PSME3IP1

Summary

PSME3IP1 (proteasome activator subunit 3 interacting protein 1, HGNC:29856) is a protein-coding gene on chromosome 16q13, encoding PSME3-interacting protein (Q9GZU8). Promotes the association of the proteasome activator complex subunit PSME3 with the 20S proteasome and regulates its activity.

Involved in negative regulation of proteasomal protein catabolic process. Located in nucleoplasm.

Source: NCBI Gene 80011 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_024946

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29856
Approved symbol	PSME3IP1
Name	proteasome activator subunit 3 interacting protein 1
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	NIP30, PIP30
Ensembl gene	ENSG00000172775
Ensembl biotype	protein_coding
OMIM	617766
Entrez	80011

Gene structure

Transcript identifiers

Ensembl transcripts: 104 — 101 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000309137, ENST00000562324, ENST00000562400, ENST00000562406, ENST00000564108, ENST00000564424, ENST00000565353, ENST00000565458, ENST00000565760, ENST00000565956, ENST00000566077, ENST00000566403, ENST00000566481, ENST00000566584, ENST00000566681, ENST00000567044, ENST00000567439, ENST00000568671, ENST00000569266, ENST00000570184, ENST00000870451, ENST00000870452, ENST00000870453, ENST00000870454, ENST00000870455, ENST00000870456, ENST00000870457, ENST00000870458, ENST00000870459, ENST00000870460, ENST00000870461, ENST00000870462, ENST00000870463, ENST00000870464, ENST00000870465, ENST00000870466, ENST00000870467, ENST00000870468, ENST00000870469, ENST00000870470, ENST00000870471, ENST00000870472, ENST00000870473, ENST00000870474, ENST00000870475, ENST00000870476, ENST00000870477, ENST00000870478, ENST00000870479, ENST00000870480, ENST00000870481, ENST00000870482, ENST00000870483, ENST00000870484, ENST00000870485, ENST00000870486, ENST00000914660, ENST00000914661, ENST00000914662, ENST00000914663, ENST00000914664, ENST00000914665, ENST00000914666, ENST00000914667, ENST00000914668, ENST00000914669, ENST00000914670, ENST00000914671, ENST00000914672, ENST00000914673, ENST00000914674, ENST00000914675, ENST00000914676, ENST00000914677, ENST00000914678, ENST00000914679, ENST00000914680, ENST00000914681, ENST00000914682, ENST00000914683, ENST00000914684, ENST00000914685, ENST00000914686, ENST00000914687, ENST00000914688, ENST00000914689, ENST00000914690, ENST00000914691, ENST00000914692, ENST00000914693, ENST00000914694, ENST00000914695, ENST00000941662, ENST00000941663, ENST00000941664, ENST00000941665, ENST00000941666, ENST00000941667, ENST00000941668, ENST00000941669, ENST00000941670, ENST00000941671, ENST00000941672, ENST00000941673

RefSeq mRNA: 26 — MANE Select: NM_024946 NM_001354078, NM_001354079, NM_001354080, NM_001354081, NM_001354082, NM_001354083, NM_001354084, NM_001354085, NM_001354086, NM_001354087, NM_001354088, NM_001354089, NM_001354090, NM_001354091, NM_001354092, NM_001354094, NM_001354095, NM_001354096, NM_001354097, NM_001354098, NM_001354099, NM_001354100, NM_001354101, NM_001354102, NM_001354103, NM_024946

CCDS: CCDS42168

Canonical transcript exons

ENST00000309137 — 7 exons

Exon	Start	End
ENSE00001289853	57152466	57154507
ENSE00001327146	57173728	57173869
ENSE00002581174	57185821	57186039
ENSE00003493560	57164001	57164065
ENSE00003498780	57172776	57172874
ENSE00003584516	57172251	57172372
ENSE00003790795	57167093	57167226

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9797 / max 731.2733, expressed in 1822 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157508	28.2028	1819
157507	2.7072	1352
157509	2.6742	1395
157505	2.5192	1302
157502	0.5354	278
157504	0.4374	172
157506	0.3230	134
157503	0.2661	112
157510	0.1753	48
157511	0.1353	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.88	gold quality
monocyte	CL:0000576	98.14	gold quality
granulocyte	CL:0000094	98.13	gold quality
right uterine tube	UBERON:0001302	98.02	gold quality
mononuclear cell	CL:0000842	97.97	gold quality
left testis	UBERON:0004533	97.88	gold quality
ganglionic eminence	UBERON:0004023	97.85	gold quality
leukocyte	CL:0000738	97.81	gold quality
rectum	UBERON:0001052	97.80	gold quality
right testis	UBERON:0004534	97.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.68	gold quality
sural nerve	UBERON:0015488	97.49	gold quality
cortical plate	UBERON:0005343	97.38	gold quality
transverse colon	UBERON:0001157	97.33	gold quality
right lung	UBERON:0002167	97.22	gold quality
colonic epithelium	UBERON:0000397	97.15	gold quality
left lobe of thyroid gland	UBERON:0001120	97.15	gold quality
right lobe of thyroid gland	UBERON:0001119	97.11	gold quality
adenohypophysis	UBERON:0002196	97.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.07	gold quality
prefrontal cortex	UBERON:0000451	97.06	gold quality
ventricular zone	UBERON:0003053	97.05	gold quality
metanephros cortex	UBERON:0010533	97.05	gold quality
spleen	UBERON:0002106	96.98	gold quality
mucosa of transverse colon	UBERON:0004991	96.96	gold quality
skin of abdomen	UBERON:0001416	96.93	gold quality
body of stomach	UBERON:0001161	96.92	gold quality
body of pancreas	UBERON:0001150	96.83	gold quality
lower esophagus mucosa	UBERON:0035834	96.81	gold quality
cerebellar hemisphere	UBERON:0002245	96.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting PSME3IP1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 3)

• data show that PIP30 deeply affects PA28gamma interactions with cellular proteins, including the 20S proteasome, demonstrating that it is an important regulator of PA28gamma in cells and thus a new player in the control of the multiple functions of the proteasome within the nucleus. (PMID:29934401)
• The REGgamma inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells. (PMID:32764536)
• Fat mass and obesity-associated protein (FTO) mediated m[6]A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay. (PMID:38556586)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psme3ip1	ENSDARG00000041631
mus_musculus	Psme3ip1	ENSMUSG00000031774
rattus_norvegicus	Psme3ip1	ENSRNOG00000017841
drosophila_melanogaster	CG14480	FBGN0034242
caenorhabditis_elegans	C25A1.1	WBGENE00007705

Protein

Protein identifiers

PSME3-interacting protein — Q9GZU8 (reviewed: Q9GZU8)

Alternative names: NEFA-interacting nuclear protein NIP30, PA28G-interacting protein

All UniProt accessions (15): Q9GZU8, H3BMX9, H3BN22, H3BNK9, H3BP64, H3BPF9, H3BPH9, H3BQQ6, H3BSF0, H3BSY6, H3BTI2, H3BTP8, H3BU93, H3BUL4, Q6P4H7

UniProt curated annotations — full annotation on UniProt →

Function. Promotes the association of the proteasome activator complex subunit PSME3 with the 20S proteasome and regulates its activity. Inhibits PSME3-mediated degradation of some proteasome substrates, probably by affecting their diffusion rate into the catalytic chamber of the proteasome. Also inhibits the interaction of PSME3 with COIL, inhibits accumulation of PSME3 in Cajal bodies and positively regulates the number of Cajal bodies in the nucleus.

Subunit / interactions. Interacts (via C-terminus) with both free and 20S proteasome-bound forms of the proteasome activator complex subunit PSME3; the interaction is direct.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylation by CK2 stabilizes the interaction with PSME3.

RefSeq proteins (26): NP_001341007, NP_001341008, NP_001341009, NP_001341010, NP_001341011, NP_001341012, NP_001341013, NP_001341014, NP_001341015, NP_001341016, NP_001341017, NP_001341018, NP_001341019, NP_001341020, NP_001341021, NP_001341023, NP_001341024, NP_001341025, NP_001341026, NP_001341027, NP_001341028, NP_001341029, NP_001341030, NP_001341031, NP_001341032, NP_079222* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019331	FAM192A/Fyv6_N	Domain
IPR039845	FAM192A	Family

Pfam: PF10187

UniProt features (16 total): modified residue 5, mutagenesis site 4, region of interest 3, compositionally biased region 3, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZU8-F1	69.12	0.22

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 (5): 222, 228, 1, 17, 139

Mutagenesis-validated functional residues (4):

Position	Phenotype
222	reduces phosphorylation by ck2 and interaction with psme3; when associated with a-228.
223–225	abolishes phosphorylation by ck2, strongly reduces interaction with psme3 and abolishes effect on proteasome activity.
228	reduces phosphorylation by ck2 and interaction with psme3; when associated with a-222.
229–231	strongly reduces phosphorylation by ck2 and interaction with psme3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): GCACCTT_MIR18A_MIR18B, RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_PROTEIN_BINDING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, COUP_01, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_BINDING, GOBP_REGULATION_OF_CATABOLIC_PROCESS, USF_01, TGIF_01, ZIC1_01

GO Biological Process (2): negative regulation of protein binding (GO:0032091), negative regulation of proteasomal protein catabolic process (GO:1901799)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
regulation of protein binding	1
negative regulation of binding	1
proteasomal protein catabolic process	1
negative regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSME3IP1	PSME3	P61289	675
PSME3IP1	TTC33	Q6PID6	565
PSME3IP1	CPNE2	Q96FN4	541
PSME3IP1	CREB3	O43889	519
PSME3IP1	BCAS4	Q8TDM0	516
PSME3IP1	ARMCX2	Q7L311	508
PSME3IP1	CMTR2	Q8IYT2	507
PSME3IP1	DDX55	Q8NHQ9	494
PSME3IP1	EXOSC6	Q5RKV6	473
PSME3IP1	COG4	Q9H9E3	472
PSME3IP1	RSPRY1	Q96DX4	453
PSME3IP1	H1-3	P16402	449
PSME3IP1	H1-6	P22492	445
PSME3IP1	HMGN5	P82970	436
PSME3IP1	DIS3L2	Q8IYB7	422

IntAct

160 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
ANKRD54	TULP3	psi-mi:“MI:0914”(association)	0.930
KIF3A	KIF3B	psi-mi:“MI:0914”(association)	0.840
RPP25	POP7	psi-mi:“MI:0914”(association)	0.810
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
IMP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.670
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
RSRP1	C1QBP	psi-mi:“MI:0914”(association)	0.640
PSMB7	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB1	PSMA7	psi-mi:“MI:0914”(association)	0.640
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
PSME3IP1	PSMA1	psi-mi:“MI:0915”(physical association)	0.620
TRAF2	PSME3IP1	psi-mi:“MI:0915”(physical association)	0.560
PSME3IP1	RPS11	psi-mi:“MI:0915”(physical association)	0.560
PSMB9	PSMD11	psi-mi:“MI:0914”(association)	0.530
HUS1B	ZBTB14	psi-mi:“MI:0914”(association)	0.530
RASL10B	AHCYL1	psi-mi:“MI:0914”(association)	0.530
RAB40A	RAB40AL	psi-mi:“MI:0914”(association)	0.530
RAB40AL	VSIG8	psi-mi:“MI:0914”(association)	0.530
TP53TG5	FNTB	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
YBX1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530

BioGRID (159): FAM192A (Two-hybrid), FAM192A (Affinity Capture-RNA), FAM192A (Affinity Capture-RNA), FAM192A (Affinity Capture-MS), FAM192A (Affinity Capture-MS), FAM192A (Affinity Capture-MS), PSMA1 (Affinity Capture-MS), CPSF7 (Affinity Capture-MS), FAM192A (Affinity Capture-MS), FAM192A (Affinity Capture-MS), FAM192A (Affinity Capture-MS), FAM192A (Affinity Capture-MS), FAM192A (Affinity Capture-MS), FAM192A (Co-fractionation), FAM192A (Co-fractionation)

ESM2 similar proteins: A0JPM9, A2AQ19, O43395, O75391, O75822, P04973, P09496, P29084, P29540, Q02614, Q0VCU8, Q13123, Q15650, Q2HJ41, Q2KIA6, Q2KJF9, Q3MHJ0, Q3UGC7, Q5BK07, Q5I0B5, Q5NVI3, Q5R5F1, Q5R8D1, Q5RAD5, Q5RE03, Q5ZJ85, Q5ZJ97, Q5ZK25, Q5ZKA4, Q66HG8, Q66JS6, Q6GMH0, Q6INR1, Q6P320, Q7SXU0, Q7SYJ9, Q7TNE3, Q8BM39, Q91WE2, Q922U1

Diamond homologs: Q91WE2, Q9GZU8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 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	9	39.5×	6e-12
Regulation of activated PAK-2p34 by proteasome mediated degradation	13	27.9×	9e-14
Cross-presentation of soluble exogenous antigens (endosomes)	14	27.3×	1e-14
Regulation of ornithine decarboxylase (ODC)	13	27.2×	9e-14
Proteasome assembly	17	26.7×	2e-17
Vpu mediated degradation of CD4	13	26.6×	9e-14
Autodegradation of the E3 ubiquitin ligase COP1	13	26.6×	9e-14
Ubiquitin-dependent degradation of Cyclin D	13	26.6×	9e-14

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	22	6.6×	3e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1516 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57154504:GGCT:G	acceptor_gain	1.0000
16:57154506:CT:C	acceptor_gain	1.0000
16:57154508:C:CC	acceptor_gain	1.0000
16:57163996:CCCA:C	donor_loss	1.0000
16:57163997:CCAC:C	donor_loss	1.0000
16:57163998:CAC:C	donor_loss	1.0000
16:57163999:ACCT:A	donor_loss	1.0000
16:57164000:CCTT:C	donor_loss	1.0000
16:57164066:C:CC	acceptor_gain	1.0000
16:57167247:CAAA:C	acceptor_gain	1.0000
16:57167251:C:CC	acceptor_gain	1.0000
16:57172222:A:AC	donor_gain	1.0000
16:57172223:C:CC	donor_gain	1.0000
16:57172256:ATT:A	donor_gain	1.0000
16:57172258:T:A	donor_gain	1.0000
16:57172368:GTTTT:G	acceptor_gain	1.0000
16:57172370:TTT:T	acceptor_gain	1.0000
16:57172370:TTTC:T	acceptor_loss	1.0000
16:57172371:TT:T	acceptor_gain	1.0000
16:57172372:TC:T	acceptor_loss	1.0000
16:57172373:C:CC	acceptor_gain	1.0000
16:57172373:CTGAG:C	acceptor_loss	1.0000
16:57172374:T:G	acceptor_loss	1.0000
16:57172774:A:AC	donor_gain	1.0000
16:57172775:C:CT	donor_gain	1.0000
16:57172775:CTG:C	donor_gain	1.0000
16:57172775:CTGA:C	donor_gain	1.0000
16:57172775:CTGAA:C	donor_gain	1.0000
16:57172790:T:A	donor_gain	1.0000
16:57172797:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000049834 (16:57181256 T>C), RS1000210351 (16:57174611 T>C), RS1000227907 (16:57168107 C>T), RS1000256645 (16:57186918 C>G,T), RS1000342220 (16:57168373 C>T), RS1000457437 (16:57161574 T>C), RS1000628903 (16:57155073 G>C), RS1000887990 (16:57186140 C>T), RS1001035786 (16:57179655 C>A,T), RS1001189145 (16:57157757 T>A,C), RS1001382815 (16:57186273 A>C), RS1001789678 (16:57175858 T>C), RS1002015262 (16:57162693 G>A,C,T), RS1002017450 (16:57170054 T>C), RS1002186676 (16:57156356 A>G)

Disease associations

OMIM: gene MIM:617766 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010241_144	Apolipoprotein A1 levels	4.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, decreases expression	2
arsenite	affects binding, increases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	decreases expression	1
Chlorpyrifos	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Plant Extracts	affects cotreatment, increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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