MultifacetedProtDB - Bologna Biocomputing Group

Structure

PDB	Resolution (Å)	PDB name
1XQ8		Human micelle-bound alpha-synuclein
2JN5		Solution Structure of a Dodecapeptide from Alpha-Synuclein Bound with Synphilin-1
2KKW		SLAS-micelle bound alpha-synuclein
2M55		NMR structure of the complex of an N-terminally acetylated alpha-synuclein peptide with calmodulin
2N0A		Atomic-resolution structure of alpha-synuclein fibrils
2X6M	1.62	Structure of a single domain camelid antibody fragment in complex with a C-terminal peptide of alpha-synuclein
3Q25	1.9	Crystal structure of human alpha-synuclein (1-19) fused to maltose binding protein (MBP)
3Q26	1.54	Cyrstal structure of human alpha-synuclein (10-42) fused to maltose binding protein (MBP)
3Q27	1.302	Cyrstal structure of human alpha-synuclein (32-57) fused to maltose binding protein (MBP)
3Q28	1.6	Cyrstal structure of human alpha-synuclein (58-79) fused to maltose binding protein (MBP)
3Q29	2.3	Cyrstal structure of human alpha-synuclein (1-19) fused to maltose binding protein (MBP)
4BXL		Structure of alpha-synuclein in complex with an engineered binding protein
4R0U	1.38	Tgvtava, an amyloid forming segment from alpha synuclein, residues 72-78
4R0W	1.5	Vvtgvta, an amyloid forming segment from alpha synuclein, residues 70-76
4RIK	1.854	Amyloid forming segment, AVVTGVTAV, from the NAC domain of Parkinson's disease protein alpha-synuclein, residues 69-77
4RIL	1.43	Structure of the amyloid forming segment, GAVVTGVTAVA, from the NAC domain of Parkinson's disease protein alpha-synuclein, residues 68-78, determined by electron diffraction
4ZNN	1.41	MicroED structure of the segment, GVVHGVTTVA, from the A53T familial mutant of Parkinson's disease protein, alpha-synuclein residues 47-56
5CRW	1.6	Crystal structure of the b'-a' domain of oxidized protein disulfide isomerase complexed with alpha-synuclein peptide (31-41)
6A6B	3.07	cryo-em structure of alpha-synuclein fiber
6CT7	1.903	Fab of anti-a-synuclein antibody BIIB054 in complex with acetylated a-synuclein peptide (1-10)
6CU7	3.5	Alpha Synuclein fibril formed by full length protein - Rod Polymorph
6CU8	3.6	Alpha Synuclein fibril formed by full length protein - Twister Polymorph
6H6B	3.4	Structure of alpha-synuclein fibrils
6I42	1.38	Structure of the alpha-Synuclein PreNAC/Cyclophilin A-complex
6L1T	3.22	Cryo-EM structure of phosphorylated Tyr39 a-synuclein amyloid fibril
6L1U	3.37	Cryo-EM structure of phosphorylated Tyr39 alpha-synuclein amyloid fibril
6L4S	3.37	cryo-em structure of alpha-synuclein fiber mutation type E46K
6LRQ	3.49	Cryo-EM structure of A53T alpha-synuclein amyloid fibril
6OSJ	2.8	Cryo-EM structure of the N-terminally acetylated full length alpha-synuclein fibrils (Ac1-140)
6OSL	3.0	Cryo-EM structure of the N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-122
6OSM	3.4	Cryo-EM structure of the N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-103
6PEO	3.3	Cryo-EM structure of alpha-synuclein H50Q Narrow Fibril
6PES	3.6	Cryo-EM structure of alpha-synuclein H50Q Wide Fibril
6RT0	3.1	cryo-em structure of alpha-synuclein fibril polymorph 2A
6RTB	3.46	cryo-em structure of alpha-synuclein fibril polymorph 2B
6SST	3.4	cryo-em structure of alpha-synuclein fibril polymorph 2B
6SSX	2.98	cryo-em structure of alpha-synuclein fibril polymorph 2A
6UFR	2.5	Structure of recombinantly assembled E46K alpha-synuclein fibrils
6XYO	2.6	Multiple system atrophy Type I alpha-synuclein filament
6XYP	3.29	Multiple system atrophy Type II-1 alpha-synuclein filament
6XYQ	3.09	Multiple system atrophy Type II-2 alpha-synuclein filament
7C1D	3.8	Cryo-EM structure of the hE46K cross-seeded hWT alpha-synuclein fibril
7E0F	3.02	CryoEM structure of G51D alpha-synuclein amyloid fibril
7L7H	4.0	Alpha-synuclein fibrils
7LC9	3.2	Cryo-EM structure of the N-terminal alpha-synuclein truncation 41-140
7NCA	3.47	Type 1A alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 2
7NCG	3.43	Type 2A alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 2
7NCH	3.84	Type 1B alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 1
7NCI	3.55	Type 2B alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 1
7NCJ	4.23	Type 2AB alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 1
7NCK	3.18	Type 3 alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 5
7OZG	3.3	PMCA-amplified alpha-synuclein fibril polymorph, Parkinson's Disease patient-derived seeds
7OZH	3.02	PMCA-amplified alpha-synuclein fibril polymorph, Multiple System Atrophy patient-derived seeds
7STX	3.14	Cryo-EM structure of human NatB in complex with CoA-Alpha-Synuclein
7UAK	3.38	Structure of recombinantly assembled A53E alpha-synuclein fibrils
7V47	2.8	Type 1A alpha-synuclein fibril seeded by cerebrospinal fluid from a preclinical Parkinson's disease patient
7V48	3.0	Type 1D alpha-synuclein fibril seeded by cerebrospinal fluid from a postmortal Parkinson's disease patient
7V49	3.4	Type 4 alpha-synuclein fibril seeded by cerebrospinal fluid from a postmortal Parkinson's disease patient
7V4A	3.2	Heparin-induced alpha-synuclein fibrils polymorph 1
7V4B	3.1	Heparin-induced alpha-synuclein fibrils polymorph 3
7V4C	3.3	Heparin-induced alpha-synuclein fibrils polymorph 4
7V4D	3.5	Heparin-remodelled alpha-synuclein fibrils
7WMM	2.6	alpha-synuclein fibril-F0502B complex
7WNZ	3.4	CryoEM structure of human alpha-synuclein A53T fibril
7WO0	2.7	CryoEM structure of human alpha-synuclein A53T fibril induced by calcium ions
7XJX	2.7	The cryo-EM structure of Fe3+ induced alpha-syn fibril.
7XO0	3.0	Minor polymorph inalpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-1) Parkinson's disease patient
7XO1	3.0	Major polymorph in alpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-1) Parkinson's disease patient
7XO2	3.0	Minor polymorph in alpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-4) Parkinson's disease patient
7XO3	2.6	Type 1C alpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-4) Parkinson's disease patient
7YK2	2.8	Cryo-EM structure of Apo-alpha-syn fibril
7YK8	2.8	Cryo-EM structure of dLAG3-alpha-syn fibril
8A4L	2.68	Lipidic alpha-synuclein fibril - polymorph L2A
8A9L	2.2	Cryo-EM structure of alpha-synuclein filaments from Parkinson's disease and dementia with Lewy bodies
8ADS	3.05	Lipidic alpha-synuclein fibril - polymorph L2B
8ADU	3.24	Lipidic alpha-synuclein fibril - polymorph L1A
8ADV	2.98	Lipidic alpha-synuclein fibril - polymorph L1B
8ADW	2.95	Lipidic alpha-synuclein fibril - polymorph L1C
8AEX	2.76	Lipidic alpha-synuclein fibril - polymorph L3A
8BQV	2.0	Cryo-EM structure of alpha-synuclein singlet filament from Juvenile-onset synucleinopathy
8BQW	2.3	Cryo-EM structure of alpha-synuclein filaments doublet from Juvenile-onset synucleinopathy
8CE7	2.7	Type1 alpha-synuclein filament assembled in vitro by wild-type and mutant (7 residues insertion) protein
8CEB	2.8	Type2 alpha-synuclein filament assembled in vitro by wild-type and mutant (7 residues insertion) protein
8FPT		STRUCTURE OF ALPHA-SYNUCLEIN FIBRILS DERIVED FROM HUMAN LEWY BODY DEMENTIA TISSUE
8H03	2.8	Major polymorph in alpha-synuclein fibril seeded by cerebrospinal fluid from a preclinical Parkinson's disease patient
8H04	3.0	Major polymorph in alpha-synuclein fibril seeded by cerebrospinal fluid from a postmortal Parkinson's disease patient
8H05	3.4	Minor polymorph in alpha-synuclein fibril seeded by cerebrospinal fluid from a postmortal Parkinson's disease patient

GO term

GO ontology	GO term	GO description
Biological Process	GO:0035493	SNARE complex assembly
Biological Process	GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
Biological Process	GO:0008344	adult locomotory behavior
Biological Process	GO:1990000	amyloid fibril formation
Biological Process	GO:0071280	cellular response to copper ion
Biological Process	GO:0071872	cellular response to epinephrine stimulus
Biological Process	GO:0034599	cellular response to oxidative stress
Biological Process	GO:0007268	chemical synaptic transmission
Biological Process	GO:0042416	dopamine biosynthetic process
Biological Process	GO:0051583	dopamine uptake involved in synaptic transmission
Biological Process	GO:0060079	excitatory postsynaptic potential
Biological Process	GO:0006631	fatty acid metabolic process
Biological Process	GO:0051179	localization
Biological Process	GO:0060291	long-term synaptic potentiation
Biological Process	GO:0001774	microglial cell activation
Biological Process	GO:0042775	mitochondrial ATP synthesis coupled electron transport
Biological Process	GO:0007006	mitochondrial membrane organization
Biological Process	GO:0043066	negative regulation of apoptotic process
Biological Process	GO:1904715	negative regulation of chaperone-mediated autophagy
Biological Process	GO:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Biological Process	GO:0051585	negative regulation of dopamine uptake involved in synaptic transmission
Biological Process	GO:0045920	negative regulation of exocytosis
Biological Process	GO:0031115	negative regulation of microtubule polymerization
Biological Process	GO:1902957	negative regulation of mitochondrial electron transport, NADH to ubiquinone
Biological Process	GO:0032769	negative regulation of monooxygenase activity
Biological Process	GO:0043524	negative regulation of neuron apoptotic process
Biological Process	GO:1901215	negative regulation of neuron death
Biological Process	GO:0051622	negative regulation of norepinephrine uptake
Biological Process	GO:0010642	negative regulation of platelet-derived growth factor receptor signaling pathway
Biological Process	GO:0006469	negative regulation of protein kinase activity
Biological Process	GO:0051612	negative regulation of serotonin uptake
Biological Process	GO:0070495	negative regulation of thrombin-activated receptor signaling pathway
Biological Process	GO:0000122	negative regulation of transcription by RNA polymerase II
Biological Process	GO:0032410	negative regulation of transporter activity
Biological Process	GO:0051402	neuron apoptotic process
Biological Process	GO:0006638	neutral lipid metabolic process
Biological Process	GO:0006644	phospholipid metabolic process
Biological Process	GO:0035543	positive regulation of SNARE complex assembly
Biological Process	GO:0043065	positive regulation of apoptotic process
Biological Process	GO:0045807	positive regulation of endocytosis
Biological Process	GO:0045921	positive regulation of exocytosis
Biological Process	GO:1903284	positive regulation of glutathione peroxidase activity
Biological Process	GO:1903285	positive regulation of hydrogen peroxide catabolic process
Biological Process	GO:0050729	positive regulation of inflammatory response
Biological Process	GO:0060732	positive regulation of inositol phosphate biosynthetic process
Biological Process	GO:1901216	positive regulation of neuron death
Biological Process	GO:0001956	positive regulation of neurotransmitter secretion
Biological Process	GO:0033138	positive regulation of peptidyl-serine phosphorylation
Biological Process	GO:0071902	positive regulation of protein serine/threonine kinase activity
Biological Process	GO:0001921	positive regulation of receptor recycling
Biological Process	GO:0051281	positive regulation of release of sequestered calcium ion into cytosol
Biological Process	GO:0031648	protein destabilization
Biological Process	GO:0051262	protein tetramerization
Biological Process	GO:0031623	receptor internalization
Biological Process	GO:0050812	regulation of acyl-CoA biosynthetic process
Biological Process	GO:0014059	regulation of dopamine secretion
Biological Process	GO:0014048	regulation of glutamate secretion
Biological Process	GO:0040012	regulation of locomotion
Biological Process	GO:0048169	regulation of long-term neuronal synaptic plasticity
Biological Process	GO:0043030	regulation of macrophage activation
Biological Process	GO:1901214	regulation of neuron death
Biological Process	GO:0051621	regulation of norepinephrine uptake
Biological Process	GO:0010517	regulation of phospholipase activity
Biological Process	GO:1905606	regulation of presynapse assembly
Biological Process	GO:1903426	regulation of reactive oxygen species biosynthetic process
Biological Process	GO:1903421	regulation of synaptic vesicle recycling
Biological Process	GO:0022898	regulation of transmembrane transporter activity
Biological Process	GO:0070555	response to interleukin-1
Biological Process	GO:0010040	response to iron(II) ion
Biological Process	GO:0032496	response to lipopolysaccharide
Biological Process	GO:0032026	response to magnesium ion
Biological Process	GO:0034341	response to type II interferon
Biological Process	GO:0009410	response to xenobiotic stimulus
Biological Process	GO:0097435	supramolecular fiber organization
Biological Process	GO:0050808	synapse organization
Biological Process	GO:0048488	synaptic vesicle endocytosis
Biological Process	GO:0016079	synaptic vesicle exocytosis
Biological Process	GO:0016082	synaptic vesicle priming
Biological Process	GO:0048489	synaptic vesicle transport
Molecular Function	GO:0030544	Hsp70 protein binding
Molecular Function	GO:0000149	SNARE binding
Molecular Function	GO:0003779	actin binding
Molecular Function	GO:0043014	alpha-tubulin binding
Molecular Function	GO:0005509	calcium ion binding
Molecular Function	GO:0005507	copper ion binding
Molecular Function	GO:1903136	cuprous ion binding
Molecular Function	GO:0043027	cysteine-type endopeptidase inhibitor activity involved in apoptotic process
Molecular Function	GO:0070840	dynein complex binding
Molecular Function	GO:0008198	ferrous iron binding
Molecular Function	GO:0042393	histone binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0019894	kinesin binding
Molecular Function	GO:0008289	lipid binding
Molecular Function	GO:0000287	magnesium ion binding
Molecular Function	GO:0060090	molecular adaptor activity
Molecular Function	GO:0016491	oxidoreductase activity
Molecular Function	GO:0005543	phospholipid binding
Molecular Function	GO:0051219	phosphoprotein binding
Molecular Function	GO:0004860	protein kinase inhibitor activity
Molecular Function	GO:0048156	tau protein binding
Molecular Function	GO:0000976	transcription cis-regulatory region binding
Molecular Function	GO:0008270	zinc ion binding
Cellular Component	GO:0015629	actin cytoskeleton
Cellular Component	GO:0030424	axon
Cellular Component	GO:0043679	axon terminus
Cellular Component	GO:0005938	cell cortex
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0005576	extracellular region
Cellular Component	GO:0005615	extracellular space
Cellular Component	GO:0030426	growth cone
Cellular Component	GO:0016234	inclusion body
Cellular Component	GO:0005764	lysosome
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:0043025	neuronal cell body
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0048471	perinuclear region of cytoplasm
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0098794	postsynapse
Cellular Component	GO:0032991	protein-containing complex
Cellular Component	GO:0099512	supramolecular fiber
Cellular Component	GO:0030672	synaptic vesicle membrane

InterPro / Pfam

InterPro	InterPro name
IPR001058	Synuclein
IPR002460	Alpha-synuclein

Pfam	Pfam name
PF01387	Synuclein

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-977225	Amyloid fiber formation	Leaf	R-HSA-392499	Metabolism of proteins

Subcellular location

Location	ECO term	Pubmed
Cell projection, axon	ECO:000025
Cytoplasm	ECO:0000269	PubMed:19762560
Cytoplasm	ECO:0000269	PubMed:24936070
Cytoplasm	ECO:0000269	PubMed:25561023
Cytoplasm	ECO:0000269	PubMed:26442590
Cytoplasm	ECO:0000269	PubMed:31034892
Membrane	ECO:0000269	PubMed:24936070
Nucleus	ECO:0000269	PubMed:12859192
Nucleus	ECO:0000269	PubMed:24936070
Secreted	ECO:0000269	PubMed:24936070
Synapse	ECO:0000269	PubMed:15282274

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000006	Autosomal dominant inheritance
HP:0000011	Neurogenic bladder
HP:0000012	Urinary urgency
HP:0000338	Hypomimic face
HP:0000514	Slow saccadic eye movements
HP:0000551	Color vision defect
HP:0000651	Diplopia
HP:0000713	Agitation
HP:0000716	Depression
HP:0000726	Dementia
HP:0000727	Frontal lobe dementia
HP:0000735	Impaired social interactions
HP:0000736	Short attention span
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000744	Low frustration tolerance
HP:0000746	Delusions
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001278	Orthostatic hypotension
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001762	Talipes equinovarus
HP:0001824	Weight loss
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002080	Intention tremor
HP:0002120	Cerebral cortical atrophy
HP:0002141	Gait imbalance
HP:0002171	Gliosis
HP:0002172	Postural instability
HP:0002283	Global brain atrophy
HP:0002304	Akinesia
HP:0002322	Resting tremor
HP:0002359	Frequent falls
HP:0002360	Sleep disturbance
HP:0002362	Shuffling gait
HP:0002367	Visual hallucinations
HP:0002375	Hypokinesia
HP:0002505	Loss of ambulation
HP:0002548	Parkinsonism with favorable response to dopaminergic medication
HP:0002578	Gastroparesis
HP:0003394	Muscle spasm
HP:0003487	Babinski sign
HP:0003584	Late onset
HP:0003587	Insidious onset
HP:0003596	Middle age onset
HP:0003676	Progressive
HP:0003678	Rapidly progressive
HP:0004409	Hyposmia
HP:0004926	Orthostatic hypotension due to autonomic dysfunction
HP:0005340	Spastic/hyperactive bladder
HP:0007159	Fluctuations in consciousness
HP:0007256	Abnormal pyramidal sign
HP:0011462	Young adult onset
HP:0011960	Substantia nigra gliosis
HP:0011999	Paranoia
HP:0012332	Abnormal autonomic nervous system physiology
HP:0012450	Chronic constipation
HP:0012452	Restless legs
HP:0025269	Panic attack
HP:0030014	Female sexual dysfunction
HP:0031435	Monotonic speech
HP:0031908	Micrographia
HP:0040307	Male sexual dysfunction
HP:0100315	Lewy bodies
HP:0100543	Cognitive impairment
HP:0100660	Dyskinesia
HP:0100710	Impulsivity
HP:0100753	Schizophrenia
HP:0100785	Insomnia

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
bone marrow	hematopoietic cells	High	Enhanced
cerebellum	molecular layer - neuropil	Low	Enhanced
cerebellum	processes in granular layer	Medium	Enhanced
cerebral cortex	neuropil	High	Enhanced
colon	peripheral nerve/ganglion	Medium	Enhanced
kidney	cells in glomeruli	High	Enhanced
skin 2	melanocytes	Medium	Enhanced
soft tissue 2	peripheral nerve	Medium	Enhanced
testis	Leydig cells	Low	Enhanced

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
lewy body dementia	MONDO:0007488	G31	chapter6, Diseases of the nervous system	OMIM:127750	Orphanet:1648
autosomal dominant parkinson disease 1	MONDO:0008200	G20	chapter6, Diseases of the nervous system	OMIM:168601	Orphanet:171695
parkinsonian-pyramidal syndrome	MONDO:0009830	G20	chapter6, Diseases of the nervous system	OMIM:260300	Orphanet:171695
autosomal dominant parkinson disease 4	MONDO:0011562	G20	chapter6, Diseases of the nervous system	OMIM:605543
obsolete hereditary late onset parkinson disease	MONDO:0018466	G20	chapter6, Diseases of the nervous system

Summary of P37840

Gene: SNCA, NACP, PARK1
Protein: Alpha-synuclein

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of P37840

Gene: SNCA, NACP, PARK1 Protein: Alpha-synuclein

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: SNCA, NACP, PARK1
Protein: Alpha-synuclein