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P37840

- SYUA_HUMAN

UniProt

P37840 - SYUA_HUMAN

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Protein

Alpha-synuclein

Gene

SNCA

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

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: ParkinsonsUK-UCL
  14. phosphoprotein binding Source: BHF-UCL
  15. tau protein binding Source: UniProtKB
  16. 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: ParkinsonsUK-UCL
  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 glutathione peroxidase activity Source: ParkinsonsUK-UCL
  37. positive regulation of hydrogen peroxide catabolic process Source: ParkinsonsUK-UCL
  38. positive regulation of inositol phosphate biosynthetic process Source: UniProtKB
  39. positive regulation of neurotransmitter secretion Source: Ensembl
  40. positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  41. positive regulation of protein serine/threonine kinase activity Source: BHF-UCL
  42. positive regulation of receptor recycling Source: UniProtKB
  43. positive regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
  44. protein destabilization Source: UniProtKB
  45. receptor internalization Source: UniProtKB
  46. regulation of acyl-CoA biosynthetic process Source: Ensembl
  47. regulation of dopamine secretion Source: UniProtKB
  48. regulation of excitatory postsynaptic membrane potential Source: Ensembl
  49. regulation of glutamate secretion Source: Ensembl
  50. regulation of locomotion Source: Ensembl
  51. regulation of long-term neuronal synaptic plasticity Source: Ensembl
  52. regulation of macrophage activation Source: Ensembl
  53. regulation of neuron death Source: ParkinsonsUK-UCL
  54. regulation of phospholipase activity Source: UniProtKB
  55. response to drug Source: Ensembl
  56. response to interferon-gamma Source: UniProtKB
  57. response to interleukin-1 Source: UniProtKB
  58. response to iron(II) ion Source: UniProtKB
  59. response to lipopolysaccharide Source: UniProtKB
  60. response to magnesium ion Source: UniProtKB
  61. synapse organization Source: Ensembl
  62. synaptic vesicle endocytosis Source: UniProtKB
Complete GO annotation...

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
Complete GO annotation...

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. 1 Publication
Mutagenesisi71 – 8212Missing: Impairs polymerization into amyloid fibrils. 1 PublicationAdd
BLAST
Mutagenesisi76 – 772Missing: Impairs polymerization into amyloid fibrils. 1 Publication
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. 1 Publication
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 – 871Phosphoserine1 Publication
Modified residuei125 – 1251Phosphotyrosine; by FYN2 Publications
Modified residuei129 – 1291Phosphoserine; by BARK1, PLK2, CK2, CK1 and GRK52 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

BgeeiP37840.
CleanExiHS_SNCA.
ExpressionAtlasiP37840. baseline and differential.
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. 416 interactions.
DIPiDIP-35354N.
IntActiP37840. 213 interactions.
MINTiMINT-2515483.
STRINGi9606.ENSP00000338345.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000016161.
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

        10         20         30         40         50
MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH
60 70 80 90 100
GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL
110 120 130 140
GKNEEGAPQE GILEDMPVDP DNEAYEMPSE EGYQDYEPEA
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:
EMBLi
GenBanki
DDBJi
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]
ENST00000618500; ENSP00000484044; ENSG00000145335. [P37840-3]
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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. 416 interactions.
DIPi DIP-35354N.
IntActi P37840. 213 interactions.
MINTi MINT-2515483.
STRINGi 9606.ENSP00000338345.

Chemistry

BindingDBi P37840.
ChEMBLi CHEMBL6152.

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 ]
ENST00000618500 ; ENSP00000484044 ; ENSG00000145335 . [P37840-3 ]
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.
GeneTreei ENSGT00390000016161.
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

Bgeei P37840.
CleanExi HS_SNCA.
ExpressionAtlasi P37840. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 176 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