SOAT1

Last updated
SOAT1
Identifiers
Aliases SOAT1 , ACACT, ACAT, ACAT-1, ACAT1, SOAT, STAT, sterol O-acyltransferase 1
External IDs OMIM: 102642 MGI: 104665 HomoloGene: 2333 GeneCards: SOAT1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001252511
NM_001252512
NM_003101

NM_009230

RefSeq (protein)

NP_001239440
NP_001239441
NP_003092

NP_033256

Location (UCSC) Chr 1: 179.29 – 179.36 Mb Chr 1: 156.25 – 156.3 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1, also known as SOAT1, is an enzyme that in humans is encoded by the SOAT1 gene. [5]

Contents

Function

Acyl-coenzyme A:cholesterol acyltransferase (EC 2.3.1.26) is an intracellular protein located in the endoplasmic reticulum that forms cholesterol esters from cholesterol. Accumulation of cholesterol esters as cytoplasmic lipid droplets within macrophages and smooth muscle cells is a characteristic feature of the early stages of atherosclerotic plaques (Cadigan et al., 1988). [5]

Structure and biogenesis

SOAT1 is a polytopic integral membrane protein belonging to the membrane-bound O-acyltransferase (MBOAT) superfamily. The structure of SOAT1 has not yet been solved but that of DltB, a bacterial MBOAT, suggests a complex arrangement of multiple transmembrane domains (TMDs). [6] Primary sequences of predicted SOAT1 TMDs indicate many unusual TMD features such as the presence of multiple charged residues within the lipid bilayer. [7] These features can render challenging the integration of a TMD into the hydrophobic phase of the membrane and might therefore require specialised chaperones. A first hint of such a chaperone assisting SOAT1 biogenesis has been the recognition of the involvement of the ER membrane protein complex (EMC), a molecular chaperone and insertase for integral membrane proteins, in maintaining SOAT1 stability. [8]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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StatinPathway WP430.png go to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
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Statin Pathway edit
  1. The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

See also


Related Research Articles

HMG-CoA reductase Mammalian protein found in Homo sapiens

HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled. This enzyme is the target of the widely available cholesterol-lowering drugs known collectively as the statins, which help treat dyslipidemia.

Lecithin–cholesterol acyltransferase

Lecithin–cholesterol acyltransferase is an enzyme, in many animals including humans, that converts free cholesterol into cholesteryl ester, which is then sequestered into the core of a lipoprotein particle, eventually making the newly synthesized HDL spherical and forcing the reaction to become unidirectional since the particles are removed from the surface. The enzyme is bound to high-density lipoproteins (HDLs) (alpha-LCAT) and LDLs (beta-LCAT) in the blood plasma. LCAT deficiency can cause impaired vision due to cholesterol corneal opacities, anemia, and kidney damage. It belongs to the family of phospholipid:diacylglycerol acyltransferases.

Mitochondrial trifunctional protein

Mitochondrial trifunctional protein (MTP) is a protein attached to the inner mitochondrial membrane which catalyzes three out of the four steps in beta oxidation. MTP is a hetero-octamer composed of four alpha and four beta subunits:

Carnitine palmitoyltransferase I

Carnitine palmitoyltransferase I (CPT1) also known as carnitine acyltransferase I, CPTI, CAT1, CoA:carnitine acyl transferase (CCAT), or palmitoylCoA transferase I, is a mitochondrial enzyme responsible for the formation of acyl carnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from coenzyme A to l-carnitine. The product is often Palmitoylcarnitine, but other fatty acids may also be substrates. It is part of a family of enzymes called carnitine acyltransferases. This "preparation" allows for subsequent movement of the acyl carnitine from the cytosol into the intermembrane space of mitochondria.

Lanosterol synthase Mammalian protein found in Homo sapiens

Lanosterol synthase is an oxidosqualene cyclase (OSC) enzyme that converts (S)-2,3-oxidosqualene to a protosterol cation and finally to lanosterol. Lanosterol is a key four-ringed intermediate in cholesterol biosynthesis. In humans, lanosterol synthase is encoded by the LSS gene.

ACAT1

Acetyl-CoA acetyltransferase, mitochondrial, also known as acetoacetyl-CoA thiolase, is an enzyme that in humans is encoded by the ACAT1 gene.

Diglyceride acyltransferase, DGAT, catalyzes the formation of triglycerides from diacylglycerol and fatty acyl-CoA]. The reaction catalyzed by DGAT is considered the terminal and only committed step in triglyceride synthesis. The conversion is essential for intestinal absorption and adipose tissue formation.

Caveolin 1 Protein-coding gene in the species Homo sapiens

Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.

Sterol regulatory element-binding protein 1 Protein-coding gene in the species Homo sapiens

Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a protein that in humans is encoded by the SREBF1 gene.

ATP citrate synthase

ATP citrate synthase is an enzyme that in animals represents an important step in fatty acid biosynthesis. By converting citrate to acetyl-CoA, the enzyme links carbohydrate metabolism, which yields citrate as an intermediate, with fatty acid biosynthesis, which consumes acetyl-CoA. In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursors of thousands of specialized metabolites, including waxes, sterols, and polyketides.

Sterol O-acyltransferase is an intracellular protein located in the endoplasmic reticulum that forms cholesteryl esters from cholesterol.

Insulin-induced gene 1 protein

Insulin induced gene 1, also known as INSIG1, is a protein which in humans is encoded by the INSIG1 gene.

SOAT2

Sterol O-acyltransferase 2, also known as SOAT2, is an enzyme that in humans is encoded by the SOAT2 gene.

MOGAT2

2-Acylglycerol O-acyltransferase 2 also known as acyl-CoA:monoacylglycerol acyltransferase 2 (MGAT2) or Diacylglycerol O-acyltransferase candidate 5 (DC5) is an enzyme that in humans is encoded by the MOGAT2 gene.

ACAT1 mRNA

Human acetyl-coA cholesterol acyltransferase (ACAT1) gene produces a chimeric mRNA through the interchromosomal processing of two discontinuous RNAs transcribed from chromosomes 1 and 7. This chimeric mRNA uses AUG as a translation initiation codon to produce the normal 50-kDa ACAT1 protein but used an alternative translation initiation codon, GGC, to produce the novel enzymatically active 56-kDa isoform.

ACAT2 Protein-coding gene in the species Homo sapiens

Acetyl-CoA acetyltransferase, cytosolic, also known as cytosolic acetoacetyl-CoA thiolase, is an enzyme that in humans is encoded by the ACAT2 gene

Monolysocardiolipin acyltransferase is a mitochondrial acyltransferase that facilitates the remodeling of monolysocardiolipin (MLCL) into cardiolipin.

The MBOAT family of membrane proteins is a family of various acyltransferase enzymes. All family members contain multiple transmembrane domains and most carry two conserved residues, a conserved histidine (His) embedded in a hydrophobic stretch of residues and an asparagine (Asn) or histidine within a more hydrophilic region some 30-50 residues upstream.

MOGAT3

Monoacylglycerol O-acyltransferase 3 is a protein that in humans is encoded by the MOGAT3 gene.

ACOT13 Protein-coding gene in the species Homo sapiens

Acyl-CoA thioesterase 13 is a protein that in humans is encoded by the ACOT13 gene. This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000057252 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026600 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: SOAT1 sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1".
  6. Ma D, Wang Z, Merrikh CN, Lang KS, Lu P, Li X, Merrikh H, Rao Z, Xu W (October 2018). "Crystal structure of a membrane-bound O-acyltransferase". Nature. 562 (7726): 286–290. Bibcode:2018Natur.562..286M. doi:10.1038/s41586-018-0568-2. PMC   6529733 . PMID   30283133.
  7. Lin S, Cheng D, Liu MS, Chen J, Chang TY (August 1999). "Human acyl-CoA:cholesterol acyltransferase-1 in the endoplasmic reticulum contains seven transmembrane domains". The Journal of Biological Chemistry. 274 (33): 23276–85. doi: 10.1074/jbc.274.33.23276 . PMID   10438503.
  8. Volkmar N, Thezenas ML, Louie SM, Juszkiewicz S, Nomura DK, Hegde RS, Kessler BM, Christianson JC (January 2019). "The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis". Journal of Cell Science. 132 (2): jcs223453. doi:10.1242/jcs.223453. PMC   6362398 . PMID   30578317.

Further reading