SGSH

Fig1. Mapping of SGSH primary and secondary structures.

What is SGSH protein?

SGSH (N-sulfoglucosamine sulfohydrolase) gene is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q25. Also known as N-sulfoglucosamine sulfohydrolase and heparan N-sulfatase, Sulfamidase/SGSH is an important member of the sulfatase family involved in the degradation of heparan sulfate (HS). Different from the HS specific endosulfatases that remove sulfate from internal GlcNAc residues, SGSH removes sulfate group from the non-reducing end glucosamine residues on HS. The SGSH protein is consisted of 502 amino acids and its molecular mass is approximately 56.7 kDa.

What is the function of SGSH protein?

Sulfated polysaccharides are a kind of important biomacromolecules, which exist widely in extracellular matrix, connective tissue and cartilage. Its degradation and synthesis are regulated by many enzymes. SGSH, as one of the key enzymes in the degradation of sulfated polysaccharides, plays an important role in maintaining the homeostasis of extracellular matrix. SGSH is an inflammation-related enzyme, and changes in its activity may affect the metabolism of extracellular matrix, thus participating in the occurrence and development of inflammatory response.

SGSH Related Signaling Pathway

SGSH has important physiological functions in cells, especially in maintaining intracellular glutathione (GSH) levels. Although it is not clear which signaling pathway SGSH is directly involved in, it may indirectly affect other signaling pathways by regulating GSH levels. Including: GSH/ REDOX signaling pathway, NF-κB signaling pathway, apoptosis signaling pathway, iron death signaling pathway and so on.

SGSH Related Diseases

The SGSH deficiency results in mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome), an autosomal recessive lysosomal storage disease characterized by neurological dysfunction but relatively mild somatic manifestations. Due to the absence or abnormal function of SGSH in adrenal cortical cells, NSG cannot be metabolized properly, resulting in congenital adrenal hyperplasia (CAH). A deficiency or abnormal function of SGSH, which results in the deposition of gangliosides in the nervous system, is ganglioside deposition disorder (GM1 ganglioside deposition disorder). Abnormal SGSH function is also associated with cirrhosis.

Bioapplications of SGSH

SGSH is widely used in drug development, especially in the development of antibiotics and antiviral drugs. SGSH can catalyze the metabolism of antibiotics and antiviral drugs, thus affecting their efficacy and toxicity. SGSH plays an important role in the treatment of mucoglycans storage disease. SGSH enzyme replacement therapy can degrade accumulated GAGs by supplementing exogenous SGSH enzymes to patients, alleviating symptoms and improving quality of life.

Case study 1: Julie Weidner, 2019

COPD is associated with gene polymorphisms in SUMF1, a master regulator of sulfatases. Sulfatases are involved in extracellular matrix remodeling and activated by SUMF1, but their role in the lung is poorly described. This article aimed to examine how sulfatases are affected in the airways of patients with COPD compared to ever smokers and never smokers. Examinations of sulfatases, including GALNS, IDS, and SGSH by mRNA, protein expression, sulfatase activity levels, and localization of have been completed. Additionally, immunohistochemistry on lung biopsies was used to test the expression of sulfatases in COPD patients. The findings showed IDS, ARSB, GNS and SGSH in fibroblasts were localized to sites other than their reported destination and the mRNA expression of them increased. This could contribute to the understanding of the disease mechanism in COPD and in the long run, to lead to more individualized therapies.

Fig1. In some, but not all, COPD patients we also observed an increase of SGSH activity. The activity of SGSH was examined in cultured lung fibroblasts from COPD patients.

Fig2. SGSH appeared to partially co-localize to the lysosomes in ever smoker and COPD fibroblasts.

Case study 2: Ruben J Boado, 2018

Mucopolysaccharidosis Type IIIA (MPSIIIA), also known as Sanfilippo A syndrome, is an inherited neurodegenerative disease caused by mutations in the lysosomal enzyme, N-sulfoglucosamine sulfohydrolase (SGSH). Treatment of MPSIIIA with intravenous recombinant SGSH is not possible because this large molecule does not cross the blood–brain barrier (BBB). BBB penetration by SGSH was enabled in the present study by re-engineering this enzyme as an IgG-SGSH fusion protein, where the IgG domain is a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), designated the cTfRMAb. In conclusion, substantial reductions in brain pathologic GAGs in a murine model of MPSIIIA are produced by chronic systemic administration of an IgG-SGSH fusion protein engineered to penetrate the BBB via receptor-mediated transport.

Fig3. Western blot with a primary antibody against either mouse IgG (left panel) or human SGSH (right panel).

Fig4. ELISA shows the binding of the cTfRMAb-SGSH fusion protein, or the mouse IgG1k control antibody, to the mouse TfR extracellular domain.

SGSH has several biochemical functions, for example, N-sulfoglucosamine sulfohydrolase activity,catalytic activity,metal ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SGSH itself. We selected most functions SGSH had, and list some proteins which have the same functions with SGSH. You can find most of the proteins on our site.

SGSH has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SGSH here. Most of them are supplied by our site. Hope this information will be useful for your research of SGSH.

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