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
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective PAPSS2 does not transfer SO4(2-) group to ATP to form APS
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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

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
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
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
Input
Participates
as an event of
Catalyst Activity

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

Physical Entity
PAPSS2 mutants [cytosol] (Homo sapiens)
Activity
sulfate adenylyltransferase (ATP) activity (GO:0004781)
Normal reaction
PAPSS1,2 transfer SO4(2-) group to ATP to form APS (Homo sapiens)
Functional status

Loss of function of PAPSS2 mutants [cytosol]

Normal Entity
Disease Entity
Status
Disease
Cross References
Mondo
Authored
Jassal, B  (2013-05-21)
Reviewed
Spillmann, D  (2014-07-09)
Created
Jassal, B  (2013-05-21)
Cite Us!