RPS2 Gene

HGNC Family	S ribosomal proteins (RPS)
Name	ribosomal protein S2
Description	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. The protein belongs to the S5P family of ribosomal proteins. It is located in the cytoplasm. This gene shares sequence similarity with mouse LLRep3. It is co-transcribed with the small nucleolar RNA gene U64, which is located in its third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRibosomal Protein S2 (RPS2), also known as uS5, plays a central role in the regulation of ribosome function and protein synthesis. It is subject to distinct posttranslational modifications that modulate its activity and stability. For instance, the protein arginine methyltransferase PRMT3 interacts with RPS2 via its zinc-finger domain to methylate an N‐terminal Arg–Gly repeat, while peptidylarginine deiminase 4 (PAD4) can citrullinate the same region in a modification that is antagonistic to methylation. These modifications appear to be critical for proper ribosome assembly and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in translation, RPS2 is intricately involved in ribosome biogenesis and extraribosomal functions. It contains a central domain that directs its nuclear import despite lacking classical nuclear localization signals, ensuring its delivery into the nucleus for incorporation into pre‐40S ribosomal subunits. Dedicated chaperones and binding partners—such as PDCD2, PDCD2L, and the zinc finger protein ZNF277—associate with RPS2 co‐translationally or during ribosome assembly, thereby stabilizing the protein and regulating its maturation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in ribosome assembly, RPS2 is emerging as a multifunctional regulator of stress response and oncogenesis. Its aberrant expression has been documented in several cancers—such as prostate cancer, hepatocellular carcinoma, and neuroblastoma—and it serves both as a tumor-associated antigen capable of eliciting cytotoxic T lymphocyte responses and as a modulator of the MDM2–p53 signaling axis. Specifically, RPS2 engages with MDM2 via its RING finger domain, influencing p53 stability under conditions of ribosomal stress, while deregulation by oncoproteins like PEG10 and specific microRNAs further underscores its role in promoting malignant cell behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, RPS2 participates in additional regulatory interactions that extend its functional repertoire. Its binding to nuclear fibroblast growth factor 3 (FGF3) suggests a role in modulating nucleolar signaling and ribosomal biogenesis, potentially contributing to cell cycle regulation. Complementing this, structural insights into the receptor interface of RPS2 have been leveraged to design cyclic peptides with affinity for bone morphogenetic protein 2 (BMP2), opening up new possible avenues for targeted therapeutic interventions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rafal Swiercz, Maria D Person, Mark T Bedford "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal protein S2 is a substrate for mammalian PRMT3 (protein arginine methyltransferase 3)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20041466"}], "href": "https://doi.org/10.1042/BJ20041466"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15473865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15473865"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Seeyoung Choi, Cho-Rok Jung, Jin-Young Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PRMT3 inhibits ubiquitination of ribosomal protein S2 and together forms an active enzyme complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2008.05.010"}], "href": "https://doi.org/10.1016/j.bbagen.2008.05.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18573314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18573314"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Qin Guo, Mark T Bedford, Walter Fast "}, {"type": "b", "children": [{"type": "t", "text": "Discovery of peptidylarginine deiminase-4 substrates by protein array: antagonistic citrullination and methylation of human ribosomal protein S2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biosyst (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1039/c1mb05089c"}], "href": "https://doi.org/10.1039/c1mb05089c"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21584310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21584310"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "M Antoine, K Reimers, W Wirz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of an unconventional nuclear localization signal in human ribosomal protein S2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.07.069"}], "href": "https://doi.org/10.1016/j.bbrc.2005.07.069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16061210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16061210"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marianne Antoine, Kerstin Reimers, Werner Wirz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fibroblast growth factor 3, a protein with a dual subcellular fate, is interacting with human ribosomal protein S2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.10.079"}], "href": "https://doi.org/10.1016/j.bbrc.2005.10.079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16263090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16263090"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anne-Marie Landry-Voyer, Sarah Bilodeau, Danny Bergeron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00303-16"}], "href": "https://doi.org/10.1128/MCB.00303-16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27697862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27697862"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kiersten L Dionne, Danny Bergeron, Anne-Marie Landry-Voyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 40S ribosomal protein uS5 (RPS2) assembles into an extraribosomal complex with human ZNF277 that competes with the PRMT3-uS5 interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.004928"}], "href": "https://doi.org/10.1074/jbc.RA118.004928"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30530495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30530495"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Anne-Marie Landry-Voyer, Danny Bergeron, Carlo Yague-Sanz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkaa1108"}], "href": "https://doi.org/10.1093/nar/gkaa1108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33245768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33245768"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "M Koga, S Shichijo, A Yamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of ribosomal proteins S2 and L10a as tumor antigens recognized by HLA-A26-restricted CTL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Antigens (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.0001-2815.2002.00009.x"}], "href": "https://doi.org/10.1046/j.0001-2815.2002.00009.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12694581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12694581"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Min Wang, Youji Hu, Mark E Stearns "}, {"type": "b", "children": [{"type": "t", "text": "RPS2: a novel therapeutic target in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1756-9966-28-6"}], "href": "https://doi.org/10.1186/1756-9966-28-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19138403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19138403"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jinhong Cho, Jinyoung Park, Sang Chul Shin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal protein S2 interplays with MDM2 to induce p53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2020.01.038"}], "href": "https://doi.org/10.1016/j.bbrc.2020.01.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31928715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31928715"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jian Zhang, Wei Liu, Ping Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of long chain noncoding RNA paternally expressed gene (PEG10) inhibits the progression of neuroblastoma by regulating microRNA-449a (miR-449a)/ribosomal protein S2 (RPS2) axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2042999"}], "href": "https://doi.org/10.1080/21655979.2022.2042999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35212607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35212607"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Batoul Abi Zamer, Bilal Rah, Manju Nidagodu Jayakumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation-mediated epigenetic regulation of oncogenic RPS2 as a novel therapeutic target and biomarker in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2023.149453"}], "href": "https://doi.org/10.1016/j.bbrc.2023.149453"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38181486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38181486"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Xiaohua Fan, Hai Xia, Xiaoyun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rational design of type-IA receptor-derived cyclic peptides to target human bone morphogenic protein 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biosci (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31894111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31894111"}]}]}]}
Synonyms	LLREP3
Proteins	RS2_HUMAN
NCBI Gene ID	6187
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RPS2 has 16,742 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for RPS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RPS2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RPS2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of RPS2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of RPS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of RPS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RPS2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of RPS2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of RPS2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of RPS2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RPS2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RPS2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RPS2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RPS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RPS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of RPS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RPS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RPS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RPS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RPS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with RPS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing RPS2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of RPS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RPS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RPS2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RPS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RPS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RPS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with RPS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with RPS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RPS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RPS2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RPS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RPS2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing RPS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RPS2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RPS2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing RPS2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RPS2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of RPS2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of RPS2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RPS2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.