Ensembl
    9. dopamine biosynthetic process Source: UniProtKB
    10. dopamine uptake involved in synaptic transmission Source: UniProtKB
    11. extracellular fibril organization Source: UniProtKB
    12. fatty acid metabolic process Source: Ensembl
    13. long-term synaptic potentiation Source: Ensembl
    14. microglial cell activation Source: Ensembl
    15. mitochondrial ATP synthesis coupled electron transport Source: Ensembl
    16. mitochondrial membrane organization Source: Ensembl
    17. negative regulation of apoptotic process Source: UniProtKB
    18. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    19. negative regulation of dopamine metabolic process Source: Ensembl
    20. negative regulation of dopamine uptake involved in synaptic transmission Source: UniProtKB
    21. negative regulation of exocytosis Source: UniProtKB
    22. negative regulation of histone acetylation Source: UniProtKB
    23. negative regulation of microtubule polymerization Source: BHF-UCL
    24. negative regulation of monooxygenase activity Source: BHF-UCL
    25. negative regulation of neuron apoptotic process Source: Ensembl
    26. negative regulation of norepinephrine uptake Source: UniProtKB
    27. negative regulation of platelet-derived growth factor receptor signaling pathway Source: UniProtKB
    28. negative regulation of protein phosphorylation Source: Ensembl
    29. negative regulation of serotonin uptake Source: UniProtKB
    30. negative regulation of thrombin receptor signaling pathway Source: UniProtKB
    31. negative regulation of transporter activity Source: UniProtKB
    32. neutral lipid metabolic process Source: Ensembl
    33. oxidation-reduction process Source: UniProtKB
    34. phospholipid metabolic process Source: Ensembl
    35. positive regulation of endocytosis Source: UniProtKB
    36. positive regulation of inositol phosphate biosynthetic process Source: UniProtKB
    37. positive regulation of neurotransmitter secretion Source: Ensembl
    38. positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
    39. positive regulation of protein serine/threonine kinase activity Source: BHF-UCL
    40. positive regulation of receptor recycling Source: UniProtKB
    41. positive regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
    42. protein destabilization Source: UniProtKB
    43. receptor internalization Source: UniProtKB
    44. regulation of acyl-CoA biosynthetic process Source: Ensembl
    45. regulation of dopamine secretion Source: UniProtKB
    46. regulation of excitatory postsynaptic membrane potential Source: Ensembl
    47. regulation of glutamate secretion Source: Ensembl
    48. regulation of locomotion Source: Ensembl
    49. regulation of long-term neuronal synaptic plasticity Source: Ensembl
    50. regulation of macrophage activation Source: Ensembl
    51. regulation of neuron death Source: ParkinsonsUK-UCL
    52. regulation of phospholipase activity Source: UniProtKB
    53. response to drug Source: Ensembl
    54. response to interferon-gamma Source: UniProtKB
    55. response to interleukin-1 Source: UniProtKB
    56. response to iron(II) ion Source: UniProtKB
    57. response to lipopolysaccharide Source: UniProtKB
    58. response to magnesium ion Source: UniProtKB
    59. synapse organization Source: Ensembl
    60. synaptic vesicle endocytosis Source: UniProtKB

    Keywords - Ligandi

    Copper, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_75925. Amyloids.
    SignaLinkiP37840.

    Protein family/group databases

    TCDBi1.C.77.1.1. the synuclein (synuclein) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alpha-synuclein
    Alternative name(s):
    Non-A beta component of AD amyloid
    Non-A4 component of amyloid precursor
    Short name:
    NACP
    Gene namesi
    Name:SNCA
    Synonyms:NACP, PARK1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:11138. SNCA.

    Subcellular locationi

    Cytoplasm. Membrane. Nucleus. Cell junctionsynapse
    Note: Membrane-bound in dopaminergic neurons.

    GO - Cellular componenti

    1. actin cytoskeleton Source: UniProtKB
    2. axon Source: UniProtKB
    3. cell cortex Source: UniProtKB
    4. cell junction Source: UniProtKB-KW
    5. cytoplasm Source: UniProtKB
    6. cytoplasmic vesicle membrane Source: Ensembl
    7. cytosol Source: UniProtKB
    8. extracellular region Source: Reactome
    9. fibril Source: UniProtKB
    10. Golgi apparatus Source: Ensembl
    11. growth cone Source: UniProtKB
    12. inclusion body Source: UniProtKB
    13. lysosome Source: ParkinsonsUK-UCL
    14. mitochondrion Source: Ensembl
    15. nuclear outer membrane Source: Ensembl
    16. nucleus Source: UniProtKB
    17. perinuclear region of cytoplasm Source: UniProtKB
    18. plasma membrane Source: UniProtKB
    19. ribosome Source: Ensembl
    20. rough endoplasmic reticulum Source: Ensembl
    21. synaptic vesicle Source: Ensembl
    22. terminal bouton Source: Ensembl

    Keywords - Cellular componenti

    Amyloid, Cell junction, Cytoplasm, Membrane, Nucleus, Synapse

    Pathology & Biotechi

    Involvement in diseasei

    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.
    Parkinson disease 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.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti30 – 301A → P in PARK1. 1 Publication
    VAR_007957
    Natural varianti46 – 461E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes. 1 Publication
    VAR_022703
    Natural varianti50 – 501H → Q in PARK1; impairs copper-binding. 2 Publications
    VAR_070171
    Natural varianti53 – 531A → T in PARK1; no effect on osmotic stress-induced phosphorylation. 1 Publication
    VAR_007454
    Parkinson disease 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 (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Dementia Lewy body (DLB) [MIM:127750]: A neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti46 – 461E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes. 1 Publication
    VAR_022703

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi2 – 21D → A: Impairs copper-binding. 1 Publication
    Mutagenesisi39 – 391Y → F: No effect on osmotic stress-induced phosphorylation. 1 Publication
    Mutagenesisi50 – 501H → A: Impairs copper-binding. 1 Publication
    Mutagenesisi67 – 715Missing: Reduces polymerization into amyloid fibrils.
    Mutagenesisi71 – 8212Missing: Impairs polymerization into amyloid fibrils. Add
    BLAST
    Mutagenesisi76 – 772Missing: Impairs polymerization into amyloid fibrils.
    Mutagenesisi76 – 761Missing: Does not affect polymerization into amyloid fibrils.
    Mutagenesisi77 – 771Missing: Does not affect polymerization into amyloid fibrils. 1 Publication
    Mutagenesisi78 – 781Missing: Does not affect polymerization into amyloid fibrils. 1 Publication
    Mutagenesisi85 – 9410Missing: Reduces polymerization into amyloid fibrils.
    Mutagenesisi125 – 1251Y → F: Abolishes osmotic stress-induced phosphorylation. 1 Publication
    Mutagenesisi133 – 1331Y → F: No effect on osmotic stress-induced phosphorylation. 1 Publication
    Mutagenesisi136 – 1361Y → F: No effect on osmotic stress-induced phosphorylation. 1 Publication

    Keywords - Diseasei

    Alzheimer disease, Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

    Organism-specific databases

    MIMi127750. phenotype.
    168600. phenotype.
    168601. phenotype.
    605543. phenotype.
    Orphaneti1648. Dementia with Lewy body.
    171695. Parkinsonian-pyramidal syndrome.
    2828. Young adult-onset Parkinsonism.
    PharmGKBiPA35986.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 140140Alpha-synucleinPRO_0000184022Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei87 – 871Phosphoserine2 Publications
    Modified residuei125 – 1251Phosphotyrosine; by FYN3 Publications
    Modified residuei129 – 1291Phosphoserine; by BARK1, PLK2, CK2, CK1 and GRK53 Publications

    Post-translational modificationi

    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.5 Publications
    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.
    Ubiquitinated. The predominant conjugate is the diubiquitinated form By similarity.By similarity
    Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP37840.
    PaxDbiP37840.
    PRIDEiP37840.

    PTM databases

    PhosphoSiteiP37840.

    Miscellaneous databases

    PMAP-CutDBP37840.

    Expressioni

    Tissue specificityi

    Expressed principally in brain but is also expressed in low concentrations in all tissues examined except in liver. Concentrated in presynaptic nerve terminals.

    Gene expression databases

    ArrayExpressiP37840.
    BgeeiP37840.
    CleanExiHS_SNCA.
    GenevestigatoriP37840.

    Organism-specific databases

    HPAiCAB010877.
    HPA005459.

    Interactioni

    Subunit structurei

    Soluble monomer which can form filamentous aggregates. Interacts with UCHL1 By similarity. Interacts with phospholipase D and histones.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself28EBI-985879,EBI-985879
    GSK3BP498412EBI-985879,EBI-373586
    HSPA1BP081077EBI-985879,EBI-629985
    HTTP428584EBI-985879,EBI-466029
    LRRK2Q5S0076EBI-985879,EBI-5323863
    MAPTP10636-83EBI-985879,EBI-366233
    MT-CO3P004143EBI-985879,EBI-3932264
    RABAC1Q9UI144EBI-985879,EBI-712367
    SLC6A3Q019593EBI-985879,EBI-6661445
    Slc6a3Q613275EBI-985879,EBI-7839708From a different organism.
    SNCAIPQ9Y6H522EBI-985879,EBI-717182
    SYN1P176002EBI-985879,EBI-717274

    Protein-protein interaction databases

    BioGridi112506. 411 interactions.
    DIPiDIP-35354N.
    IntActiP37840. 212 interactions.
    MINTiMINT-2515483.
    STRINGi9606.ENSP00000338345.

    Structurei

    Secondary structure

    1
    140
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 119
    Helixi21 – 3212
    Helixi41 – 444
    Beta strandi45 – 473
    Helixi52 – 554
    Helixi66 – 683
    Beta strandi110 – 1134
    Turni120 – 1223
    Turni124 – 1263

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1XQ8NMR-A1-140[»]
    2JN5NMR-A1-12[»]
    2KKWNMR-A1-140[»]
    2M55NMR-B1-19[»]
    2X6MX-ray1.62B132-140[»]
    3Q25X-ray1.90A1-19[»]
    3Q26X-ray1.54A10-42[»]
    3Q27X-ray1.30A32-57[»]
    3Q28X-ray1.60A58-79[»]
    3Q29X-ray2.30A/C1-19[»]
    4BXLNMR-C35-56[»]
    DisProtiDP00070.
    ProteinModelPortaliP37840.
    SMRiP37840. Positions 1-140.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP37840.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati20 – 30111Add
    BLAST
    Repeati31 – 41112Add
    BLAST
    Repeati42 – 56153; approximateAdd
    BLAST
    Repeati57 – 67114Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni20 – 67484 X 11 AA tandem repeats of [EGS]-K-T-K-[EQ]-[GQ]-V-X(4)Add
    BLAST

    Domaini

    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.1 Publication

    Sequence similaritiesi

    Belongs to the synuclein family.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG44393.
    HOGENOMiHOG000008691.
    HOVERGENiHBG000481.
    InParanoidiP37840.
    KOiK04528.
    OMAiMPPEEEY.
    OrthoDBiEOG7034KG.
    PhylomeDBiP37840.
    TreeFamiTF332776.

    Family and domain databases

    Gene3Di1.10.287.700. 1 hit.
    InterProiIPR001058. Synuclein.
    IPR002460. Synuclein_alpha.
    [Graphical view]
    PANTHERiPTHR13820. PTHR13820. 1 hit.
    PfamiPF01387. Synuclein. 1 hit.
    [Graphical view]
    PRINTSiPR01212. ASYNUCLEIN.
    PR01211. SYNUCLEIN.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P37840-1) [UniParc]FASTAAdd to Basket

    Also known as: NACP140

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH    50
    GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL 100
    GKNEEGAPQE GILEDMPVDP DNEAYEMPSE EGYQDYEPEA 140
    Length:140
    Mass (Da):14,460
    Last modified:October 1, 1994 - v1
    Checksum:i6BB2F12128931663
    GO
    Isoform 2-4 (identifier: P37840-2) [UniParc]FASTAAdd to Basket

    Also known as: NACP112

    The sequence of this isoform differs from the canonical sequence as follows:
         103-130: Missing.

    Show »
    Length:112
    Mass (Da):11,372
    Checksum:i16EA234777EFA89E
    GO
    Isoform 2-5 (identifier: P37840-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         41-54: Missing.

    Show »
    Length:126
    Mass (Da):13,109
    Checksum:i0F87D9A60E831E02
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti30 – 301A → P in PARK1. 1 Publication
    VAR_007957
    Natural varianti46 – 461E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes. 1 Publication
    VAR_022703
    Natural varianti50 – 501H → Q in PARK1; impairs copper-binding. 2 Publications
    VAR_070171
    Natural varianti53 – 531A → T in PARK1; no effect on osmotic stress-induced phosphorylation. 1 Publication
    VAR_007454

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei41 – 5414Missing in isoform 2-5. 1 PublicationVSP_006363Add
    BLAST
    Alternative sequencei103 – 13028Missing in isoform 2-4. 2 PublicationsVSP_006364Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L08850 mRNA. Translation: AAA16117.1.
    L36674 mRNA. Translation: AAA98493.1.
    L36675 mRNA. Translation: AAA98487.1.
    D31839 mRNA. Translation: BAA06625.1.
    U46901
    , U46897, U46898, U46899 Genomic DNA. Translation: AAC02114.1.
    AF163864 Genomic DNA. Translation: AAG30302.1.
    AF163864 Genomic DNA. Translation: AAG30303.1.
    AY049786 mRNA. Translation: AAL15443.1.
    AK290169 mRNA. Translation: BAF82858.1.
    CR457058 mRNA. Translation: CAG33339.1.
    DQ088379 Genomic DNA. Translation: AAY88735.1.
    CH471057 Genomic DNA. Translation: EAX06036.1.
    BC013293 mRNA. Translation: AAH13293.1.
    BC108275 mRNA. Translation: AAI08276.1.
    CCDSiCCDS3634.1. [P37840-1]
    CCDS43252.1. [P37840-2]
    PIRiA49669.
    S56746.
    RefSeqiNP_000336.1. NM_000345.3. [P37840-1]
    NP_001139526.1. NM_001146054.1. [P37840-1]
    NP_001139527.1. NM_001146055.1. [P37840-1]
    NP_009292.1. NM_007308.2. [P37840-2]
    UniGeneiHs.21374.

    Genome annotation databases

    EnsembliENST00000336904; ENSP00000338345; ENSG00000145335. [P37840-1]
    ENST00000345009; ENSP00000343683; ENSG00000145335. [P37840-2]
    ENST00000394986; ENSP00000378437; ENSG00000145335. [P37840-1]
    ENST00000394989; ENSP00000378440; ENSG00000145335. [P37840-3]
    ENST00000394991; ENSP00000378442; ENSG00000145335. [P37840-1]
    ENST00000420646; ENSP00000396241; ENSG00000145335. [P37840-2]
    ENST00000505199; ENSP00000421485; ENSG00000145335. [P37840-3]
    ENST00000506244; ENSP00000422238; ENSG00000145335. [P37840-1]
    ENST00000508895; ENSP00000426955; ENSG00000145335. [P37840-1]
    GeneIDi6622.
    KEGGihsa:6622.
    UCSCiuc003hsp.3. human. [P37840-1]

    Polymorphism databases

    DMDMi586067.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L08850 mRNA. Translation: AAA16117.1 .
    L36674 mRNA. Translation: AAA98493.1 .
    L36675 mRNA. Translation: AAA98487.1 .
    D31839 mRNA. Translation: BAA06625.1 .
    U46901
    , U46897 , U46898 , U46899 Genomic DNA. Translation: AAC02114.1 .
    AF163864 Genomic DNA. Translation: AAG30302.1 .
    AF163864 Genomic DNA. Translation: AAG30303.1 .
    AY049786 mRNA. Translation: AAL15443.1 .
    AK290169 mRNA. Translation: BAF82858.1 .
    CR457058 mRNA. Translation: CAG33339.1 .
    DQ088379 Genomic DNA. Translation: AAY88735.1 .
    CH471057 Genomic DNA. Translation: EAX06036.1 .
    BC013293 mRNA. Translation: AAH13293.1 .
    BC108275 mRNA. Translation: AAI08276.1 .
    CCDSi CCDS3634.1. [P37840-1 ]
    CCDS43252.1. [P37840-2 ]
    PIRi A49669.
    S56746.
    RefSeqi NP_000336.1. NM_000345.3. [P37840-1 ]
    NP_001139526.1. NM_001146054.1. [P37840-1 ]
    NP_001139527.1. NM_001146055.1. [P37840-1 ]
    NP_009292.1. NM_007308.2. [P37840-2 ]
    UniGenei Hs.21374.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1XQ8 NMR - A 1-140 [» ]
    2JN5 NMR - A 1-12 [» ]
    2KKW NMR - A 1-140 [» ]
    2M55 NMR - B 1-19 [» ]
    2X6M X-ray 1.62 B 132-140 [» ]
    3Q25 X-ray 1.90 A 1-19 [» ]
    3Q26 X-ray 1.54 A 10-42 [» ]
    3Q27 X-ray 1.30 A 32-57 [» ]
    3Q28 X-ray 1.60 A 58-79 [» ]
    3Q29 X-ray 2.30 A/C 1-19 [» ]
    4BXL NMR - C 35-56 [» ]
    DisProti DP00070.
    ProteinModelPortali P37840.
    SMRi P37840. Positions 1-140.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112506. 411 interactions.
    DIPi DIP-35354N.
    IntActi P37840. 212 interactions.
    MINTi MINT-2515483.
    STRINGi 9606.ENSP00000338345.

    Chemistry

    ChEMBLi CHEMBL6152.
    DrugBanki DB01065. Melatonin.

    Protein family/group databases

    TCDBi 1.C.77.1.1. the synuclein (synuclein) family.

    PTM databases

    PhosphoSitei P37840.

    Polymorphism databases

    DMDMi 586067.

    Proteomic databases

    MaxQBi P37840.
    PaxDbi P37840.
    PRIDEi P37840.

    Protocols and materials databases

    DNASUi 6622.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000336904 ; ENSP00000338345 ; ENSG00000145335 . [P37840-1 ]
    ENST00000345009 ; ENSP00000343683 ; ENSG00000145335 . [P37840-2 ]
    ENST00000394986 ; ENSP00000378437 ; ENSG00000145335 . [P37840-1 ]
    ENST00000394989 ; ENSP00000378440 ; ENSG00000145335 . [P37840-3 ]
    ENST00000394991 ; ENSP00000378442 ; ENSG00000145335 . [P37840-1 ]
    ENST00000420646 ; ENSP00000396241 ; ENSG00000145335 . [P37840-2 ]
    ENST00000505199 ; ENSP00000421485 ; ENSG00000145335 . [P37840-3 ]
    ENST00000506244 ; ENSP00000422238 ; ENSG00000145335 . [P37840-1 ]
    ENST00000508895 ; ENSP00000426955 ; ENSG00000145335 . [P37840-1 ]
    GeneIDi 6622.
    KEGGi hsa:6622.
    UCSCi uc003hsp.3. human. [P37840-1 ]

    Organism-specific databases

    CTDi 6622.
    GeneCardsi GC04M090646.
    GeneReviewsi SNCA.
    HGNCi HGNC:11138. SNCA.
    HPAi CAB010877.
    HPA005459.
    MIMi 127750. phenotype.
    163890. gene.
    168600. phenotype.
    168601. phenotype.
    605543. phenotype.
    neXtProti NX_P37840.
    Orphaneti 1648. Dementia with Lewy body.
    171695. Parkinsonian-pyramidal syndrome.
    2828. Young adult-onset Parkinsonism.
    PharmGKBi PA35986.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG44393.
    HOGENOMi HOG000008691.
    HOVERGENi HBG000481.
    InParanoidi P37840.
    KOi K04528.
    OMAi MPPEEEY.
    OrthoDBi EOG7034KG.
    PhylomeDBi P37840.
    TreeFami TF332776.

    Enzyme and pathway databases

    Reactomei REACT_75925. Amyloids.
    SignaLinki P37840.

    Miscellaneous databases

    ChiTaRSi SNCA. human.
    EvolutionaryTracei P37840.
    GeneWikii Alpha-synuclein.
    GenomeRNAii 6622.
    NextBioi 25791.
    PMAP-CutDB P37840.
    PROi P37840.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P37840.
    Bgeei P37840.
    CleanExi HS_SNCA.
    Genevestigatori P37840.

    Family and domain databases

    Gene3Di 1.10.287.700. 1 hit.
    InterProi IPR001058. Synuclein.
    IPR002460. Synuclein_alpha.
    [Graphical view ]
    PANTHERi PTHR13820. PTHR13820. 1 hit.
    Pfami PF01387. Synuclein. 1 hit.
    [Graphical view ]
    PRINTSi PR01212. ASYNUCLEIN.
    PR01211. SYNUCLEIN.
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease."
      Ueda K., Fukushima H., Masliah E., Xia Y., Iwai A., Yoshimoto M., Otero D.A., Kondo J., Ihara Y., Saitoh T.
      Proc. Natl. Acad. Sci. U.S.A. 90:11282-11286(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 61-95.
      Tissue: Brain.
    2. "The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease."
      Campion D., Martin C., Heilig R., Charbonnier F., Moreau V., Flaman J.-M., Petit J.-L., Hannequin D., Brice A., Frebourg T.
      Genomics 26:254-257(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2-4 AND 2-5).
    3. "Tissue-dependent alternative splicing of mRNA for NACP, the precursor of non-A beta component of Alzheimer's disease amyloid."
      Ueda K., Saitoh T., Mori H.
      Biochem. Biophys. Res. Commun. 205:1366-1372(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2-4).
      Tissue: Brain.
    4. Xia Y., Silva R.D., Chen X.H., Saitoh T.
      Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element."
      Touchman J.W., Dehejia A., Chiba-Falek O., Cabin D.E., Schwartz J.R., Orrison B.M., Polymeropoulos M.H., Nussbaum R.L.
      Genome Res. 11:78-86(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2-4).
    6. Hu X., Xu Y., Peng X., Yuan J., Qiang B.
      Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    7. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Thalamus.
    8. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    9. NIEHS SNPs program
      Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    10. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    11. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Uterus.
    12. Lubec G., Chen W.-Q., Sun Y.
      Submitted (DEC-2008) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 59-96, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Fetal brain cortex.
    13. "Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein."
      Okochi M., Walter J., Koyama A., Nakajo S., Baba M., Iwatsubo T., Meijer L., Kahle P.J., Haass C.
      J. Biol. Chem. 275:390-397(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-87 AND SER-129 BY CK1 AND CK2.
    14. "Synucleins are a novel class of substrates for G protein-coupled receptor kinases."
      Pronin A.N., Morris A.J., Surguchov A., Benovic J.L.
      J. Biol. Chem. 275:26515-26522(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY G-PROTEIN COUPLED RECEPTOR KINASE.
    15. "Activated Fyn phosphorylates alpha-synuclein at tyrosine residue 125."
      Nakamura T., Yamashita H., Takahashi T., Nakamura S.
      Biochem. Biophys. Res. Commun. 280:1085-1092(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-125 BY FYN.
    16. "Alpha-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells."
      Ahn B.H., Rhim H., Kim S.Y., Sung Y.M., Lee M.Y., Choi J.Y., Wolozin B., Chang J.S., Lee Y.H., Kwon T.K., Chung K.C., Yoon S.H., Hahn S.J., Kim M.S., Jo Y.H., Min do S.
      J. Biol. Chem. 277:12334-12342(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PHOSPHOLIPASE D.
    17. Cited for: PHOSPHORYLATION AT SER-129.
    18. Cited for: INTERACTION WITH HISTONES, SUBCELLULAR LOCATION.
    19. Cited for: ROLE OF THE C-TERMINUS IN FIBRILLOGENESIS.
    20. "Recent advances on alpha-synuclein cell biology: functions and dysfunctions."
      Alves da Costa C.
      Curr. Mol. Med. 3:17-24(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    21. "Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation."
      Takahashi T., Yamashita H., Nagano Y., Nakamura T., Ohmori H., Avraham H., Avraham S., Yasuda M., Matsumoto M.
      J. Biol. Chem. 278:42225-42233(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF TYR-39; TYR-125; TYR-133 AND TYR-136, CHARACTERIZATION OF VARIANT THR-53, PHOSPHORYLATION AT TYR-125.
    22. "Lipid rafts mediate the synaptic localization of alpha-synuclein."
      Fortin D.L., Troyer M.D., Nakamura K., Kubo S., Anthony M.D., Edwards R.H.
      J. Neurosci. 24:6715-6723(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    23. "Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization."
      Waxman E.A., Mazzulli J.R., Giasson B.I.
      Biochemistry 48:9427-9436(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FIBRILS FORMATION, DOMAIN NAC, MUTAGENESIS OF 67-GLY--VAL-71; 71-VAL--VAL-82; 76-ALA-VAL-77; VAL-77; ALA-78 AND 85-ALA--PHE-94.
    24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    25. "Coordination features and affinity of the Cu(2)+ site in the alpha-synuclein protein of Parkinson's disease."
      Dudzik C.G., Walter E.D., Millhauser G.L.
      Biochemistry 50:1771-1777(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: COPPER-BINDING, MUTAGENESIS OF ASP-2 AND HIS-50.
    26. "N-Terminal acetylation is critical for forming alpha-helical oligomer of alpha-synuclein."
      Trexler A.J., Rhoades E.
      Protein Sci. 21:601-605(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION AT MET-1.
    27. "Structure and dynamics of micelle-bound human alpha-synuclein."
      Ulmer T.S., Bax A., Cole N.B., Nussbaum R.L.
      J. Biol. Chem. 280:9595-9603(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR IN COMPLEX WITH DETERGENT MICELLES.
    28. Cited for: VARIANT PARK1 THR-53.
    29. "Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease."
      Krueger R., Kuhn W., Mueller T., Woitalla D., Graeber M., Koesel S., Przuntek H., Epplen J.T., Schoels L., Riess O.
      Nat. Genet. 18:106-108(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PARK1 PRO-30.
    30. Cited for: VARIANT PARK1/DLB LYS-46.
    31. "Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein."
      Choi W., Zibaee S., Jakes R., Serpell L.C., Davletov B., Crowther R.A., Goedert M.
      FEBS Lett. 576:363-368(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT LYS-46.
    32. Cited for: VARIANT PARK1 GLN-50.
    33. Cited for: VARIANT PARK1 GLN-50, CHARACTERIZATION OF VARIANT PARK1 GLN-50.

    Entry informationi

    Entry nameiSYUA_HUMAN
    AccessioniPrimary (citable) accession number: P37840
    Secondary accession number(s): A8K2A4
    , Q13701, Q4JHI3, Q6IAU6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1994
    Last sequence update: October 1, 1994
    Last modified: October 1, 2014
    This is version 174 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3