PROSITE documentation PDOC50156Sterol-sensing domain (SSD) profile
The sterol-sensing domain (SSD) is an around 180 residues long cluster of five membrane-spanning segments. The SSD domain is conserved across phyla and confers sensitivity to regulation by sterol. Although the SSD domain appears to function as a regulatory domain involved in linking vesicle trafficking and protein localization with such varied processes as cholesterol homeostasis, cell signalling and cytokinesis, its exact mode of action is not clear. It is not known whether it interacts with sterols, such as cholesterol, or whether it interacts with another-sterol regulated protein. Alternatively, the SSD may interact with lipids other than cholesterol [1,2,3].
Some proteins known to contain a SSD are listed below:
- Patched from Drosophila. It is receptor for the cholesterol-activated protein sonic hedghog.
- 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR).
- Sterol regulatory element binding-protein cleavage-activating protein (SCAP).
- The Niemann-Pick type C (NPC1) protein [4]. It is involved in the intracellular trafficking of cholesterol.
In addition to the proteins above, the SSD is also found in a number of bacterial drug resistance proteins.
The profile we developed covers the entire SSD domain.
Last update:April 2002 / Text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Nohturfft A. Brown M.S. Goldstein J.L. |
| Title | Topology of SREBP cleavage-activating protein, a polytopic membrane protein with a sterol-sensing domain. | |
| Source | J. Biol. Chem. 273:17243-17250(1998). | |
| PubMed ID | 9642295 |
| 2 | Authors | Davies J.P. Ioannou Y.A. |
| Title | Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating protein. | |
| Source | J. Biol. Chem. 275:24367-24374(2000). | |
| PubMed ID | 10821832 | |
| DOI | 10.1074/jbc.M002184200 |
| 3 | Authors | Kuwabara P.E. Labouesse M. |
| Title | The sterol-sensing domain: multiple families, a unique role? | |
| Source | Trends Genet. 18:193-201(2002). | |
| PubMed ID | 11932020 |
| 4 | Authors | Loftus S.K. Morris J.A. Carstea E.D. Gu J.Z. Cummings C. Brown A. Ellison J. Ohno K. Rosenfeld M.A. Tagle D.A. Pentchev P.G. Pavan W.J. |
| Title | Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene. | |
| Source | Science 277:232-235(1997). | |
| PubMed ID | 9211850 |
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