3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic isoform X5 [Mus musculus]
Protein Classification
hydroxymethylglutaryl-CoA lyase( domain architecture ID 10168151)
hydroxymethylglutaryl-CoA lyase catalyzes the formation of acetoacetate and acetyl-CoA from 3-hydroxy-3-methylglutaryl-CoA
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||
| DRE_TIM_HMGL | cd07938 | 3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ... |
50-265 | 1.36e-139 | ||||
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". : Pssm-ID: 163676 Cd Length: 274 Bit Score: 393.30 E-value: 1.36e-139
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| Name | Accession | Description | Interval | E-value | ||||
| DRE_TIM_HMGL | cd07938 | 3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ... |
50-265 | 1.36e-139 | ||||
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". Pssm-ID: 163676 Cd Length: 274 Bit Score: 393.30 E-value: 1.36e-139
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| PRK05692 | PRK05692 | hydroxymethylglutaryl-CoA lyase; Provisional |
44-265 | 3.46e-139 | ||||
hydroxymethylglutaryl-CoA lyase; Provisional Pssm-ID: 180206 Cd Length: 287 Bit Score: 392.71 E-value: 3.46e-139
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| HMGL-like | pfam00682 | HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ... |
48-265 | 4.65e-50 | ||||
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase. Pssm-ID: 459902 [Multi-domain] Cd Length: 264 Bit Score: 165.21 E-value: 4.65e-50
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| LeuA | COG0119 | Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ... |
56-265 | 2.64e-12 | ||||
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis Pssm-ID: 439889 [Multi-domain] Cd Length: 452 Bit Score: 65.96 E-value: 2.64e-12
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| Name | Accession | Description | Interval | E-value | |||||
| DRE_TIM_HMGL | cd07938 | 3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ... |
50-265 | 1.36e-139 | |||||
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". Pssm-ID: 163676 Cd Length: 274 Bit Score: 393.30 E-value: 1.36e-139
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| PRK05692 | PRK05692 | hydroxymethylglutaryl-CoA lyase; Provisional |
44-265 | 3.46e-139 | |||||
hydroxymethylglutaryl-CoA lyase; Provisional Pssm-ID: 180206 Cd Length: 287 Bit Score: 392.71 E-value: 3.46e-139
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| PLN02746 | PLN02746 | hydroxymethylglutaryl-CoA lyase |
26-265 | 7.57e-138 | |||||
hydroxymethylglutaryl-CoA lyase Pssm-ID: 178347 Cd Length: 347 Bit Score: 391.85 E-value: 7.57e-138
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| DRE_TIM_metallolyase | cd03174 | DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes ... |
51-265 | 5.13e-85 | |||||
DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". Pssm-ID: 163674 [Multi-domain] Cd Length: 265 Bit Score: 254.69 E-value: 5.13e-85
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| HMGL-like | pfam00682 | HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ... |
48-265 | 4.65e-50 | |||||
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase. Pssm-ID: 459902 [Multi-domain] Cd Length: 264 Bit Score: 165.21 E-value: 4.65e-50
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| LeuA | COG0119 | Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ... |
56-265 | 2.64e-12 | |||||
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis Pssm-ID: 439889 [Multi-domain] Cd Length: 452 Bit Score: 65.96 E-value: 2.64e-12
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| DRE_TIM_HCS | cd07948 | Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel ... |
48-265 | 1.10e-08 | |||||
Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel domain; Homocitrate synthase (HCS) catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, the first step in the lysine biosynthesis pathway. This family includes the Yarrowia lipolytica LYS1 protein as well as the Saccharomyces cerevisiae LYS20 and LYS21 proteins. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". Pssm-ID: 163685 Cd Length: 262 Bit Score: 54.65 E-value: 1.10e-08
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| DRE_TIM_IPMS | cd07940 | 2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate ... |
211-265 | 2.25e-07 | |||||
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". Pssm-ID: 163678 Cd Length: 268 Bit Score: 50.52 E-value: 2.25e-07
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| aksA | PRK11858 | trans-homoaconitate synthase; Reviewed |
45-265 | 7.50e-06 | |||||
trans-homoaconitate synthase; Reviewed Pssm-ID: 183341 [Multi-domain] Cd Length: 378 Bit Score: 46.32 E-value: 7.50e-06
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| PLN03228 | PLN03228 | methylthioalkylmalate synthase; Provisional |
47-264 | 2.63e-05 | |||||
methylthioalkylmalate synthase; Provisional Pssm-ID: 178767 [Multi-domain] Cd Length: 503 Bit Score: 44.91 E-value: 2.63e-05
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| PRK00915 | PRK00915 | 2-isopropylmalate synthase; Validated |
215-265 | 5.62e-05 | |||||
2-isopropylmalate synthase; Validated Pssm-ID: 234864 [Multi-domain] Cd Length: 513 Bit Score: 43.95 E-value: 5.62e-05
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| DRE_TIM_PC_TC_5S | cd07937 | Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes ... |
196-265 | 3.38e-03 | |||||
Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes the carboxyltransferase domains of pyruvate carboxylase (PC) and the transcarboxylase (TC) 5S subunit. Transcarboxylase 5S is a cobalt-dependent metalloenzyme subunit of the biotin-dependent transcarboxylase multienzyme complex. Transcarboxylase 5S transfers carbon dioxide from the 1.3S biotin to pyruvate in the second of two carboxylation reactions catalyzed by TC. The first reaction involves the transfer of carbon dioxide from methylmalonyl-CoA to the 1.3S biotin, and is catalyzed by the 12S subunit. These two steps allow a carboxylate group to be transferred from oxaloacetate to propionyl-CoA to yield pyruvate and methylmalonyl-CoA. The catalytic domain of transcarboxylase 5S has a canonical TIM-barrel fold with a large C-terminal extension that forms a funnel leading to the active site. Transcarboxylase 5S forms a homodimer and there are six dimers per complex. In addition to the catalytic domain, transcarboxylase 5S has several other domains including a carbamoyl-phosphate synthase domain, a biotin carboxylase domain, a carboxyltransferase domain, and an ATP-grasp domain. Pyruvate carboxylase, like TC, is a biotin-dependent enzyme that catalyzes the carboxylation of pyruvate to produce oxaloacetate. In mammals, PC has critical roles in gluconeogenesis, lipogenesis, glyceroneogenesis, and insulin secretion. Inherited PC deficiencies are linked to serious diseases in humans such as lactic acidemia, hypoglycemia, psychomotor retardation, and death. PC is a single-chain enzyme and is active only in its homotetrameric form. PC has three domains, an N-terminal biotin carboxylase domain, a carboxyltransferase domain (this alignment model), and a C-terminal biotin-carboxyl carrier protein domain. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". Pssm-ID: 163675 Cd Length: 275 Bit Score: 38.18 E-value: 3.38e-03
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| DRE_TIM_CMS | cd07945 | Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic ... |
215-265 | 6.55e-03 | |||||
Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic TIM barrel domain; Citramalate synthase (CMS) catalyzes the conversion of pyruvate and acetyl-CoA to (R)-citramalate in the first dedicated step of the citramalate pathway. Citramalate is only found in Leptospira interrogans and a few other microorganisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM". Pssm-ID: 163683 [Multi-domain] Cd Length: 280 Bit Score: 37.36 E-value: 6.55e-03
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