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

Stable Identifier
R-HSA-3560794
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
9771708 Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse

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

Nat Genet 1998
9714015 Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred

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

Am. J. Med. Genet. 1998
19474428 Inactivating PAPSS2 mutations in a patient with premature pubarche

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

N. Engl. J. Med. 2009
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
sulfate adenylyltransferase (ATP) activity of PAPSS2 mutants [cytosol]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
spondyloepimetaphyseal dysplasia 0080027
Authored
Reviewed
Created
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