RPL18A (also known as eL20 in the standardized ribosomal protein nomenclature) encodes a structural component of the 60S large ribosomal subunit. The protein is essential for ribosome assembly and function, contributing to the architecture of the mature 60S subunit that participates in cytoplasmic translation. RPL18A is 176 amino acids in length and is expressed ubiquitously across human tissues. The RPL18A gene co-transcribes with snoRNA U68 from its third intron, coordinating ribosomal protein production with rRNA processing. Cryo-EM structural studies have directly visualized RPL18A within the human 80S ribosome and pre-60S assembly intermediates. Beyond its core ribosomal function, RPL18A has been reported to interact with the Hepatitis C virus IRES element, potentially influencing viral translation. Orthology evidence in C. elegans (rpl-20/eL20) indicates the protein is essential for 60S biogenesis and organismal viability, and a 2023 chemical-proteomics study identified a ROS-sensitive cysteine (C22) in RPL18A, suggesting possible redox-linked modulation of translation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003735 structural constituent of ribosome | IBA GO_REF:0000033 | ACCEPT | Summary: RPL18A (eL20) is a well-characterized structural component of the 60S large ribosomal subunit. Multiple cryo-EM structures (PMID:23636399, PMID:32669547, PMID:25957688, PMID:25901680) have directly resolved RPL18A within the human ribosome. The protein contributes to ribosomal architecture by binding rRNA and neighboring ribosomal proteins. This IBA annotation is strongly supported by phylogenetic inference across eukaryotes and is consistent with direct structural evidence. Reason: Core ribosomal function supported by multiple high-resolution cryo-EM structures directly visualizing RPL18A in the human ribosome. IBA annotation is appropriate and represents the primary molecular function of this protein. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps PMID:32669547 Here we present four structures of human pre-60S particles isolated through a nuclear export factor NMD3, representing assembly stages immediately before and after nuclear export file:human/RPL18A/RPL18A-deep-research-falcon.md RPL18A/eL20 is a ribosomal protein of the **cytosolic 60S large ribosomal subunit**. Ribosomal proteins stabilize rRNA structure, contribute to assembly, and support translation by forming part of the ribosomeβs structural framework. |
| GO:0022625 cytosolic large ribosomal subunit | IBA GO_REF:0000033 | ACCEPT | Summary: RPL18A is a bona fide component of the cytosolic large ribosomal subunit (60S). This is supported by multiple structural studies that directly visualize RPL18A as an integral part of the 60S subunit (PMID:23636399, PMID:32669547, PMID:25901680). UniProt also confirms this localization based on structural evidence. Reason: Core cellular component annotation representing the primary localization of RPL18A. Directly supported by cryo-EM structural evidence showing RPL18A within the 60S subunit. Supporting Evidence: PMID:32669547 Here we report the cryo-EM structures of human pre-60S particles in four sequential assembly states, which provide numerous details for the general principles and human-specific mechanisms of ribosome assembly in stages immediately before and after nuclear export file:human/RPL18A/RPL18A-deep-research-falcon.md - **Predominantly cytoplasmic localization as part of mature 60S/80S ribosomes engaged in translation**. |
| GO:0002181 cytoplasmic translation | IBA GO_REF:0000033 | ACCEPT | Summary: As a component of the 60S ribosomal subunit, RPL18A is directly involved in cytoplasmic translation. The ribosome is the macromolecular machine that catalyzes protein synthesis, and RPL18A contributes to the structural integrity required for this process (PMID:25957688). Reason: Core biological process annotation. RPL18A is essential for ribosome function, and cytoplasmic translation is the primary process in which the ribosome operates. Orthology evidence (C. elegans rpl-20) reinforces essentiality: a missense substitution reduces 60S biogenesis and 80S ribosomes, and a full deletion is early larval lethal (file:human/RPL18A/RPL18A-deep-research-falcon.md). Supporting Evidence: PMID:25957688 The ribosome is an archetypical molecular machine, synthesizing proteins based on the primary sequence information encoded in messenger RNA (mRNA) templates file:human/RPL18A/RPL18A-deep-research-falcon.md an amino-acid substitution in this protein is associated with **reduced biogenesis of the 60S subunit**, leading to **reduced 80S ribosomes**. The same paper reports that a deletion allele removing the coding region is **homozygous early larval lethal**, supporting an essential role for the eL20 family protein in organismal viability consistent with fundamental ribosome function. |
| GO:0003735 structural constituent of ribosome | IEA GO_REF:0000120 | ACCEPT | Summary: This IEA annotation is a broader electronic annotation that captures the same core function as the IBA annotation. RPL18A is indeed a structural constituent of the ribosome as confirmed by multiple structural studies. Reason: Correct annotation consistent with the core molecular function. While duplicative with the IBA annotation, IEA annotations provide independent computational support. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: RPL18A is localized to the cytoplasm as part of mature 80S ribosomes. This general localization is correct though more specific terms (cytosolic large ribosomal subunit) better capture its precise localization. Reason: Correct but general annotation. Cytoplasm is an accurate broader localization for a cytosolic ribosomal protein. |
| GO:0005840 ribosome | IEA GO_REF:0000120 | ACCEPT | Summary: RPL18A is a component of the ribosome. This is a general term that is correct though less specific than cytosolic large ribosomal subunit (GO:0022625). Reason: Correct general annotation. While more specific terms exist, this IEA provides accurate broader classification. |
| GO:0006412 translation | IEA GO_REF:0000002 | ACCEPT | Summary: RPL18A participates in translation as a structural component of the ribosome. This general term is correct, though cytoplasmic translation (GO:0002181) is more specific and appropriate for a cytosolic ribosomal protein. Reason: Correct general annotation capturing the biological process in which the ribosome functions. |
| GO:1990904 ribonucleoprotein complex | IEA GO_REF:0000043 | ACCEPT | Summary: The ribosome is a ribonucleoprotein complex containing both rRNA and ribosomal proteins. RPL18A as a ribosomal protein is correctly annotated to this term. However, this is a very general term; the more specific term cytosolic large ribosomal subunit is preferred. Reason: Correct but very general annotation. The ribosome is indeed a ribonucleoprotein complex. |
| GO:0005515 protein binding | IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by... | MARK AS OVER ANNOTATED | Summary: This annotation derives from a large-scale proteomics study mapping protein-protein interactions. While RPL18A does interact with many proteins (primarily other ribosomal proteins), the term protein binding is uninformative for a ribosomal protein whose primary function involves binding both rRNA and other ribosomal proteins as part of its structural role. Reason: Protein binding is too general and uninformative. As a ribosomal protein, RPL18A inherently binds other ribosomal proteins; the more informative annotation is structural constituent of ribosome. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: This annotation derives from a high-throughput interactome study. The protein binding term is uninformative for RPL18A, which functions as a structural component of the ribosome and necessarily interacts with other ribosomal proteins. Reason: Protein binding is too general. Ribosomal proteins inherently bind other proteins as part of ribosome assembly; structural constituent of ribosome is more informative. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | MARK AS OVER ANNOTATED | Summary: This annotation from a crosslinking mass spectrometry study detected RPL18A interacting with histones. While interesting, protein binding is too general to be informative. The interaction may reflect ribosome-chromatin proximity during translation of histone mRNAs or other indirect associations. Reason: Protein binding is uninformative. The specific interaction context (histone binding) would require more specific annotation if biologically meaningful. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: This annotation from a proteome-scale interactome study. Protein binding is uninformative for a ribosomal protein that inherently interacts with many other proteins as part of ribosome assembly and function. Reason: Protein binding is too general and uninformative for a ribosomal protein. |
| GO:0002181 cytoplasmic translation | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for cytoplasmic translation based on ortholog transfer. This is consistent with the core function of RPL18A as a ribosomal protein. Reason: Correct core biological process annotation for a cytosolic ribosomal protein. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This annotation suggests RPL18A localizes to the postsynaptic density. While ribosomes are known to be present in neuronal dendrites and postsynaptic compartments for local protein synthesis, this is a specialized localization rather than a core function of RPL18A. The annotation likely reflects presence of ribosomes at this site rather than a specific role for RPL18A. Reason: Ribosomes are present at postsynaptic densities for local translation, but this is not a core localization - it is a tissue/cell-type specific context. |
| GO:0022625 cytosolic large ribosomal subunit | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for cytosolic large ribosomal subunit localization. This is the core cellular component for RPL18A. Reason: Correct core cellular component annotation, consistent with structural evidence. |
| GO:0002181 cytoplasmic translation | ISO GO_REF:0000114 | ACCEPT | Summary: ISO annotation based on sequence orthology for cytoplasmic translation. Consistent with the core function of cytosolic ribosomal proteins. Reason: Correct core biological process annotation. |
| GO:0002181 cytoplasmic translation | NAS PMID:25901680 Structure of the human 80S ribosome. | ACCEPT | Summary: NAS annotation based on the human 80S ribosome structure paper. The structure shows RPL18A as part of the functional ribosome, supporting its role in translation. Reason: Core biological process annotation supported by structural evidence showing RPL18A in the context of translating ribosomes. |
| GO:0005737 cytoplasm | ISO GO_REF:0000114 | ACCEPT | Summary: ISO annotation for cytoplasm localization based on sequence orthology. Correct general localization for a cytosolic ribosomal protein. Reason: Correct general cellular component annotation. |
| GO:0005737 cytoplasm | NAS PMID:25901680 Structure of the human 80S ribosome. | ACCEPT | Summary: NAS annotation for cytoplasm localization based on the human ribosome structure. The 80S ribosome is a cytoplasmic complex. Reason: Correct general localization supported by structural context. |
| GO:0006941 striated muscle contraction | NAS PMID:34081545 Knockdown of Muscle-Specific Ribosomal Protein L3-Like Enhan... | REMOVE | Summary: This annotation appears to be based on a study of RPL3L (muscle-specific ribosomal protein L3-like), not RPL18A directly. The cited paper investigates RPL3L knockdown effects on muscle function. RPL18A may be part of muscle ribosomes but does not have a specific role in muscle contraction distinct from its general ribosomal function. Reason: This annotation appears to be incorrectly transferred. The cited study is about RPL3L, not RPL18A. Striated muscle contraction is not a core function of a general ribosomal protein. |
| GO:0007283 spermatogenesis | NAS PMID:36517592 A male germ-cell-specific ribosome controls male fertility. | MARK AS OVER ANNOTATED | Summary: This annotation references a study about male germ-cell-specific ribosomes. While RPL18A is present in ribosomes including those in germ cells, this does not constitute a specific role in spermatogenesis beyond general protein synthesis. The annotation may reflect specialized ribosome composition in germ cells but does not indicate a specific role for RPL18A in spermatogenesis. Reason: RPL18A participates in translation in all cells including germ cells, but this does not constitute a specific involvement in spermatogenesis beyond general housekeeping function. |
| GO:0022625 cytosolic large ribosomal subunit | ISO GO_REF:0000114 | ACCEPT | Summary: ISO annotation for cytosolic large ribosomal subunit based on sequence orthology. This is the core cellular component for RPL18A. Reason: Core cellular component annotation consistent with RPL18A function. |
| GO:0022625 cytosolic large ribosomal subunit | IPI PMID:25901680 Structure of the human 80S ribosome. | ACCEPT | Summary: IPI annotation based on the human 80S ribosome structure which directly shows RPL18A as a component of the large ribosomal subunit at near-atomic resolution. Reason: Core cellular component annotation with direct structural evidence from cryo-EM. |
| GO:1901740 negative regulation of myoblast fusion | NAS PMID:26684695 Expression of Muscle-Specific Ribosomal Protein L3-Like Impa... | REMOVE | Summary: This annotation appears to be based on a study of RPL3L (muscle-specific ribosomal protein L3-like), not RPL18A. The cited paper title mentions RPL3L affecting myotube growth. This annotation is likely incorrectly associated with RPL18A. Reason: This annotation appears to be incorrectly transferred. The cited study is about RPL3L, not RPL18A. There is no evidence that RPL18A specifically regulates myoblast fusion. |
| GO:0022626 cytosolic ribosome | IDA PMID:23636399 Structures of the human and Drosophila 80S ribosome. | ACCEPT | Summary: IDA annotation based on cryo-EM structure of the human 80S ribosome. This directly demonstrates RPL18A as a component of the cytosolic ribosome. The term cytosolic ribosome (80S) is appropriate as RPL18A is part of the large subunit which assembles with the small subunit to form the complete ribosome. Reason: Core cellular component annotation with direct experimental structural evidence from high-resolution cryo-EM. |
| GO:0003735 structural constituent of ribosome | IDA PMID:32669547 Structural snapshots of human pre-60S ribosomal particles be... | ACCEPT | Summary: IDA annotation based on cryo-EM structures of human pre-60S ribosomal particles. The study directly visualizes RPL18A within the pre-60S assembly intermediates, demonstrating its structural role in ribosome biogenesis and function. Reason: Core molecular function annotation with direct experimental structural evidence from multiple cryo-EM states of pre-60S particles. Supporting Evidence: PMID:32669547 Here we present four structures of human pre-60S particles isolated through a nuclear export factor NMD3, representing assembly stages immediately before and after nuclear export |
| GO:0022625 cytosolic large ribosomal subunit | IDA PMID:32669547 Structural snapshots of human pre-60S ribosomal particles be... | ACCEPT | Summary: IDA annotation based on cryo-EM structures of human pre-60S particles. RPL18A is directly visualized as a component of the large ribosomal subunit during assembly and after nuclear export. Reason: Core cellular component annotation with direct structural evidence from cryo-EM showing RPL18A in the 60S subunit. Supporting Evidence: PMID:32669547 Here we report the cryo-EM structures of human pre-60S particles in four sequential assembly states, which provide numerous details for the general principles and human-specific mechanisms of ribosome assembly in stages immediately before and after nuclear export |
| GO:0002181 cytoplasmic translation | IC PMID:23636399 Structures of the human and Drosophila 80S ribosome. | ACCEPT | Summary: IC annotation inferring cytoplasmic translation from the structural role of RPL18A in the ribosome. This is a reasonable inference since the ribosome carries out translation. Reason: Correct inference from structural evidence. As a ribosomal protein, RPL18A participates in cytoplasmic translation. |
| GO:0003735 structural constituent of ribosome | IDA PMID:23636399 Structures of the human and Drosophila 80S ribosome. | ACCEPT | Summary: IDA annotation based on the cryo-EM structure of the human 80S ribosome at near-atomic resolution, which directly demonstrates RPL18A as an integral structural component of the ribosome. Reason: Core molecular function annotation with direct experimental evidence from high-resolution cryo-EM structure of the human ribosome. Supporting Evidence: PMID:23636399 Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps |
| GO:0002181 cytoplasmic translation | IDA PMID:25957688 Structural snapshots of actively translating human ribosomes... | ACCEPT | Summary: IDA annotation based on cryo-EM structures of actively translating human ribosomes derived from polysomes. This study directly visualizes translation intermediates, demonstrating RPL18A function in active translation. Reason: Core biological process annotation with direct experimental evidence from structures of actively translating ribosomes. Supporting Evidence: PMID:25957688 The ribosome is an archetypical molecular machine, synthesizing proteins based on the primary sequence information encoded in messenger RNA (mRNA) templates |
| GO:0022625 cytosolic large ribosomal subunit | IDA PMID:25957688 Structural snapshots of actively translating human ribosomes... | ACCEPT | Summary: IDA annotation based on cryo-EM structures of actively translating human ribosomes. RPL18A is directly visualized as part of the large ribosomal subunit in functional translation complexes. Reason: Core cellular component annotation with direct structural evidence from actively translating ribosome complexes. |
| GO:0005515 protein binding | IPI PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... | MARK AS OVER ANNOTATED | Summary: This annotation derives from a study of pestivirus Npro protease interactions with host ribonucleoprotein complex components. While interesting for viral biology, protein binding is uninformative for a ribosomal protein. Reason: Protein binding is too general and uninformative for a ribosomal protein. The viral interaction context is specialized but does not warrant this generic term. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: This HDA annotation from a membrane proteome study likely reflects ribosomes associated with the endoplasmic reticulum membrane during translation of secretory/membrane proteins. RPL18A is not a membrane protein itself but may be detected in membrane fractions due to ER-associated ribosomes. Reason: Not a core localization. RPL18A is a cytosolic ribosomal protein that may associate with ER membranes when ribosomes are translating membrane-targeted proteins. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: HDA annotation from an atlas of mRNA-binding proteins. As a ribosomal protein, RPL18A binds rRNA and is part of the ribosome that interacts with mRNA during translation. RNA binding is an inherent property of ribosomal proteins. Reason: Correct annotation. RPL18A binds rRNA as part of its structural function in the ribosome. RNA binding is intrinsic to ribosomal protein function. The falcon deep research additionally documents that eL20/RPL18A can interact with structured viral RNA (HCV IRES), consistent with an RNA-binding capacity. Supporting Evidence: file:human/RPL18A/RPL18A-deep-research-falcon.md eL20 (RPL18A)** can **interact with hepatitis C virus (HCV) IRES RNA** and that adding eL20 protein to **in vitro translation extracts** **moderately stimulated HCV IRES activity**. This supports a capacity for RPL18A/eL20 to contribute to specialized modes of translation initiation involving structured RNAs, beyond a purely passive structural role. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: HDA annotation from mRNA-bound proteome analysis. RPL18A was detected bound to mRNA transcripts, consistent with its role as a ribosomal protein engaged in translation. Reason: Correct annotation. Ribosomal proteins bind RNA as part of their function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-156826 | ACCEPT | Summary: TAS annotation from Reactome pathway for L13a-mediated translational silencing. Cytosol is the correct localization for cytosolic ribosomal proteins. Reason: Correct general cellular component annotation consistent with cytosolic ribosome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1799332 | ACCEPT | Summary: TAS annotation from Reactome SRP-dependent cotranslational targeting pathway. Cytosol is correct for the ribosome during translation. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1799335 | ACCEPT | Summary: TAS annotation from Reactome for nascent polypeptide synthesis. Cytosol is correct for cytosolic ribosomes. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-192704 | ACCEPT | Summary: TAS annotation from Reactome viral protein synthesis pathway. Cytosol is the correct location. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-192841 | ACCEPT | Summary: TAS annotation from Reactome viral mRNA translation pathway. Reason: Correct general localization for cytosolic ribosome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6791218 | ACCEPT | Summary: TAS annotation from Reactome rRNA processing pathway. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72671 | ACCEPT | Summary: TAS annotation from Reactome translation initiation pathway (eIF5B hydrolysis). Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72672 | ACCEPT | Summary: TAS annotation from Reactome for 60S subunit joining during translation initiation. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72673 | ACCEPT | Summary: TAS annotation from Reactome for ribosomal subunit release. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927789 | ACCEPT | Summary: TAS annotation from Reactome nonsense-mediated decay pathway. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927813 | ACCEPT | Summary: TAS annotation from Reactome NMD pathway (UPF1 recruitment). Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927832 | ACCEPT | Summary: TAS annotation from Reactome NMD pathway. Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927836 | ACCEPT | Summary: TAS annotation from Reactome NMD pathway (SMG6 mRNA hydrolysis). Reason: Correct general localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927889 | ACCEPT | Summary: TAS annotation from Reactome NMD pathway (SMG1 phosphorylation). Reason: Correct general localization. |
| GO:0003735 structural constituent of ribosome | NAS PMID:12962325 Characterization and analysis of posttranslational modificat... | ACCEPT | Summary: NAS annotation based on mass spectrometry characterization of human large ribosomal subunit proteins. The study identified RPL18A as one of the 60S subunit proteins, confirming its structural role. Reason: Core molecular function annotation supported by mass spectrometry identification of RPL18A in the human 60S ribosomal subunit. |
| GO:0006412 translation | NAS PMID:12962325 Characterization and analysis of posttranslational modificat... | ACCEPT | Summary: NAS annotation for translation based on RPL18A identification as a ribosomal protein. As a component of the translation machinery, RPL18A participates in translation. Reason: Correct general biological process annotation for a ribosomal protein. |
| GO:0022625 cytosolic large ribosomal subunit | HDA PMID:12962325 Characterization and analysis of posttranslational modificat... | ACCEPT | Summary: HDA annotation based on mass spectrometry identification of RPL18A in the human large ribosomal subunit fraction from placenta. Reason: Core cellular component annotation supported by proteomic identification. |
| GO:0003723 RNA binding | TAS PMID:9582194 A map of 75 human ribosomal protein genes. | ACCEPT | Summary: TAS annotation for RNA binding based on the mapping of human ribosomal protein genes. Ribosomal proteins inherently bind RNA as part of ribosome structure. Reason: Correct molecular function annotation. Ribosomal proteins bind rRNA. |
| GO:0003735 structural constituent of ribosome | TAS PMID:9582194 A map of 75 human ribosomal protein genes. | ACCEPT | Summary: TAS annotation for structural constituent of ribosome based on the genomic mapping study that identified RPL18A as a ribosomal protein gene. Reason: Core molecular function annotation. |
| GO:0006412 translation | TAS PMID:9582194 A map of 75 human ribosomal protein genes. | ACCEPT | Summary: TAS annotation for translation based on identification of RPL18A as a ribosomal protein gene. Reason: Correct general biological process annotation. |
| GO:0022625 cytosolic large ribosomal subunit | TAS PMID:9582194 A map of 75 human ribosomal protein genes. | ACCEPT | Summary: TAS annotation for cytosolic large ribosomal subunit based on identification of RPL18A as a large subunit ribosomal protein gene (the L designation indicates large subunit). Reason: Core cellular component annotation. |
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