3'-Phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2)

3'-Phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) is a bifunctional enzyme that catalyzes the formation of PAPS, the universal sulfate donor required for all biological sulfation reactions[2][4]. PAPSS2 mediates two key steps: transfer of inorganic sulfate to ATP (ATP sulfurylase activity) to form adenosine 5'-phosphosulfate (APS), and subsequent phosphorylation of APS (APS kinase activity) to generate PAPS[1][4]. It is central for biochemical processes including sulfation of steroids (regulating androgen activity), extracellular matrix proteoglycans, neurotransmitters, thyroid hormones, and a range of xenobiotics[2][1]. PAPSS2 is essential for skeletal growth and cartilage homeostasis, and loss-of-function mutations cause various skeletal dysplasias with short stature and bone deformities[2][3][4]. In oncology, PAPSS2-driven sulfation pathways have been linked to epithelial-to-mesenchymal transition and tumor metastasis, offering a potential target for antimetastatic therapy[5].

Other names

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2Sulfate adenylyltransferaseAdenylyl-sulfate kinasePAPS synthase 2ATPSK2SK2Sulfurylase kinase 2APS kinaseAdenosine-5'-phosphosulfate 3'-phosphotransferaseBifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 2BCYM4

Inhibition of PAPSS2 leads to reduced production of activated sulfate (PAPS), which decreases sulfation of target molecules such as hormones, proteoglycans, and xenobiotics[5][1]. In cancer, inhibition of PAPSS2 suppresses cell migration and metastasis by interfering with sulfated proteoglycan production[5].