Flotillin
From Proteopedia
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==Your Heading Here (maybe something like 'Structure')== | ==Your Heading Here (maybe something like 'Structure')== | ||
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
| - | + | Flotillins, also called reggie proteins, form a family of two ubiquitously expressed and highly | |
| - | + | conserved proteins, i.e., flotillin-1 and flotillin-2. Despite being products of different genes, both flotillins have a molecular weight of approximately | |
| + | 48 kDa and their sequences are quite similar (50% identity on mRNA level and 44% on protein level). | ||
| + | Flotillins are expressed in all mammals but they are also present in bacteria, plants, fungi and | ||
| + | metazoans, but not e.g. in the budding yeast and C. elegant. | ||
| + | |||
| + | Flotillins are highly conserved | ||
| + | among species. For example, mouse and human flotillin-1 share a 98.1% identical amino acid | ||
| + | sequence. Even between vertebrates and invertebrates the similarity is more than 60%, | ||
| + | implicating that flotillins are important for cell physiology. | ||
| + | Officially, flotillins belong to the group of SPFH domain containing proteins. <scene name='60/607923/Mouse_flotillin_2/3'>TextToBeDisplayed</scene>==Your Heading Here (maybe something like 'Structure')== | ||
| + | <StructureSection load='3rec' size='350' side='right' caption='Escherichia coli reca protein-bound DNA (PDB entry [[3rec]])' scene=''></StructureSection> This SPFH | ||
| + | (stomatin/prohibitin/flotillin/HflK/C) domain and a C-terminal “flotillin domain” comprising alanine | ||
| + | and glutamic acid repeats are the only recognizable domains within the flotillin protein. The SPFH | ||
| + | domain, also referred to as prohibitin homology (PHB) domain, was first identified in stomatin | ||
| + | and is shared by several pro- and eukaryotic proteins. However, the function of the SPFH domain is | ||
| + | still unknown. Most SPFH domain containing proteins tend to form oligomers, as was shown for | ||
| + | stomatin, podocin, prohibitin and flotillins, although the SPFH domain does not | ||
| + | mediate the oligomerization of flotillins. Another common feature of SPFH proteins is their | ||
| + | association with lipid rafts. | ||
| + | Typical with the SPFH domain containing proteins, flotillins also tend to form hetero- as well as | ||
| + | homo-oligomers, but this oligomerization requires the flotillin domain [20,21] and tyrosine | ||
| + | residue 163 of flotillin-2. Flotillins stabilize each other, which became obvious upon siRNA | ||
| + | mediated knockdown of either flotillin-1 or -2 and concomitant decrease in the expression of the other | ||
| + | one. Notably, this interdependency is stronger in the case of flotillin-1, since flotillin-1 | ||
| + | depletion typically results in only a moderate or even no depletion of flotillin-2, suggesting that | ||
| + | flotillin-1 is more dependent on flotillin-2 than vice versa. | ||
| + | Flotillins were originally believed to be transmembrane proteins that are enriched in caveolae which | ||
| + | are a subtype of membrane rafts. However, this has been disputed in later studies where it was | ||
| + | clearly shown that flotillins reside within non-caveolar rafts. In general, membrane rafts are | ||
| + | defined as dynamic, nanoscale membrane microdomains enriched in cholesterol and glycosphingolipids, | ||
| + | which function as sorting platforms for various cellular processes. Meanwhile, flotillins are | ||
| + | widely used as membrane raft marker proteins. In contrast to what was assumed originally, they do not | ||
| + | traverse the membrane, but are attached to the cytosolic leaflet of the plasma membrane by means of | ||
| + | fatty acid modifications and possibly hydrophobic stretches in the case of flotillin-1. | ||
| + | Furthermore, flotillins harbor several putative, conserved phosphorylation sites , for some of | ||
| + | which (i.e., Tyr160 for flotillin-1, Tyr163 for flotillin-2) a functional role has been shown. | ||
| + | Flotillins are expressed ubiquitously, and their expression is particularly high in brain, heart, lung, | ||
| + | and placenta, but fairly low in pancreas and liver. Despite their ubiquitous tissue distribution, | ||
| + | the expression of flotillins underlies, at least to some extent, transcriptional regulation and can be finetuned | ||
| + | by different transcription factors. | ||
| + | |||
| + | <scene name='60/607923/Mouse_flotillin_2/1'>TextToBeDisplayed</scene> | ||
| + | <scene name='60/607923/Mouse_flotillin_2/2'>TextToBeDisplayed</scene> | ||
== Function == | == Function == | ||
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== Structural highlights == | == Structural highlights == | ||
| - | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
1. Banning A, Kurrle N, Meister M and Tikkanen R, Flotillins in Receptor Tyrosine Kinase Signaling and Cancer. Cells. 2014 Feb 19;3(1):129-49. | 1. Banning A, Kurrle N, Meister M and Tikkanen R, Flotillins in Receptor Tyrosine Kinase Signaling and Cancer. Cells. 2014 Feb 19;3(1):129-49. | ||
Revision as of 14:02, 18 November 2014
Contents |
Your Heading Here (maybe something like 'Structure')
| |||||||||||
(stomatin/prohibitin/flotillin/HflK/C) domain and a C-terminal “flotillin domain” comprising alanine and glutamic acid repeats are the only recognizable domains within the flotillin protein. The SPFH domain, also referred to as prohibitin homology (PHB) domain, was first identified in stomatin and is shared by several pro- and eukaryotic proteins. However, the function of the SPFH domain is still unknown. Most SPFH domain containing proteins tend to form oligomers, as was shown for stomatin, podocin, prohibitin and flotillins, although the SPFH domain does not mediate the oligomerization of flotillins. Another common feature of SPFH proteins is their association with lipid rafts. Typical with the SPFH domain containing proteins, flotillins also tend to form hetero- as well as homo-oligomers, but this oligomerization requires the flotillin domain [20,21] and tyrosine residue 163 of flotillin-2. Flotillins stabilize each other, which became obvious upon siRNA mediated knockdown of either flotillin-1 or -2 and concomitant decrease in the expression of the other one. Notably, this interdependency is stronger in the case of flotillin-1, since flotillin-1 depletion typically results in only a moderate or even no depletion of flotillin-2, suggesting that flotillin-1 is more dependent on flotillin-2 than vice versa. Flotillins were originally believed to be transmembrane proteins that are enriched in caveolae which are a subtype of membrane rafts. However, this has been disputed in later studies where it was clearly shown that flotillins reside within non-caveolar rafts. In general, membrane rafts are defined as dynamic, nanoscale membrane microdomains enriched in cholesterol and glycosphingolipids, which function as sorting platforms for various cellular processes. Meanwhile, flotillins are widely used as membrane raft marker proteins. In contrast to what was assumed originally, they do not traverse the membrane, but are attached to the cytosolic leaflet of the plasma membrane by means of fatty acid modifications and possibly hydrophobic stretches in the case of flotillin-1. Furthermore, flotillins harbor several putative, conserved phosphorylation sites , for some of which (i.e., Tyr160 for flotillin-1, Tyr163 for flotillin-2) a functional role has been shown. Flotillins are expressed ubiquitously, and their expression is particularly high in brain, heart, lung, and placenta, but fairly low in pancreas and liver. Despite their ubiquitous tissue distribution, the expression of flotillins underlies, at least to some extent, transcriptional regulation and can be finetuned by different transcription factors.
Function
Flotillins are highly conserved proteins that localize into specific cholesterol rich microdomains in cellular membranes. They have been shown to be associated with, for example, various signaling pathways, cell adhesion, membrane trafficking and axonal growth. Recent findings have revealed that flotillins are frequently overexpressed in various types of human cancers.
Disease
Relevance
Structural highlights
</StructureSection>
References
1. Banning A, Kurrle N, Meister M and Tikkanen R, Flotillins in Receptor Tyrosine Kinase Signaling and Cancer. Cells. 2014 Feb 19;3(1):129-49.
