Defective PAPSS2 does not transfer SO4(2-) group to ATP to form APS

Stable Identifier
Reaction [transition]
Homo sapiens
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In the first step of PAPS biosynthesis, ATP and sulfate react to form adenylyl sulfate (APS) and pyrophosphate (PPi), catalyzed by the ATP sulfurylase domains of the bifunctional enzymes PAPS synthases 1 and 2 (PAPSS1 and 2). PAPSS2 is essential for the sulfation of glycosaminoglycan chains in proteoglycans, a necessary post translational modification. Defective PAPSS2 results in undersulfation of the glycosaminoglycan chains in proteoglycans which causes spondyloepimetaphyseal dysplasia Pakistani type (SEMD PA; MIM:612847), a bone disease characterized by epiphyseal dysplasia with mild metaphyseal abnormalities. Mutations resulting in SEMD PA include S438*, T48R and R329* (Ahmad et al. 1998, ul Haque et al. 1998, Noordam et al. 2009).
Literature References
PubMed ID Title Journal Year
9714015 Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred

Lachman, RS, Krakow, D, Faiyaz Ul Haque, M, Ahmad, W, Cohn, DH, Haque, S, Abbas, H, Ahmad, M, Rimoin, DL

Am. J. Med. Genet. 1998
9771708 Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse

Superti-Furga, A, Krakow, D, Ahmad, W, Cohn, DH, Rusiniak, ME, Haque, S, Abbas, H, King, LM, Ahmad, M, Swank, RT, ul Haque, MF, Cantor, RM

Nat Genet 1998
19474428 Inactivating PAPSS2 mutations in a patient with premature pubarche

Sweep, FC, Arlt, W, Schlereth, F, Krone, N, Claahsen-van der Grinten, HL, Smeets, R, McNelis, JC, Dhir, V, Smeitink, JA, Hanley, NA, Noordam, C

N. Engl. J. Med. 2009
Catalyst Activity

sulfate adenylyltransferase (ATP) activity of PAPSS2 mutants [cytosol]

Normal reaction
Functional status

Loss of function of PAPSS2 mutants [cytosol]

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