This web page was produced
as an assignment for an undergraduate course at Davidson College.
MY
FAVORITE YEAST PROTEINS
Fig.
1 Picture of Chromosome XV. Both
AUS 1 and YOR012W are closely located on this chromosome of Saccharomyces
Cerevisiae. (Permission
pending from SGD, <http://genome-www4.stanford.edu/cgi-bin/SGD/ORFMAP/ORFmap?sgdid=S0005537>
)
The Known Gene: AUS1/ YORO11 W
To
see general information on this gene, click
here
Where is AUS 1 located on the chromosome?
AUS 1 is located on Chromosome 15
between 349678 and 353862. It
is part of the first exon (SGD, <http://genome-www4.stanford.edu/cgi-bin/SGD/locus.pl?featureName=YOR011W>).
What is the DNA
and protein sequence of AUS 1?
The
genomic DNA sequence for AUS 1 can be viewed at the SGD
site (<http://genome-www4.stanford.edu/cgi-bin/SGD/getSeq?seq=YOR011W&flankl=0&flankr=0&map=a3map>).
The
protein sequence for AUS1 can be viewed at the SGD
site (<http://genome-www4.stanford.edu/cgi-bin/SGD/getSeq?seq=YOR011W&flankl=0&flankr=0&map=p3map
>).
Where in the cell is this protein expressed?
This protein is expressed in the cellular membrane (SGD, <http://genome-www4.stanford.edu/cgi-bin/SGD/locus.pl?featureName=YOR011W>) .
What is the
Biological Function & Process of the AUS 1 gene?
AUS
1 is a protein found in yeast that serves as an ATP- Binding Cassette
transporter (ABC transporter). ABC proteins are the largest family of proteins.
Its primary function is to transport sterols from the endoplasmic
reticulum to the plasma membrane. Since
the concentration of sterols is the highest in the plasma membrane, this
protein works against the concentration gradient (Menon,
2002, <http://www.biochem.wisc.edu/menon/>).
In order to pump these proteins against the gradient, the
transporter must bind ATP (Locer,
2002, <http://www-ssrl.slac.stanford.edu/research/highlights_archive/Rees_ABC.html
>).
For more information regarding sterols, check out these websites:
MeadowLea: FAQ's Plant Sterols <http://www.logicol.com.au/faqs/plant_sterols.asp>
FeLV: What are Sterols? <http://www.felineleukemia.org/sterols.html>
Canola Council: Sterols <http://www.canola-council.org/pubs/Chemical7-12.pdf>
At the present time, scientists are unsure of the exact mechanism
of how this process works, though there are many laboratories that are
currently investigating this question.
What happens if
there is a mutation in AUS 1?
A
cell with a mutated AUS 1 gene is still viable.
The only observed phenotype difference between a mutated and wild type cell
is that the mutated cell does not show as high cholesterol accumulation
as the wild type (SGD, <http://genome-www4.stanford.edu/cgi-bin/SGD/locus.pl?featureName=YOR011W>
and Wilcox et al, 2002).
Are there any
orthologs of this gene?
The
SGD (<http://genome-www.stanford.edu/cgi-bin/SGD/Sacch3D/getblast?name=YOR011W&db=mammal>)
revealed similarities to proteins
found in humans, mice, rats, and sheep.
Entrez protein (<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein>)
showed many similarities in a wide variety of bacteria.
Why do we want
to learn about this gene?
Yeast
are being used in order to better understand the mechanics of
cholesterol transfer in humans. Thus,
by understanding the cellular processes in yeast, scientists may be able
to understand this process in humans.
Perhaps such knowledge would lead to a better understanding of
the effects of sterols in human cells.
To
see general information on this gene, click
here (<http://genome-www4.stanford.edu/cgi-bin/SGD/locus.pl?featureName=YOR012W>).
The
genomic sequence for this gene can be found on the SGD site here
(<http://genome-www4.stanford.edu/cgi-bin/SGD/getSeq?seq=YOR012W&flankl=0&flankr=0&map=a3map>)
The
protein sequence for this gene can also be found on the SGD site here
(<http://genome-www4.stanford.edu/cgi-bin/SGD/getSeq?seq=YOR012W&flankl=0&flankr=0&map=p3map>)
Where is this gene found?
The YOR012W gene is found on
Chromosome 15 in Saccharomyces Cerevisiae between 356542 and
356955. It is located in
the first exon (SGD,
<http://genome-www4.stanford.edu/cgi-bin/SGD/locus.pl?featureName=YOR012W>).
What is the
structure of this protein?
Predator
(http://npsa-pbil.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_preda.html)
predicts that the structure of
the protein is 42.34% Alpha helix, 9.49% extended strand and 48.18%
random coil.
Where is the
protein located in the cell?
The location of the protein
is dependent upon a number of factors. First, the function of the
protein may help to determine where the protein is located.
Since the function of this protein is unknown, it cannot be used
to determine its location.
Another
factor that plays a role in the location of a protein depends on the
proteins relation to water- if it is hydropathic or hydrophilic.
A good way to determine the hydropathy rating for a protein is to
use a Kyte-Doolitte
hydropathy plot (http://occawlonline.pearsoned.com/bookbind/pubbooks/bc_mcampbell_genomics_1/medialib/activities/kd/kyte-doolittle.htm).
The plot for this protein is shown below in figure 2:
Figure
2. This Kyte-Doolitte plot
shows a red line at 1.8. This
protein does not cross the red line at any point in the graph. (Permission
pending)
Because
the plot of the YOR012W protein remains below 1.8, it is safe to assume
that the protein is not a transmembrane protein.
Thus, it is possible that this protein is located in the
cytoplasm.
Are there any
orthologs of this protein in other animals?
BLAST found no similarities
in any yeast or worm proteins (BLAST,
<http://genome-www.stanford.edu/cgi-bin/SGD/worm/getblast2.pl?name=YOR012W&db=worm>).
BLAST
found that the YOR012W protein is similar to Mouse proliferin (p= 0.52),
Human proliferin (0.64), and Human prolactin (0.996).
In
humans, the proliferin protein is related in sequence to the hormone
prolactin. These proteins
are regulated by growth factors and typically secreted by fetal and
adult cells. The proteins
are thought to be involved with message carrying between the fetus and
the mother during pregnancy. Typically,
these messages would stimulate uterine growth, though scientists are not
exactly sure of the mechanics of this process (Nielson-Hamilton,
http://www.bb.iastate.edu/faculty/nilsham.html)
What could be
the function of this protein?
Before hypothesizing the function of the protein, the YOR012W gene must be proven to be in a coding region of the genome. Further analysis of this sequence would have to be performed before such conclusions can be drawn. For now, lets assume that it is in a coding region.
Though this protein’s sequence is similar to proteins associated with uterine growth during pregnancy in mammals, there is no such process in yeast. Thus, this is probably not the protein’s exact function. The protein may still be associated with growth and reproduction and perhaps is used to trigger cell division during replication.
References:
Locher, K; Douglas, A.; Caltech R. 2002. ABC Transporter Aritchture and Mechanism. http://www-ssrl.slac.stanford.edu/research/highlights_archive/Rees_ABC.html Accessed 10-3-02
Menon,
A. 2002. Department of Biochem at UW-Madison.
Membrane biogenesis; biosynthesis of
glycosyl-phosphatidylinositol anchored membrane proteins; transbilayer
movement of phospholipids; intracellular sterol transport. http://www.biochem.wisc.edu/menon/
Accessed 10-3-02.
Phillips,
T.; Brinen, L. X-Ray
Crystal Structure ofA Bacterial ATP-Binding Cassette Transporter
Determined at 4.5 A. http://www-ssrl.slac.stanford.edu/research/highlights_archive/g_chang.html
Accessed 10-3-02.
-----.
Margaret Nilsen-Hamilton: Professor of Biochemsitry and
Molecular Biology. Iowa State University.
http://www.bb.iastate.edu/faculty/nilsham.html
Accessed 10/4/02.
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Copyright 2002 Department of Biology, Davidson College, Davidson, NC
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