SMIM5 (formerly C17orf109) is a 77-amino-acid protein with a single predicted helical transmembrane segment (residues 32-52), immediately followed by a cluster of cysteine residues and a short basic, proline-rich C terminus. It is classed as a single-pass membrane protein on the basis of this sequence feature; its topology and the membrane in which it resides have not been determined experimentally. SMIM5 belongs to the SMIM5/SMIM18/SMIM22 family (Pfam PF15831). Of that family only SMIM22 has been studied functionally, and nothing about SMIM22 has been shown to apply to SMIM5. SMIM5 mRNA is enriched in kidney. Its reported partners come from a single proteome-scale yeast two-hybrid screen and include the cytosolic membrane-protein quality-control factor SGTA. Altered SMIM5 mRNA levels have been noted in several transcriptomic studies of disease tissue, but no molecular function, biological process or loss-of-function phenotype has been reported.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI yeast two-hybrid interaction between SMIM5 and SGTA, a cytosolic co-chaperone that handles exposed hydrophobic transmembrane domains of mislocalized membrane proteins. Reason: SGTA engages exposed hydrophobic transmembrane domains (PMID:23129660), so an SGTA hit for a single-pass transmembrane peptide is expected client recognition. It reports SMIM5's hydrophobic helix, not a function of SMIM5. No more informative molecular function is supported, so the row is removed rather than modified. Removal does not imply that the interaction is false. Supporting Evidence: PMID:32296183 yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. PMID:23129660 SGTA does not simply mask the exposed hydrophobic transmembrane domain of a mislocalized protein |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI yeast two-hybrid interaction between SMIM5 and ARFIP1 (arfaptin-1). Reason: Single high-throughput Y2H hit with no follow-up. Bare protein binding is uninformative and no specific molecular function can be inferred from it. Supporting Evidence: PMID:32296183 the majority of PPIs in HuRI were found in only one screen |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI yeast two-hybrid interaction between SMIM5 and EHHADH, a peroxisomal bifunctional enzyme of fatty-acid beta-oxidation. Reason: Single high-throughput Y2H hit with no follow-up. There is no evidence that SMIM5 is peroxisomal or regulates EHHADH. Bare protein binding is uninformative. Supporting Evidence: PMID:32296183 the majority of PPIs in HuRI were found in only one screen |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI yeast two-hybrid interaction between SMIM5 and PRRT2, a transmembrane synaptic protein. Reason: Single high-throughput Y2H hit between two membrane proteins, with no follow-up. PRRT2 is neuronal and SMIM5 is mainly expressed in kidney, so the interaction has no obvious physiological context. Bare protein binding is uninformative. Supporting Evidence: PMID:32296183 the majority of PPIs in HuRI were found in only one screen |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI yeast two-hybrid interaction between SMIM5 and RBFA, a mitochondrial ribosome-binding factor. Reason: Single high-throughput Y2H hit with no follow-up and no evidence that SMIM5 is mitochondrial. Bare protein binding is uninformative. Supporting Evidence: PMID:32296183 the majority of PPIs in HuRI were found in only one screen |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI yeast two-hybrid interaction between SMIM5 and ZFYVE21. Reason: Single high-throughput Y2H hit with no follow-up. Bare protein binding is uninformative and no specific molecular function can be inferred from it. Supporting Evidence: PMID:32296183 the majority of PPIs in HuRI were found in only one screen |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI yeast two-hybrid interaction between SMIM5 and SH3GLB1 (endophilin-B1). Reason: Single high-throughput Y2H hit with no follow-up. Bare protein binding is uninformative and no specific molecular function can be inferred from it. Supporting Evidence: PMID:32296183 the majority of PPIs in HuRI were found in only one screen |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to membrane, based on the single predicted helical transmembrane segment (residues 32-52). Reason: Correct but general. No experiment places SMIM5 in a specific membrane, so a more specific term cannot be assigned. Supporting Evidence: file:human/SMIM5/SMIM5-uniprot.txt SUBCELLULAR LOCATION: Membrane |
Loading supporting content…
Download this section (compressed HTML)Q: Does SMIM5 share any activity with its family member SMIM22 (CASIMO1), which interacts with and raises the protein level of squalene epoxidase? The two proteins share a transmembrane region and a following cysteine cluster, but SMIM5 has not been tested.
Q: Is the cysteine cluster after the transmembrane helix S-palmitoylated, and does it determine which membrane SMIM5 occupies?
Experiment: Tag endogenous SMIM5 in a kidney epithelial cell line and determine its localization by co-staining with organelle markers and by carbonate extraction and protease protection, then test acyl-biotin exchange for palmitoylation of the post-transmembrane cysteines.
Hypothesis: SMIM5 is an integral membrane protein of a defined organelle in kidney epithelium.
Type: localization and biochemical fractionation
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)