This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
BTBD9 Protein
BTB/POZ domain containing 9, BTBD9, protein has a molecular weight of 69.20 kiloDaltons and an isoelectric point at pH=5.48 [1]. BTBD9, is primarily a cytosolic protein highly expressed in human nervous system and embryonic kidney cell lines, but is also found throughout all body tissues, see Figure 1 [6]. In the mammalian brain, BTBD9 is highly expressed in dopaminergic neurons, which may explain a link between BTBD9 and restless leg syndrome, as people with disorder are sometimes found to have low dopamine levels [2]. The Uniprot number is Q96Q07, accession number is NP_001092742.1 (The NP prefix means that this number describes a protein), and the protein FASTA sequence can be found here [4]. Please see the other pages from the Protein drop-down menu for more information about this protein.
BTBD9 protein localization
Figure 1: This image shows were BTBD9 protein localizes within the human body: 10 being the highest localization and 0 being no localization. As is shown, the brain has the highest amount of BTBD9, followed by thyroid and ovary. It makes sense to see the most protein in the brain as restless leg syndrome is described as a neurological disorder, affecting the brain and neurons. The ovary has a little higher amount of BTBD9 than the testis, which may reflect the reason women are more susceptible to restless leg syndrome [5].
Alternative Splicing
There are eight transcripts produced from alternative splicing of the BTBD9 mRNA. These transcripts have different base pair and amino acid lengths, for details, see Figure 2. Most transcripts are in protein coding regions, except BTBD9-006 which is a nonsense RNA. This alternative splicing of BTBD9 has led to three protein isoforms. Isoform 1 has a 612 amino acid sequence, and is labeled BTBD9 Isoform 1. There are two isoforms of the 612 amino acid protein, which I will use as the reference protein. Isoform 2, 582 amino acids long, is missing amino acids 1 through 61 and has the amino acid sequence -MC- in it's first two positions; isoform 2 also has an added 20 amino acid sequence at position 383 of protein isoform 1. Isoform 3, 544 amino acids long, is missing amino acids 1 though 68 in the protein sequence [3].
Figure 2: A chart showing the eight different transcripts produced from alternative splicing of the BTBD9 mRNA [7].
References
[1] http://www.geneinfinity.org/index.html?dp=5
[2] Freeman, A., et al. (2012). Sleep Fragmentation and Motor Restlessness in a Drosophila Model of Restless Legs Syndrome. Current Biology, 22(12), 1142-1148. doi:10.1016/j.cub.2012.04.027
[3] http://www.uniprot.org/uniprot/Q96Q07
[4] http://www.ncbi.nlm.nih.gov/projects/RefSeq/key.html
[5] http://www-test.ebi.ac.uk/gxa/experiments/E-MTAB-513;jsessionid=8511CDEC703226FCFC06821C2A784508?serializedFilterFactors=&queryFactorType=ORGANISM_PART&heatmapMatrixSize=50&displayLevels=false&displayGeneDistribution=false&geneQuery=btbd9&exactMatch=true&_exactMatch=on&_queryFactorValues=1&specific=true&_specific=on&cutoff=0.5
[6] http://www.ebi.ac.uk/gxa/gene/ENSG00000183826?ef=organism_part
[7] http://useast.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?g=ENSG00000183826;r=6:38136227-38607700;t=ENST00000481247
[2] Freeman, A., et al. (2012). Sleep Fragmentation and Motor Restlessness in a Drosophila Model of Restless Legs Syndrome. Current Biology, 22(12), 1142-1148. doi:10.1016/j.cub.2012.04.027
[3] http://www.uniprot.org/uniprot/Q96Q07
[4] http://www.ncbi.nlm.nih.gov/projects/RefSeq/key.html
[5] http://www-test.ebi.ac.uk/gxa/experiments/E-MTAB-513;jsessionid=8511CDEC703226FCFC06821C2A784508?serializedFilterFactors=&queryFactorType=ORGANISM_PART&heatmapMatrixSize=50&displayLevels=false&displayGeneDistribution=false&geneQuery=btbd9&exactMatch=true&_exactMatch=on&_queryFactorValues=1&specific=true&_specific=on&cutoff=0.5
[6] http://www.ebi.ac.uk/gxa/gene/ENSG00000183826?ef=organism_part
[7] http://useast.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?g=ENSG00000183826;r=6:38136227-38607700;t=ENST00000481247