RPL3 Gene

HGNC Family	L ribosomal proteins (RPL)
Name	ribosomal protein L3
Description	Ribosomes, the complexes 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 60S subunit. The protein belongs to the L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene's introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. 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": "\nRPL3 (also referred to as uL3) exerts important extra‐ribosomal functions by directly modulating cell cycle progression and apoptosis. In several studies, ribosome‐free uL3 was shown to positively regulate the cyclin‐dependent kinase inhibitor p21 through its interaction with the transcription factor Sp1, thereby triggering G1/S cell cycle arrest and promoting mitochondrial‐dependent apoptosis. In addition, uL3 can negatively regulate the E2F1 promoter and downmodulate Cyclin D1 expression—further pinpointing its role as a key regulator of cell proliferation and cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn response to nucleolar stress induced by chemotherapeutic agents such as 5‑fluorouracil (5‑FU) and oxaliplatin, uL3 becomes released from ribosomes and acts as a potent proapoptotic factor independent of p53. Under these conditions, uL3 negatively regulates the transcription of cystathionine‑β‑synthase (CBS), thereby altering its stability and triggering mitochondrial apoptosis via altered Bax/Bcl‑2 ratios, cytochrome c release and caspase activation. Moreover, enhanced expression of ribosome‐free uL3 is critical for the cytotoxic effects of these drugs, can reduce drug efflux by modulating P‑glycoprotein levels, and its deregulation is associated with malignant progression and multidrug resistance in colon cancer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cell cycle and stress responses, RPL3 regulates its own expression through an autoregulatory mechanism involving alternative pre‑mRNA splicing coupled to nonsense‑mediated decay. Splicing factors such as hnRNP H1, KHSRP and NPM associate with the rpL3 pre‑mRNA to fine‑tune the production of functional protein. In parallel, post‑translational modifications have been reported; for example, the methyltransferase METTL18 specifically methylates RPL3 at His‑245—a modification that modulates translation elongation rates at tyrosine codons and ensures proper nascent protein folding. In addition, expression analyses have correlated rpL3 levels with telomerase activity, further highlighting its multifaceted roles in maintaining cellular homeostasis and genome integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Annapina Russo, Davide Esposito, Morena Catillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human rpL3 induces G₁/S arrest or apoptosis by modulating p21 (waf1/cip1) levels in a p53-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.22963"}], "href": "https://doi.org/10.4161/cc.22963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23255119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23255119"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Annalisa Pecoraro, Pietro Carotenuto, Giulia Russo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-51723-7"}], "href": "https://doi.org/10.1038/s41598-019-51723-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31659203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31659203"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valentina Pagliara, Assunta Saide, Emma Mitidieri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-β-synthase in colon cancer cells lacking p53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.10385"}], "href": "https://doi.org/10.18632/oncotarget.10385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27385096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27385096"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Davide Esposito, Elvira Crescenzi, Vinay Sagar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2591"}], "href": "https://doi.org/10.18632/oncotarget.2591"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25473889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25473889"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Annapina Russo, Sara Maiolino, Valentina Pagliara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhancement of 5-FU sensitivity by the proapoptotic rpL3 gene in p53 null colon cancer cells through combined polymer nanoparticles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.13216"}], "href": "https://doi.org/10.18632/oncotarget.13216"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27835895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27835895"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Annalisa Pecoraro, Antonella Virgilio, Veronica Esposito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "uL3 Mediated Nucleolar Stress Pathway as a New Mechanism of Action of Antiproliferative G-quadruplex TBA Derivatives in Colon Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom10040583"}], "href": "https://doi.org/10.3390/biom10040583"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32290083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32290083"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ning Deng, Xiupeng Zhang, Yong Zhang "}, {"type": "b", "children": [{"type": "t", "text": "BAIAP2L1 accelerates breast cancer progression and chemoresistance by activating AKT signaling through binding with ribosomal protein L3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.15632"}], "href": "https://doi.org/10.1111/cas.15632"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36308067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36308067"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Annapina Russo, Morena Catillo, Davide Esposito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autoregulatory circuit of human rpL3 expression requires hnRNP H1, NPM and KHSRP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkr461"}], "href": "https://doi.org/10.1093/nar/gkr461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21705779"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21705779"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Annapina Russo, Gabriella Siciliano, Morena Catillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hnRNP H1 and intronic G runs in the splicing control of the human rpL3 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2010.01.008"}], "href": "https://doi.org/10.1016/j.bbagrm.2010.01.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20100605"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20100605"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jędrzej M Małecki, Marie-Francoise Odonohue, Yeji Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkab088"}], "href": "https://doi.org/10.1093/nar/gkab088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33693809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33693809"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "M Bergqvist, D Brattström, D Brodin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genes associated with telomerase activity levels in esophageal carcinoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Esophagus (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1442-2050.2006.00532.x"}], "href": "https://doi.org/10.1111/j.1442-2050.2006.00532.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16364039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16364039"}]}]}]}
Synonyms	ASC-1, TARBP-B
Proteins	RL3_HUMAN
NCBI Gene ID	6122
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RPL3 has 17,132 functional associations with biological entities spanning 8 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) extracted from 115 datasets.

Click the + buttons to view associations for RPL3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RPL3 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 RPL3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of RPL3 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 RPL3 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 RPL3 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 RPL3 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 RPL3 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 RPL3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of RPL3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RPL3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RPL3 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 RPL3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RPL3 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 RPL3 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 RPL3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RPL3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RPL3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RPL3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RPL3 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 RPL3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing RPL3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RPL3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RPL3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RPL3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RPL3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with RPL3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RPL3 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 RPL3 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 RPL3 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 RPL3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RPL3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for RPL3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RPL3 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 RPL3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RPL3 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 RPL3 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 RPL3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RPL3 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 RPL3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RPL3 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 RPL3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.