We report the cloning and characterization of DANGER, a novel protein which physiologically binds to inositol 1,4,5-trisphosphate receptors (IP(3)R). DANGER is a membrane-associated protein predicted to contain a partial MAB-21 domain. It is expressed in a wide variety of neuronal cell lineages where it localizes to membranes in the cell periphery together with IP(3)R. DANGER interacts with IP(3)R in vitro and co-immunoprecipitates with IP(3)R from cellular preparations. DANGER robustly enhances Ca(2+)-mediated inhibition of IP(3) RCa(2+) release without affecting IP(3) binding in microsomal assays and inhibits gating in single-channel recordings of IP(3)R. DANGER appears to allosterically modulate the sensitivity of IP(3) RtoCa(2+) inhibition, which likely alters IP(3)R-mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed.
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:comment |
We report the cloning and characterization of DANGER, a novel protein which physiologically binds to inositol 1,4,5-trisphosphate receptors (IP(3)R). DANGER is a membrane-associated protein predicted to contain a partial MAB-21 domain. It is expressed in a wide variety of neuronal cell lineages where it localizes to membranes in the cell periphery together with IP(3)R. DANGER interacts with IP(3)R in vitro and co-immunoprecipitates with IP(3)R from cellular preparations. DANGER robustly enhances Ca(2+)-mediated inhibition of IP(3) RCa(2+) release without affecting IP(3) binding in microsomal assays and inhibits gating in single-channel recordings of IP(3)R. DANGER appears to allosterically modulate the sensitivity of IP(3) RtoCa(2+) inhibition, which likely alters IP(3)R-mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed.
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| skos:exactMatch | |
| uniprot:name |
J. Biol. Chem.
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| uniprot:author |
Barrow R.K.,
Burkholder S.G.,
Cheung K.-H.,
Foskett J.K.,
Gessell G.S.,
Patterson R.L.,
Snyder S.H.,
Syrovatkina V.,
Watkins D.N.,
van Rossum D.B.
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| uniprot:date |
2006
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| uniprot:pages |
37111-37116
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| uniprot:title |
DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor activity.
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| uniprot:volume |
281
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| dc-term:identifier |
doi:10.1074/jbc.M608760200
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