PSMG3

Summary

PSMG3 (proteasome assembly chaperone 3, HGNC:22420) is a protein-coding gene on chromosome 7p22.3, encoding Proteasome assembly chaperone 3 (Q9BT73). Chaperone protein which promotes assembly of the 20S proteasome. It is a common-essential gene (DepMap: required in 96.1% of cancer cell lines).

Enables molecular adaptor activity. Involved in chaperone-mediated protein complex assembly. Predicted to be located in cytosol. Predicted to be part of protein-containing complex.

Source: NCBI Gene 84262 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 14 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 96.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_032302

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22420
Approved symbol	PSMG3
Name	proteasome assembly chaperone 3
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC10911, PAC3
Ensembl gene	ENSG00000157778
Ensembl biotype	protein_coding
OMIM	617528
Entrez	84262

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000252329, ENST00000288607, ENST00000404674, ENST00000968094

RefSeq mRNA: 2 — MANE Select: NM_032302 NM_001134340, NM_032302

CCDS: CCDS5327

Canonical transcript exons

ENST00000288607 — 2 exons

Exon	Start	End
ENSE00001279347	1569124	1570032
ENSE00001822759	1567332	1567850

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 95.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1751 / max 76.6373, expressed in 1773 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82435	11.1751	1773

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.17	gold quality
lower esophagus mucosa	UBERON:0035834	95.15	gold quality
upper arm skin	UBERON:0004263	94.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.03	gold quality
skin of leg	UBERON:0001511	93.26	gold quality
gingival epithelium	UBERON:0001949	93.26	gold quality
skin of abdomen	UBERON:0001416	92.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.82	gold quality
right frontal lobe	UBERON:0002810	92.58	gold quality
anterior cingulate cortex	UBERON:0009835	92.36	gold quality
zone of skin	UBERON:0000014	92.13	gold quality
esophagus mucosa	UBERON:0002469	92.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.06	gold quality
right uterine tube	UBERON:0001302	92.00	gold quality
gingiva	UBERON:0001828	91.84	gold quality
middle temporal gyrus	UBERON:0002771	91.24	gold quality
granulocyte	CL:0000094	91.22	gold quality
nasal cavity epithelium	UBERON:0005384	91.14	gold quality
nasal cavity mucosa	UBERON:0001826	90.83	gold quality
stromal cell of endometrium	CL:0002255	90.29	gold quality
parotid gland	UBERON:0001831	90.24	gold quality
amygdala	UBERON:0001876	90.19	gold quality
metanephros cortex	UBERON:0010533	89.86	gold quality
apex of heart	UBERON:0002098	89.76	gold quality
hypothalamus	UBERON:0001898	89.75	gold quality
adenohypophysis	UBERON:0002196	89.65	gold quality
spleen	UBERON:0002106	89.58	gold quality
nipple	UBERON:0002030	89.57	gold quality
body of stomach	UBERON:0001161	89.56	gold quality
primary visual cortex	UBERON:0002436	89.39	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	no	2.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting PSMG3, 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-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4790-5P	96.67	67.45	167

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• we report the identification of a chaperone, designated PAC3, as a component of alpha rings. PAC3 dissociates before the formation of half-proteasomes, a process coupled with the recruitment of beta subunits and hUmp1.[PAC3] (PMID:17189198)
• Anaplasma phagocytophilum AptA enhances the UPS, autophagy, and anti-apoptosis of host cells by PSMG3. (PMID:34126152)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmg3	ENSDARG00000098391
mus_musculus	Psmg3	ENSMUSG00000029551
rattus_norvegicus	Psmg3	ENSRNOG00000001273

Protein

Protein identifiers

Proteasome assembly chaperone 3 — Q9BT73 (reviewed: Q9BT73)

Alternative names: Proteasome chaperone homolog 3

All UniProt accessions (1): Q9BT73

UniProt curated annotations — full annotation on UniProt →

Function. Chaperone protein which promotes assembly of the 20S proteasome. May cooperate with PSMG1-PSMG2 heterodimers to orchestrate the correct assembly of proteasomes.

Subunit / interactions. Homodimer. Interacts with PSMG4. Interacts directly with alpha and beta subunits of the 20S proteasome but dissociates before the formation of half-proteasomes, probably upon recruitment of POMP.

Similarity. Belongs to the PSMG3 family.

RefSeq proteins (2): NP_001127812, NP_115678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018788	Proteasome_assmbl_chp_3	Family
IPR053720	Psm_Assembly_Chaperone	Homologous_superfamily

Pfam: PF10178

UniProt features (11 total): strand 7, helix 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6JPT	X-RAY DIFFRACTION	0.96
2Z5E	X-RAY DIFFRACTION	2
8QYJ	ELECTRON MICROSCOPY	2.73
8TM3	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT73-F1	93.14	0.87

Functional residue map

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

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 76 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_PROTEASOME_ASSEMBLY, GOBP_CHAPERONE_MEDIATED_PROTEIN_COMPLEX_ASSEMBLY, chr7p22, NIKOLSKY_BREAST_CANCER_7P22_AMPLICON, BOCHKIS_FOXA2_TARGETS, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, WHITFIELD_CELL_CYCLE_G2_M, MARTENS_TRETINOIN_RESPONSE_DN, GOCC_PROTEIN_FOLDING_CHAPERONE_COMPLEX, GOMF_PROTEIN_CONTAINING_COMPLEX_BINDING, CBX5_TARGET_GENES, DIDO1_TARGET_GENES, GREB1_TARGET_GENES, HES2_TARGET_GENES

GO Biological Process (2): proteasome assembly (GO:0043248), chaperone-mediated protein complex assembly (GO:0051131)

GO Molecular Function (3): protein-containing complex binding (GO:0044877), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
protein-containing complex assembly	2
molecular_function	1
cytoplasm	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

722 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMG3	PSMG4	Q5JS54	997
PSMG3	DYSF	O75923	828
PSMG3	PSMG2	Q969U7	789
PSMG3	POMP	Q9Y244	788
PSMG3	PAAF1	Q9BRP4	640
PSMG3	PSMG1	O95456	525
PSMG3	PSMD3	O43242	457
PSMG3	GPR146	Q96CH1	449
PSMG3	ALG14	Q96F25	447
PSMG3	SLC13A4	Q9UKG4	445
PSMG3	PSMB10	P40306	444
PSMG3	PSME4	Q14997	444
PSMG3	ECPAS	Q5VYK3	432
PSMG3	ADRM1	Q16186	402
PSMG3	COX19	Q49B96	397

IntAct

136 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
PSMA2	PSMA7	psi-mi:“MI:0914”(association)	0.850
PSMG2	PSMG1	psi-mi:“MI:0914”(association)	0.850
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMB7	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
POMP	PSMA7	psi-mi:“MI:0915”(physical association)	0.720
IMP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.670
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB7	PSMD11	psi-mi:“MI:0914”(association)	0.640
NDUFB5	NDUFB3	psi-mi:“MI:0914”(association)	0.640
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
LINC02913	PSMG3	psi-mi:“MI:0915”(physical association)	0.590
IGFBP6	TCAF2	psi-mi:“MI:0914”(association)	0.530
APBB3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530

BioGRID (157): PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5AG16, A7SP74, A8IYS6, A8X3V8, A8XEZ1, B4GH42, C5DGI8, C5E4V9, F4K0C4, P0C7N9, P23225, P34343, P38751, P47112, P90986, Q00681, Q0JBY9, Q0P426, Q12245, Q24050, Q2M1D1, Q2NKS3, Q38E83, Q3V3R1, Q4W9G3, Q5B7V0, Q5JS54, Q5XIB4, Q69RJ0, Q6C9Z2, Q6VEU3, Q751N0, Q753S8, Q75BE7, Q7XZU0, Q8I7F8, Q8SAB7, Q8TGA2, Q9BI63, Q9BT73

Diamond homologs: A7SP74, Q2NKS3, Q9BT73, Q9CZH3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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
Antigen processing: Ub, ATP-independent proteasomal degradation	8	47.6×	2e-11
Proteasome assembly	18	38.2×	9e-22
Regulation of activated PAK-2p34 by proteasome mediated degradation	13	37.7×	3e-16
AUF1 (hnRNP D0) binds and destabilizes mRNA	14	36.2×	1e-16
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	14	36.2×	1e-16
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	14	36.2×	1e-16
Vpu mediated degradation of CD4	13	36.0×	4e-16
Autodegradation of the E3 ubiquitin ligase COP1	13	36.0×	4e-16

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	17	7.0×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

428 predictions. Top by Δscore:

Variant	Effect	Δscore
7:1569118:CTTTA:C	donor_loss	1.0000
7:1569119:TTTA:T	donor_loss	1.0000
7:1569120:TTA:T	donor_loss	1.0000
7:1569121:TACCT:T	donor_loss	1.0000
7:1569122:ACC:A	donor_loss	1.0000
7:1569123:C:CA	donor_loss	1.0000
7:1569127:AT:A	donor_gain	1.0000
7:1569368:T:C	acceptor_gain	1.0000
7:1569368:T:TC	acceptor_gain	1.0000
7:1569373:T:C	acceptor_gain	1.0000
7:1569373:T:TC	acceptor_gain	1.0000
7:1567829:T:C	acceptor_gain	0.9900
7:1567846:AGAGG:A	acceptor_gain	0.9900
7:1567847:GAGG:G	acceptor_gain	0.9900
7:1567848:AGG:A	acceptor_gain	0.9900
7:1567849:GG:G	acceptor_gain	0.9900
7:1567850:GC:G	acceptor_loss	0.9900
7:1567851:C:CC	acceptor_gain	0.9900
7:1567852:T:A	acceptor_loss	0.9900
7:1569128:T:TA	donor_gain	0.9900
7:1569171:CGTCA:C	donor_gain	0.9900
7:1569358:CAG:C	acceptor_gain	0.9900
7:1569363:T:C	acceptor_gain	0.9900
7:1569363:T:TC	acceptor_gain	0.9900
7:1569366:A:AC	acceptor_gain	0.9900
7:1569367:T:TC	acceptor_gain	0.9900
7:1569372:G:C	acceptor_gain	0.9900
7:1569372:G:GC	acceptor_gain	0.9900
7:1567829:T:TC	acceptor_gain	0.9800
7:1567854:G:C	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000016624 (7:1571228 C>T), RS1000280730 (7:1568013 G>GAAC), RS1001090438 (7:1567514 A>C,T), RS1001139105 (7:1571708 C>T), RS1001177038 (7:1567115 G>A), RS1001659271 (7:1566942 G>A,T), RS1001690650 (7:1566925 C>T), RS1001776921 (7:1571428 C>T), RS1002260836 (7:1567772 C>T), RS1002341270 (7:1570617 C>A,T), RS1003293919 (7:1569394 A>C,G), RS1003376188 (7:1568971 T>C), RS1003671074 (7:1568809 A>C,G), RS1003905832 (7:1570398 G>T), RS1004069158 (7:1570295 C>A,G)

Disease associations

OMIM: gene MIM:617528 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004336_1	Executive inhibition (Stroop WIT and CIT) in attention deficit hyperactivity disorder	5.000000e-09
GCST007327_85	Smoking status (ever vs never smokers)	6.000000e-10
GCST012490_396	Femur bone mineral density x serum urate levels interaction	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007969	cognitive inhibition measurement
EFO:0004318	smoking behavior
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075137 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	CHEMBL4435319
6.70	IC50	200	nM	CHEMBL1097925

PubChem BioAssay actives

2 with measured affinity, of 51 total; 2 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
4-[4-[5-[4-(4-carboxy-3-methoxy-2,5,6-trimethylphenoxy)carbonyl-3-methoxy-2,5,6-trimethylphenoxy]carbonyl-2,4-dihydroxy-3,6-dimethylphenoxy]-2-methoxy-3,5,6-trimethylbenzoyl]oxy-2-methoxy-3,5,6-trimethylbenzoic acid	1585758: Inhibition of PAC3 homodimer (unknown origin) protein-protein interaction	ic50	0.0200	uM
(2S)-2-[[(2S,4E)-4-[[(1R,2R,4aS,8aR)-2-methyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-hydroxymethylidene]-1-methyl-3,5-dioxopyrrolidin-2-yl]methyl]-2-hydroxy-3-methylbutanoic acid	477400: Inhibition of PAC3 homodimerization by protein fragment complementation assay	ic50	0.2000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	3
bisphenol A	decreases expression, increases methylation	2
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
trichostatin A	affects expression	1
manganese chloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Atrazine	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ketoconazole	increases expression	1
Manganese	decreases expression, increases abundance	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1111851	Binding	Inhibition of PAC3 homodimerization by protein fragment complementation assay	JBIR-22, an inhibitor for protein-protein interaction of the homodimer of proteasome assembly factor 3. — J Nat Prod

Clinical trials (associated diseases)

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