SMIM10L1

UniProt ID: P0DMW3
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

SMIM10L1 is a 68-amino-acid protein of the SMIM10 family (Pfam DUF4560), paralogous to SMIM10, with a disordered alanine/proline-rich N-terminus and a hydrophobic C-terminal half predicted to be alpha-helical and membrane-associated. It is expressed in all tissues. A high-confidence proteomic inventory of human mitochondria includes it. In adipose progenitor cells its transcript falls sharply after PTEN knockdown, and its own knockdown increases PI3K/AKT/mTOR signalling and enhances adipocyte differentiation. Its membrane topology, mitochondrial sub-compartment and molecular activity are unknown.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an...
ACCEPT
Summary: High-throughput assignment to mitochondria from the MitoCoP high-confidence human mitochondrial proteome.
Reason: MitoCoP assigns proteins by combining subtractive and spatial proteomics, import assays and curation under stringent criteria. The per-protein evidence for SMIM10L1 sits in supplementary tables not in our cache, so we defer to the curator. It is the only location evidence for SMIM10L1 and fits a small protein with a hydrophobic C-terminal segment. The mitochondrial sub-compartment is not established.
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

Core Functions

No molecular activity is known for SMIM10L1. Proteomics places it in mitochondria; knockdown in adipose progenitor cells raises PI3K/AKT/mTOR signalling and enhances adipogenesis, but how it acts is unknown, so no function is asserted here.

Cellular Locations:
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
  • PMID:35290761
    SMIM10L1 downregulation in APCs led to an enhanced adipocyte differentiation

References

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Suggested Questions for Experts

Q: Is SMIM10L1 an integral mitochondrial membrane protein, and in which membrane (outer or inner) and orientation does it sit?

Q: How does loss of a mitochondrial microprotein lower PTEN and increase PI3K/AKT/mTOR signalling in adipose progenitors: directly or through a metabolic signal?

Suggested Experiments

Experiment: Fractionate mitochondria from cells expressing endogenously tagged SMIM10L1, test carbonate resistance and protease protection with outer- and inner-membrane markers, and confirm by immunofluorescence or proximity labelling.

Hypothesis: SMIM10L1 is a mitochondrial membrane protein.

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Notes

(SMIM10L1-notes.md)

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