ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

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	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:ACHE

Protein Summary

Gene summary

Gene name: ACHE
ASpdb.0 ID: 43
	Gene
Gene symbol	ACHE
Gene ID	43
Gene name	acetylcholinesterase (Yt blood group)
Synonyms	ACEE\|ARACHE\|N-ACHE\|YT
Cytomap	7q22.1
Type of gene	protein-coding
Description	acetylcholinesteraseYt blood groupacetylcholinesterase (Cartwright blood group)apoptosis-related acetylcholinesterase
Modification date	20240411
UniProtAcc	P22303

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	ACHE	GO:0003990	acetylcholinesterase activity	1517212
Gene	ACHE	GO:0004104	cholinesterase activity	1517212
Gene	ACHE	GO:0005518	collagen binding	12524166
Gene	ACHE	GO:0005576	extracellular region	1517212
Gene	ACHE	GO:0005794	Golgi apparatus	15454088
Gene	ACHE	GO:0006581	acetylcholine catabolic process	1517212
Gene	ACHE	GO:0007155	cell adhesion	15454088
Gene	ACHE	GO:0016020	membrane	16262697
Gene	ACHE	GO:0016787	hydrolase activity	1517212
Gene	ACHE	GO:0017171	serine hydrolase activity	3954986
Gene	ACHE	GO:0042166	acetylcholine binding	8349597
Gene	ACHE	GO:0043236	laminin binding	12524166
Gene	ACHE	GO:0045202	synapse	8460160
Gene	ACHE	GO:0048471	perinuclear region of cytoplasm	14766237

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
P22303-1	P22303-1_4bdt_A.pdb	4BDT	X-ray	3.1	A	36	598

ASpdb's canonical and alternatively spliced isoform information.

accession_id

gene_name

canonical_id

alternative_id

canonical_length

alternative_length

canonical_start

canonical_end

type

originalSEQ

variationSEQ

alternative_start

alternative_end

P22303

ACHE

P22303-1

P22303-2

614

617

575

614

Substitution

DTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL

ASEAPSTCPGFTHGEAAPRPGLPLPLLLLHQLLLLFLSHLRRL

575

617

P22303

ACHE

P22303-1

P22303-3

614

526

357

444

Deletion

none

356

P22303

ACHE

P22303-1

P22303-4

614

603

575

603

Substitution

DTLDEAERQWKAEFHRWSSYMVHWKNQFD

GMQGPAGSAGRRGVGARQCNPSLLPLASE

575

603

P22303

ACHE

P22303-1

P22303-4

614

603

604

614

Deletion

none

603

Multiple sequence alignment of our canonical and alternatively spliced ACHE

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ACHE

UniProt-id	ENSG	ENST	ENSP
P22303-1	ENSG00000087085.16	ENST00000241069.11	ENSP00000241069.5
P22303-1	ENSG00000087085.16	ENST00000412389.5	ENSP00000394976.1
P22303-1	ENSG00000087085.16	ENST00000428317.7	ENSP00000414858.1
P22303-2	ENSG00000087085.16	ENST00000302913.8	ENSP00000303211.4
P22303-2	ENSG00000087085.16	ENST00000411582.4	ENSP00000404865.1
P22303-3	ENSG00000087085.16	ENST00000419336.6	ENSP00000403474.2

UniProt-id	NM ID	NP ID
P22303-1	NM_000665.4	NP_000656.1
P22303-1	NM_001302622.1	NP_001289551.1
P22303-2	NM_001302621.1	NP_001289550.1
P22303-3	NM_001282449.1	NP_001269378.1

Amino acid sequences of our canonical and alternatively spliced ACHE

accession_id	Protein sequence
P22303-1	MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPKQPWSGV VDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSM NYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATV GMGEARRRATQLAHLVGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVG VVKDEGSYFLVYGAPGFSKDNESLISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGDHNVVCPVAQLAGRLA AQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGAQQ
P22303-2	MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPKQPWSGV VDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSM NYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATV GMGEARRRATQLAHLVGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVG VVKDEGSYFLVYGAPGFSKDNESLISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGDHNVVCPVAQLAGRLA AQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGAQQ
P22303-3	MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPKQPWSGV VDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSM NYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATV GMGEARRRATQLAHLVGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQLAGR LAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGA
P22303-4	MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPKQPWSGV VDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSM NYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATV GMGEARRRATQLAHLVGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVG VVKDEGSYFLVYGAPGFSKDNESLISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGDHNVVCPVAQLAGRLA AQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGAQQ

Protein Functional Features

Main function of this protein. (from UniProt)

ACHE (go to UniProt):P22303

Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Gene Isoform Structures and Expression Levels for ACHE

Gene structures of our canonical and alternative spliced genes of ACHE
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

3D view using mol* of P22303-1

3D view using mol* of P22303-2

3D view using mol* of P22303-3

3D view using mol* of P22303-4

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of P22303-1

pLDDT distribution across the protein length of P22303-2

pLDDT distribution across the protein length of P22303-3

pLDDT distribution across the protein length of P22303-4

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of P22303-1

Ramachandran plot of P22303-3

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
P22303-1	1.069	171	1.089	381.073	0.534	0.787	1.038	0.634	0.991	0.64	0.587	103,104,105,107,114,117,118,119,150,151,152,153,15 5,156,157,158,161,164,233,234,317,320,322,323,324, 325,326,327,328,368,369,372,373,478,479,480
P22303-2	1.165	102	1.069	223.636	0.427	0.944	1.32	0.55	1.34	0.411	0.463	103,104,105,106,107,114,117,118,119,148,150,151,15 2,153,155,156,157,161,164,233,234,317,328,368,369, 372,478,479,482
P22303-3	1.076	106	1.103	395.136	0.603	0.784	0.929	0.636	0.943	0.674	0.525	103,105,107,108,113,114,117,118,148,150,151,152,15 3,155,156,157,161,164,233,234,317,320,323,324,325, 326,327,328,382,390,392,394
P22303-4	1.066	182	1.094	393.078	0.524	0.767	0.989	0.556	0.939	0.592	0.68	102,103,104,105,106,107,117,118,119,150,151,152,15 3,155,156,157,161,164,233,234,317,320,322,323,324, 325,326,327,328,368,369,372,373,396,478,479

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of P22303-1_P22303-1_4bdt_A.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P22303-1_4bdt_A_P22303-2.pdb

3D view using mol* of P22303-1_4bdt_A_P22303-3.pdb

3D view using mol* of P22303-1_4bdt_A_P22303-4.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P22303-1_P22303-2.pdb

3D view using mol* of P22303-1_P22303-3.pdb

3D view using mol* of P22303-1_P22303-4.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/P22303-1_vs_P22303-2.png

./stats/secondary_structure/figure/P22303-1_vs_P22303-3.png

./stats/secondary_structure/figure/P22303-1_vs_P22303-4.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/P22303-1_vs_P22303-2.png

./stats/relative_asa/P22303-1_vs_P22303-3.png

./stats/relative_asa/P22303-1_vs_P22303-4.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to ACHE

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
P22303	ACHE	DB04614	(R)-tacrine(10)-hupyridone	experimental
P22303	ACHE	DB07846	(3,4,8b-Trimethyl-3-oxido-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-3-ium-7-yl) N-(2-ethylphenyl)carbamate	experimental
P22303	ACHE	DB00677	Isoflurophate	approved, investigational, withdrawn	inhibitor
P22303	ACHE	DB13503	Tyrothricin	approved	inhibitor
P22303	ACHE	DB04615	(S)-tacrine(10)-hupyridone	experimental
P22303	ACHE	DB04616	TACRINE(8)-4-AMINOQUINOLINE	experimental
P22303	ACHE	DB07555	Hydroxy(oxo)(2-{(1S)-2,2,2-trifluoro-1-[2-(trimethylarsonio)ethoxy]ethyl}phenyl)ammonium	experimental
P22303	ACHE	DB02226	3,8-Diamino-6-Phenyl-5-[6-[1-[2-[(1,2,3,4-Tetrahydro-9-Acridinyl)Amino]Ethyl]-1h-1,2,3-Triazol-4-Yl]Hexyl]-Phenanthridinium	experimental
P22303	ACHE	DB08615	2-[4-(DIMETHYLAMINO)PHENYL]-6-HYDROXY-3-METHYL-1,3-BENZOTHIAZOL-3-IUM	experimental
P22303	ACHE	DB08357	Diethylene glycol diethyl ether	experimental
P22303	ACHE	DB00122	Choline	approved, nutraceutical	product of
P22303	ACHE	DB04556	NAP-226-90	experimental
P22303	ACHE	DB02404	1-Deoxy-1-Thio-Heptaethylene Glycol	experimental
P22303	ACHE	DB00449	Dipivefrin	approved	inhibitor
P22303	ACHE	DB02166	Propidium	experimental
P22303	ACHE	DB00898	Ethanol	approved	activator
P22303	ACHE	DB00545	Pyridostigmine	approved, investigational	inhibitor
P22303	ACHE	DB01805	Monoisopropylphosphorylserine	experimental
P22303	ACHE	DB03740	N-acetyl-alpha-D-glucosamine	experimental
P22303	ACHE	DB01400	Neostigmine	approved, vet_approved	inhibitor
P22303	ACHE	DB01122	Ambenonium	approved	inhibitor
P22303	ACHE	DB03814	2-(N-morpholino)ethanesulfonic acid	experimental
P22303	ACHE	DB04617	(9S)-9-[(8-AMMONIOOCTYL)AMINO]-1,2,3,4,9,10-HEXAHYDROACRIDINIUM	experimental
P22303	ACHE	DB02343	3,6,9,12,15-Pentaoxaheptadecane	experimental
P22303	ACHE	DB00843	Donepezil	approved	inhibitor
P22303	ACHE	DB01010	Edrophonium	approved	inhibitor
P22303	ACHE	DB03359	M-(N,N,N-Trimethylammonio)-2,2,2-Trifluoro-1,1-Dihydroxyethylbenzene	experimental
P22303	ACHE	DB00863	Ranitidine	approved, withdrawn	inhibitor
P22303	ACHE	DB00733	Pralidoxime	approved, vet_approved	activator
P22303	ACHE	DB14006	Choline salicylate	approved, nutraceutical	product of
P22303	ACHE	DB04864	Huperzine A	approved, experimental	inhibitor
P22303	ACHE	DB02825	Methylphosphinate	experimental
P22303	ACHE	DB03283	beta-L-fucose	experimental
P22303	ACHE	DB01199	Tubocurarine	approved	inhibitor
P22303	ACHE	DB00805	Minaprine	approved	inhibitor
P22303	ACHE	DB00483	Gallamine triethiodide	approved	inhibitor
P22303	ACHE	DB03005	3,8-Diamino-6-Phenyl-5-[6-[1-[2-[(1,2,3,4-Tetrahydro-9-Acridinyl)Amino]Ethyl]-1h-1,2,3-Triazol-5-Yl]Hexyl]-Phenanthridinium	experimental
P22303	ACHE	DB04114	3-Chloro-9-Ethyl-6,7,8,9,10,11-Hexahydro-7,11-Methanocycloocta[B]Quinolin-12-Amine	experimental
P22303	ACHE	DB12816	Terpinen-4-ol	investigational	inhibitor
P22303	ACHE	DB06525	Ganstigmine	investigational
P22303	ACHE	DB01245	Decamethonium	approved	inhibitor
P22303	ACHE	DB04892	Phenserine	investigational
P22303	ACHE	DB08996	Dimetacrine	experimental, withdrawn	antagonist
P22303	ACHE	DB07756	1-[3-({[(4-AMINO-5-FLUORO-2-METHYLQUINOLIN-3-YL)METHYL]THIO}METHYL)PHENYL]-2,2,2-TRIFLUOROETHANE-1,1-DIOL	experimental
P22303	ACHE	DB00944	Demecarium	approved	inhibitor
P22303	ACHE	DB04021	MF268	experimental
P22303	ACHE	DB00382	Tacrine	approved, investigational, withdrawn	inhibitor
P22303	ACHE	DB02845	Methylphosphinic Acid	experimental
P22303	ACHE	DB08167	Methylthioninium	experimental, investigational
P22303	ACHE	DB00989	Rivastigmine	approved, investigational	inhibitor
P22303	ACHE	DB00674	Galantamine	approved	inhibitor
P22303	ACHE	DB03348	Huperzine B	investigational
P22303	ACHE	DB04859	Zanapezil	investigational
P22303	ACHE	DB07701	1-BENZYL-4-[(5,6-DIMETHOXY-1-INDANON-2-YL)METHYL]PIPERIDINE	experimental
P22303	ACHE	DB00981	Physostigmine	approved, investigational	inhibitor
P22303	ACHE	DB02673	(4aS,6R,8aS)-11-[8-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)octyl]-6-hydroxy-3-methoxy-5,6,9,10-tetrahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-11-ium	experimental
P22303	ACHE	DB04924	Itopride	investigational	inhibitor

Related Diseases to ACHE

Previous studies relating to the alternative splicing of ACHE and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
ACHE	16516310	Virtues and woes of AChE alternative splicing in stress-related neuropathologies.	The ACh hydrolyzing enzyme acetylcholinesterase (AChE) is a combinatorial series of proteins with variant N and C termini generated from alternate promoter usage and 3' alternative splicing. Neuronal AChE variants show indistinguishable enzymatic activity yet differ in their expression, multimeric assembly and membrane-association patterns. Differentially induced under stress, they show distinct non-hydrolytic properties and interact with different protein partners. Recent findings suggest that transcriptional and post-transcriptional regulation of AChE pre-mRNA is a neuroprotection strategy but might involve long-term damage. Specifically, variant-specific causal involvement of AChE in the progression of both neurodegenerative diseases (e.g. Alzheimer's and Parkinson's diseases) and neuromuscular syndromes (e.g. myasthenia gravis) raises the possibility that future therapeutic drugs might target specific AChE variant(s) or the corresponding RNA transcripts.	D019636	Neurodegenerative Diseases
ACHE	16516310	Virtues and woes of AChE alternative splicing in stress-related neuropathologies.	The ACh hydrolyzing enzyme acetylcholinesterase (AChE) is a combinatorial series of proteins with variant N and C termini generated from alternate promoter usage and 3' alternative splicing. Neuronal AChE variants show indistinguishable enzymatic activity yet differ in their expression, multimeric assembly and membrane-association patterns. Differentially induced under stress, they show distinct non-hydrolytic properties and interact with different protein partners. Recent findings suggest that transcriptional and post-transcriptional regulation of AChE pre-mRNA is a neuroprotection strategy but might involve long-term damage. Specifically, variant-specific causal involvement of AChE in the progression of both neurodegenerative diseases (e.g. Alzheimer's and Parkinson's diseases) and neuromuscular syndromes (e.g. myasthenia gravis) raises the possibility that future therapeutic drugs might target specific AChE variant(s) or the corresponding RNA transcripts.	D009468	Neuromuscular Diseases
ACHE	17476278	Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia.	Hematological changes induced by various stress stimuli are accompanied by replacement of the primary acetylcholinesterase (AChE) 3' splice variant acetylcholinesterase-S (AChE-S) with the myelopoietic acetylcholinesterase-R (AChE-R) variant. To search for putative acetylcholinesterase-S interactions with hematopoietic pathways, we employed a yeast two-hybrid screen. The transcriptional co-repressor C-terminal binding protein (CtBP) was identified as a protein partner of the AChE-S C terminus. In erythroleukemic K562 cells, AChE-S displayed nuclear colocalization and physical interaction with CtBP. Furthermore, co-transfected AChE-S reduced the co-repressive effect of CtBP over the hematopoietic transcription factor, Ikaros. In transgenic mice, overexpressed human (h) AChE-S mRNA induced selective bone marrow upregulation of Ikaros while suppressing FOG, another transcriptional partner of CtBP. Transgenic bone marrow cells showed a correspondingly elevated potential for producing progenitor colonies, compared with controls, while peripheral blood showed increased erythrocyte counts as opposed to reduced platelets, granulocytes and T lymphocytes. AChE's 3' alternative splicing, and the corresponding changes in AChE-S/CtBP interactions, thus emerge as being actively involved in controlling hematopoiesis and the potential for modulating immune functions, supporting reports on malfunctioning immune reactions under impaired splice site selection.	D008231	Lymphopenia

Clinically important variants in ACHE

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance