MRPS22 encodes mitochondrial ribosomal protein mS22, a mitochondrion-specific protein (no bacterial ribosomal homolog) of the 28S small subunit of the 55S mitochondrial ribosome. The mitoribosome translates the 13 mtDNA-encoded subunits of the oxidative phosphorylation complexes, and mS22 is a structural component of the small subunit; its loss lowers 12S mt-rRNA, the RNA core of that subunit. Biallelic MRPS22 variants cause combined oxidative phosphorylation deficiency 5, an antenatal-onset disorder with oedema, hypertrophic cardiomyopathy, tubulopathy and hypotonia, in which patient fibroblasts show reduced 12S rRNA and multiple respiratory chain deficiency rescued by wild-type MRPS22. Other homozygous missense variants cause isolated primary ovarian insufficiency (ovarian dysgenesis 7) with no detectable fibroblast defect; the Drosophila ortholog mRpS22 is required cell-autonomously in female germ cells, and complete Mrps22 loss in mouse is embryonic lethal.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003735 structural constituent of ribosome | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference that mS22 family members are structural constituents of the mitoribosome. Reason: Core molecular function. mS22 is a protein of the human 28S small subunit (cryo-EM structure; UniProt SUBUNIT), and patient MRPS22 deficiency reduces 12S rRNA, the core of the small subunit, which is restored by wild-type cDNA. The PTN node covers the metazoan mS22 family, which lacks bacterial homologs. Supporting Evidence: PMID:25838379 It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules file:human/MRPS22/MRPS22-uniprot.txt Component of the mitochondrial small ribosomal subunit (mt-SSU) PMID:17873122 Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts |
| GO:0003735 structural constituent of ribosome | IDA PMID:10938081 A proteomics approach to the identification of mammalian mit... | ACCEPT | Summary: Koc et al. 2000 identified MRPS22 by mass spectrometry of proteins resolved from purified mammalian 28S mitoribosomal small subunits. Reason: Identification as a purified small-subunit protein, later confirmed by the cryo-EM structure, supports the structural-constituent annotation. Core function. Supporting Evidence: PMID:10938081 Mammalian mitochondrial small subunit ribosomal proteins were separated by two-dimensional polyacrylamide gel electrophoresis PMID:25838379 It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: High-throughput interaction screens report binding to MRPS18B (Q9Y676), another protein of the 28S small subunit. Reason: Generic protein binding is uninformative. The partner, MRPS18B, is a fellow small-subunit protein, so the interaction reflects co-membership of the mitoribosome, already captured by mitochondrial small ribosomal subunit (GO:0005763) and structural constituent of ribosome (GO:0003735). Removal does not dispute the interaction. Supporting Evidence: file:human/MRPS22/MRPS22-uniprot.txt P82650; Q9Y676: MRPS18B; NbExp=5 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interaction screens report binding to MRPS18B (Q9Y676), another protein of the 28S small subunit. Reason: Generic protein binding is uninformative. The partner, MRPS18B, is a fellow small-subunit protein, so the interaction reflects co-membership of the mitoribosome, already captured by mitochondrial small ribosomal subunit (GO:0005763) and structural constituent of ribosome (GO:0003735). Removal does not dispute the interaction. Supporting Evidence: file:human/MRPS22/MRPS22-uniprot.txt P82650; Q9Y676: MRPS18B; NbExp=5 |
| GO:0005739 mitochondrion | EXP PMID:25838379 Ribosome. The structure of the human mitochondrial ribosome. | ACCEPT | Summary: mS22 resolved as part of the human mitoribosome by cryo-EM. Reason: Correct; the mitoribosome is a matrix particle. Supporting Evidence: PMID:25838379 The highly divergent ribosomes of human mitochondria (mitoribosomes) synthesize 13 essential proteins of oxidative phosphorylation complexes |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Detected in the high-confidence human mitochondrial proteome (MitoCoP). Reason: Consistent with structural and genetic data. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence localizes MRPS22 to mitochondria. Reason: Consistent with mitoribosome membership. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to mitochondrion. Reason: Correct. |
| GO:0005743 mitochondrial inner membrane | NAS PMID:27023846 Structure and Function of the Mitochondrial Ribosome. | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419261 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419264 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419271 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419273 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419277 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419281 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937394 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937412 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937415 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937719 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937724 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events and a mitoribosome review. Reason: The mammalian mitoribosome is peripherally tethered to the matrix face of the inner membrane (through large-subunit contacts) for co-translational insertion of its hydrophobic products. mS22 is a small-subunit protein of the matrix-exposed particle, not a membrane protein, so its primary location is the mitochondrial small ribosomal subunit. Kept as non-core, reflecting whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005761 mitochondrial ribosome | NAS PMID:10938081 A proteomics approach to the identification of mammalian mit... | ACCEPT | Summary: Koc et al. 2000 describe MRPS22 as a mitochondrial ribosomal protein. Reason: Correct but less specific than mitochondrial small ribosomal subunit (GO:0005763), which is also annotated. Note that the qualifier here is located_in rather than part_of; the claim is still true. Supporting Evidence: PMID:10938081 Mammalian mitochondrial small subunit ribosomal proteins from six different classes of ribosomal proteins were identified |
| GO:0005763 mitochondrial small ribosomal subunit | IBA GO_REF:0000033 | ACCEPT | Summary: MRPS22 (mS22) is a component of the mitochondrial small (28S) ribosomal subunit. Reason: Core cellular component, supported by isolation from purified small subunits, the cryo-EM structure of the human mitoribosome, and the loss of 12S rRNA (the small-subunit core) in patient cells. Supporting Evidence: PMID:25838379 It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules file:human/MRPS22/MRPS22-uniprot.txt Component of the mitochondrial small ribosomal subunit (mt-SSU) PMID:17873122 Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts |
| GO:0005763 mitochondrial small ribosomal subunit | IDA PMID:10938081 A proteomics approach to the identification of mammalian mit... | ACCEPT | Summary: MRPS22 (mS22) is a component of the mitochondrial small (28S) ribosomal subunit. Reason: Core cellular component, supported by isolation from purified small subunits, the cryo-EM structure of the human mitoribosome, and the loss of 12S rRNA (the small-subunit core) in patient cells. Supporting Evidence: PMID:25838379 It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules file:human/MRPS22/MRPS22-uniprot.txt Component of the mitochondrial small ribosomal subunit (mt-SSU) PMID:17873122 Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts |
| GO:0005763 mitochondrial small ribosomal subunit | NAS PMID:25838379 Ribosome. The structure of the human mitochondrial ribosome. | ACCEPT | Summary: MRPS22 (mS22) is a component of the mitochondrial small (28S) ribosomal subunit. Reason: Core cellular component, supported by isolation from purified small subunits, the cryo-EM structure of the human mitoribosome, and the loss of 12S rRNA (the small-subunit core) in patient cells. Supporting Evidence: PMID:25838379 It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules file:human/MRPS22/MRPS22-uniprot.txt Component of the mitochondrial small ribosomal subunit (mt-SSU) PMID:17873122 Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts |
| GO:0032543 mitochondrial translation | NAS PMID:27023846 Structure and Function of the Mitochondrial Ribosome. | ACCEPT | Summary: MRPS22 participates in mitochondrial translation as a small-subunit mitoribosomal protein. Reason: Core process. Patient MRPS22 deficiency causes multiple respiratory chain complex deficiency with reduced 12S rRNA, normalised by wild-type MRPS22 cDNA, the expected signature of a mitochondrial translation defect. Supporting Evidence: PMID:17873122 Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts PMID:17873122 Transfection of the patient cells with wild-type MRPS22 cDNA increased the 12s rRNA content and normalised the enzymatic activities PMID:21189481 Analysis of mitochondrial protein synthesis revealed a marked impairment in mitochondrial translation PMID:21189481 Transfection of patient fibroblasts, in which MRPS22 was undetectable, with the wild-type MRPS22 cDNA restored the amount and activity of OXPHOS complex IV, as well as the 12S rRNA transcript level to normal values |
Loading supporting content…
Download this section (compressed HTML)Q: Why do the ODG7 missense variants (p.R135Q, p.R202H) cause isolated ovarian insufficiency with no detectable fibroblast rRNA or OXPHOS defect, whereas the COXPD5 variant abolishes 12S rRNA accumulation? Do the POI variants impair mS22 only in a germline-specific context?
Q: At what stage of 28S subunit assembly is mS22 incorporated, and which neighbouring small-subunit proteins depend on it?
Experiment: Mitoribosome assembly profiling (sucrose gradients with quantitative proteomics) in MRPS22-knockout cells complemented with wild-type, COXPD5 and ODG7 variants, to test whether the POI variants are hypomorphic for small-subunit assembly.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)