| ABHD5 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | ABHD5 , CDS, CGI58, IECN2, NCIE2, abhydrolase domain containing 5, abhydrolase domain containing 5, lysophosphatidic acid acyltransferase | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 604780 MGI: 1914719 HomoloGene: 41088 GeneCards: ABHD5 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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1-acylglycerol-3-phosphate O-acyltransferase ABHD5, also known as comparative gene identification-58 (CGI-58), [5] is an enzyme that in humans is encoded by the ABHD5 gene. [6] [7]
The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [7] [8]
CGI-58 is known to be a co-activator of adipose triglyceride lipase (ATGL/PNPLA2) that associates with lipid droplets in association with perilipin proteins. [5] Phosphorylation of certain perilipins by protein kinase A causes dissociation of CGI-58 from the perilipins and permits interaction with ATGL. [5] CGI-58 additionally interacts with beclin 1, [5] [9] and CGI-58 has been shown to promote autophagy in colorectal cancer in a PNPLA2-independent manner. [9] [10]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Plasma immunoglobulins | Normal |
| Haematology | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Salmonella infection | Normal [11] |
| Citrobacter infection | Normal [12] |
| All tests and analysis from [13] [14] |
Model organisms have been used in the study of ABHD5 function. A conditional knockout mouse line, called Abhd5tm1a(KOMP)Wtsi [15] [16] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. [17] [18] [19]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [13] [20] Twenty three tests were carried out on mutant mice but no significant abnormalities were observed. [13]
Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important regulatory hormone in lipolysis is insulin; lipolysis can only occur when insulin action falls to low levels, as occurs during fasting. Other hormones that affect lipolysis include glucagon, epinephrine, norepinephrine, growth hormone, atrial natriuretic peptide, brain natriuretic peptide, and cortisol.
Perilipin, also known as lipid droplet-associated protein, perilipin 1, or PLIN, is a protein that, in humans, is encoded by the PLIN gene. The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphorylation of perilipin is essential for the mobilization of fats in adipose tissue.
Starvation response in animals is a set of adaptive biochemical and physiological changes, triggered by lack of food or extreme weight loss, in which the body seeks to conserve energy by reducing the amount of calories it burns.
Hormone-sensitive lipase (EC 3.1.1.79, HSL), also previously known as cholesteryl ester hydrolase (CEH), sometimes referred to as triacylglycerol lipase, is an enzyme that, in humans, is encoded by the LIPE gene, and catalyzes the following reaction:
Adipose differentiation-related protein, also known as perilipin 2, ADRP or adipophilin, is a protein which belongs from PAT family of cytoplasmic lipid droplet(CLD) binding protein. In humans it is encoded by the ADFP gene. This protein surrounds the lipid droplet along with phospholipids and are involved in assisting the storage of neutral lipids within the lipid droplets.
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating is an enzyme that in humans is encoded by the NSDHL gene. This enzyme is localized in the endoplasmic reticulum and is involved in cholesterol biosynthesis.
Centromere protein J is a protein that in humans is encoded by the CENPJ gene. It is also known as centrosomal P4.1-associated protein (CPAP). During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein.
Adipose triglyceride lipase, also known as patatin-like phospholipase domain-containing protein 2 and ATGL, is an enzyme that in humans is encoded by the PNPLA2 gene. ATGL catalyses the first reaction of lipolysis, where triacylglycerols are hydrolysed to diacylglycerols.
Protein HIRA is a protein that in humans is encoded by the HIRA gene. This gene is mapped to 22q11.21, centromeric to COMT.
Kaptin is a protein that in humans is encoded by the KPTN gene.
SLC35F6 is a protein that in humans is encoded by the SLC35F6 gene. The orthologue in mice is 4930471M23Rik.
Microsomal glutathione S-transferase 3 is an enzyme that in humans is encoded by the MGST3 gene.
Neutral lipid storage disease is a congenital autosomal recessive disorder characterized by accumulation of triglycerides in the cytoplasm of leukocytes[1], muscle, liver, fibroblasts, and other tissues. It commonly occurs as one of two subtypes, cardiomyopathic neutral lipid storage disease (NLSD-M), or ichthyotic neutral lipid storage disease (NLSD-I) which is also known as Chanarin–Dorfman syndrome), which are characterized primarily by myopathy and ichthyosis, respectively. Normally, the ichthyosis that is present is typically non-bullous congenital ichthyosiform erythroderma which appears as white scaling.
Solute carrier family 52, member 3, formerly known as chromosome 20 open reading frame 54 and riboflavin transporter 2, is a protein that in humans is encoded by the SLC52A3 gene.
Pirinixic acid is a peroxisome proliferator-activated receptor alpha (PPARα) agonist that is under experimental investigation for prevention of severe cardiac dysfunction, cardiomyopathy and heart failure as a result of lipid accumulation within cardiac myocytes. Treatment is primarily aimed at individuals with an adipose triglyceride lipase (ATGL) enzyme deficiency or mutation because of the essential PPAR protein interactions with free fatty acid monomers derived from the ATGL catalyzed lipid oxidation reaction. It was discovered as WY-14,643 in 1974.
Lysophospholipase-like 1 is a protein in humans that is encoded by the LYPLAL1 gene. The protein is a α/β-hydrolase of uncharacterized metabolic function. Genome-wide association studies in humans have linked the gene to fat distribution and waist-to-hip ratio. The protein's enzymatic function is unclear. LYPLAL1 was reported to act as a triglyceride lipase in adipose tissue and another study suggested that the protein may play a role in the depalmitoylation of calcium-activated potassium channels. However, LYPLAL1 does not depalmitoylate the oncogene Ras and a structural and enzymatic study concluded that LYPLAL1 is generally unable to act as a lipase and is instead an esterase that prefers short-chain substrates, such as acetyl groups. Structural comparisons have suggested that LYPLAL1 might be a protein deacetylase, but this has not been experimentally tested.
ANGPTL8 is a protein that in humans is encoded by the C19orf80 gene.
Fat storage-inducing transmembrane protein 2 is a protein that in humans is encoded by the FITM2 gene. It plays a role in fat storage. Its location is 20q13.12 and it contains 2 exons. It is also a member of the FIT protein family that has been conserved throughout evolution. Conserved from Saccharomyces cerevisiae to humans is the capability to take fat and store it as cytoplasmic triglyceride droplets. While FIT proteins facilitate the segregation of triglycerides (TGs) into cytosolic lipid droplets, they are not involved in triglyceride biosynthesis. In mammals, both FIT2 and FIT1 from the same family are present, embedded in the wall of the endoplasmic reticulum (ER) where they regulate lipid droplet formation in the cytosol. In S. cerevisiae, it also plays a role in the metabolism of phospholipids. These TGs are in the cytoplasm, encapsulated by a phospholipid monolayer in configurations or organelles that have been given many different names including lipid particles, oil bodies, adiposomes, eicosasomes, and most prevalent in scientific research – lipid droplets.
Perilipin 4, also known as S3-12, is a protein that in humans is encoded by the PLIN4 gene on chromosome 19. It is highly expressed in white adipose tissue, with lower expression in heart, skeletal muscle, and brown adipose tissue. PLIN4 coats lipid droplets in adipocytes to protect them from lipases. The PLIN4 gene may be associated with insulin resistance and obesity risk.
Jordans' anomaly is a familial abnormality of white blood cell morphology. Individuals with this condition exhibit persistent vacuolation of granulocytes and monocytes in the peripheral blood and bone marrow. Jordans' anomaly is associated with neutral lipid storage diseases.
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