PPME1

Summary

PPME1 (protein phosphatase methylesterase 1, HGNC:30178) is a protein-coding gene on chromosome 11q13.4, encoding Protein phosphatase methylesterase 1 (Q9Y570). Demethylates proteins that have been reversibly carboxymethylated. It is a selective cancer dependency (DepMap: 20.0% of cell lines).

This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51400 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 20.0% of screened cell lines
• MANE Select transcript: NM_016147

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30178
Approved symbol	PPME1
Name	protein phosphatase methylesterase 1
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	PME-1, ABDH19
Ensembl gene	ENSG00000214517
Ensembl biotype	protein_coding
OMIM	611117
Entrez	51400

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000328257, ENST00000398427, ENST00000535205, ENST00000538501, ENST00000539021, ENST00000541340, ENST00000542710, ENST00000543525, ENST00000544401, ENST00000856423, ENST00000856424, ENST00000856425, ENST00000856426, ENST00000856427, ENST00000856428, ENST00000921187, ENST00000921188, ENST00000970219, ENST00000970220, ENST00000970221, ENST00000970222

RefSeq mRNA: 2 — MANE Select: NM_016147 NM_001271593, NM_016147

CCDS: CCDS44678, CCDS60891

Canonical transcript exons

ENST00000328257 — 14 exons

Exon	Start	End
ENSE00001625904	74230245	74230399
ENSE00001647456	74222312	74222369
ENSE00001727754	74235901	74235966
ENSE00001754180	74230912	74231002
ENSE00001772925	74225205	74225256
ENSE00002301751	74171289	74171522
ENSE00003482700	74247079	74247123
ENSE00003494768	74253492	74254703
ENSE00003524157	74203728	74203821
ENSE00003527203	74251648	74251715
ENSE00003591583	74239133	74239256
ENSE00003623923	74204353	74204445
ENSE00003651857	74246076	74246205
ENSE00003682884	74250954	74251018

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.4721 / max 861.2169, expressed in 1817 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115845	32.3410	1817
115846	2.4321	1056
115844	1.8429	959
206384	0.5561	316
115843	0.2999	133

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	96.12	gold quality
middle temporal gyrus	UBERON:0002771	95.51	gold quality
frontal cortex	UBERON:0001870	95.38	gold quality
cortical plate	UBERON:0005343	95.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.35	gold quality
cerebellar cortex	UBERON:0002129	95.23	gold quality
cerebellar hemisphere	UBERON:0002245	95.23	gold quality
neocortex	UBERON:0001950	95.12	gold quality
right frontal lobe	UBERON:0002810	95.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.90	gold quality
cerebellum	UBERON:0002037	94.86	gold quality
cingulate cortex	UBERON:0003027	94.75	gold quality
anterior cingulate cortex	UBERON:0009835	94.75	gold quality
cerebral cortex	UBERON:0000956	94.58	gold quality
superior frontal gyrus	UBERON:0002661	94.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.55	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.43	gold quality
right testis	UBERON:0004534	94.32	gold quality
parietal lobe	UBERON:0001872	94.22	gold quality
left testis	UBERON:0004533	94.22	gold quality
postcentral gyrus	UBERON:0002581	94.21	gold quality
nucleus accumbens	UBERON:0001882	94.09	gold quality
telencephalon	UBERON:0001893	94.07	gold quality
stromal cell of endometrium	CL:0002255	94.04	gold quality
primary visual cortex	UBERON:0002436	93.97	gold quality
forebrain	UBERON:0001890	93.85	gold quality
hypothalamus	UBERON:0001898	93.78	gold quality
brain	UBERON:0000955	93.77	gold quality
entorhinal cortex	UBERON:0002728	93.68	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	25.41
E-ANND-3	yes	8.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

131 targeting PPME1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-4319	99.76	69.83	2586

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• We propose that stabilization of this inactive, nuclear PP2A pool is a major in vivo function of PME-1. (PMID:17803990)
• Observations identify PME-1 expression as one mechanism by which ERK pathway activity is maintained in cancer cells and suggest an important functional role for PME-1 in the disease progression of human astrocytic gliomas. (PMID:19293187)
• Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors. (PMID:21398589)
• Data indicate that PP2A holoenzyme biogenesis and activity are controlled by five PP2A modulators, consisting of alpha4, PTPA, LCMT1, PME-1 and TIPRL1, which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled. (PMID:22443683)
• GSK-3beta can inhibit PP2A by increasing the inhibitory L309-demethylation involving upregulation of PME-1 and inhibition of PPMT1 (PMID:22732552)
• PPME1 could be an attractive therapeutic target for a subset of gastric cancer and lung cancer. (PMID:24253382)
• this study suggests that the tightly linked regulatory loop comprised of the SIK2-PP2A and CaMKI and PME-1 networks may function in fine-tuning cell proliferation and stress response. (PMID:24841198)
• LCMT1-PME-1 methylation equilibrium is critical for regulating mitotic spindle size and thereby proper cell division (PMID:25839665)
• Data suggest that discovery of more potent protein phosphatase methylesterase-1 (PME-1) inhibitors may be beneficial for the treatment of endometrial cancer. (PMID:27048286)
• We demonstrate that NNMT outcompetes leucine carboxyl methyl transferase 1 (LCMT1) for methyl transfer from principal methyl donor SAM in biological systems. Inhibiting NNMT increased the availability of methyl groups for LCMT1 to methylate PP2A, resulting in the inhibition of oncogenic serine/threonine kinases (STK). (PMID:27810903)
• Studies indicate that protein phosphatase methylesterase-1 (PME-1) negatively regulates protein phosphatase 2A (PP2A) activity by highly complex mechanisms. (PMID:27913678)
• USP36 regulates PME-1 as a DUB and participates in the ERK and Akt signaling pathways (PMID:29577269)
• Authors found that PME-1 is exported from the nucleus to the cytoplasm upon H2O2 treatment and redistributes dem-p-PP2Ac in subcellular compartments. These findings offer new insight into the regulation of PME-1 localization and PP2A demethylation under oxidative stress. (PMID:30340029)
• Glycogen synthase kinase-3beta suppresses the expression of protein phosphatase methylesterase-1 through beta-catenin. (PMID:31714894)
• Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1. (PMID:32071079)
• DNAH17-AS1 promotes pancreatic carcinoma by increasing PPME1 expression via inhibition of miR-432-5p. (PMID:32351291)
• PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers. (PMID:36461911)
• The luciferase-based in vivo protein-protein interaction assay revealed that CHK1 promotes PP2A and PME-1 interaction. (PMID:38588804)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppme1	ENSDARG00000009771
mus_musculus	Ppme1	ENSMUSG00000030718
rattus_norvegicus	Ppme1	ENSRNOG00000017227
drosophila_melanogaster	CG5068	FBGN0035951
caenorhabditis_elegans		WBGENE00007188

Protein

Protein identifiers

Protein phosphatase methylesterase 1 — Q9Y570 (reviewed: Q9Y570)

All UniProt accessions (2): A0A140VK39, Q9Y570

UniProt curated annotations — full annotation on UniProt →

Function. Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.

Subunit / interactions. Binds PPP2CA and PPP2CB.

Post-translational modifications. Phosphorylated by SIK1 following increases in intracellular sodium, leading to dissociation from the protein phosphatase 2A (PP2A) complex and subsequent dephosphorylation of sodium/potassium-transporting ATPase ATP1A1.

Similarity. Belongs to the AB hydrolase superfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y570-1	1	yes
Q9Y570-2	2
Q9Y570-3	3
Q9Y570-4	4

RefSeq proteins (2): NP_001258522, NP_057231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR016812	PPase_methylesterase_euk	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF12697

Enzyme classification (BRENDA):

• EC 3.1.1.89 — protein phosphatase methylesterase-1 (BRENDA: 7 organisms, 18 substrates, 9 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• [phosphatase 2A protein]-C-terminal L-leucine methyl ester + H2O = [phosphatase 2A protein]-C-terminal L-leucine + methanol + H(+) (RHEA:48548)

UniProt features (49 total): strand 16, helix 15, modified residue 4, splice variant 4, active site 3, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3C5V	X-RAY DIFFRACTION	2
3C5W	X-RAY DIFFRACTION	2.8
7SOY	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y570-F1	83.13	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 156; 181; 349

Post-translational modifications (4): 16, 16, 42, 15

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition

MSigDB gene sets: 180 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, TGCGCANK_UNKNOWN, CMYB_01, GOBP_CELL_CYCLE_PHASE_TRANSITION, AP2_Q3, CAGGTCC_MIR492, chr11q13, EFC_Q6, E2F_Q3, GOBP_MITOTIC_CELL_CYCLE, GOBP_CELL_CYCLE_G2_M_PHASE_TRANSITION, AACTTT_UNKNOWN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, TGGNNNNNNKCCAR_UNKNOWN, ELK1_01

GO Biological Process (2): G2/M transition of mitotic cell cycle (GO:0000086), protein demethylation (GO:0006482)

GO Molecular Function (11): protein phosphatase inhibitor activity (GO:0004864), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), cadherin binding (GO:0045296), protein phosphatase 2A binding (GO:0051721), protein methylesterase activity (GO:0051723), lncRNA binding (GO:0106222), protein binding (GO:0005515), hydrolase activity (GO:0016787), obsolete protein C-terminal methylesterase activity (GO:0051722), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (1): nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
G2/M Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
protein dealkylation	1
demethylation	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
kinase binding	1
phosphatase binding	1
cell adhesion molecule binding	1
protein phosphatase binding	1
carboxylic ester hydrolase activity	1
catalytic activity, acting on a protein	1
RNA binding	1
binding	1
catalytic activity	1
hydrolase activity, acting on ester bonds	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPME1	LCMT1	Q9UIC8	915
PPME1	PPP2CA	P05323	905
PPME1	PPP2R1A	P30153	896
PPME1	PTPA	Q15257	726
PPME1	CIP2A	Q8TCG1	673
PPME1	RBBP9	O75884	673
PPME1	PPP2R2A	P50409	651
PPME1	MINK1	Q8N4C8	507
PPME1	PPP2R5A	Q15172	502
PPME1	CNOT1	A5YKK6	502
PPME1	PPP6C	O00743	501
PPME1	ABHD17B	Q5VST6	493
PPME1	PPP2R3A	Q06190	480
PPME1	STRN	O43815	473
PPME1	TIPRL	O75663	470

IntAct

102 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	PPP2CA	psi-mi:“MI:0915”(physical association)	0.990
PPP2R1A	PPP2CA	psi-mi:“MI:0414”(enzymatic reaction)	0.990
PAIP1	PABPC1	psi-mi:“MI:0914”(association)	0.970
PPME1	PPP2R1A	psi-mi:“MI:0914”(association)	0.950
RAD51B	RAD51C	psi-mi:“MI:0914”(association)	0.940
PPP4R3A	PPP4C	psi-mi:“MI:0914”(association)	0.920
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
PPME1	PPP2CA	psi-mi:“MI:0914”(association)	0.880
PPP2CA	STRN	psi-mi:“MI:0914”(association)	0.840
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TGM3	PPME1	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (221): PPME1 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), ACY1 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), PPP4R2 (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), PPME1 (Affinity Capture-Western), PPME1 (Biochemical Activity), PPME1 (Biochemical Activity), HK2 (Co-fractionation), PPME1 (Co-fractionation), PPME1 (Co-fractionation), PPME1 (Co-fractionation), PPME1 (Co-fractionation), PPME1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZNK2, A6QPY8, B5KFL3, F8RP11, O23877, O43100, O43102, O60832, O88506, O88600, O95747, P04574, P04632, P06813, P0DPI2, P12829, P13135, P34932, Q0U6E7, Q12906, Q2TFN9, Q4FZT2, Q4I665, Q4KM49, Q4WJM6, Q503Y7, Q58DN4, Q5B5W1, Q5R495, Q5R7Z5, Q5R8T5, Q5RDM4, Q5ZJ08, Q5ZJH9, Q61166, Q61316, Q66HR2, Q66T82, Q6P4K8, Q6P9R2

Diamond homologs: P0CO62, P0CO63, P38796, Q2URJ0, Q4FZT2, Q4IQC1, Q4WKB2, Q54TN3, Q58DN4, Q5ALW7, Q5BGN7, Q5R4F9, Q6BZG3, Q6CGE1, Q6CQZ5, Q6FNL6, Q74Z47, Q7SGG8, Q8BVQ5, Q9BIB3, Q9P7D2, Q9Y570, C8CP46, Q99685, Q8IUS5, A0A061B0Q2, A2BGU9, W3XA95, Q15KI9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CAMK1	“down-regulates activity”	PPME1	phosphorylation
PP2CA_R1A_R2A	“up-regulates activity”	PPME1	dephosphorylation
CAMK1	“up-regulates activity”	PPME1	phosphorylation
PPME1	“down-regulates activity”	PPP2CA	demethylation
PPME1	“down-regulates activity”	PPP2CB	demethylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cyclin A/B1/B2 associated events during G2/M transition	5	23.4×	2e-04
Negative regulation of MAPK pathway	5	20.1×	4e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	7.3×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

45 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2395 predictions. Top by Δscore:

Variant	Effect	Δscore
11:74203726:A:AG	acceptor_gain	1.0000
11:74203727:G:GG	acceptor_gain	1.0000
11:74203793:TAG:T	donor_gain	1.0000
11:74203794:AGA:A	donor_gain	1.0000
11:74203819:GATA:G	donor_gain	1.0000
11:74203851:G:GG	donor_gain	1.0000
11:74225252:GCAAA:G	donor_gain	1.0000
11:74225253:CAAA:C	donor_gain	1.0000
11:74225254:AAA:A	donor_gain	1.0000
11:74225255:AA:A	donor_gain	1.0000
11:74225256:AG:A	donor_loss	1.0000
11:74225257:GTAA:G	donor_gain	1.0000
11:74225258:T:A	donor_loss	1.0000
11:74230239:TTGCA:T	acceptor_loss	1.0000
11:74230240:TGCA:T	acceptor_loss	1.0000
11:74230241:GCA:G	acceptor_loss	1.0000
11:74230243:A:AG	acceptor_gain	1.0000
11:74230243:A:T	acceptor_loss	1.0000
11:74230244:G:GC	acceptor_gain	1.0000
11:74230244:GA:G	acceptor_gain	1.0000
11:74230244:GAGA:G	acceptor_gain	1.0000
11:74230244:GAGAC:G	acceptor_gain	1.0000
11:74230396:GAAG:G	donor_gain	1.0000
11:74230399:GGTG:G	donor_loss	1.0000
11:74230400:G:GA	donor_loss	1.0000
11:74230401:T:A	donor_loss	1.0000
11:74235899:A:AG	acceptor_gain	1.0000
11:74235900:G:GG	acceptor_gain	1.0000
11:74235967:G:GG	donor_gain	1.0000
11:74239242:G:GT	donor_gain	1.0000

AlphaMissense

2548 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:74204408:G:A	G84E	1.000
11:74204413:G:C	G86R	1.000
11:74204414:G:A	G86D	1.000
11:74204431:T:A	W92R	1.000
11:74204431:T:C	W92R	1.000
11:74225205:G:A	G116D	1.000
11:74225205:G:T	G116V	1.000
11:74230307:G:A	G154E	1.000
11:74230313:G:T	S156I	1.000
11:74230318:G:C	G158R	1.000
11:74230319:G:A	G158D	1.000
11:74230387:G:C	D181H	1.000
11:74230388:A:C	D181A	1.000
11:74230388:A:G	D181G	1.000
11:74230388:A:T	D181V	1.000
11:74230389:T:A	D181E	1.000
11:74230389:T:G	D181E	1.000
11:74230397:A:T	E184V	1.000
11:74230918:C:A	A187D	1.000
11:74230926:G:C	A190P	1.000
11:74230930:T:A	L191H	1.000
11:74230930:T:C	L191P	1.000
11:74230951:T:C	L198S	1.000
11:74230971:T:C	F205L	1.000
11:74230972:T:C	F205S	1.000
11:74230973:C:A	F205L	1.000
11:74230973:C:G	F205L	1.000
11:74230989:G:C	A211P	1.000
11:74230990:C:A	A211D	1.000
11:74230998:T:A	W214R	1.000

dbSNP variants (sampled 300 via entrez): RS1000012989 (11:74245454 A>G), RS1000014785 (11:74229298 C>G), RS1000084104 (11:74196742 A>G), RS1000087998 (11:74231169 C>T), RS1000094759 (11:74246379 C>T), RS1000125678 (11:74253859 A>G), RS1000141215 (11:74192518 A>G,T), RS1000160615 (11:74209299 C>T), RS1000167971 (11:74225826 T>C), RS1000212252 (11:74191619 C>G,T), RS1000259848 (11:74190210 G>A), RS1000275466 (11:74233338 T>C), RS1000326408 (11:74186107 G>A,C,T), RS1000448930 (11:74216946 C>G), RS1000498543 (11:74208052 G>A)

Disease associations

OMIM: gene MIM:611117 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293320 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 3.1.1.- Carboxylic Ester Hydrolases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
ABL127	Inhibition	7.92	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SR-01000786812	IC50	10 nM

ChEMBL bioactivities

14 potent at pChembl≥5 of 18 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	CHEMBL1475741
7.33	Kd	46.73	nM	CHEMBL5653589
7.33	ED50	46.73	nM	CHEMBL5653589
6.30	IC50	500	nM	CHEMBL1550905
6.22	IC50	600	nM	CHEMBL1550905
6.19	IC50	640	nM	CHEMBL1316687
5.60	IC50	2500	nM	CHEMBL1699083
5.52	IC50	3000	nM	CHEMBL1706554
5.52	IC50	3000	nM	CHEMBL1719837
5.47	IC50	3400	nM	CHEMBL1701914
5.46	IC50	3500	nM	CHEMBL1550905
5.40	IC50	4000	nM	CHEMBL1729870
5.32	IC50	4800	nM	CHEMBL1718102
5.17	IC50	6800	nM	CHEMBL1711185

PubChem BioAssay actives

4 with measured affinity, of 19 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
dimethyl (3R)-3-cyclopentyl-4-oxo-3-phenyldiazetidine-1,2-dicarboxylate	712211: Inhibition of PME1 binding to FP-rhodamine in human MDA-MB-231 cells after 30 mins by fluorescence polarization activity-based protein profiling assay	ic50	0.0100	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149048: Binding affinity to human PPME1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0467	uM
(E)-2-(4-fluorophenyl)sulfonyl-3-[1-(3-nitrophenyl)sulfonylpyrrol-2-yl]prop-2-enenitrile	712205: Inhibition of PME1 binding to FP-rhodamine in human HEK293T cells after 45 mins by fluorescence polarization activity-based protein profiling assay	ic50	0.6000	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases methylation, increases expression, increases reaction	3
bisphenol A	decreases expression, decreases methylation, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
chromium hexavalent ion	affects expression, decreases expression, increases abundance	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic Trioxide	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
polyhexamethyleneguanidine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
morroniside	decreases reaction, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
incobotulinumtoxinA	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1

ChEMBL screening assays

18 unique, capped per target: 14 binding, 3 functional, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613855	Functional	PUBCHEM_BIOASSAY: Late stage results from the probe development effort to identify inhibitors of the protein methylesterase PME-1: Gel-based Activity-Based Protein Profiling (ABPP) IC50: Purified enzyme. (Class of assay: confirmatory) [Rela	PubChem BioAssay data set
CHEMBL1738413	Unclassified	PUBCHEM_BIOASSAY: Late stage results from the probe development effort to identify inhibitors of the protein methylesterase PME-1: Gel-based Activity-Based Protein Profiling (ABPP) IC50. (Class of assay: confirmatory) [Related pubchem assay	PubChem BioAssay data set
CHEMBL2209035	Binding	Inhibition of PME1 expressed in untransfected HEK293T cells assessed as reduction in demethylated PP2A level at 500 nM after 1 hr by Western blot analysis	Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2HE	HAP1 PPME1 (-) 1	Cancer cell line	Male
CVCL_E2HF	HAP1 PPME1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.