SMIM8 (formerly C6orf162) is a 97-amino-acid protein with a disordered, charged N-terminal region (residues 1-24) and a single predicted helical transmembrane segment (residues 48-70). It belongs to the SMIM8 family (Pfam PF14937, DUF4500), which has no characterized members. Quantitative proteomics of purified human mitochondria places SMIM8 in the high-confidence mitochondrial proteome; which mitochondrial membrane it occupies and its orientation are not known. Human SMIM8 mRNA is broadly expressed, whereas the mouse gene is predominantly testicular. Mice lacking Smim8 are viable and the males are fertile. In human skeletal muscle transcriptome studies, SMIM8 mRNA levels correlate positively with improvement in insulin sensitivity. No molecular function or biological process has been demonstrated.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput localization from MitoCoP, a quantitative proteomic definition of the human mitochondrial proteome, in which SMIM8 is classified as a high-confidence mitochondrial protein. Reason: This is the only experimental localization for SMIM8, and the MitoCoP classification is based on quantitative enrichment in purified mitochondria rather than mere detection. It is consistent with SMIM8 having a single transmembrane helix. The sub-mitochondrial compartment is unknown, so the general term is appropriate. Supporting Evidence: PMID:34800366 We defined a human mitochondrial high-confidence proteome (MitoCoP) of 1,134 protein-coding genes, including 91 proteins previously not localized to mitochondria experimentally. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to membrane, based on the single predicted helical transmembrane segment (residues 48-70). Reason: Correct but general. Together with the mitochondrion annotation this implies a mitochondrial membrane, but which one (outer or inner) has not been determined, so a more specific term cannot be assigned. Supporting Evidence: file:human/SMIM8/SMIM8-uniprot.txt SUBCELLULAR LOCATION: Membrane PMID:34290169 Smim8 and Smim9 each containing one transmembrane domain |
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Download this section (compressed HTML)Q: Is SMIM8 in the outer or the inner mitochondrial membrane, and which way does its charged N-terminal region face?
Q: Does the co-variation of SMIM8 mRNA with mitochondrial catabolic enzymes and with insulin sensitivity reflect a role in mitochondrial metabolism, or only co-regulation with mitochondrial biogenesis?
Experiment: Determine sub-mitochondrial localization and topology by protease protection of intact mitochondria and mitoplasts, carbonate extraction, and super-resolution imaging of tagged SMIM8 against outer- and inner-membrane markers; then look for respiratory or metabolic phenotypes in SMIM8-knockout cells.
Hypothesis: SMIM8 is an integral protein of a specific mitochondrial membrane.
Type: subcellular fractionation and protease protection
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