A member of a family of sulfate-activating enzymes causes murine brachymorphism.
Sulfation is critical to the function of a wide variety of biomolecules. This common modification requires the enzymatic synthesis of an activated sulfate donor, phosphoadenosine-phosphosulfate (PAPS). In higher organisms PAPS synthesis is catalyzed by a bifunctional sulfurylase kinase (SK) polypeptide having both ATP-sulfurylase and adenosine-phosphosulfate kinase activities. We report the identification of a gene family encoding murine SK proteins with these two activities. A family member, SK2, colocalizes with the locus for the autosomal recessive murine phenotype brachymorphism. Brachymorphic mice have normal lifespans, but abnormal hepatic detoxification, bleeding times, and postnatal growth, the latter being attributed to undersulfation of cartilage proteoglycan. A missense mutation in the SK2 coding sequence of bm mice that alters a highly conserved amino acid residue destroys adenosine-phosphosulfate kinase activity and therefore the ability of SK2 to synthesize PAPS. We conclude that a family of SK genes are responsible for sulfate activation in mammals, that a mutation in SK2 causes murine brachymorphism, and that members of this gene family have nonredundant, tissue-specific roles.
Duke Scholars
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- Sulfate Adenylyltransferase
- Recombinant Proteins
- Phosphotransferases (Alcohol Group Acceptor)
- Phosphoadenosine Phosphosulfate
- Multienzyme Complexes
- Molecular Sequence Data
- Mice
- DNA, Complementary
- Cloning, Molecular
- Chromosome Mapping
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sulfate Adenylyltransferase
- Recombinant Proteins
- Phosphotransferases (Alcohol Group Acceptor)
- Phosphoadenosine Phosphosulfate
- Multienzyme Complexes
- Molecular Sequence Data
- Mice
- DNA, Complementary
- Cloning, Molecular
- Chromosome Mapping