| TCID | Name | Domain | Kingdom/Phylum | Protein(s) |
|---|---|---|---|---|
|
2.A.50.1.1 | Putative glycerol:H+ symporter of 546 aas and 12 TMSs, GUP1. In yeast, Gup1 is associated with a high number and diversity of biological functions, namely polarity establishment, secretory/endocytic pathway functionality, vacuole morphology, wall and membrane composition, structure and maintenance, cell death, morphogenesis and differentiation (Lucas et al. 2016). The protein HHAT (Hedgehog O-acyltransferase) modifies Hh morphogens prior to their secretion, while HHATL (Hh O-acyltransferase-like) negatively regulates the pathway. HHAT and HHATL are homologous to Saccharomyces cerevisiae Gup2 and Gup1, respectively (Lucas et al. 2016). | Eukaryota |
Fungi, Ascomycota | GUP1 of Saccharomyces cerevisiae |
|
2.A.50.1.2 | Protein-cysteine N-palmitoyltransferase HHAT-like protein (Glycerol uptake/transporter homologue) (Hedgehog acyltransferase-like protein) | Eukaryota |
Metazoa, Chordata | HHATL protein of Mus musculus |
|
2.A.50.1.3 | Protein-cysteine N-palmitoyltransferase HHAT (EC 2.3.1.-) (Hedgehog acyltransferase) (Skinny hedgehog protein) | Eukaryota |
Metazoa, Chordata | Hhat of Mus musculus |
|
2.A.50.1.4 | SKI1, HHAT or MART2 (The Sonic Hedgehog) of 493 aas and 11 - 13 TMSs. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). Jiang et al. 2021 presented cryo-EM structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures revealed how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis (Jiang et al. 2021). The Sonic Hedgehog (SHH) morphogen pathway is fundamental for embryonic development and stem cell maintenance and is implicated in various cancers. A key step in signaling is transfer of a palmitate group to the SHH N terminus, catalyzed by HHAT. Coupland et al. 2021 presented a high-resolution cryo-EM structure of HHAT bound to substrate analog palmityl-coenzyme A and a SHH-mimetic megabody, revealing a heme group bound to HHAT that is essential for HHAT function. A structure of HHAT bound to potent small-molecule inhibitor IMP-1575 revealed conformational changes in the active site that occlude substrate binding. The analysis provided a detailed view of the mechanism by which HHAT adapts the membrane environment to transfer an acyl chain across the endoplasmic reticulum membrane. This structure of a membrane-bound O-acyltransferase (MBOAT) superfamily member provides a blueprint for other protein-substrate MBOATs and a template for future drug discovery (Coupland et al. 2021). | Eukaryota |
Metazoa, Chordata | SKI1 of Homo sapiens |
|
2.A.50.1.5 | Skinny or Sightless (Rasp, Cmn, Sit, Ski) of 500 aas and 12 TMSs. It is required in hedgehog (hh) expressing cells for
production of appropriate signaling activity in embryos and in the
imaginal precursors of adult tissues. It acts within the secretory pathway
to catalyze N-terminal palmitoylation of Hh; this lipid modification is
required for the embryonic and larval patterning activities of the Hh
signal, but is not required for Wg signaling (Chamoun et al. 2001; Lee and Treisman 2001). | Eukaryota |
Metazoa, Arthropoda | Skinny of Drosophila melanogaster |
|
2.A.50.2.1 | The alanyl teichoic acid synthesis protein, DltB of 395 aas and 12 TMSs. It may transport activated alanine across the membrane (Perego et al., 1995). Crystal structures of DltB, a membrane-bound O-acyl transferase, MBOAT, responsible for the D-alanylation of cell-wall teichoic acid in Gram-positive bacteri, both alone and in complex with the D-alanyl donor protein DltC (an acyl carrier protein) have been solved (Ma et al. 2018). DltB contains a ring of 11 peripheral transmembrane helices, which shield a highly conserved extracellular structural funnel extending into the middle of the lipid bilayer. The conserved catalytic histidine residue is located at the bottom of this funnel and is connected to the intracellular DltC (acyl carrier protein) through a narrow tunnel. Mutation of either the catalytic histidine or the DltC-binding site of DltB abolishes D-alanylation of lipoteichoic acid and sensitizes Bacillus subtilis to cell-wall stress, which suggests cross-membrane catalysis involving the tunnel. Structure-guided sequence comparisons among DltB and vertebrate MBOATs reveals a conserved structural core and suggests that MBOATs from different organisms have similar catalytic mechanisms (Ma et al. 2018). | Bacteria |
Bacillota | DltB of Bacillus subtilis (P39580) DltC of Bacillus subtiois (P39579) |
|
2.A.50.2.2 | MBOAT family protein of 494 aas and 10 - 12 TMSs. | Bacteria |
Spirochaetota | MBOAT family protein of Leptospira santarosai |
|
2.A.50.2.3 | Uncharacterized MBOAT family protein of 461 aas and 12 TMSs, AlgI, possibly a poly(beta-D-mannuronate) O-acetylase. | Bacteria |
Bacteroidota | UP of Lunatimonas lonarensis |
|
2.A.50.2.4 | Uncharacterized MBOAT family protein of 483 aas and 11 TMSs. | Eukaryota |
Evosea | UP of Entamoeba histolytica |
|
2.A.50.2.5 | MBOAT7, also called BB1, LENG4, OCT7, of 472 aas and possibly 12 TMSs as 3 sets of 4 putative TMSs, where in each set, the last two TMSs are closs together. Caddeo et al. 2019 reported that the protein is anchored to the endo membrane via a 6 TMS domain. The predicted catalytic dyad of the protein, composed of the conserved asparagine in position 321 (Asn-321) and the preserved histidine in position 356 (His-356), has a lumenal localization. This is compatible with the role of MBOAT7 in remodeling the acyl chain composition of endomembranes. Obesity-linked suppression of MBOAT7 drives non-alcoholic fatty liver disease (Helsley et al. 2019). It may be involved in nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) (Di Sessa et al. 2021; | Eukaryota |
Metazoa, Chordata | MBOAT7 of Homo sapiens |
|
2.A.50.2.6 | MBOAT4, GOAT, or OACT4 of 435 aas and 7 - 9 TMSs in a 4 - 6 + 3 TMS arrangement. It mediates the octanoylation of ghrelin at 'Ser-3',but can use a variety of fatty acids as substrates including octanoic acid, decanoic acid and tetradecanoic acid (Gutierrez et al. 2008). Campaña et al. 2019 reported a structural model of a eukaryotic membrane-bound O-acyltransferase (MBOAT), ghrelin O-acyltransferase (GOAT), which modifies the metabolism-regulating hormone, ghrelin. The proposed structure revealed a strategy for transmembrane protein acylation with catalysis occurring in an internal channel connecting the endoplasmic reticulum (ER) lumen and the cytoplasm (Campaña et al. 2019).
| Metazoa, Chordata | MBOAT4 of Homo sapiens | |
|
2.A.50.2.7 | Uncharacterized membrane-bound O-acyltransferase domain-containing 2-like protein of 452 aas and 10 TMSs in a 7 + 3 TMS arrangement. | Eukaryota |
Metazoa, Porifera | UAT of Amphimedon queenslandica |
|
2.A.50.2.8 | Uncharacterized membrane-bound O-acyl transferase, MBOAT of 511 aas and ~11 TMSs in a 7 - 9 + 3 - 4 TMS arrangement. MBOAT exhibits broad substrate specificity (Matsuda et al. 2008). It is required for incorporation of unsaturated fatty acids into phosphatidylinositol (Lee et al. 2008). | Metazoa, Nematoda | MBOAT of Caenorhabditis elegans | |
|
2.A.50.2.9 | Uncharacterized acyltransferase of 461 aas and probably 10 TMSs in an 8 + 3 or 4 TMS arrangement. | Eukaryota |
Ciliophora | U-AT of Paramecium tetraurelia |
|
2.A.50.2.10 | Lysophospholipid acyltransferase 1-like protein of 459 aas and ~ 10 TMSs. | Eukaryota |
Viridiplantae, Streptophyta | AT of Solanum pennellii |
|
2.A.50.3.1 | Porcupine, a protein-serine O-palmitoleoyltransferase
that acts as a key regulator of the Wnt signaling pathway by mediating
the attachment of palmitoleate, a 16-carbon mono-unsaturated fatty acid
(C16:1), to Wnt proteins. Serine palmitoleylation of WNT proteins is
required for efficient binding to frizzled receptors (Caricasole et al. 2002; Coombs et al. 2010; Gao and Hannoush 2014). It also regulates the AMPA/TARP complex in a TARP-dependent manner (Kato and Witkin 2018). | Eukaryota |
Metazoa, Chordata | Porcupine of Homo sapiens |
|
2.A.50.3.2 | Porcupine (Por) of 525 aas and 9 - 11 TMSs. Por is a protein-serine O-palmitoleoyltransferase
that acts as a key regulator of the Wnt signaling pathway by mediating
the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid
(C16:1), to Wnt proteins. Serine palmitoleylation of Wnt proteins is
required for efficient binding to frizzled receptors (Herr and Basler 2012) | Eukaryota |
Metazoa, Arthropoda | Por of Drosophila melanogaster |
|
2.A.50.3.3 | Uncharacterized protein of 408 aas and 11 probable TMSs. | Eukaryota |
Metazoa, Nematoda | UP of Haemonchus placei |
|
2.A.50.4.1 | Diacylglycerol O-acyltransferase 1, DGAT1 or AGRP1, of 488 aas and 9 TMSs. The cryoEM structure has been determined (Wang et al. 2020). It synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans. DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins. Wang et al. 2020 addressed how human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions. They revealed the structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold, the MBOAT fold. It forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 exists as either a homodimer or a homotetramer, and the two forms have similar enzymatic activities. The N terminus of DGAT1 interacts with the neighbouring protomer, and these interactions are required for enzymatic activity (Wang et al. 2020). In liver it plays a role in esterifying exogenous fatty acids to glycerol and is the major acyl-CoA retinol acyltransferase in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity, leading to skin and hair disorders. It exhibits additional acyltransferase activities, including acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthesis (Ma et al. 2017). | Eukaryota |
Metazoa, Chordata | DGAT1 of Homo sapiens |
|
2.A.50.4.2 | Diacylglycerol O-acyltransferase 1 of 742 aas and 4 or 5 TMSs. A predicted transmembrane region in plant diacylglycerol acyltransferase 2 regulates specificity towards very long chain acyl-CoAs (Jeppson et al. 2020). | Eukaryota |
Viridiplantae, Streptophyta | Acyltransferase of Salvia splendens |
|
2.A.50.4.3 | Uncharacterized protein of 349 aas and 6 - 8 TMSs | Eukaryota |
Metazoa, Arthropoda | UP of Ooceraea biroi (clonal raider ant) |
|
2.A.50.4.4 | Uncharacterized protein of 228 aas and 5 or 6 TMSs in a 2 or 3 + 3 TMS arrangement. | Eukaryota |
Ciliophora | UP of Paramecium tetraurelia |
|
2.A.50.4.5 | Uncharacterized protein of 7 - 9 TMSs | Eukaryota |
Fungi, Ascomycota | UP of Coleophoma cylindrospora |
|
2.A.50.4.6 | Uncharacterized protein of 322 aas and 9 TMSs. | Planctomycetota | UP of Planctomycetes bacterium | |
|
2.A.50.4.7 | Sterol or diacylglycerol O-acyltransferase of 785 aas and 10 or 11 TM | Eukaryota |
Acyltransferase of Ectocarpus siliculosus
| |
|
2.A.50.4.8 | Uncharacterized protein of 466 aas and 4 C-terminal TMSs | Eukaryota |
Bacillariophyta | UP of Thalassiosira oceanica |
|
2.A.50.4.9 | Uncharacterized protein of 494 aas and 8 or 9 TMSs | Eukaryota |
Bacillariophyta | UP of Fragilariopsis cylindrus |
|
2.A.50.4.10 | Diacylglycerol O-acyltransferase 2, DGAT2, of 341 aas and 8 or 9 TMSs. It is involved in the pathway for triacylglycerol biosynthesis, which is important for providing triglycerides in seeds. A predicted transmembrane region in plant diacylglycerol acyltransferase 2 regulates specificity towards very long chain acyl-CoAs (Jeppson et al. 2020).
| Eukaryota |
Viridiplantae, Streptophyta | DGAT2 of Brassica napus |
|
2.A.50.4.11 | Sterol O-acyltransferase 2, SOAT2, ACAT2 or ACACT2, of 522 aas and 7 - 10 TMSs. See also TC# 9.B.418.1.2. | Eukaryota |
Metazoa, Chordata | SOAT2 of Homo sapiens |