PTGES3

Summary

PTGES3 (prostaglandin E synthase 3, HGNC:16049) is a protein-coding gene on chromosome 12q13.3, encoding Prostaglandin E synthase 3 (Q15185). Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).

This gene encodes an enzyme that converts prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). This protein functions as a co-chaperone with heat shock protein 90 (HSP90), localizing to response elements in DNA and disrupting transcriptional activation complexes. Alternative splicing results in multiple transcript variants. There are multiple pseudogenes of this gene on several different chromosomes.

Source: NCBI Gene 10728 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 22 total
• Druggable target: yes
• MANE Select transcript: NM_006601

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16049
Approved symbol	PTGES3
Name	prostaglandin E synthase 3
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	p23, TEBP, cPGES
Ensembl gene	ENSG00000110958
Ensembl biotype	protein_coding
OMIM	607061
Entrez	10728

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000262033, ENST00000414274, ENST00000436399, ENST00000448157, ENST00000456859, ENST00000537473, ENST00000614328, ENST00000878310, ENST00000878311, ENST00000939417, ENST00000939418, ENST00000939419, ENST00000959250

RefSeq mRNA: 6 — MANE Select: NM_006601 NM_001282601, NM_001282602, NM_001282603, NM_001282604, NM_001282605, NM_006601

CCDS: CCDS31836, CCDS61158, CCDS61159, CCDS61160, CCDS73485

Canonical transcript exons

ENST00000262033 — 8 exons

Exon	Start	End
ENSE00001248701	56687998	56688284
ENSE00003237254	56666204	56666266
ENSE00003478503	56672952	56673065
ENSE00003513659	56670275	56670364
ENSE00003544965	56671749	56671847
ENSE00003553484	56672740	56672809
ENSE00003592441	56664776	56664800
ENSE00003845114	56663349	56664498

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 305.0318 / max 2248.1256, expressed in 1828 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131577	167.9219	1828
131575	52.3552	1821
131576	46.0845	1824
206746	12.8859	1789
131573	12.6920	1797
131574	12.5166	1787
131568	0.3705	159
131569	0.2054	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.78	gold quality
bronchial epithelial cell	CL:0002328	99.75	gold quality
oocyte	CL:0000023	99.74	gold quality
adult organism	UBERON:0007023	99.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.53	gold quality
epithelium of bronchus	UBERON:0002031	99.49	gold quality
bronchus	UBERON:0002185	99.46	gold quality
caput epididymis	UBERON:0004358	99.44	gold quality
colonic mucosa	UBERON:0000317	99.42	gold quality
ventricular zone	UBERON:0003053	99.40	gold quality
embryo	UBERON:0000922	99.35	gold quality
ganglionic eminence	UBERON:0004023	99.32	gold quality
corpus epididymis	UBERON:0004359	99.32	gold quality
trabecular bone tissue	UBERON:0002483	99.30	gold quality
cartilage tissue	UBERON:0002418	99.28	gold quality
epithelium of nasopharynx	UBERON:0001951	99.26	gold quality
seminal vesicle	UBERON:0000998	99.25	gold quality
nasopharynx	UBERON:0001728	99.24	gold quality
cauda epididymis	UBERON:0004360	99.22	gold quality
endometrium	UBERON:0001295	99.18	gold quality
oral cavity	UBERON:0000167	99.17	gold quality
skin of hip	UBERON:0001554	99.16	gold quality
right uterine tube	UBERON:0001302	99.12	gold quality
cortical plate	UBERON:0005343	99.12	gold quality
upper leg skin	UBERON:0004262	99.11	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.11	gold quality
mammalian vulva	UBERON:0000997	99.10	gold quality
superficial temporal artery	UBERON:0001614	99.04	gold quality
ovary	UBERON:0000992	99.03	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2210.50
E-MTAB-10283	yes	1943.52
E-CURD-122	yes	29.33
E-GEOD-125970	yes	21.46
E-CURD-114	yes	10.69
E-MTAB-9801	yes	5.89
E-MTAB-8060	no	1319.17
E-MTAB-7008	no	1127.78
E-MTAB-6108	no	749.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting PTGES3, 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-4668-3P	100.00	68.74	2635
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-122B-3P	99.21	68.90	1333

Literature-anchored findings (GeneRIF, showing 36)

• localizes in vivo to genomic response elements in a hormone-dependent manner, disrupting receptor-mediated transcriptional activation in vivo and in vitro (PMID:12077419)
• TEP1, hTR, hsp90, p23, and dyskerin remained at high and unchanged levels throughout up- or down regulation of telomerase activity. (PMID:12135483)
• acts in vivo to stabilize hsp90 binding to client protein [hsp90 cochaperone p23] (PMID:14507910)
• A role proposed for co-chaperone p23 is to lock individual subunits of Hsp90 in an ATP-dependent conformational state that has a high affinity for client proteins. (PMID:16403413)
• p23 differentially regulates ER target genes and is involved in the control of distinct cellular processes in breast tumor development (PMID:16809759)
• Carbonyl reductase-1 (CBR1), microsomal prostaglandin E synthase-1 and 2 (mPGES-1, mPGES-2), cytosolic prostaglandin E synthase (cPGES), aldoketoreductase (AKR1C1) and prostaglandin F synthase (AKR1C3) were all expressed in hair follicles. (PMID:17697149)
• Data show that cytosolic prostaglandin E synthase 2 is found in microglia, neurons, and endothelium of control human middle frontal gyrus and that its levels decrease in pyramidal cells of Alzheimer’s disease brains. (PMID:19001348)
• all three terminal prostaglandin synthases, mPGES-1, mPGES-2, and cPGES, are over-expressed in human gliomas (PMID:19347995)
• Overexpression of Delta p23 resulted in a decrease in hTERT levels, and a down-regulation in telomerase activity. (PMID:19740745)
• the interaction of the Hsp90-p23 complex with hTERT is critical for regulation of the nuclear localization of telomerase (PMID:19751963)
• Data show that the small molecule celastrol inhibits the Hsp90 chaperoning machinery by inactivating the co-chaperone p23, resulting in a more selective destabilization of steroid receptors. (PMID:19996313)
• High levels of Hsp90 cochaperone p23 promote tumor progression in breast cancer by increasing lymph node metastases and drug resistance. (PMID:20847343)
• the N-terminal domain of human Hsp90 triggers binding to the cochaperone p23 (PMID:21183720)
• Patients with severe Alzheimer disease displayed a consistent reduction in brain p23 levels. Cleavage product p19 was not seen in AD brain samples. (PMID:21691801)
• The p23 cochaperone of Hsp90, which plays a major role in glucocorticoid receptor folding and function, associates with influenza virus polymerase. (PMID:21853119)
• a small increase in the expression of p23 amplifies ER-binding genome wide and, in combination with ER, elicits an invasive phenotype in breast cancer (PMID:22074947)
• In cytosol only one protein called p23 hsp90 binds to Bax but the binding protein does not affect the subcellular localization and pro-apoptotic activity of Bax. (PMID:22277657)
• As an anti-apoptotic factor, p23 is able to be a potential target for anti-leukemic therapy. (PMID:22677230)
• p23 co-chaperone protects the aryl hydrocarbon receptor from degradation (PMID:22759865)
• The effects of p23 on androgen receptor (AR) activity are at least partly HSP90 independent, a mutant form of p23, unable to bind HSP90, increases AR activity. (PMID:22899854)
• p23 recruits PHD2 to the HSP90 machinery to facilitate HIF-1alpha hydroxylation (PMID:23413029)
• FKBP4, p23, and Aha1 cooperatively regulate the progression of hAgo2 through the chaperone cycle. (PMID:23741051)
• increased p23 expression may allow cells to acquire a more aggressive phenotype, contributing to disease progression (PMID:25241147)
• dysregulation of GR, MR, FKBP5, and PTGES3 in autistic spectrum disorder (ASD) and suggest a possible role of inflammation in altered GR function in ASD. (PMID:25912394)
• Even if p23 predominantly binds the Hsp90 dimer, p23 is also able to interact with Hsp90 oligomers, shifting the Hsp90 dimer-oligomers equilibrium toward dimer. (PMID:26151834)
• The Hsp90 independence of the interaction between p23 and p53 DNA-binding domain, together with the competition of p23 versus DNA for p53, raises the intriguing possibility that p23, like other small charged proteins, may affect p53 in hitherto unknown ways. (PMID:29334217)
• This study evaluated the mechanism by which p23 triggers degradation of AHR, and the role of HSP90 in this process. (PMID:29555469)
• Computational aided mechanistic understanding of Camellia sinensis bioactive compounds against co-chaperone p23 as potential anticancer agent. (PMID:31257629)
• A cytosolic heat shock protein 90 and co-chaperone p23 complex activates RIPK3/MLKL during necroptosis of endothelial cells in acute respiratory distress syndrome. (PMID:32072232)
• Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone. (PMID:32414129)
• Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle. (PMID:33547294)
• PTGES3 is a Putative Prognostic Marker in Breast Cancer. (PMID:34920330)
• Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism. (PMID:34937936)
• p23 and Aha1: Distinct Functions Promote Client Maturation. (PMID:36520307)
• Effect of PTGES3 on the Prognosis and Immune Regulation in Lung Adenocarcinoma. (PMID:37416927)
• The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment. (PMID:38245717)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptges3a	ENSDARG00000037284
danio_rerio	ptges3b	ENSDARG00000089626
mus_musculus	Ptges3	ENSMUSG00000071072
rattus_norvegicus	Ptges3	ENSRNOG00000002642
drosophila_melanogaster	p23	FBGN0037728
caenorhabditis_elegans		WBGENE00022599

Paralogs (1): PTGES3L (ENSG00000267060)

Protein

Protein identifiers

Prostaglandin E synthase 3 — Q15185 (reviewed: Q15185)

Alternative names: Cytosolic prostaglandin E2 synthase, Hsp90 co-chaperone, Progesterone receptor complex p23, Telomerase-binding protein p23

All UniProt accessions (3): Q15185, A0A087WYT3, B4DDC6

UniProt curated annotations — full annotation on UniProt →

Function. Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes. Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway.

Subunit / interactions. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2. Binds to the progesterone receptor. Interacts with TERT; the interaction, together with HSP90AA1, is required for correct assembly and stabilization of the telomerase holoenzyme complex. Interacts (via PXLE motif) with EGLN1/PHD2, recruiting EGLN1/PHD2 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with HSP90AA1, FLCN, FNIP1 and FNIP2.

Subcellular location. Cytoplasm.

Post-translational modifications. Proteolytically cleaved by caspase-7 (CASP7) in response to apoptosis, leading to its inactivation.

Domain organisation. The PXLE motif mediates interaction with EGLN1/PHD2.

Pathway. Lipid metabolism; prostaglandin biosynthesis.

Similarity. Belongs to the p23/wos2 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15185-1	1	yes
Q15185-2	2
Q15185-3	3
Q15185-4	4

RefSeq proteins (6): NP_001269530, NP_001269531, NP_001269532, NP_001269533, NP_001269534, NP_006592* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007052	CS_dom	Domain
IPR008978	HSP20-like_chaperone	Homologous_superfamily
IPR045250	p23-like	Family

Pfam: PF04969

Catalyzed reactions (Rhea), 1 shown:

• prostaglandin H2 = prostaglandin E2 (RHEA:12893)

UniProt features (32 total): modified residue 9, strand 9, splice variant 3, cross-link 2, turn 2, chain 1, domain 1, region of interest 1, short sequence motif 1, helix 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1EJF	X-RAY DIFFRACTION	2.49
7KRJ	ELECTRON MICROSCOPY	2.56
9W5I	ELECTRON MICROSCOPY	2.63
7L7J	ELECTRON MICROSCOPY	3.1
7L7I	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15185-F1	86.16	0.68

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 (1): 142–143 (cleavage; by caspase-7)

Post-translational modifications (11): 113, 118, 148, 151, 35, 65, 130, 33, 44, 85, 100

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-3371511	HSF1 activation
R-HSA-3371568	Attenuation phase
R-HSA-8937144	Aryl hydrocarbon receptor signalling
R-HSA-8939211	ESR-mediated signaling
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-211859	Biological oxidations
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-2142753	Arachidonate metabolism
R-HSA-2262752	Cellular responses to stress
R-HSA-3371556	Cellular response to heat stress
R-HSA-3371571	HSF1-dependent transactivation
R-HSA-556833	Metabolism of lipids
R-HSA-5663205	Infectious disease
R-HSA-8953897	Cellular responses to stimuli
R-HSA-8978868	Fatty acid metabolism
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 339 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_BIOLOGICAL_OXIDATIONS, MORF_ESPL1, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, PAX4_01, TGCGCANK_UNKNOWN, PID_TELOMERASE_PATHWAY, GCM_MSN, CGGAARNGGCNG_UNKNOWN, MORF_RRM1, MORF_HDAC1

GO Biological Process (14): telomere maintenance (GO:0000723), prostaglandin biosynthetic process (GO:0001516), protein folding (GO:0006457), telomere maintenance via telomerase (GO:0007004), signal transduction (GO:0007165), positive regulation of telomere maintenance via telomerase (GO:0032212), prostanoid biosynthetic process (GO:0046457), protein stabilization (GO:0050821), chaperone-mediated protein complex assembly (GO:0051131), telomerase holoenzyme complex assembly (GO:1905323), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), prostaglandin metabolic process (GO:0006693)

GO Molecular Function (8): telomerase activity (GO:0003720), prostaglandin-E synthase activity (GO:0050220), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), Hsp90 protein binding (GO:0051879), DNA polymerase binding (GO:0070182), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (8): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), telomerase holoenzyme complex (GO:0005697), cytosol (GO:0005829), protein-containing complex (GO:0032991), protein folding chaperone complex (GO:0101031), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Cellular responses to stress	2
Cellular response to heat stress	2
Metabolism	2
Arachidonate metabolism	1
HSF1-dependent transactivation	1
Phase I - Functionalization of compounds	1
Signaling by Nuclear Receptors	1
ESR-mediated signaling	1
SARS-CoV Infections	1
Biological oxidations	1
Fatty acid metabolism	1
Cellular responses to stimuli	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
prostanoid metabolic process	2
DNA metabolic process	1
telomere organization	1
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
protein maturation	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
unsaturated fatty acid biosynthetic process	1
icosanoid biosynthetic process	1
regulation of protein stability	1
protein-containing complex assembly	1
protein-RNA complex assembly	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
RNA-directed DNA polymerase activity	1
intramolecular oxidoreductase activity	1
protein binding	1
heat shock protein binding	1
enzyme binding	1
binding	1
catalytic activity	1
chromosomal region	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2873 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGES3	HSP90AB1	P08238	993
PTGES3	HSP90AA1	P07900	992
PTGES3	AHSA1	O95433	974
PTGES3	PTGES	O14684	971
PTGES3	CDC37	Q16543	948
PTGES3	PTGES2	Q9H7Z7	939
PTGES3	FKBP4	Q02790	910
PTGES3	HSPA4	P34932	869
PTGES3	STIP1	P31948	863
PTGES3	CDC37L1	Q7L3B6	819
PTGES3	NUDC	Q9Y266	811
PTGES3	NUDCD3	Q8IVD9	781
PTGES3	FKBP5	Q13451	763
PTGES3	STUB1	Q9UNE7	760
PTGES3	PPID	Q08752	760

IntAct

167 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
HSP90AA1	PTGES3	psi-mi:“MI:0915”(physical association)	0.860
PTGES3	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.860
HSP90AB1	PTGES3	psi-mi:“MI:0407”(direct interaction)	0.850
HSP90AB1	PTGES3	psi-mi:“MI:0915”(physical association)	0.850
NR3C1	HSP90AA1	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSP90AA1	CHUK	psi-mi:“MI:0914”(association)	0.670
PTGES3	POLR3A	psi-mi:“MI:0915”(physical association)	0.670
PTGES3	URI1	psi-mi:“MI:0915”(physical association)	0.670
FKBP5	IKBKB	psi-mi:“MI:0914”(association)	0.640
FLII	TMOD1	psi-mi:“MI:0914”(association)	0.640
IRS4	PIK3R2	psi-mi:“MI:0914”(association)	0.640
PPP5C	IRS4	psi-mi:“MI:0914”(association)	0.570
SIM2	PTGES3	psi-mi:“MI:0915”(physical association)	0.570
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
HSP90AA1	USP19	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
ANKMY2	ADCY3	psi-mi:“MI:0914”(association)	0.530

BioGRID (617): PTGES3 (Reconstituted Complex), HSP90AB1 (Reconstituted Complex), PTGES3 (Biochemical Activity), PTGES3 (Biochemical Activity), HSP90AA1 (Affinity Capture-Western), HSP90AB1 (Affinity Capture-Western), HSP90AA1 (PCA), PTGES3 (Affinity Capture-Western), HSP90AA1 (Reconstituted Complex), PTGES3 (Affinity Capture-MS), PTGES3 (Affinity Capture-MS), PTGES3 (Affinity Capture-MS), PTGES3 (Affinity Capture-MS), PTGES3 (Two-hybrid), PTGES3 (Affinity Capture-RNA)

ESM2 similar proteins: A0JN27, A0PJN4, A1L167, A2VEA3, B1H1E4, F1LTR1, G1TGF1, O95164, P49407, P61201, P61202, P61203, P83868, Q07G17, Q13888, Q15185, Q2KJ29, Q2TA46, Q2TBV5, Q32NS4, Q3KNV8, Q3ZBF7, Q5BJT2, Q5F398, Q5NVM4, Q5NVP9, Q5RBN9, Q5SP67, Q5TDH0, Q5XIT1, Q6AYU1, Q6IQT4, Q6IR75, Q6NW85, Q6P1K8, Q6PER3, Q6PFJ9, Q6PWL5, Q86TJ2, Q8BTQ0

Diamond homologs: E9PB15, G1TGF1, P83868, Q15185, Q3ZBF7, Q5NVM4, Q6PWL5, Q9D9A7, Q9R0Q7, P28707, Q11118, Q23280, Q90955, Q9FR62, Q6ID70, Q8L7U4, A7YY55, P0C8Z0, Q5NVQ2, Q5ZM57, Q6YYB0, Q7SY06, Q8K2C9, Q9P035, Q9VH95

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	PTGES3	phosphorylation
PTGES3	“up-regulates activity”	HSP90AA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
Transcriptional Regulation by NPAS4	5	22.1×	2e-04
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	5	20.1×	3e-04
Transcriptional Regulation by MECP2	7	17.2×	5e-05
Attenuation phase	5	15.8×	6e-04
PIWI-interacting RNA (piRNA) biogenesis	5	15.3×	6e-04
HSF1 activation	5	14.8×	7e-04
Regulation of MECP2 expression and activity	5	14.3×	7e-04
NOD1/2 Signaling Pathway	5	12.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
piRNA processing	5	25.2×	3e-04
stress-activated MAPK cascade	5	21.0×	6e-04
regulatory ncRNA-mediated gene silencing	5	20.2×	7e-04
obsolete positive regulation of NF-kappaB transcription factor activity	10	12.3×	6e-06
cellular response to heat	5	10.3×	8e-03
tumor necrosis factor-mediated signaling pathway	5	9.9×	1e-02
negative regulation of autophagy	6	9.3×	4e-03
protein folding	14	8.7×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1123 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56664774:A:AC	donor_gain	1.0000
12:56664775:C:CC	donor_gain	1.0000
12:56666202:A:AC	donor_gain	1.0000
12:56666203:C:CC	donor_gain	1.0000
12:56666267:C:CC	acceptor_gain	1.0000
12:56666276:G:GC	acceptor_gain	1.0000
12:56670365:C:CC	acceptor_gain	1.0000
12:56671744:CCTA:C	donor_loss	1.0000
12:56671745:CTACC:C	donor_loss	1.0000
12:56671746:TA:T	donor_loss	1.0000
12:56671747:A:AC	donor_gain	1.0000
12:56671748:C:A	donor_loss	1.0000
12:56671748:C:CC	donor_gain	1.0000
12:56671846:TC:T	acceptor_gain	1.0000
12:56671847:CC:C	acceptor_gain	1.0000
12:56671848:C:CC	acceptor_gain	1.0000
12:56671848:C:CG	acceptor_loss	1.0000
12:56671855:C:CT	acceptor_gain	1.0000
12:56672738:A:AC	donor_gain	1.0000
12:56672739:C:CC	donor_gain	1.0000
12:56672807:CAA:C	acceptor_gain	1.0000
12:56672810:C:CC	acceptor_gain	1.0000
12:56672812:G:C	acceptor_gain	1.0000
12:56672949:TAC:T	donor_loss	1.0000
12:56672950:A:AC	donor_gain	1.0000
12:56672950:AC:A	donor_gain	1.0000
12:56672951:C:CA	donor_gain	1.0000
12:56672951:CC:C	donor_gain	1.0000
12:56672951:CCT:C	donor_gain	1.0000
12:56672951:CCTGA:C	donor_gain	1.0000

AlphaMissense

1102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56670332:C:A	W106C	1.000
12:56670332:C:G	W106C	1.000
12:56670334:A:G	W106R	1.000
12:56670334:A:T	W106R	1.000
12:56670341:G:C	F103L	1.000
12:56670341:G:T	F103L	1.000
12:56670342:A:C	F103C	1.000
12:56670343:A:G	F103L	1.000
12:56670358:A:G	W98R	1.000
12:56670358:A:T	W98R	1.000
12:56671778:A:G	W86R	1.000
12:56671778:A:T	W86R	1.000
12:56673024:A:T	V15D	1.000
12:56673046:A:G	W8R	1.000
12:56673046:A:T	W8R	1.000
12:56670325:A:G	W109R	0.999
12:56670325:A:T	W109R	0.999
12:56670333:C:G	W106S	0.999
12:56670342:A:G	F103S	0.999
12:56670343:A:C	F103V	0.999
12:56670343:A:T	F103I	0.999
12:56670348:A:T	V101D	0.999
12:56670354:A:G	L99P	0.999
12:56670354:A:T	L99H	0.999
12:56671768:A:G	L89S	0.999
12:56671776:C:A	W86C	0.999
12:56671776:C:G	W86C	0.999
12:56671797:T:A	K79N	0.999
12:56671797:T:G	K79N	0.999
12:56671811:A:G	C75R	0.999

dbSNP variants (sampled 300 via entrez): RS1000051164 (12:56680350 T>C), RS1000065572 (12:56675348 T>C), RS1000081915 (12:56680209 G>A), RS1000118670 (12:56669644 G>A,T), RS1000257448 (12:56675267 T>A), RS1000350996 (12:56662933 T>C), RS1000460750 (12:56679841 A>C,G,T), RS1000642466 (12:56675948 C>G), RS1000661575 (12:56666082 C>G,T), RS1000716371 (12:56665045 T>C), RS1001084425 (12:56688387 G>A,T), RS1001295489 (12:56679834 C>A), RS1001298126 (12:56680143 C>A,G,T), RS1001353258 (12:56684321 T>C), RS1001368142 (12:56684845 G>A)

Disease associations

OMIM: gene MIM:607061 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001335_23	Mean platelet volume	7.000000e-14
GCST001337_35	Platelet count	2.000000e-10
GCST004612_121	High light scatter reticulocyte percentage of red cells	4.000000e-09
GCST008916_110	Asthma	1.000000e-27
GCST008916_18	Asthma	8.000000e-18
GCST90002385_230	High light scatter reticulocyte count	2.000000e-13
GCST90002405_306	Reticulocyte count	2.000000e-14
GCST90011898_18	Alanine aminotransferase levels	4.000000e-12
GCST90013405_81	Liver enzyme levels (alanine transaminase)	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3341580 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Prostaglandin synthases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, affects cotreatment, increases abundance (+1 more)	4
Tobacco Smoke Pollution	affects expression, increases expression	4
bisphenol A	decreases expression	2
Vorinostat	decreases expression	2
Copper	affects binding, decreases expression	2
Ivermectin	decreases expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
beauvericin	affects cotreatment, increases expression	1
uranyl acetate	affects expression	1
1,12-benzoperylene	increases expression	1
diethyl phthalate	affects cotreatment, affects reaction, decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
diisononyl phthalate	affects reaction, decreases expression, affects cotreatment	1
arsenite	affects binding, increases reaction	1
chelerythrine	increases cleavage	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	affects cotreatment, increases expression	1
diisobutyl phthalate	affects reaction, decreases expression, affects cotreatment	1
butylbenzyl phthalate	affects cotreatment, affects reaction, decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases degradation, increases reaction	1
chloropicrin	increases expression	1
enniatins	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-	affects binding, decreases reaction	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3389829	Binding	Inhibition of recombinant cPGES (unknown origin) at 10 uM	Development of 2-aryl substituted quinazolin-4(3H)-one, pyrido[4,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as microsomal prostaglandin E(2) synthase-1 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3F9	Abcam HEK293T PTGES3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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