Details of the Target

General Information of Target

Target ID LDTP03848
Target Name Alpha-synuclein (SNCA)
Gene Name SNCA
Gene ID 6622
Synonyms
NACP; PARK1; Alpha-synuclein; Non-A beta component of AD amyloid; Non-A4 component of amyloid precursor; NACP
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP
DNEAYEMPSEEGYQDYEPEA
Target Type
Clinical trial
Target Bioclass
Transporter and channel
Family
Synuclein family
Subcellular location
Cytoplasm
Function
Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores. Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis. Acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5. This chaperone activity is important to sustain normal SNARE-complex assembly during aging. Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity.
TTD ID
T03644
Uniprot ID
P37840
DrugMap ID
TTPO9ZI
Ensemble ID
ENST00000336904.7
HGNC ID
HGNC:11138
ChEMBL ID
CHEMBL6152

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
DU4475 SNV: p.A107S .
PEO1 SNV: p.E130G .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
HHS-482
 Probe Info  		Y39(1.60)  LDD0285  [1]
HHS-475
 Probe Info  		Y39(0.97)  LDD0264  [2]
ATP probe
 Probe Info  		N.A.  LDD0199  [3]
NHS
 Probe Info  		K21(0.00); K12(0.00)  LDD0010  [4]
Acrolein
 Probe Info  		N.A.  LDD0217  [5]
HHS-465
 Probe Info  		Y39(0.00); K43(0.00)  LDD2240  [6]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0116  HHS-0101 DM93 Y39(0.97)  LDD0264  [2]
 LDCM0117  HHS-0201 DM93 Y39(0.89)  LDD0265  [2]
 LDCM0118  HHS-0301 DM93 Y39(0.73)  LDD0266  [2]
 LDCM0119  HHS-0401 DM93 Y39(0.96)  LDD0267  [2]
 LDCM0120  HHS-0701 DM93 Y39(0.93)  LDD0268  [2]
 LDCM0123  JWB131 DM93 Y39(1.60)  LDD0285  [1]
 LDCM0124  JWB142 DM93 Y39(2.85)  LDD0286  [1]
 LDCM0125  JWB146 DM93 Y39(2.29)  LDD0287  [1]
 LDCM0126  JWB150 DM93 Y39(5.51)  LDD0288  [1]
 LDCM0127  JWB152 DM93 Y39(3.88)  LDD0289  [1]
 LDCM0128  JWB198 DM93 Y39(7.24)  LDD0290  [1]
 LDCM0129  JWB202 DM93 Y39(1.67)  LDD0291  [1]
 LDCM0130  JWB211 DM93 Y39(2.77)  LDD0292  [1]
 LDCM0109  NEM HeLa N.A.  LDD0223  [5]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 39 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
26S proteasome regulatory subunit 4 (PSMC1) AAA ATPase family P62191
26S proteasome regulatory subunit 6A (PSMC3) AAA ATPase family P17980
Alpha/beta hydrolase domain-containing protein 17C (ABHD17C) ABHD17 family Q6PCB6
Ubiquitin-like-conjugating enzyme ATG10 (ATG10) ATG10 family Q9H0Y0
COP9 signalosome complex subunit 3 (COPS3) CSN3 family Q9UNS2
Cytochrome c oxidase subunit 3 (MT-CO3) Cytochrome c oxidase subunit 3 family P00414
Polyamine deacetylase HDAC10 (HDAC10) Histone deacetylase family Q969S8
L-lactate dehydrogenase A-like 6B (LDHAL6B) LDH family Q9BYZ2
Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2) L-isoaspartyl/D-aspartyl protein methyltransferase family Q9NV79
Methionine-R-sulfoxide reductase B2, mitochondrial (MSRB2) MsrB Met sulfoxide reductase family Q9Y3D2
Nucleoside diphosphate kinase, mitochondrial (NME4) NDK family O00746
Caspase-6 (CASP6) Peptidase C14A family P55212
Ubiquitin thioesterase OTUB1 (OTUB1) Peptidase C65 family Q96FW1
MPN domain-containing protein (MPND) Peptidase M67 family Q8N594
Kallikrein-6 (KLK6) Peptidase S1 family Q92876
ATP-dependent Clp protease proteolytic subunit, mitochondrial (CLPP) Peptidase S14 family Q16740
E3 SUMO-protein ligase PIAS1 (PIAS1) PIAS family O75925
Protein kinase C alpha type (PRKCA) AGC Ser/Thr protein kinase family P17252
Protein kinase C epsilon type (PRKCE) AGC Ser/Thr protein kinase family Q02156
Glycogen synthase kinase-3 beta (GSK3B) CMGC Ser/Thr protein kinase family P49841
Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) TKL Ser/Thr protein kinase family Q5S007
Tyrosine-protein kinase ABL1 (ABL1) Tyr protein kinase family P00519
Tyrosine-protein kinase Fyn (FYN) Tyr protein kinase family P06241
Tyrosine-protein kinase Lyn (LYN) Tyr protein kinase family P07948
E3 ubiquitin-protein ligase RNF10 (RNF10) RNF10 family Q8N5U6
E3 ubiquitin-protein ligase RNF168 (RNF168) RNF168 family Q8IYW5
ADP-ribosylation factor-like protein 16 (ARL16) Arf family Q0P5N6
GTP-binding nuclear protein Ran (RAN) Ran family P62826
Tubulin polymerization-promoting protein (TPPP) TPPP family O94811
RING finger protein 112 (RNF112) GB1/RHD3 GTPase family Q9ULX5
Septin-4 (SEPTIN4) Septin GTPase family O43236
E3 ubiquitin-protein ligase TRIM21 (TRIM21) TRIM/RBCC family P19474
Tubulin alpha-1B chain (TUBA1B) Tubulin family P68363
G/T mismatch-specific thymine DNA glycosylase (TDG) TDG/mug family Q13569
E3 ubiquitin-protein ligase LNX (LNX1) . Q8TBB1
E3 ubiquitin-protein ligase RNF138 (RNF138) . Q8WVD3
E3 ubiquitin-protein ligase RNF183 (RNF183) . Q96D59
Methyltransferase-like protein 27 (METTL27) . Q8N6F8
NEDD4-like E3 ubiquitin-protein ligase WWP2 (WWP2) . O00308
Transporter and channel
Click To Hide/Show 16 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Apolipoprotein E (APOE) Apolipoprotein A1/A4/E family P02649
Amyloid-beta precursor protein (APP) APP family P05067
Apoptosis regulator BAX (BAX) Bcl-2 family Q07812
Bcl-2-like protein 1 (BCL2L1) Bcl-2 family Q07817
Cytochrome c (CYCS) Cytochrome c family P99999
Huntingtin (HTT) Huntingtin family P42858
Prenylated Rab acceptor protein 1 (RABAC1) PRA1 family Q9UI14
Exocyst complex component 5 (EXOC5) SEC10 family O00471
Sodium-dependent dopamine transporter (SLC6A3) Sodium:neurotransmitter symporter (SNF) family Q01959
Vesicle-associated membrane protein 2 (VAMP2) Synaptobrevin family P63027
Syntaxin-1A (STX1A) Syntaxin family Q16623
Alpha-synuclein (SNCA) Synuclein family P37840
Beta-synuclein (SNCB) Synuclein family Q16143
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2) WD repeat G protein beta family P62879
Integrin beta-1-binding protein 1 (ITGB1BP1) . O14713
Syntenin-1 (SDCBP) . O00560
Transcription factor
Click To Hide/Show 15 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein Hox-C4 (HOXC4) Antp homeobox family P09017
Cyclic AMP-dependent transcription factor ATF-3 (ATF3) BZIP family P18847
Homeobox protein DLX-3 (DLX3) Distal-less homeobox family O60479
Transcription factor E2F8 (E2F8) E2F/DP family A0AVK6
Zinc finger protein 296 (ZNF296) Krueppel C2H2-type zinc-finger protein family Q8WUU4
Zinc finger protein 57 (ZNF57) Krueppel C2H2-type zinc-finger protein family Q68EA5
Krueppel-like factor 15 (KLF15) Sp1 C2H2-type zinc-finger protein family Q9UIH9
Deformed epidermal autoregulatory factor 1 homolog (DEAF1) . O75398
Forkhead box protein R1 (FOXR1) . Q6PIV2
LIM/homeobox protein Lhx5 (LHX5) . Q9H2C1
LIM/homeobox protein Lhx6 (LHX6) . Q9UPM6
T-box brain protein 1 (TBR1) . Q16650
Transcription factor HES-4 (HES4) . Q9HCC6
Twist-related protein 2 (TWIST2) . Q8WVJ9
Zinc finger protein 366 (ZNF366) . Q8N895
Cytokine and receptor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cytokine receptor-like factor 3 (CRLF3) Cytokine receptor-like factor 3 family Q8IUI8
Other
Click To Hide/Show 42 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
14-3-3 protein eta (YWHAH) 14-3-3 family Q04917
AP-3 complex subunit beta-1 (AP3B1) Adaptor complexes large subunit family O00203
Ankyrin repeat and SOCS box protein 13 (ASB13) Ankyrin SOCS box (ASB) family Q8WXK3
Apolipoprotein A-I (APOA1) Apolipoprotein A1/A4/E family P02647
Protein BRICK1 (BRK1) BRK1 family Q8WUW1
Clusterin (CLU) Clusterin family P10909
RNA polymerase II elongation factor ELL2 (ELL2) ELL/occludin family O00472
Ferritin light chain (FTL) Ferritin family P02792
Centromere protein V (CENPV) Gfa family Q7Z7K6
Histone H3.1 (H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12) Histone H3 family P68431
Histone H3.2 (H3C15; H3C14; H3C13) Histone H3 family Q71DI3
Baculoviral IAP repeat-containing protein 5 (BIRC5) IAP family O15392
Alpha-internexin (INA) Intermediate filament family Q16352
Keratin-associated protein 9-2 (KRTAP9-2) KRTAP type 9 family Q9BYQ4
Metallothionein-2 (MT2A) Type 1 family P02795
Phosphofurin acidic cluster sorting protein 1 (PACS1) PACS family Q6VY07
Oocyte-secreted protein 2 (OOSP2) PLAC1 family Q86WS3
Histone deacetylase complex subunit SAP30 (SAP30) SAP30 family O75446
Charged multivesicular body protein 1a (CHMP1A) SNF7 family Q9HD42
U6 snRNA-associated Sm-like protein LSm8 (LSM8) SnRNP Sm proteins family O95777
Signal transducing adapter molecule 2 (STAM2) STAM family O75886
Toll-interacting protein (TOLLIP) Tollip family Q9H0E2
Tubulin beta chain (TUBB) Tubulin family P07437
Ubiquitin-ribosomal protein eL40 fusion protein (UBA52) Ubiquitin family; Eukaryotic ribosomal protein eL40 family P62987
Fasciculation and elongation protein zeta-2 (FEZ2) Zygin family Q9UHY8
ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3) . Q9NP61
Enkurin (ENKUR) . Q8TC29
Kelch-like protein 20 (KLHL20) . Q9Y2M5
Ligand of Numb protein X 2 (LNX2) . Q8N448
PDZK1-interacting protein 1 (PDZK1IP1) . Q13113
Pleckstrin homology domain-containing family G member 7 (PLEKHG7) . Q6ZR37
Protein MGARP (MGARP) . Q8TDB4
RING1 and YY1-binding protein (RYBP) . Q8N488
Sequestosome-1 (SQSTM1) . Q13501
Spermatogenesis-associated protein 22 (SPATA22) . Q8NHS9
Splicing regulator RBM11 (RBM11) . P57052
Superkiller complex protein 8 (SKIC8) . Q9GZS3
Synphilin-1 (SNCAIP) . Q9Y6H5
Ubiquitin D (UBD) . O15205
Ubiquitin-associated domain-containing protein 1 (UBAC1) . Q9BSL1
Uncharacterized protein C6orf141 (C6orf141) . Q5SZD1
Zinc finger matrin-type protein 2 (ZMAT2) . Q96NC0

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Dequalinium Small molecular drug DB04209
Copper . DB09130
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Resveratrol Small molecular drug DB02709

References

1 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
2 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
3 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
4 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
5 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
6 Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022 Dec 15;29(12):1709-1720.e7. doi: 10.1016/j.chembiol.2022.11.008. Epub 2022 Dec 6.
Mass spectrometry data entry: PXD038010