SUMF1 Human
Description
Introduction to SUMF1 Human
SUMF1 Human, also known as sulfatase-modifying factor 1, is an enzyme encoded by the SUMF1 gene in humans. This enzyme plays a crucial role in the post-translational modification of sulfatases, which are essential for the hydrolysis of sulfate esters such as glycosaminoglycans, sulfolipids, and steroid sulfates . The modification involves converting a cysteine residue in sulfatases into C-alpha-formylglycine, a critical step for sulfatase activation .
Function and Importance of SUMF1
SUMF1 is vital for the activation of all known sulfatases. These enzymes are involved in the breakdown of various sulfate-containing molecules, which are crucial for cellular metabolism and function . Without SUMF1, sulfatases remain inactive, leading to the accumulation of sulfate esters, which can result in cellular dysfunction and disease .
Key Functions of SUMF1:
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Post-translational modification: Converts cysteine residues in sulfatases to C-alpha-formylglycine, enabling their catalytic activity .
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Enzyme activation: Essential for the activation of sulfatases, which are involved in the hydrolysis of sulfate esters .
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Cellular metabolism: Plays a role in maintaining cellular homeostasis by facilitating the breakdown of sulfate-containing molecules .
Structure and Production of SUMF1
SUMF1 is produced as a single polypeptide chain containing 347 amino acids, with a molecular mass of approximately 38.1 kDa . It is often expressed with a His tag for purification purposes and can be produced in insect cells like Sf9 cells .
Physical and Chemical Properties:
Health Implications of SUMF1 Deficiency
Mutations in the SUMF1 gene can lead to Multiple Sulfatase Deficiency (MSD), a rare autosomal recessive disorder characterized by severe neurological decline, ichthyosis, and skeletal abnormalities . MSD results from the impaired activity of multiple sulfatases due to the inability to convert cysteine residues to C-alpha-formylglycine .
Clinical Features of MSD:
Research and Therapeutic Developments
Recent studies have explored gene therapy approaches to treat MSD by delivering functional SUMF1 genes using viral vectors like AAV9 . These studies have shown promising results in animal models, with improved survival rates and restoration of sulfatase activity .
Gene Therapy Approaches:
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Viral Vectors: Use of AAV9 vectors for delivering SUMF1 genes .
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Animal Models: Successful treatment in mouse models of MSD, showing improved survival and reduced symptoms .
Table 1: Key Features of SUMF1
| Feature | Description |
|---|---|
| Gene | SUMF1 |
| Function | Post-translational modification of sulfatases |
| Structure | Single polypeptide chain, 347 amino acids |
| Molecular Mass | Approximately 38.1 kDa |
Table 2: Clinical Features of Multiple Sulfatase Deficiency
| Feature | Description |
|---|---|
| Inheritance | Autosomal recessive |
| Symptoms | Neurological decline, ichthyosis, skeletal abnormalities |
| Age of Onset | Early childhood |
Table 3: Gene Therapy Outcomes in Animal Models
| Outcome | Description |
|---|---|
| Survival | Extended lifespan in treated mice |
| Sulfatase Activity | Restored activity in brain tissues |
| Behavioral Outcomes | Normal behavior maintained in treated mice |
Product Specs
Q&A
Basic Research Questions
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What is the molecular function of SUMF1 in human cells?
SUMF1 encodes the formylglycine-generating enzyme (FGE) that post-translationally activates all newly synthesized sulfatases by converting a specific cysteine residue to formylglycine, which is the catalytic residue essential for sulfatase activity. This modification is required for the proper functioning of all 17 sulfatases encoded in the human genome. FGE recognizes a conserved sequence motif in sulfatases and executes this unique modification within the endoplasmic reticulum . Methodologically, researchers typically assess SUMF1 function by measuring the activities of multiple sulfatases in patient-derived cells or in experimental models with modified SUMF1 expression. Enzyme activity assays using artificial substrates for specific sulfatases (such as arylsulfatase A, B, and C) provide quantitative measures of SUMF1 functionality .
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How do researchers establish genotype-phenotype correlations in SUMF1-associated disorders?
Researchers establish genotype-phenotype correlations through integrated analysis of:
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Clinical phenotyping - comprehensive assessment of neurological, skeletal, dermatological, and visceral manifestations
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Genetic analysis - identification of specific SUMF1 variants through whole-exome sequencing (WES) or targeted gene panels
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Functional studies - measuring residual FGE activity and protein stability
Multiple studies have demonstrated that patients with identical mutations display comparable clinical phenotypes, confirming that phenotypic outcomes in Multiple Sulfatase Deficiency (MSD) depend on both residual FGE activity and protein stability . For instance, patients with the homozygous missense mutation p.Gln262Arg display a consistent phenotype characterized by developmental regression, intellectual disability, and ichthyosis, but notably lack organomegaly and skeletal abnormalities typically seen in other MSD cohorts .
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What experimental approaches effectively assess SUMF1 protein stability and activity?
Several complementary experimental approaches are used to assess SUMF1 protein stability and activity:
When conducting stability studies, both steady-state levels and degradation kinetics should be evaluated to determine if mutations affect protein production, folding, or turnover rate .
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What are the most effective diagnostic approaches for SUMF1-related disorders?
Diagnosis of SUMF1-related disorders requires a multifaceted approach:
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Clinical evaluation - assessment of characteristic symptoms including developmental regression, intellectual disability, ichthyosis, and periventricular white matter disease
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Biochemical testing - measurement of multiple sulfatase activities in patient cells
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Genetic analysis - a combination of copy-number variation sequencing (CNV-seq) and whole-exome sequencing (WES) is particularly effective for identifying complex mutations in SUMF1
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Neuroimaging - magnetic resonance imaging (MRI) to detect characteristic white matter abnormalities
Current diagnostic challenges include the variable clinical presentation and the potential for complex mutations like microdeletions, which may be missed by standard sequencing approaches . A comprehensive genetic approach combining CNV analysis with sequencing is recommended, as demonstrated in a recent Chinese case that identified a novel compound heterozygous mutation with a 240.55 kb microdeletion on 3p26.1 encompassing exons 4-9 of the SUMF1 gene and a missense mutation c.671G>A (p.Arg224Gln) .
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Product Science Overview
SUMF1 is a 42 kDa protein that belongs to the sulfatase-modifying factor family . It is a soluble glycoprotein located in the endoplasmic reticulum (ER) lumen and binds calcium ions (Ca²⁺) . The primary function of SUMF1 is to oxidize the cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, also known as C-alpha-formylglycine . This modification is essential for the catalytic activity of sulfatases, which are enzymes that hydrolyze sulfate ester bonds from a wide variety of substrates .
Sulfatases are involved in numerous biological processes, including hormone regulation, cellular signaling, and degradation of glycosaminoglycans . Deficiencies in sulfatase activity can lead to various human inherited diseases. For instance, mutations in the SUMF1 gene cause Multiple Sulfatase Deficiency (MSD), a lysosomal storage disorder characterized by the accumulation of sulfated molecules due to the lack of active sulfatases .
The mechanism by which SUMF1 modifies sulfatases has been highly conserved throughout evolution . This conservation underscores the critical role of SUMF1 in maintaining the proper function of sulfatases across different species. Studies have shown that the active site of sulfatases, which is the target of SUMF1’s modification, is the most evolutionarily constrained region, indicating its importance in the enzyme’s function .
Understanding the function and mechanism of SUMF1 has significant implications for the development of therapeutic strategies for diseases caused by sulfatase deficiencies . By targeting the SUMF1 pathway, it may be possible to develop treatments that restore the activity of defective sulfatases, thereby alleviating the symptoms of related disorders.
