Acyl-CoA thioesterase 9
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Acyl-CoA thioesterase 9 is a protein that is encoded by the human ACOT9 gene. It is a member of the acyl-CoA thioesterase superfamily, which is a group of enzymes that hydrolyze Coenzyme A esters. There is no known function, however it has been shown to act as a long-chain thioesterase at low concentrations, and a short-chain thioesterase at high concentrations.
The ACOT9 gene is located at p22.11 on chromosome X. Located on the minus strand of the chromosome, the start is at 23,721,777 bp and the end is at 23,761,407 bp, which is a span of 39,631 base pairs.
There are many orthologs of ACOT9, the house mouse (Mus musculus) being one of the most similar, where the ACOT9 gene is found at 72.38cM on chromosome X. The range of orthologs extends to mammals, birds, amphibians, anamorphic fungi, and others.
|Sequence number||Genus and species||Common name||Date of divergence (MYA)||Accession number||Sequence length||Sequence identity||Sequence similarity||Notes|
|2||Mus musculus||House mouse||91||NP_062710.2||439||83%||90%||Rodent|
|3||Pteropus alecto||Black flying fox||97.4||XP_006911668.1||480||81%||91%||Bat|
|5||Pseudopodoces humilis||Ground tit||324.5||XP_005516751.1||417||68%||85%||Bird|
|6||Columba livia||Rock dove||324.5||XP_005503782.1||402||67%||86%||Bird|
|7||Geospiza fortis||Medium ground finch||324.5||XP_005424946.1||417||67%||85%||Bird|
|8||Pelodiscus sinensis||Chinese soft shelled turtle||324.5||XP_006112565.1||439||67%||85%||Reptile|
|9||Xenopus tropicalis||Western clawed frog||361.2||AAI61600.1||418||65%||82%||Amphibian|
|11||Ceratitis capitata||Mediterranean fruit fly||910||JAB97119.1||433||32%||58%||Insect|
|12||Glarea lozoyensis 74030||Anamorphic fungus||1368||EHL00310.1||350||24%||47%||Fungus|
In mice, which is one of the closest orthologs, ACOT10 is a known paralog of the ACOT9 gene.
Expression of the ACOT9 is ubiquitous throughout the tissues in humans. Tissues with a value of over 500 in the large-scale analysis of the human transcriptome were the globus pallidus and colorectal adenocarcinoma. The expressed sequence tag (or EST) abundance profile also shows ubiquitous/near ubiquitous, expression throughout human tissues.
There are numerous transcription factors throughout the ACOT9 promotor sequence. Some of the notable factors are heat shock factors and transcription factor II B (TFIIB) recognition elements.
|X gene core promotor element 1||683||693||-||ggGCGGgaccg|
|Doublesex and mab-3 related transcription factor 1||81||101||+||tttttttgagacaTTGTctcc|
|cAMP-responsive element binding protein 1||491||511||-||agggcgTGACgtcgagaagag|
|Sp4 transcription factor||660||676||-||ccagggGGCGtggccgc|
|Stimulating protein 1, ubiquitous zinc finger transcription factor||682||698||-||tccggGGGCgggaccgc|
|Heat shock factor 1||24||48||+||caggactaaactAGAAtctccagcc|
|E2F transcription factor 2||808||824||+||ccatcGCGCgcacggca|
|Nuclear factor of activated T-cells 5||380||398||+||tttGGAAagttgcccagga|
|ZF5 POZ domain zinc finger, zinc finger protein 161 (secondary DNA binding preference)||811||825||+||tcgCGCGcacggcag|
|B-cell-specific activator protein||678||706||-||cagcggtgtccgggGGCGggaccgcggcg|
|Pax-6 paired domain binding site||54||72||+||gtctcAAGCatcagttttt|
|ZF5 POZ domain zinc finger, zinc finger protein 161 (secondary DNA binding preference)||651||665||-||ggcCGCGctgtgccg|
|Pax-6 paired domain binding site||758||776||+||ttttaTCGCctcagtttcc|
|Mammalian C-type LTR TATA box||751||767||-||ggcgaTAAAagacgcac|
|Nuclear factor Y (Y-box binding factor)||624||638||+||cccgCCAAtgaacgg|
|Transcription factor II B (TFIIB) recognition element||356||362||+||ccgCGCC|
|Transcription factor II B (TFIIB) recognition element||440||446||-||ccgCGCC|
|Transcription factor II B (TFIIB) recognition element||734||740||-||ccgCGCC|
|Nuclear factor Y (Y-box binding factor)||581||595||-||ccacTCAAtcagttg|
|CCAAT/enhancer binding protein alpha||529||543||-||tcggttgaGTAAacg|
There are two regions in the ACOT9 gene sequence that are labeled as BFIT (Brown Fat Inducible Thioesterase) and BACH (Brain Acyl CoA Hydrolase) regions. These regions are part of a hotdog fold superfamily, which has been found to be used in a variety of cell roles. Predictions show there to be various alpha-helices throughout the structure, suggesting it is a transmembrane protein.
A mitochondrial cleavage site can be found at amino acid 30 in the ACOT9 sequence, and the probability of export to the mitochondria is 0.9374. The Acyl-CoA thioesterase 9 protein is estimated to be 60.9% mitochondrial, 21.7% cytoplasmic, 8.7% nuclear, 4.3% in the plasma membrane, and 4.3% in the endoplasmic reticulum.
The ACOT9 protein has been found to interact with the following proteins either experimentally or through co-expression:
- Tillander V, Arvidsson Nordström E, Reilly J, Strozyk M, Van Veldhoven PP, Hunt MC, Alexson SE (2014). "Acyl-CoA thioesterase 9 (ACOT9) in mouse may provide a novel link between fatty acid and amino acid metabolism in mitochondria". Cellular and Molecular Life Sciences : CMLS 71 (5): 933–48. doi:10.1007/s00018-013-1422-1. PMID 23864032.
- Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D (June 12, 2002). "Human Feb. 2009 (GRCh37/hg19) Assembly". The human genome browser at UCSC. UCSC Genome Bioinformatics. Retrieved March 12, 2014.
- Gu J, MacHugh DE, McGivney BA, Park SD, Katz LM, Hill EW (2010). "Association of sequence variants in CKM (creatine kinase, muscle) and COX4I2 (cytochrome c oxidase, subunit 4, isoform 2) genes with racing performance in Thoroughbred horses". Equine Veterinary Journal. Supplement (38): 569–75. doi:10.1111/j.2042-3306.2010.00181.x. PMID 21059062.
- Poupon V, Bègue B, Gagnon J, Dautry-Varsat A, Cerf-Bensussan N, Benmerah A (1999). "Molecular cloning and characterization of MT-ACT48, a novel mitochondrial acyl-CoA thioesterase". The Journal of Biological Chemistry 274 (27): 19188–94. doi:10.1074/jbc.274.27.19188. PMID 10383425.
- "ACOT9 gene detail". Mouse Genome Database. Retrieved 2014-06-19.
- "Gene: Acot9". Ensembl release 75.
- "Large-scale analysis of the human transcriptome (HG-U133A)". National Center for Biotechnology Information. Retrieved 10 May 2014.
- "EST Profile Hs.298885 - ACOT9: Acyl-CoA thioesterase 9". Retrieved 10 May 2014.
- Dillon SC, Bateman A (2004). "The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases". BMC Bioinformatics 5: 109. doi:10.1186/1471-2105-5-109. PMC 516016. PMID 15307895.
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