SMIM2 (formerly C13orf44) is an 85-amino-acid protein with a single predicted helical transmembrane segment (residues 21-43) followed by a polar, disordered C-terminal tail (residues 51-85). It is classed as a single-pass membrane protein on the basis of this sequence feature; its membrane topology and the organelle in which it resides have not been determined experimentally. Its mRNA is largely restricted to testis. SMIM2 has its own protein family (InterPro IPR062622) with no characterized members. Its only reported partners are the cytosolic ubiquilins UBQLN1 and UBQLN2, which were found in proteome-scale yeast two-hybrid screens. No molecular function, biological process or loss-of-function phenotype has been reported.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Yeast two-hybrid hit between SMIM2 and UBQLN1 from the HI-II-14 proteome-scale interactome map. Bare protein binding conveys no function. Reason: Ubiquilins are cytosolic chaperones that capture exposed transmembrane domains of membrane proteins (PMID:27345149). Binding of UBQLN1 to SMIM2's single hydrophobic helix in yeast is what that client-recognition activity predicts, so the hit tells us that SMIM2 has a transmembrane domain, not what SMIM2 does. 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:25416956 A proteome-scale map of the human interactome network. PMID:27345149 We show that Ubiquilin family proteins bind transmembrane domains in the cytosol to prevent aggregation and temporarily allow opportunities for membrane targeting. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Same HI-II-14 yeast two-hybrid interaction as the previous row, recorded against UBQLN1 isoform 2. Reason: As for the UBQLN1 row: a ubiquilin binding a transmembrane helix is a chaperone-client contact (PMID:27345149) and does not support an informative molecular function for SMIM2. Supporting Evidence: PMID:27345149 These findings define Ubiquilins as a family of chaperones for cytosolically exposed transmembrane domains |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Yeast two-hybrid hit between SMIM2 and UBQLN2 from the HuRI binary interactome map. Reason: UBQLN2 is a paralogue of UBQLN1 with the same transmembrane-domain chaperone activity (PMID:27345149). The HuRI screen is a valuable resource, but a single Y2H hit to a ubiquilin does not identify a function of SMIM2. No informative replacement term is supported. 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:27345149 We show that Ubiquilin family proteins bind transmembrane domains in the cytosol to prevent aggregation |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to membrane, based on the single predicted helical transmembrane segment (residues 21-43). Reason: Correct but general. SMIM2 has one hydrophobic helix and is very probably an integral membrane protein. No experiment places it in a specific membrane, so a more specific term cannot be assigned. Supporting Evidence: file:human/SMIM2/SMIM2-uniprot.txt SUBCELLULAR LOCATION: Membrane |
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Download this section (compressed HTML)Q: Is SMIM2 translated in testis, and in which membrane does it reside? The protein has a single predicted transmembrane helix and testis-restricted mRNA, but neither its expression at the protein level in germ cells nor its organelle has been established.
Experiment: Raise an antibody or tag the endogenous locus in mouse to determine the cell stage and membrane compartment in which SMIM2 is expressed, and assess male fertility, sperm count and sperm morphology in a knockout.
Hypothesis: SMIM2 is a germ-cell membrane protein required for spermatogenesis or sperm function.
Type: knockout mouse with localization
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