RPL36AL encodes a 106-residue, highly basic eL42-family protein that is an integral component of the cytosolic 60S large ribosomal subunit. The gene is an intronless autosomal retrocopy of the X-linked RPL36A gene and is ubiquitously expressed. RPL36AL and RPL36A encode nearly identical proteins, differing only at residue 38 (arginine in RPL36AL and lysine in RPL36A). Within the human 80S ribosome, RPL36AL occupies the large-subunit E-site region and contacts the CCA end of deacylated tRNA in the P/E hybrid state; recombinant RPL36AL also binds tRNA with nanomolar affinity. These contacts couple its structural role in the large subunit to tRNA positioning during cytoplasmic translation. A specialized translational program unique to RPL36AL rather than RPL36A has not been established.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002181 cytoplasmic translation | IBA GO_REF:0000033 | ACCEPT | Summary: RPL36AL is an eL42-family component of the cytosolic 60S subunit. Direct work on human ribosomes places RPL36AL at the E-site in contact with P/E-state tRNA, supporting its participation in cytoplasmic translation. Reason: This is the core biological process for a cytosolic large-subunit ribosomal protein. The phylogenetic inference is consistent with RPL36AL-specific biochemical evidence and the reviewed UniProt family and complex assignments. Supporting Evidence: PMID:25191528 We have demonstrated previously that the E-site specific protein RPL36AL present in human ribosomes can be crosslinked with the CCA-end of a P-tRNA in situ. |
| GO:0003735 structural constituent of ribosome | IBA GO_REF:0000033 | ACCEPT | Summary: RPL36AL is a small, highly basic eL42-family protein incorporated into the human cytosolic large ribosomal subunit, where it contacts tRNA at the subunit E-site. Reason: ComplexPortal, UniProt family assignment, phylogenetic inference, and RPL36AL-specific crosslinking in human 80S ribosomes converge on a bona fide structural role in the ribosome. Supporting Evidence: PMID:22865768 the RPL36AL protein of the large subunit of mammalian ribosomes |
| GO:0022625 cytosolic large ribosomal subunit | IBA GO_REF:0000033 | ACCEPT | Summary: RPL36AL is an eL42-family constituent of the human cytosolic 60S large ribosomal subunit. Its E-site position and contact with P/E-state tRNA have been demonstrated biochemically. Reason: This specific complex term captures RPL36AL's primary cellular location and is supported independently by phylogeny, reviewed database records, and RPL36AL-directed biochemical studies. Supporting Evidence: PMID:25191528 the E-site specific protein RPL36AL present in human ribosomes |
| GO:0003735 structural constituent of ribosome | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro assigns RPL36AL to the conserved eukaryotic eL42/L44e ribosomal protein family, matching the experimentally supported structural role. Reason: The electronic domain-to-GO mapping is correct and agrees with the independent IBA annotation and direct biochemical evidence. The duplicate term is retained because it represents a separate evidence route. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: RPL36AL functions in the cytoplasm as a constituent of cytosolic 60S and 80S ribosomes. Reason: Cytoplasm is a correct broad localization, although cytosolic large ribosomal subunit is the more informative functional location. |
| GO:0005840 ribosome | IEA GO_REF:0000002 | ACCEPT | Summary: The eL42/L44e family assignment and direct human-ribosome studies establish that RPL36AL is a ribosomal protein. Reason: This broad component term is correct and consistent with the more specific cytosolic large ribosomal subunit annotation. |
| GO:0006412 translation | IEA GO_REF:0000002 | ACCEPT | Summary: RPL36AL participates in translation as an eL42-family constituent of the cytosolic large ribosomal subunit and contacts deacylated tRNA at the ribosomal E-site. Reason: Translation is a correct broad process annotation. The IBA term cytoplasmic translation provides the more specific process assignment. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: A proteome-scale binary-interaction screen recorded an interaction between RPL36AL and KRTAP10-7. The interaction record can be retained, but generic protein binding does not describe RPL36AL's ribosomal molecular function. Reason: The high-throughput assay supports a physical interaction under screening conditions, not a defined partner-specific biochemical activity. GO:0005515 is uninformative compared with the established structural and tRNA-binding activities of RPL36AL. Supporting Evidence: PMID:25416956 a systematic map of ?14,000 high-quality human binary protein-protein interactions |
| GO:0005634 nucleus | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | UNDECIDED | Summary: The source study localized GFP-tagged candidates from an E-cadherin proximity-proteomics screen, and the GOA record assigns RPL36AL to the nucleus. The accessible narrative does not identify RPL36AL by name; the candidate-specific call is confined to a supplementary table that could not be inspected in this review. Reason: Nuclear transit is biologically plausible for a ribosomal protein, and the experimental curator may have had access to the candidate-level imaging result. Because the RPL36AL-specific evidence cannot be verified from the accessible article text, this experimental annotation is neither rejected nor promoted to a core location. |
| GO:0000049 tRNA binding | IDA PMID:25191528 The CCA-end of P-tRNA Contacts Both the Human RPL36AL and th... | NEW | Summary: Purified recombinant human RPL36AL bound full-length and truncated tRNAs with nanomolar affinity, while poly(A) and poly(U) controls did not bind. RPL36AL also crosslinked to the CCA end of P/E-state tRNA in human 80S ribosomes. Reason: GO:0000049 directly captures a demonstrated RPL36AL molecular activity that is absent from the fetched GOA set. The assignment is gene-product-specific: PMID:25191528 used a recombinant RPL36AL construct and endogenous human ribosomes, and PMID:22865768 independently mapped the contact to RPL36AL Lys53. Supporting Evidence: PMID:25191528 The KD values in the nanomolar range reflect high tRNA-binding affinities with full length and truncated tRNA species. PMID:22865768 the crosslink was formed most efficiently with C74 and C75 of P/E-tRNA, but could also connect the ultimate A of this tRNA with Lys53 of protein RPL36AL file:human/RPL36AL/RPL36AL-deep-research-manual.md RPL36AL is a ubiquitously expressed autosomal eL42 paralog whose directly demonstrated molecular activity is tRNA binding within the cytosolic 60S ribosomal subunit. |
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Download this section (compressed HTML)Q: What fraction of human cytosolic ribosomes contains RPL36AL rather than RPL36A in each tissue and cell state, and are mixed populations functionally distinguishable?
Q: Does the sole K38R difference between RPL36A and RPL36AL alter assembly, post-translational modification, tRNA dynamics, or translational selectivity?
Q: Does endogenous RPL36AL accumulate in the nucleus as a reproducible ribosome biogenesis intermediate, or was the published nuclear call specific to the GFP-tagged localization assay?
Experiment: Develop paralog-specific targeted mass spectrometry around the residue-38 peptide and endogenous epitope-tagged cell lines, then quantify RPL36AL and RPL36A in purified 60S, 80S, and polysome fractions across representative tissues and stress conditions.
Hypothesis: RPL36AL and RPL36A are both incorporated into human 60S subunits, but their relative occupancy varies by tissue without creating major ribosome specialization.
Experiment: Create RPL36AL and RPL36A single and double acute-depletion backgrounds and perform reciprocal rescue with wild-type proteins and K38R/R38K swap variants. Measure ribosome assembly, polysome profiles, global translation, fidelity, E-site tRNA release, and ribosome profiling in matched expression conditions.
Hypothesis: The K38R difference is dispensable for basal translation but may tune local eL42 interactions or post-translational regulation.
Experiment: Use paralog-specific endogenous tagging, live-cell imaging, nucleolar markers, and pulse-chase ribosome-assembly assays. Compare untagged antibody staining and C-terminal GFP fusions to detect tag-dependent localization artifacts.
Hypothesis: Nuclear RPL36AL represents transient import and 60S assembly rather than a separate nuclear function.
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