SMIM12 (formerly C1orf212) is a 92-amino-acid (about 10.8 kDa) protein of the SMIM12 family (Pfam UPF0767). It has a single predicted transmembrane helix near the N terminus (residues 15-34) followed by a hydrophilic, charge-rich C-terminal tail of about 58 residues. The protein is detected in a high-confidence mass-spectrometry inventory of the human mitochondrial proteome, and antibody immunofluorescence in the Human Protein Atlas also places it in mitochondria. Which mitochondrial membrane it occupies, and its orientation, have not been determined. The transcript is expressed broadly across tissues. No molecular activity, binding partner or biological process has been established for SMIM12; the only reported interactions are unconfirmed yeast two-hybrid hits.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Yeast two-hybrid interaction with PRPF40A isoform 2, a nuclear pre-mRNA splicing factor, from a neurodegeneration-focused interactome screen. Reason: Bare protein binding carries no functional information, and no more informative molecular function can be supported. The hit comes from a single high-throughput yeast two-hybrid screen, has not been confirmed by another method, and pairs a mitochondrial membrane protein with a nuclear splicing factor. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Yeast two-hybrid interaction with LAMP2 isoform B, a lysosomal membrane glycoprotein, from the same screen. Reason: Bare protein binding carries no functional information, and no more informative molecular function can be supported. A single yeast two-hybrid hit between two transmembrane proteins that reside in different organelles (lysosome and mitochondrion) does not indicate a function. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Yeast two-hybrid interaction with SH3GLB1 (endophilin-B1), from the same screen. Reason: Bare protein binding carries no functional information, and no more informative molecular function can be supported. SH3GLB1 can associate with mitochondrial membranes, so this is the most compartment-plausible of the three SMIM12 hits, but it remains a single unconfirmed yeast two-hybrid result with no functional follow-up. Removal does not imply that the reported interaction is false. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: SMIM12 was assigned to the MitoCoP high-confidence human mitochondrial proteome on the basis of quantitative mass spectrometry of mitochondrial preparations. Reason: MitoCoP was built to separate genuine mitochondrial proteins from contaminants, and the assignment is independently supported by Human Protein Atlas antibody immunofluorescence, which gives mitochondria as the main location. This is the only localisation of SMIM12 supported by experimental data and the most specific term available; the sub-mitochondrial compartment is unknown. Supporting Evidence: PMID:34800366 We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). HPA:ENSG00000163866 Main location Mitochondria |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping of the UniProt subcellular location "Membrane; Single-pass membrane protein", which is itself inferred from the predicted transmembrane helix. Reason: Correct but uninformative. A single hydrophobic helix of 20 residues is a reliable indicator of membrane integration; the more specific organelle is captured by the mitochondrion annotation. Supporting Evidence: UniProt:Q96EX1 SUBCELLULAR LOCATION: Membrane |
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Download this section (compressed HTML)Q: Which mitochondrial membrane does SMIM12 occupy, and which side does its charged C-terminal tail face? An N-terminal anchor with a long C-terminal tail would fit an outer-membrane, cytosol-facing protein, but this has not been tested.
Q: Does SMIM12 depletion produce any measurable mitochondrial phenotype (respiration, morphology, protein import), or is it dispensable in cultured cells?
Experiment: Fractionate mitochondria from cells expressing endogenously tagged SMIM12 and test sodium carbonate extraction, protease protection with and without outer-membrane swelling, and super-resolution co-localisation with TOMM20 and inner-membrane markers.
Hypothesis: SMIM12 is an integral protein of the mitochondrial outer membrane with its C-terminal tail in the cytosol.
Experiment: Perform affinity purification-mass spectrometry or proximity labelling from endogenously tagged SMIM12 in a mitochondria-rich cell line, and test whether the candidate partner SH3GLB1 is recovered.
Hypothesis: SMIM12 has stable interaction partners in mitochondria.
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