What is PAPSS2 Protein

      PAPSS2 protein, scientifically known as Phosphoadenosine phosphosulfate synthase 2, is a crucial protein encoded by the PAPSS2 gene found in the human body.

      The PAPSS2 protein was relatively recently discovered, with most of the research about its properties and roles being conducted in the past few decades. Ever since its discovery, the PAPSS2 protein has been of significant interest in the scientific community owing to its crucial role in various biological processes such as sulfate conjugation and steroid hormone biosynthesis.

      Gene Locus and Protein Structure

      The PAPSS2 gene locus is located at 10q23-q24 on chromosome 10 in the human genome. The protein PAPSS2 encoded by the PAPSS2 gene consists of 636 amino acids and has a bipartite structure. One part is responsible for ATP sulfurylase activity, and the other one is for APS kinase activity. The protein has a molecular weight of about 72 KD. When viewing the PAPSS2 protein structure, it comprises a complex configuration signifying its special role in sulfation, a process vital for numerous metabolic pathways.

      Function of PAPSS2 Protein

      PAPSS2 protein performs an instrumental function in the synthesis of PAPS (3'-phosphoadenosine-5'-phosphosulfate). PAPS is the universal sulfate donor in numerous sulfate conjugation reactions, including steroids, bile acids, thyroid hormones, and neurotransmitters. These compounds conjugated with sulfate are more water-soluble, thus can be excreted more easily from the organisms. Additionally, the sulfation process also activates some compounds, like steroids and neurotransmitters, making it essential for proper bodily functions.

      PAPSS2 Protein Related Signal Pathway

      The PAPSS2 protein plays an essential role in the Sulfation Biogenesis pathway. By synthesizing 3'-phosphoadenosine-5'-phosphosulfate (PAPS), PAPSS2 facilitates the transfer of a sulfate group to various acceptor molecules. The sulfation of different compounds is vital in a range of biological responses, including detoxification, steroid modulation, and protein post-translational modifications, to name a few.

      Fig1. Mechanistic pathway involving PAPSS2 in the generation of PAPS (Perez-Garcia, E. M., et al. 2022)

      Fig1. Mechanistic pathway involving PAPSS2 in the generation of PAPS (Perez-Garcia, E. M., et al. 2022)

      PAPSS2 Protein-Related Diseases

      PAPSS2 protein mutations have been implicated in several medical conditions. A notable disease in this respect is the Autosomal Recessive PAPSS2-Related Spondyloepimetaphyseal Dysplasia (SEMD). SEMD is a disorder associated with bone growth, primarily influencing the spine and the ends of long bones. One clear symptom is a short stature. Studies show that this condition results from mutations of the PAPSS2 gene, which resultantly hamper the normal function of the PAPSS2 protein, hence affecting sulfation pathways in the cells.

      PAPSS2 Protein's Applications in Biomedicine

      Knowledge about the PAPSS2 protein and its functions can be useful in biomedical applications. For instance, understanding the mutation in PAPSS2 protein can help in the diagnosis and treatment of some growth disorders such as SEMD. Explore the manipulation of PAPSS2 protein can open new approaches for therapeutic treatments.

      In drug metabolism studies, the conclusions about the sulfonation process play a significant role. Since PAPSS2 is responsible for the synthesis of the universal sulfate donor, any imbalances or disruptions in its activity can critically affect drug metabolism and pharmacokinetics.

      Furthermore, recognizing the role of PAPSS2 protein in sulfate conjugation of various hormones provides another avenue for biomedical research. It may facilitate new knowledge about hormonal imbalance related diseases and potential therapeutic strategies.

      In conclusion, the PAPSS2 protein plays an indispensable role in various biological and metabolic mechanisms. It contributes massively to sulfate conjugation reactions necessary for biological functions. However, mutations can lead to severe medical conditions, emphasizing its significance in the relevant biological domains. Therefore, the expanding research on PAPSS2 protein's role in disease pathogenesis and potential treatment methodologies carries great promise in the biomedical field.

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      Reference

      • Perez-Garcia, E. M., Whalen, P., & Gurtunca, N. (2022). Novel Inactivating Homozygous PAPSS2 Mutation in Two Siblings With Disproportionate Short Stature. AACE Clinical Case Reports, 8(2), 89-92. https://doi.org/10.1016/j.aace.2021.11.003