RPS3

Summary

RPS3 (ribosomal protein S3, HGNC:10420) is a protein-coding gene on chromosome 11q13.4, encoding Small ribosomal subunit protein uS3 (P23396). Component of the small ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit, where it forms part of the domain where translation is initiated. The protein belongs to the S3P family of ribosomal proteins. Studies of the mouse and rat proteins have demonstrated that the protein has an extraribosomal role as an endonuclease involved in the repair of UV-induced DNA damage. The protein appears to be located in both the cytoplasm and nucleus but not in the nucleolus. Higher levels of expression of this gene in colon adenocarcinomas and adenomatous polyps compared to adjacent normal colonic mucosa have been observed. This gene is co-transcribed with the small nucleolar RNA genes U15A and U15B, which are located in its first and fifth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6188 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10420
Approved symbol	RPS3
Name	ribosomal protein S3
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	FLJ26283, FLJ27450, MGC87870, S3, uS3
Ensembl gene	ENSG00000149273
Ensembl biotype	protein_coding
OMIM	600454
Entrez	6188

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 37 protein_coding, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000278572, ENST00000422465, ENST00000524851, ENST00000525690, ENST00000525933, ENST00000526248, ENST00000526608, ENST00000527273, ENST00000527446, ENST00000528439, ENST00000528847, ENST00000529173, ENST00000529285, ENST00000530164, ENST00000530170, ENST00000530721, ENST00000531188, ENST00000532872, ENST00000534440, ENST00000534555, ENST00000862149, ENST00000862150, ENST00000922394, ENST00000922395, ENST00000922396, ENST00000922397, ENST00000922398, ENST00000922399, ENST00000922400, ENST00000922401, ENST00000922402, ENST00000922403, ENST00000922404, ENST00000922405, ENST00000922406, ENST00000922407, ENST00000922408, ENST00000922409, ENST00000922410, ENST00000922411, ENST00000922412, ENST00000922413, ENST00000922414, ENST00000922415, ENST00000943085, ENST00000943086

RefSeq mRNA: 4 — MANE Select: NM_001005 NM_001005, NM_001256802, NM_001260506, NM_001260507

CCDS: CCDS58161, CCDS8236

Canonical transcript exons

ENST00000531188 — 7 exons

Exon	Start	End
ENSE00001039654	75399518	75399577
ENSE00002170641	75405614	75406907
ENSE00003523518	75404672	75404868
ENSE00003524915	75402352	75402446
ENSE00003590782	75404020	75404207
ENSE00003606545	75401640	75401733
ENSE00003619431	75400694	75400824

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 925.6184 / max 8471.4439, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115896	925.6184	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.93	gold quality
right ovary	UBERON:0002118	99.92	gold quality
right uterine tube	UBERON:0001302	99.90	gold quality
ventricular zone	UBERON:0003053	99.89	gold quality
granulocyte	CL:0000094	99.88	gold quality
stromal cell of endometrium	CL:0002255	99.88	gold quality
colonic epithelium	UBERON:0000397	99.88	gold quality
endocervix	UBERON:0000458	99.88	gold quality
ganglionic eminence	UBERON:0004023	99.88	gold quality
cortical plate	UBERON:0005343	99.88	gold quality
lower esophagus mucosa	UBERON:0035834	99.88	gold quality
rectum	UBERON:0001052	99.87	gold quality
skin of abdomen	UBERON:0001416	99.87	gold quality
body of uterus	UBERON:0009853	99.87	gold quality
ectocervix	UBERON:0012249	99.87	gold quality
mucosa of transverse colon	UBERON:0004991	99.86	gold quality
left uterine tube	UBERON:0001303	99.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.85	gold quality
right lobe of thyroid gland	UBERON:0001119	99.84	gold quality
transverse colon	UBERON:0001157	99.84	gold quality
adenohypophysis	UBERON:0002196	99.84	gold quality
upper lobe of left lung	UBERON:0008952	99.84	gold quality
left lobe of thyroid gland	UBERON:0001120	99.83	gold quality
body of stomach	UBERON:0001161	99.83	gold quality
gall bladder	UBERON:0002110	99.83	gold quality
right lung	UBERON:0002167	99.83	gold quality
monocyte	CL:0000576	99.82	gold quality
skin of leg	UBERON:0001511	99.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.82	gold quality
peripheral nervous system	UBERON:0000010	99.81	gold quality

Single-cell (SCXA)

Detected in 54 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	10029.23
E-CURD-112	yes	9274.12
E-MTAB-10042	yes	6816.59
E-MTAB-10553	yes	5922.01
E-HCAD-9	yes	5091.83
E-MTAB-9801	yes	4726.95
E-MTAB-9221	yes	4513.18
E-MTAB-6678	yes	3919.91
E-CURD-122	yes	101.79
E-CURD-88	yes	69.57
E-CURD-46	yes	54.23
E-MTAB-9067	yes	34.52
E-GEOD-135922	yes	27.71
E-MTAB-9543	yes	19.38
E-HCAD-35	yes	8.10

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BCL2L11	Activation
HRK	Activation
NFKBIA

Upstream regulators (CollecTRI, top): NFKB1, RELB

miRNA regulators (miRDB)

56 targeting RPS3, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-224-3P	98.91	68.42	1815

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Electron paramagnetic resonance study reveals a putative iron-sulfur cluster in human rpS3 protein. (PMID:11911468)
• RPS3 is involved in apoptosis. (PMID:14988002)
• Using surface plasmon resonance technology, the authors show that ribosomal protein S3 positively interacts with the human base excision repair enzymes N-glycosylase/apurinic-apyrimidinic lyase OGG1 and APE/Ref-1. (PMID:15518571)
• The S3-K132A mutant retained the ability to cleave abasic DNA, but its capacity to bind 8-oxoG was abrogated completely. (PMID:16737853)
• PEP-1-rpS3 fusion protein can be used in protein therapy for various disorders related to UV, including skin aging and cancer (PMID:17140567)
• S3 is a key protein at the mRNA binding site neighboring mRNA downstream of the codon at the decoding site in the human ribosome. (PMID:17179743)
• RPS3 is an essential but previously unknown subunit of NF-kappaB involved in the regulation of key genes in rapid cellular activation responses. (PMID:18045535)
• hRpS3 may be involved in the uracil-excision pathway, probably by participating in the DNA repair mechanism to remove uracil generated by the deamination of cytosine in DNA, and by preventing C/G–>T/A transition mutations. (PMID:18973764)
• The destiny of rpS3 molecules between translation and DNA repair is regulated by PKCdelta-dependent phosphorylation. (PMID:19059439)
• Protein S3 fragments neighboring mRNA during elongation and translation termination on the human ribosome (PMID:19088750)
• oxidative stress regulates the phosphorylation status of nonribosomal rpS3 by both activating PKCdelta and blocking the PP2A interaction with rpS3 (PMID:19458393)
• these results clearly show that arginine methylation of rpS3 plays a critical role in its import into the nucleolus, as well as in small subunit assembly of the ribosome. (PMID:19460357)
• DNA pull-down assays using a 7,8-dihydro-8-oxoguanine duplex oligonucleotide as a substrate found that RPS3 acted as a scaffold for the additional binding of MDM2 and p53. (PMID:19656744)
• when Flag-tagged rpS3 was transiently transfected into 293T cells, the level of endogenous rpS3 gradually decreased regardless of transcription (PMID:20217897)
• PEP-1-rpS3 inhibits inflammatory response cytokines and enzymes by blocking NF-kappaB and MAP kinase, prompting the suggestion that PEP-1-rpS3 can be used as a therapeutic agent against skin inflammation. (PMID:20709134)
• Data show that the IKKbeta-dependent modification of a specific amino acid in RPS3 promoted specific NF-kappaB functions that underlie the molecular pathogenetic mechanisms of E. coli O157:H7. (PMID:21399639)
• The phosphorylation of rpS3 by Cdk1 occurs at Thr221 during G2/M phase. (PMID:21871177)
• rpS3 is covalently modified by SUMO-1 and this post-translational modification regulates rpS3 function by increasing rpS3 protein stability. (PMID:21968017)
• rpS3 is recruited to the DISC and plays a critical role in both genotoxic stress and cytokine induced apoptosis. (PMID:22510408)
• An N-terminal fragment of p65 (amino acids 21-186) can selectively modulate NF-kappaB gene transcription by competing for RPS3 binding to p65. (PMID:23115242)
• rpS3 acts as a microtubule associated protein and regulates spindle dynamics during mitosis. (PMID:23131551)
• A novel radioresistance mechanism through functional orchestration of rpS3, TRAF2, and NF-kappaB in non-small cell lung cancer cells, is reported. (PMID:23188828)
• rpS3 accumulates in the mitochondria to repair damaged DNA due to the decreased interaction between rpS3 and HSP90 in the cytosol. (PMID:23911537)
• These findings suggest that the secreted rpS3 protein is an indicator of malignant tumors. (PMID:24211576)
• RPS3, a component of basic translation machinery operates at initiation and most probably elongation of protein synthesis, is also implicated in various events of the cell life as an extraribosomal player. [Review] (PMID:24239944)
• IkappaBalpha sequesters not only p65 but also RPS3 in the cytoplasm. (PMID:24457201)
• Increased RPS3 expression is associated with osteosarcoma invasion. (PMID:25449781)
• Data show that ribosomal protein S3 (RPS3) knockdown decreased mitochondrial calcium uptake 1 protein (MICU1) expression. (PMID:26336993)
• a novel cell fate determination mechanism to ensure cells undergo programed cell death through interfering with RPS3/NF-kappaB-conferred anti-apoptotic transcription by the fragment from partial p65 cleavage by activated Caspase-3 (PMID:26526615)
• Asn 165 residue of rpS3 is a critical site for N-linked glycosylation and passage through the ER-Golgi secretion pathway. (PMID:27384988)
• findings suggest that uS3 residing in the 40S ribosome might perform extra-ribosomal functions related to control of DNA quality (PMID:28334742)
• Short 5’UTR mRNAs are enriched with TISU (translation initiator of short 5’UTR), a 12-nucleotide element directing efficient scanning-independent translation. This study demonstrate that TISU is particularly dependent on eukaryotic initiation factor 1A (eIF1A) which interacts with both RPS3 and RPS10e. (PMID:28584194)
• Results found that BfrB subverts the host innate immune system by binding the NF-kappaB subunit RPS3 and promotes the survival of mycobacteria in macrophages by inhibiting cytokine production in host cells. (PMID:29018126)
• These results reveal that RPS3 upregulates XIAP independently of the NF-kappaB pathway in human breast cancer cells (PMID:29048653)
• RpS3 is a crucial substrate of ubiquitination by RNF138 in glioblastoma.RpS3 role in the radioresistance of glioblastoma. (PMID:29371697)
• These results suggest that Tat inhibits cell proliferation via an interaction with RPS3 and thereby disrupts mitotic spindle formation during HIV-1 infection. These results might provide insight into the mechanism underlying lymphocyte pathogenesis during HIV-1 infection. (PMID:29875444)
• abasic sites, which can occur in mRNAs due to oxidative stress and ageing, are able to interact directly with the uS3 fragment exposed on the 40S subunit surface near the mRNA entry channel during translation. (PMID:30594661)
• Quantitative model is presented for a tandem arrangement of two helicase active sites on the ribosome are tested. One of the proteins involved in helicase activity is RPS3. (PMID:30972734)
• our results revealed the previously unknown crucial role of the uS3 tetrapeptide (60)GEKG(63) in translation initiation related to maintaining the proper structure of the 48S complex, most likely via the prevention of premature mRNA loading into the ribosomal channel. (PMID:31356988)
• Ribosomal protein S3 selectively affects colon cancer growth by modulating the levels of p53 and lactate dehydrogenase. (PMID:32748020)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps3	ENSDARG00000103007
drosophila_melanogaster	RpS3	FBGN0002622
caenorhabditis_elegans		WBGENE00004472

Paralogs (1): GET1 (ENSG00000182093)

Protein

Protein identifiers

Small ribosomal subunit protein uS3 — P23396 (reviewed: P23396)

Alternative names: 40S ribosomal protein S3

All UniProt accessions (14): P23396, E9PJH4, E9PJN9, E9PK82, E9PL09, E9PPU1, E9PQ96, E9PQX2, E9PSF4, F2Z2S8, H0YCJ7, H0YES8, H0YEU2, H0YF32

UniProt curated annotations — full annotation on UniProt →

Function. Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Has endonuclease activity and plays a role in repair of damaged DNA. Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA. Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS). Has also been shown to bind with similar affinity to intact and damaged DNA. Stimulates the N-glycosylase activity of the base excision protein OGG1. Enhances the uracil excision activity of UNG1. Also stimulates the cleavage of the phosphodiester backbone by APEX1. When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage. Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide. Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes. Represses its own translation by binding to its cognate mRNA. Binds to and protects TP53/p53 from MDM2-mediated ubiquitination. Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization. Involved in induction of apoptosis through its role in activation of CASP8. Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5. Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation.

Subunit / interactions. Component of the 40S small ribosomal subunit. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with HNRPD. Interacts with PRMT1; the interaction methylates RPS3. Interacts with SUMO1; the interaction sumoylates RPS3. Interacts with UBC9. Interacts with CDK1; the interaction phosphorylates RPS3. Interacts with PRKCD; the interaction phosphorylates RPS3. Interacts with PKB/AKT; the interaction phosphorylates RPS3. Interacts with E2F1; the interaction occurs in the absence of nerve growth factor and increases transcription of pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5. Interacts with the base excision repair proteins APEX1 and OGG1; interaction with OGG1 increases OGG1 N-glycosylase activity. Interacts with UNG; the interaction increases the uracil excision activity of UNG1. Interacts with HSP90; the interaction prevents the ubiquitination and proteasome-dependent degradation of RPS3 and is suppressed by increased ROS levels. Interacts with TOM70; the interaction promotes translocation of RPS3 to the mitochondrion. Interacts (via N-terminus) with RELA (via N-terminus); the interaction enhances the DNA-binding activity of the NF-kappa-B p65-p50 complex. Interacts with NFKBIA; the interaction is direct and may bridge the interaction between RPS3 and RELA. Interacts with IKKB; the interaction phosphorylates RPS3 and enhances its translocation to the nucleus. Interacts (via KH domain) with MDM2 and TP53. Interacts with TRADD. Interacts (via N-terminus) with E.coli O157:H7 (strain EDL933) nleH1 and nleH2; the interaction with nleH1 inhibits phosphorylation by IKKB, reduces RPS3 nuclear abundance and inhibits transcriptional activation by the NF-kappa-B p65-p50 complex. Interacts with ASCC3. Identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon. Interacts with CRY1. Interacts (when monoubiquitinated at Lys-214) with RIOK3.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Mitochondrion inner membrane. Cytoskeleton. Spindle.

Post-translational modifications. Methylation by PRMT1 is required for import into the nucleolus and for ribosome assembly. Sumoylation by SUMO1 enhances protein stability through increased resistance to proteolysis. Sumoylation occurs at one or more of the three consensus sites, Lys-18, Lys-214 and Lys-230. Phosphorylation at Thr-221 by CDK1 occurs mainly in G2/M phase. Phosphorylation by PRKCD occurs on a non-ribosomal-associated form which results in translocation of RPS3 to the nucleus and enhances its endonuclease activity. Phosphorylated on Ser-209 by IKKB in response to activation of the NF-kappa-B p65-p50 complex which enhances the association of RPS3 with importin-alpha and mediates the nuclear translocation of RPS3. Phosphorylation by MAPK is required for translocation to the nucleus following exposure of cells to DNA damaging agents such as hydrogen peroxide. Phosphorylation by PKB/AKT mediates RPS3 nuclear translocation, enhances RPS3 endonuclease activity and suppresses RPS3-induced neuronal apoptosis. Ubiquitinated; ubiquitination is prevented by interaction with HSP90 which stabilizes the protein. Monoubiquitinated at Lys-214 by RNF10 and ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide. Monoubiquitination at Lys-214 promotes interaction with RIOK3. Deubiquitinated at Lys-214 by USP10, preventing degradation by the proteasome and promoting 40S ribosome subunit recycling following ribosome dissociation. Ufmylated by UFL1.

Activity regulation. Endonuclease activity is inhibited by MgCl2 on apurinic/apyrimidinic DNA but not on UV-irradiated DNA.

Similarity. Belongs to the universal ribosomal protein uS3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P23396-1	1	yes
P23396-2	2

RefSeq proteins (4): NP_000996, NP_001243731, NP_001247435, NP_001247436 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001351	Ribosomal_uS3_C	Domain
IPR004044	KH_dom_type_2	Domain
IPR005703	Ribosomal_uS3_euk_arc	Family
IPR009019	KH_sf_prok-type	Homologous_superfamily
IPR015946	KH_dom-like_a/b	Homologous_superfamily
IPR018280	Ribosomal_uS3_CS	Conserved_site
IPR036419	Ribosomal_S3_C_sf	Homologous_superfamily
IPR057258	Ribosomal_uS3	Family

Pfam: PF00189, PF07650

Catalyzed reactions (Rhea), 1 shown:

• 2’-deoxyribonucleotide-(2’-deoxyribose 5’-phosphate)-2’-deoxyribonucleotide-DNA = a 3’-end 2’-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5’-phosphate)-DNA + a 5’-end 5’-phospho-2’-deoxyribonucleoside-DNA + H(+) (RHEA:66592)

UniProt features (67 total): modified residue 16, mutagenesis site 16, strand 11, helix 9, cross-link 5, sequence conflict 3, initiator methionine 1, chain 1, domain 1, splice variant 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

202 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8GLP	ELECTRON MICROSCOPY	1.67
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
7R4X	ELECTRON MICROSCOPY	2.15
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8YOP	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5
8JDJ	ELECTRON MICROSCOPY	2.5
9RUC	ELECTRON MICROSCOPY	2.5
8G60	ELECTRON MICROSCOPY	2.54
8IFE	ELECTRON MICROSCOPY	2.57
9P7D	ELECTRON MICROSCOPY	2.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23396-F1	91.39	0.83

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 (21): 64, 65, 67, 70, 104, 132, 209, 220, 221, 224, 242, 90, 202, 214, 214, 230, 2, 6, 35, 42 …

Mutagenesis-validated functional residues (16):

Position	Phenotype
6	no effect on phosphorylation by cdk1. greatly reduced phosphorylation by prkcd. abolishes phosphorylation by prkcd; when
18	no effect on sumoylation. abolishes sumoylation; when associated with r-214 and r-230.
35	no effect on phosphorylation by prkcd.
42	abolishes phosphorylation by mapk and translocation to the nucleus following exposure of cells to hydrogen peroxide. no
42	phosphomimetic mutant which is detected exclusively in the nucleus.
70	no effect on phosphorylation by prkcd. abolishes phosphorylation by pkb.
70	abolishes phosphorylation by pkb.
132	does not affect ability to cleave dna but abolishes binding to 8-oxog.
139	no effect on phosphorylation by prkcd.
149	no effect on phosphorylation by prkcd.
195	no effect on phosphorylation by prkcd.
209	reduced phosphorylation by ikkb.
214	no effect on sumoylation. abolishes sumoylation; when associated with r-18 and r-230. abolished ubiquitination by rnf10
221	no effect on phosphorylation by mapk. significantly reduces phosphorylation by cdk1 and nuclear accumulation. greatly re
227	does not affect ubiquitination in response to ribosome stalling.
230	no effect on sumoylation. abolishes sumoylation; when associated with r-18 and r-214. does not affect ubiquitination in

Function

Pathways and Gene Ontology

Reactome pathways

50 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-192823	Viral mRNA Translation
R-HSA-2408557	Selenocysteine synthesis
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9735869	SARS-CoV-1 modulates host translation machinery
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-156842	Eukaryotic Translation Elongation
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168273	Influenza Viral RNA Transcription and Replication
R-HSA-2262752	Cellular responses to stress
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-376176	Signaling by ROBO receptors
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 443 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOMF_ENDONUCLEASE_ACTIVITY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOMF_NUCLEASE_ACTIVITY, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, HSIAO_HOUSEKEEPING_GENES, GOBP_TRANSLATIONAL_INITIATION, GOCC_RUFFLE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (34): cytoplasmic translation (GO:0002181), cytoplasmic translational initiation (GO:0002183), DNA repair (GO:0006281), base-excision repair (GO:0006284), apoptotic process (GO:0006915), DNA damage response (GO:0006974), chromosome segregation (GO:0007059), positive regulation of gene expression (GO:0010628), negative regulation of translation (GO:0017148), positive regulation of microtubule polymerization (GO:0031116), negative regulation of protein ubiquitination (GO:0031397), cellular response to reactive oxygen species (GO:0034614), regulation of apoptotic process (GO:0042981), negative regulation of DNA repair (GO:0045738), positive regulation of DNA repair (GO:0045739), spindle assembly (GO:0051225), cell division (GO:0051301), response to TNF agonist (GO:0061481), cellular response to hydrogen peroxide (GO:0070301), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902231), positive regulation of base-excision repair (GO:1905053), positive regulation of DNA-templated transcription initiation (GO:2000144), positive regulation of apoptotic signaling pathway (GO:2001235), translation (GO:0006412), translational initiation (GO:0006413), regulation of translation (GO:0006417), positive regulation of protein-containing complex assembly (GO:0031334), positive regulation of endodeoxyribonuclease activity (GO:0032079), positive regulation of interleukin-2 production (GO:0032743), positive regulation of activated T cell proliferation (GO:0042104), positive regulation of T cell receptor signaling pathway (GO:0050862), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), cellular response to tumor necrosis factor (GO:0071356)

GO Molecular Function (28): DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), damaged DNA binding (GO:0003684), RNA binding (GO:0003723), mRNA binding (GO:0003729), structural constituent of ribosome (GO:0003735), DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0003906), DNA endonuclease activity (GO:0004520), microtubule binding (GO:0008017), tubulin binding (GO:0015631), enzyme binding (GO:0019899), kinase binding (GO:0019900), protein kinase binding (GO:0019901), Hsp70 protein binding (GO:0030544), oxidized purine DNA binding (GO:0032357), oxidized pyrimidine DNA binding (GO:0032358), ubiquitin-like protein conjugating enzyme binding (GO:0044390), protein kinase A binding (GO:0051018), iron-sulfur cluster binding (GO:0051536), Hsp90 protein binding (GO:0051879), small ribosomal subunit rRNA binding (GO:0070181), supercoiled DNA binding (GO:0097100), class I DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0140078), DNA-binding transcription factor binding (GO:0140297), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), protein binding (GO:0005515), lyase activity (GO:0016829), protein-containing complex binding (GO:0044877)

GO Cellular Component (25): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), ribosome (GO:0005840), plasma membrane (GO:0005886), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), ruffle membrane (GO:0032587), extracellular exosome (GO:0070062), NF-kappaB complex (GO:0071159), mitotic spindle (GO:0072686), ribonucleoprotein complex (GO:1990904), mitochondrion (GO:0005739), spindle (GO:0005819), cytoskeleton (GO:0005856), small ribosomal subunit (GO:0015935), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	2
Ribosome-associated quality control	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA repair	3
translation	2
regulation of DNA repair	2
nucleic acid binding	2
ribosome	2
protein binding	2
enzyme binding	2
heat shock protein binding	2
oxidized DNA binding	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
cytoplasmic translation	1
translational initiation	1
DNA metabolic process	1
DNA damage response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
cell cycle process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1

Protein interactions and networks

STRING

6116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS3	MDM2	Q00987	941
RPS3	RPS2	P15880	926
RPS3	BYSL	Q13895	923
RPS3	RPL3	P39023	878
RPS3	RPS8	P09058	876
RPS3	RPL14	P50914	875
RPS3	RPS14	P06366	872
RPS3	RPS10	P46783	869
RPS3	RPS19	P39019	858
RPS3	RPS20	P17075	848
RPS3	LTV1	Q96GA3	838
RPS3	RPS13	P19116	834
RPS3	RPL36	Q9Y3U8	830
RPS3	RPL4	P36578	822
RPS3	RPS16	P17008	820

IntAct

503 interactions, top by confidence:

A	B	Type	Score
RELA	RPS3	psi-mi:“MI:0915”(physical association)	0.800
RPS3	RELA	psi-mi:“MI:0915”(physical association)	0.800
RPS3	LTV1	psi-mi:“MI:0915”(physical association)	0.800
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MDM2	RPS3	psi-mi:“MI:0915”(physical association)	0.690
RPS3	RPS10	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
BYSL	PARN	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RPS3	NFKB1	psi-mi:“MI:0915”(physical association)	0.620
RPS3	NFKB1	psi-mi:“MI:0914”(association)	0.620
NFKB1	RPS3	psi-mi:“MI:0915”(physical association)	0.620
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
RPS3	IKBKB	psi-mi:“MI:0915”(physical association)	0.600
IKBKB	RPS3	psi-mi:“MI:0915”(physical association)	0.600
IKBKB	RPS3	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
RPS3	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1198): RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-RNA), RPS3 (Affinity Capture-RNA), RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-MS), RPS3 (Affinity Capture-RNA), MRPL3 (Co-fractionation), MRPS12 (Co-fractionation), RPL10A (Co-fractionation), RPL12 (Co-fractionation)

ESM2 similar proteins: A0A1D8PSV5, A0RVX9, A4YCX2, A5FRY1, A9NED9, B1AIM6, B2KEL5, B2S2E2, B3PMP1, B5ZB46, E2RH47, G1TNM3, O31161, O60128, O83225, P02350, P02353, P05750, P0DJ09, P0DJ10, P23396, P29223, P41117, P41118, P41119, P47835, P48152, P48153, P62908, P62909, P79891, P90526, Q06559, Q0Z8U2, Q3T169, Q3Z975, Q3ZZL8, Q4A8H7, Q4AAE6, Q5R465

Diamond homologs: A0A1D8PSV5, A0B9W4, A0RM17, A1RXG6, A2BMC5, A2SPK9, A3DNB3, A3MTL3, A4FWB6, A4YCX2, A5UL83, A6UQ49, A6UWU3, A8AA20, B6YSL9, B9KEE6, C5A280, C6A165, E2RH47, G1TNM3, O26116, O28360, O59424, O60128, P02350, P05750, P23396, P47835, P48152, P48153, P54034, P62908, P62909, P79891, P90526, Q06559, Q0W1Y3, Q0Z8U2, Q18GF5, Q2FT39

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	RPS3	phosphorylation
MAPK3	up-regulates	RPS3	phosphorylation
MAPK1	up-regulates	RPS3	phosphorylation
MAPK3	unknown	RPS3	phosphorylation
PPP2CA	down-regulates	RPS3	dephosphorylation
PRKCD	up-regulates	RPS3	phosphorylation
CDK1	up-regulates	RPS3	phosphorylation
PRKCD	“up-regulates activity”	RPS3	phosphorylation
Gbeta	unknown	RPS3	phosphorylation
ERK1/2	unknown	RPS3	phosphorylation
IKBKB	“up-regulates activity”	RPS3	phosphorylation
AKT1	“up-regulates activity”	RPS3	phosphorylation
AKT	“up-regulates activity”	RPS3	phosphorylation
RPS3	“form complex”	“40S cytosolic small ribosomal subunit”	binding
“Host translation inhibitor nsp1”	“down-regulates activity”	RPS3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 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
RIP-mediated NFkB activation via ZBP1	6	29.2×	2e-06
TRAF6 mediated NF-kB activation	7	23.2×	1e-06
SARS-CoV-1 modulates host translation machinery	8	17.9×	1e-06
TAK1-dependent IKK and NF-kappa-B activation	8	17.4×	1e-06
TNFR1-induced NF-kappa-B signaling pathway	7	17.0×	6e-06
Eukaryotic Translation Initiation	7	15.7×	9e-06
Cap-dependent Translation Initiation	7	15.7×	9e-06
Nonsense-Mediated Decay (NMD)	9	15.2×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	5	24.9×	3e-04
response to muscle stretch	5	22.7×	4e-04
ribosome biogenesis	6	22.2×	5e-05
canonical NF-kappaB signal transduction	9	19.5×	9e-07
tumor necrosis factor-mediated signaling pathway	8	15.6×	1e-05
mRNA stabilization	6	13.0×	8e-04
intrinsic apoptotic signaling pathway	6	12.7×	8e-04
cytoplasmic translation	11	12.1×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

875 predictions. Top by Δscore:

Variant	Effect	Δscore
11:75399573:GGAAG:G	donor_gain	1.0000
11:75399574:GAAGG:G	donor_gain	1.0000
11:75399575:A:T	donor_gain	1.0000
11:75399577:GGTG:G	donor_loss	1.0000
11:75399578:G:GC	donor_loss	1.0000
11:75399579:T:G	donor_loss	1.0000
11:75400686:T:TA	acceptor_gain	1.0000
11:75400687:G:A	acceptor_gain	1.0000
11:75400690:TTAGT:T	acceptor_loss	1.0000
11:75400692:A:AG	acceptor_gain	1.0000
11:75400692:A:C	acceptor_loss	1.0000
11:75400692:AGTTT:A	acceptor_gain	1.0000
11:75400693:G:GT	acceptor_gain	1.0000
11:75400693:GT:G	acceptor_gain	1.0000
11:75400693:GTT:G	acceptor_gain	1.0000
11:75400693:GTTT:G	acceptor_gain	1.0000
11:75400693:GTTTG:G	acceptor_gain	1.0000
11:75400822:CAG:C	donor_loss	1.0000
11:75400824:GG:G	donor_loss	1.0000
11:75401638:A:AG	acceptor_gain	1.0000
11:75401639:G:GG	acceptor_gain	1.0000
11:75401639:GA:G	acceptor_gain	1.0000
11:75401639:GAA:G	acceptor_gain	1.0000
11:75401639:GAAC:G	acceptor_gain	1.0000
11:75401639:GAACA:G	acceptor_gain	1.0000
11:75401731:GAG:G	donor_gain	1.0000
11:75401732:AG:A	donor_loss	1.0000
11:75401733:GG:G	donor_loss	1.0000
11:75401735:TGAG:T	donor_loss	1.0000
11:75404016:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000054178 (11:75399132 G>T), RS1000123523 (11:75402683 G>A), RS1000183412 (11:75408742 C>T), RS1000319533 (11:75408526 A>G), RS1000408533 (11:75398795 T>A,C), RS1000433104 (11:75402824 C>G,T), RS1000462896 (11:75421516 G>A), RS1000522825 (11:75402820 G>T), RS1000580940 (11:75408371 G>A), RS1000881003 (11:75397716 C>A,T), RS1000912168 (11:75398107 C>T), RS1001087129 (11:75403589 G>A,C), RS1001097961 (11:75408185 A>G), RS1001308616 (11:75411091 T>A,C), RS1001464930 (11:75397700 A>G,T)

Disease associations

OMIM: gene MIM:600454 | 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 (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6066939 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

50 potent at pChembl≥5 of 54 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.41	Kd	3.858	nM	CHEMBL3752910
8.41	ED50	3.858	nM	CHEMBL3752910
7.39	Kd	40.59	nM	CHEMBL5653589
7.39	ED50	40.59	nM	CHEMBL5653589
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

48 with measured affinity, of 215 total; 28 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-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149305: Binding affinity to human RPS3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0039	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149305: Binding affinity to human RPS3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0406	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, affects binding, decreases reaction, decreases activity	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
2,6-dichloro-4-nitrophenol	increases expression	1
3,3’-diindolylmethane	decreases reaction, increases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
methacrylaldehyde	affects expression, increases abundance, affects cotreatment	1
chloropicrin	decreases expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	increases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	increases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1

ChEMBL screening assays

96 unique, capped per target: 96 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1920845	Binding	Induction of ribosome to readthrough in human A-T lymphoblastoid cells assessed as ATM ser1981 autophosphorylation at 30 uM after 4 days by PTT-ELISA assay	Synthesis and evaluation of compounds that induce readthrough of premature termination codons. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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