PAPSS2 Gene - Function, Mutations, and Associated Diseases

PAPSS2 encodes the bifunctional enzyme 3'-phosphoadenosine 5'-phosphosulfate synthase 2, which catalyzes the synthesis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the universal sulfate donor for sulfation reactions. Sulfation is critical for the modification of proteoglycans, hormones, neurotransmitters, and xenobiotics. The enzyme has both ATP sulfurylase and APS kinase activities. Mutations in PAPSS2 cause autosomal recessive spondyloepimetaphyseal dysplasia (SEMD) Pakistani type and are associated with androgen excess and bone growth defects.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Sulfate assimilation and activation (Reactome: R-HSA-174403)

• Sulfur metabolism (KEGG: hsa00920)

• Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (KEGG: hsa00532)

PAPSS2 is a bifunctional enzyme (56 kDa) that catalyzes two sequential reactions: first, ATP sulfurylase converts ATP and sulfate to adenosine 5'-phosphosulfate (APS) and pyrophosphate; second, APS kinase phosphorylates APS to form PAPS. The enzyme is localized in the cytoplasm and is highly expressed in liver, adrenal gland, and cartilage. PAPSS2 is the major isoform in tissues requiring high sulfation capacity, such as cartilage and adrenal cortex.