Q9QYR9 Q6P2K2 few aa different The mouse ACOT gene cluster comprises six genes with localizations in cytosol (ACOT1), mitochondria (ACOT2), and peroxisomes (ACOT3-6). The corresponding human gene cluster contains only three genes (ACOT1, ACOT2, and ACOT4) coding for full-length thioesterase proteins only ACOT4 is peroxisomal
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Eukaryota: NE > Opisthokonta: NE > Metazoa: NE > Eumetazoa: NE > Bilateria: NE > Deuterostomia: NE > Chordata: NE > Craniata: NE > Vertebrata: NE > Gnathostomata: NE > Teleostomi: NE > Euteleostomi: NE > Sarcopterygii: NE > Dipnotetrapodomorpha: NE > Tetrapoda: NE > Amniota: NE > Mammalia: NE > Theria: NE > Eutheria: NE > Boreoeutheria: NE > Euarchontoglires: NE > Glires: NE > Rodentia: NE > Myomorpha: NE > Muroidea: NE > Muridae: NE > Murinae: NE > Mus [genus]: NE > Mus [subgenus]: NE > Mus musculus: NE
MVASSFAVLRASRLCQQDWKSWARLFVPPPLSTGGRTTWARTNATLSVEP
EGRSCWDEPLSIAVRGLAPEQPVTLRSALRDEKGALFRAHARYRADAGGE
LNLARAPALGGSFSGLEPMGLLWAMEPERPLWRLIKRDVQTPFLVELEVL
DGHEPDGGQRLAHAVHERHFLAPGVRRVPVREGRVRATLFLPPEPGPFPG
IIDLFGVGGGLLEYRASLLAGKGFAVMALAYYNYDDLPKSIETMHMEYFE
EAVNYLRSHPEVKGPGIGLLGISKGGELGLAMASFLKGITAAVVINGSVA
AVGNTISYKDETIPPVSLVRNQVKMTKDGLLDVVEALQSPLVDKKSFIPV
ERSDTTFLFLVGQDDHNWKSEFYADEISKRLQAHGKEKPQIICYPAAGHY
IEPPYFPLCSAGMHLLVGANITFGGEPRAHAVAQVDAWQQLQTFFHKQLG
SKS
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MVASSFAVLRASRLCQQDWKSWARLFVPPPLSTGGRTTWARTNATLSVEP EGRSCWDEPLSIAVRGLAPEQPVTLRSALRDEKGALFRAHARYRADAGGE LNLARAPALGGSFSGLEPMGLLWAMEPERPLWRLIKRDVQTPFLVELEVL DGHEPDGGQRLAHAVHERHFLAPGVRRVPVREGRVRATLFLPPEPGPFPG IIDLFGVGGGLLEYRASLLAGKGFAVMALAYYNYDDLPKSIETMHMEYFE EAVNYLRSHPEVKGPGIGLLGISKGGELGLAMASFLKGITAAVVINGSVA AVGNTISYKDETIPPVSLVRNQVKMTKDGLLDVVEALQSPLVDKKSFIPV ERSDTTFLFLVGQDDHNWKSEFYADEISKRLQAHGKEKPQIICYPAAGHY IEPPYFPLCSAGMHLLVGANITFGGEPRAHAVAQVDAWQQLQTFFHKQLG SKS
References
Title: Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs Hunt MC, Rautanen A, Westin MA, Svensson LT, Alexson SE Ref: FASEB Journal, 20:1855, 2006 : PubMed
The maintenance of cellular levels of free fatty acids and acyl-CoAs, the activated form of free fatty acids, is extremely important, as imbalances in lipid metabolism have serious consequences for human health. Acyl-coenzyme A (CoA) thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. We previously identified and characterized a mouse ACOT gene cluster comprised of six genes that apparently arose by gene duplications encoding acyl-CoA thioesterases with localizations in cytosol (ACOT1), mitochondria (ACOT2), and peroxisomes (ACOT3-6). However, the corresponding human gene cluster contains only three genes (ACOT1, ACOT2, and ACOT4) coding for full-length thioesterase proteins, of which only one is peroxisomal (ACOT4). We therefore set out to characterize the human genes, and we show here that the human ACOT4 protein catalyzes the activities of three mouse peroxisomal ACOTs (ACOT3, 4, and 5), being active on succinyl-CoA and medium to long chain acyl-CoAs, while ACOT1 and ACOT2 carry out similar functions to the corresponding mouse genes. These data strongly suggest that the human ACOT4 gene has acquired the functions of three mouse genes by a functional convergent evolution that also provides an explanation for the unexpectedly low number of human genes.
Acyl-CoA thioesterases hydrolyze acyl-CoAs to the corresponding free fatty acid plus coenzyme A. The activity is strongly induced in rat and mouse liver after feeding the animals peroxisome proliferators (PPs). To elucidate the role of these enzymes in lipid metabolism, the authors have cloned the cDNAs corresponding to the inducible cytosolic and mitochondrial type I enzymes (CTE-I and MTE-I), and studied tissue expression and nutritional regulation of expression of the mRNAs in mice. The constitutive expression of both mRNAs was low in liver, with CTE-I expressed mainly in kidney and brown adipose tissue, and MTE-I expressed in brown adipose tissue and heart. As expected, the expression in liver of both the CTE-I and MTE-I mRNAs were strongly induced (> 50-fold) by treatment with clofibrate. A similar level of induction was observed by fasting and a time-course study showed that the CTE-I and MTE-I mRNAs were increased already at 6 h after removal of the diet. Refeeding normal chow diet to mice fasted for 24 h normalized the mRNA levels with a T1/2 of about 3-4 h. Feeding mice a fat-free diet further decreased the expression, possibly indicating repression of expression. The strong expression of MTE-I and CTE-I in the heart was increased about 10-fold by fasting. To further characterize these highly regulated enzymes, the authors have cloned the corresponding genes and promoter regions. The structures of the two genes were found to be very similar, consisting of three exons and two introns. Exon-intron borders conform to general consensus sequences, and, especially, the first exon appears to be highly conserved. The promoter regions of both the CTE-I and MTE-I genes contain putative PP response elements, suggesting an involvement of PP-activated receptors in the regulation of these genes.
Title: Peroxisome proliferator-induced long chain acyl-CoA thioesterases comprise a highly conserved novel multi-gene family involved in lipid metabolism Hunt MC, Nousiainen SE, Huttunen MK, Orii KE, Svensson LT, Alexson SE Ref: Journal of Biological Chemistry, 274:34317, 1999 : PubMed
Long chain acyl-CoA esters are important intermediates in degradation and synthesis of fatty acids, as well as having important functions in regulation of intermediary metabolism and gene expression. Although the physiological functions for most acyl-CoA thioesterases have not yet been elucidated, previous data suggest that these enzymes may be involved in lipid metabolism by modulation of cellular concentrations of acyl-CoAs and fatty acids. In line with this, we have cloned four highly homologous acyl-CoA thioesterase genes from mouse, showing multiple compartmental localizations. The nomenclature for these genes has tentatively been assigned as CTE-I (cytosolic), MTE-I (mitochondrial), and PTE-Ia and Ib (peroxisomal), based on the identification of putative targeting signals. Although the various isoenzymes show between 67% and 94% identity at amino acid level, each individual enzyme shows a specific tissue expression. Our data suggest that all four genes are located within a very narrow cluster on chromosome 12 in mouse, similar to a sequence cluster on human chromosome 14, which identified four genes homologous to the mouse thioesterase genes. Four related genes were also identified in Caenorhabditis elegans, all containing putative PTS1 targeting signals, suggesting that the ancestral type I thioesterase gene(s) is/are of peroxisomal origin. All four thioesterases are differentially expressed in tissues examined, but all are inducible at mRNA level by treatment with the peroxisome proliferator clofibrate, or during the physiological condition of fasting, both of which conditions cause a perturbation in overall lipid homeostasis. These results strongly support the existence of a novel multi-gene family cluster of mouse acyl-CoA thioesterases, each with a distinct function in lipid metabolism.
Mus musculus (Mouse) Abhydrolase domain-containing protein 10, mitochondrial