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Conserved domains on  [gi|568961031|ref|XP_006511012|]
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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

Graphical summary

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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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  50 IVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRWVPQMADHAEVMRGIRQYPGVRYPVLTPNLQGFQ 129
Cdd:cd07938    1 IVEVGPRDGLQNEKTFIPTEDKIELIDALSAAGLRRIEVTSFVSPKWVPQMADAEEVLAGLPRRPGVRYSALVPNLRGAE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 130 HAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRGYVSCALGCPYEGSITPQKVTEVSKRLYG 209
Cdd:cd07938   81 RALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRVRGYVSTAFGCPYEGEVPPERVAEVAERLLD 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568961031 210 MGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:cd07938  161 LGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALANILAALE 216
 
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  50 IVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRWVPQMADHAEVMRGIRQYPGVRYPVLTPNLQGFQ 129
Cdd:cd07938    1 IVEVGPRDGLQNEKTFIPTEDKIELIDALSAAGLRRIEVTSFVSPKWVPQMADAEEVLAGLPRRPGVRYSALVPNLRGAE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 130 HAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRGYVSCALGCPYEGSITPQKVTEVSKRLYG 209
Cdd:cd07938   81 RALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRVRGYVSTAFGCPYEGEVPPERVAEVAERLLD 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568961031 210 MGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:cd07938  161 LGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALANILAALE 216
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  44 LPEYVKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRWVPQMADHAEVMRGIRQYPGVRYPVLTP 123
Cdd:PRK05692   1 LPKRVKIVEVGPRDGLQNEKRFIPTADKIALIDRLSAAGLSYIEVASFVSPKWVPQMADAAEVMAGIQRRPGVTYAALTP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 124 NLQGFQHAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRGYVSCALGCPYEGSITPQKVTEV 203
Cdd:PRK05692  81 NLKGLEAALAAGADEVAVFASASEAFSQKNINCSIAESLERFEPVAEAAKQAGVRVRGYVSCVLGCPYEGEVPPEAVADV 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568961031 204 SKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:PRK05692 161 AERLFALGCYEISLGDTIGVGTPGQVRAVLEAVLAEFPAERLAGHFHDTYGQALANIYASLE 222
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
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031   48 VKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVtsfvssrWVPQMA-DHAEVMRGIRQYPGVR--YPVLTPN 124
Cdd:pfam00682   2 VAICDTTLRDGEQALGVAFSIDEKLAIARALDAAGVDEIEV-------GFPAASeDDFEVVRAIAKVIPHAriLVLCRAR 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  125 LQGFQHAVA----AGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIpvrgyvSCALGCPYEGSITPQKV 200
Cdd:pfam00682  75 EHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVKAARSRGI------DVEFSPEDASRTDPEFL 148

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568961031  201 TEVSKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQ 265
Cdd:pfam00682 149 AEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNKAiISVHCHNDLGMAVANSLAAVE 214
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  56 RDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSrwvpqmADHAEVMRGIRQYpgvrypVLTPNLQGFQHAV--- 132
Cdd:COG0119   12 RDGEQAPGVSFSVEEKLRIARLLDELGVDEIEAGFPAAS------PGDFEAVRRIAEL------GLDATICALARARrkd 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 133 ---------AAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRgyVSCalgcpyE-GSIT-PQKVT 201
Cdd:COG0119   80 idaalealkGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAKEHGLEVE--FSA------EdATRTdPDFLL 151

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568961031 202 EVSKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:COG0119  152 EVLEAAIEAGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVE 215
 
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  50 IVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRWVPQMADHAEVMRGIRQYPGVRYPVLTPNLQGFQ 129
Cdd:cd07938    1 IVEVGPRDGLQNEKTFIPTEDKIELIDALSAAGLRRIEVTSFVSPKWVPQMADAEEVLAGLPRRPGVRYSALVPNLRGAE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 130 HAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRGYVSCALGCPYEGSITPQKVTEVSKRLYG 209
Cdd:cd07938   81 RALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRVRGYVSTAFGCPYEGEVPPERVAEVAERLLD 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568961031 210 MGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:cd07938  161 LGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALANILAALE 216
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  44 LPEYVKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRWVPQMADHAEVMRGIRQYPGVRYPVLTP 123
Cdd:PRK05692   1 LPKRVKIVEVGPRDGLQNEKRFIPTADKIALIDRLSAAGLSYIEVASFVSPKWVPQMADAAEVMAGIQRRPGVTYAALTP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 124 NLQGFQHAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRGYVSCALGCPYEGSITPQKVTEV 203
Cdd:PRK05692  81 NLKGLEAALAAGADEVAVFASASEAFSQKNINCSIAESLERFEPVAEAAKQAGVRVRGYVSCVLGCPYEGEVPPEAVADV 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568961031 204 SKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:PRK05692 161 AERLFALGCYEISLGDTIGVGTPGQVRAVLEAVLAEFPAERLAGHFHDTYGQALANIYASLE 222
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  26 DSVAGALDAAQEASQLP-GLPEYVKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRWVPQMADHA 104
Cdd:PLN02746  24 SSSSNEVGVAHMHNKLLkGLPKFVKIVEVGPRDGLQNEKNIVPTSVKVELIQRLVSSGLPVVEATSFVSPKWVPQLADAK 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 105 EVMRGIRQYPGVRYPVLTPNLQGFQHAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRGYVS 184
Cdd:PLN02746 104 DVMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPVRGYVS 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 185 CALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTAL 264
Cdd:PLN02746 184 CVVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALANILVSL 263


                 .
gi 568961031 265 Q 265
Cdd:PLN02746 264 Q 264
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  51 VEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRWVPQMADHAEVMRGIRQY-PGVRYPVLTPN-LQGF 128
Cdd:cd03174    1 TDTTLRDGLQSEGATFSTEDKLEIAEALDEAGVDSIEVGSGASPKAVPQMEDDWEVLRAIRKLvPNVKLQALVRNrEKGI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 129 QHAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRGYVSCALGCPYegsiTPQKVTEVSKRLY 208
Cdd:cd03174   81 ERALEAGVDEVRIFDSASETHSRKNLNKSREEDLENAEEAIEAAKEAGLEVEGSLEDAFGCKT----DPEYVLEVAKALE 156

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 568961031 209 GMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:cd03174  157 EAGADEISLKDTVGLATPEEVAELVKALREALPDVPLGLHTHNTLGLAVANSLAALE 213
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
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031   48 VKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVtsfvssrWVPQMA-DHAEVMRGIRQYPGVR--YPVLTPN 124
Cdd:pfam00682   2 VAICDTTLRDGEQALGVAFSIDEKLAIARALDAAGVDEIEV-------GFPAASeDDFEVVRAIAKVIPHAriLVLCRAR 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  125 LQGFQHAVA----AGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIpvrgyvSCALGCPYEGSITPQKV 200
Cdd:pfam00682  75 EHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVKAARSRGI------DVEFSPEDASRTDPEFL 148

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568961031  201 TEVSKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQ 265
Cdd:pfam00682 149 AEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNKAiISVHCHNDLGMAVANSLAAVE 214
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  56 RDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSrwvpqmADHAEVMRGIRQYpgvrypVLTPNLQGFQHAV--- 132
Cdd:COG0119   12 RDGEQAPGVSFSVEEKLRIARLLDELGVDEIEAGFPAAS------PGDFEAVRRIAEL------GLDATICALARARrkd 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 133 ---------AAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRgyVSCalgcpyE-GSIT-PQKVT 201
Cdd:COG0119   80 idaalealkGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAKEHGLEVE--FSA------EdATRTdPDFLL 151

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568961031 202 EVSKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:COG0119  152 EVLEAAIEAGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVE 215
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  48 VKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSrwvPQMADHAEVMRGIrqypGVRYPVLTP---N 124
Cdd:cd07948    1 FKIIDSTLREGEQFANAFFDTEDKIEIAKALDAFGVDYIELTSPAAS---PQSRADCEAIAKL----GLKAKILTHircH 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 125 LQGFQHAVAAGATEIAVFGAASE---SFSK-KNINCSIEESMgrfqEVISSARHMDIPVRgyVSCalgcpyEGSITpqkv 200
Cdd:cd07948   74 MDDARIAVETGVDGVDLVFGTSPflrEASHgKSITEIIESAV----EVIEFVKSKGIEVR--FSS------EDSFR---- 137

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568961031 201 TEVSK--RLYG----MGCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGaLAVHCHDTYGQALANILTALQ 265
Cdd:cd07948  138 SDLVDllRVYRavdkLGVNRVGIADTVGIATPRQVYELVRTLRGVVSCD-IEFHGHNDTGCAIANAYAALE 207
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
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 568961031 211 GCYEISLGDTIGVGTPGSMKMMLESVMKEIPPGA--LAVHCHDTYGQALANILTALQ 265
Cdd:cd07940  156 GATTINIPDTVGYLTPEEFGELIKKLKENVPNIKvpISVHCHNDLGLAVANSLAAVE 212
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  45 PEYVKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTsfvssrwVPQM-ADHAEVMRGIRQYpGVRYPVLT- 122
Cdd:PRK11858   2 PKDIEIVDTTLRDGEQTPGVVFTNEEKLAIARMLDEIGVDQIEAG-------FPAVsEDEKEAIKAIAKL-GLNASILAl 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 123 --PNLQGFQHAVAAGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMDIPVRgyVScalgcPYEGSITPQK- 199
Cdd:PRK11858  74 nrAVKSDIDASIDCGVDAVHIFIATSDIHIKHKLKKTREEVLERMVEAVEYAKDHGLYVS--FS-----AEDASRTDLDf 146

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 200 VTEVSKRLYGMGCYEISLGDTIGVGTPGSM----KMMLESVMKEIppgalAVHCHDTYGQALANILTALQ 265
Cdd:PRK11858 147 LIEFAKAAEEAGADRVRFCDTVGILDPFTMyelvKELVEAVDIPI-----EVHCHNDFGMATANALAGIE 211
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
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031  47 YVKIVEVGPRDGLQNEKVIVPTDIKIELINQLSQTGLSVIEVTSFVSSRwvpqmaDHAEVMRGIRQYPGVRYPVLT---P 123
Cdd:PLN03228  84 YVRVLDTTLRDGEQSPGGSLTPPQKLEIARQLAKLRVDIMEVGFPGSSE------EEFEAVKTIAKTVGNEVDEETgyvP 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961031 124 NLQGFQHAVA------------AGATEIAVFGAASESFSKKNINCSIEESMGRFQEVISSARHMdipvrGYVSCALGCPY 191
Cdd:PLN03228 158 VICGIARCKKrdieaawealkyAKRPRILAFTSTSDIHMKYKLKKTKEEVIEMAVSSIRYAKSL-----GFHDIQFGCED 232

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568961031 192 EGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVmKEIPPGA----LAVHCHDTYGQALANILTAL 264
Cdd:PLN03228 233 GGRSDKEFLCKILGEAIKAGATSVGIADTVGINMPHEFGELVTYV-KANTPGIddivFSVHCHNDLGLATANTIAGI 308
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
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568961031 215 ISLGDTIGVGTPGSMKMMLESVMKEIPPGALA---VHCHDTYGQALANILTALQ 265
Cdd:PRK00915 166 INIPDTVGYTTPEEFGELIKTLRERVPNIDKAiisVHCHNDLGLAVANSLAAVE 219
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
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568961031 196 TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKMMLESVMKEIP-PgaLAVHCHDTYGQALANILTALQ 265
Cdd:cd07937  147 TLEYYVKLAKELEDMGADSICIKDMAGLLTPYAAYELVKALKKEVGlP--IHLHTHDTSGLAVATYLAAAE 215
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
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568961031 215 ISLGDTIGVGTPGSMKMMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 265
Cdd:cd07945  164 IMLPDTLGILSPFETYTYISDMVKRYPNLHFDFHAHNDYDLAVANVLAAVK 214
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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