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Conserved domains on  [gi|76159293|ref|NP_444283|]
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acyl-coenzyme A thioesterase THEM4 [Homo sapiens]

Protein Classification

PaaI family thioesterase( domain architecture ID 10130874)

PaaI family thioesterase is a member of the broader hot dog-fold acyl-CoA thioesterase family that catalyzes the conversion of acyl-CoAs back to free fatty acids and coenzyme A, similar to human acyl-coenzyme A thioesterase THEM5, which plays an important role in mitochondrial fatty acid metabolism, and in remodeling of the mitochondrial lipid cardiolipin

EC:  3.1.2.-
Gene Ontology:  GO:0047617|GO:0016790
PubMed:  15307895|16464851
TCDB:  9.B.371

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PaaI_thioesterase cd03443
PaaI_thioesterase is a tetrameric acyl-CoA thioesterase with a hot dog fold and one of several ...
 119-231 5.42e-22

PaaI_thioesterase is a tetrameric acyl-CoA thioesterase with a hot dog fold and one of several proteins responsible for phenylacetic acid (PA) degradation in bacteria. Although orthologs of PaaI exist in archaea and eukaryotes, their function has not been determined. Sequence similarity between PaaI, E. coli medium chain acyl-CoA thioesterase II, and human thioesterase III suggests they all belong to the same thioesterase superfamily. The conserved fold present in these thioesterases is referred to as an asymmetric hot dog fold, similar to those of 4-hydroxybenzoyl-CoA thioesterase (4HBT) and the beta-hydroxydecanoyl-ACP dehydratases (FabA/FabZ).


:

Pssm-ID: 239527 [Multi-domain]  Cd Length: 113  Bit Score: 87.23  E-value: 5.42e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76159293 119 LGFEYVmfyNDIEKRMVCLFQGGPYLEGPPGFIHGGAIATMIDATVGMCAMMA---GGIVMTANLNINYKRPIPLcSVVM 195
Cdd:cd03443   2 LGIRVV---EVGPGRVVLRLPVRPRHLNPGGIVHGGAIATLADTAGGLAALSAlppGALAVTVDLNVNYLRPARG-GDLT 77

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 76159293 196 INSQLDKVEGRKFFVSCNVQSVDEKtLYSEATSLFI 231
Cdd:cd03443  78 ARARVVKLGRRLAVVEVEVTDEDGK-LVATARGTFA 112
 
Name Accession Description Interval E-value
PaaI_thioesterase cd03443
PaaI_thioesterase is a tetrameric acyl-CoA thioesterase with a hot dog fold and one of several ...
 119-231 5.42e-22

PaaI_thioesterase is a tetrameric acyl-CoA thioesterase with a hot dog fold and one of several proteins responsible for phenylacetic acid (PA) degradation in bacteria. Although orthologs of PaaI exist in archaea and eukaryotes, their function has not been determined. Sequence similarity between PaaI, E. coli medium chain acyl-CoA thioesterase II, and human thioesterase III suggests they all belong to the same thioesterase superfamily. The conserved fold present in these thioesterases is referred to as an asymmetric hot dog fold, similar to those of 4-hydroxybenzoyl-CoA thioesterase (4HBT) and the beta-hydroxydecanoyl-ACP dehydratases (FabA/FabZ).


Pssm-ID: 239527 [Multi-domain]  Cd Length: 113  Bit Score: 87.23  E-value: 5.42e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76159293 119 LGFEYVmfyNDIEKRMVCLFQGGPYLEGPPGFIHGGAIATMIDATVGMCAMMA---GGIVMTANLNINYKRPIPLcSVVM 195
Cdd:cd03443   2 LGIRVV---EVGPGRVVLRLPVRPRHLNPGGIVHGGAIATLADTAGGLAALSAlppGALAVTVDLNVNYLRPARG-GDLT 77

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 76159293 196 INSQLDKVEGRKFFVSCNVQSVDEKtLYSEATSLFI 231
Cdd:cd03443  78 ARARVVKLGRRLAVVEVEVTDEDGK-LVATARGTFA 112
PaaI COG2050
Acyl-CoA thioesterase PaaI, contains HGG motif [Secondary metabolites biosynthesis, transport ...
 100-237 1.49e-17

Acyl-CoA thioesterase PaaI, contains HGG motif [Secondary metabolites biosynthesis, transport and catabolism];


Pssm-ID: 441653 [Multi-domain]  Cd Length: 138  Bit Score: 76.14  E-value: 1.49e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76159293 100 MKEEQMSQAQLFTRS-FDDGLGFEYVmfynDIEK-RMVCLFQGGPYLEGPPGFIHGGAIATMIDATVGMCAMMA---GGI 174
Cdd:COG2050   1 MSDPLERLEGFLAANpFAELLGIELV----EVEPgRAVLRLPVRPEHLNPPGTVHGGALAALADSAAGLAANSAlppGRR 76

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 76159293 175 VMTANLNINYKRPIPLCSVVMINSQLDKVEGRKFFVSCNVqSVDEKTLYSEATSLFIKLNPAK 237
Cdd:COG2050  77 AVTIELNINFLRPARLGDRLTAEARVVRRGRRLAVVEVEV-TDEDGKLVATATGTFAVLPKRP 138
4HBT pfam03061
Thioesterase superfamily; This family contains a wide variety of enzymes, principally ...
 149-222 2.36e-12

Thioesterase superfamily; This family contains a wide variety of enzymes, principally thioesterases. This family includes 4HBT (EC 3.1.2.23) which catalyzes the final step in the biosynthesis of 4-hydroxybenzoate from 4-chlorobenzoate in the soil dwelling microbe Pseudomonas CBS-3. This family includes various cytosolic long-chain acyl-CoA thioester hydrolases. Long-chain acyl-CoA hydrolases hydrolyse palmitoyl-CoA to CoA and palmitate, they also catalyze the hydrolysis of other long chain fatty acyl-CoA thioesters.


Pssm-ID: 427116 [Multi-domain]  Cd Length: 79  Bit Score: 60.73  E-value: 2.36e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 76159293   149 GFIHGGAIATMIDATVGMCAMMAGG---IVMTANLNINYKRPIPLCSVVMINSQLDKVEGRKFFVSCNVQSVDEKTL 222
Cdd:pfam03061   2 GVVHGGVYLALADEAAGAAARRLGGsqqVVVVVELSIDFLRPARLGDRLTVEARVVRLGRTSAVVEVEVRDEDGRLV 78
unchar_dom_1 TIGR00369
uncharacterized domain 1; Most proteins containing this domain consist almost entirely of a ...
 147-206 4.39e-04

uncharacterized domain 1; Most proteins containing this domain consist almost entirely of a single copy of this domain. A protein from C. elegans consists of two tandem copies of the domain. The domain is also found as the N-terminal region of an apparent initiation factor eIF-2B alpha subunit of Aquifex aeolicus. The function of the domain is unknown.


Pssm-ID: 161843 [Multi-domain]  Cd Length: 117  Bit Score: 38.87  E-value: 4.39e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 76159293   147 PPGFIHGGAIATMIDATVGMCAMM---AGGIVMTANLNINYKRP------IPLCSVVMINSQLDKVEGR 206
Cdd:TIGR00369  31 PFGSLHGGVSAALADTAGSAAGYLcnsGGQAVVGLELNANHLRParegkvRAIAQVVHLGRQTGVAEIE 99
 
Name Accession Description Interval E-value
PaaI_thioesterase cd03443
PaaI_thioesterase is a tetrameric acyl-CoA thioesterase with a hot dog fold and one of several ...
 119-231 5.42e-22

PaaI_thioesterase is a tetrameric acyl-CoA thioesterase with a hot dog fold and one of several proteins responsible for phenylacetic acid (PA) degradation in bacteria. Although orthologs of PaaI exist in archaea and eukaryotes, their function has not been determined. Sequence similarity between PaaI, E. coli medium chain acyl-CoA thioesterase II, and human thioesterase III suggests they all belong to the same thioesterase superfamily. The conserved fold present in these thioesterases is referred to as an asymmetric hot dog fold, similar to those of 4-hydroxybenzoyl-CoA thioesterase (4HBT) and the beta-hydroxydecanoyl-ACP dehydratases (FabA/FabZ).


Pssm-ID: 239527 [Multi-domain]  Cd Length: 113  Bit Score: 87.23  E-value: 5.42e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76159293 119 LGFEYVmfyNDIEKRMVCLFQGGPYLEGPPGFIHGGAIATMIDATVGMCAMMA---GGIVMTANLNINYKRPIPLcSVVM 195
Cdd:cd03443   2 LGIRVV---EVGPGRVVLRLPVRPRHLNPGGIVHGGAIATLADTAGGLAALSAlppGALAVTVDLNVNYLRPARG-GDLT 77

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 76159293 196 INSQLDKVEGRKFFVSCNVQSVDEKtLYSEATSLFI 231
Cdd:cd03443  78 ARARVVKLGRRLAVVEVEVTDEDGK-LVATARGTFA 112
PaaI COG2050
Acyl-CoA thioesterase PaaI, contains HGG motif [Secondary metabolites biosynthesis, transport ...
 100-237 1.49e-17

Acyl-CoA thioesterase PaaI, contains HGG motif [Secondary metabolites biosynthesis, transport and catabolism];


Pssm-ID: 441653 [Multi-domain]  Cd Length: 138  Bit Score: 76.14  E-value: 1.49e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76159293 100 MKEEQMSQAQLFTRS-FDDGLGFEYVmfynDIEK-RMVCLFQGGPYLEGPPGFIHGGAIATMIDATVGMCAMMA---GGI 174
Cdd:COG2050   1 MSDPLERLEGFLAANpFAELLGIELV----EVEPgRAVLRLPVRPEHLNPPGTVHGGALAALADSAAGLAANSAlppGRR 76

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 76159293 175 VMTANLNINYKRPIPLCSVVMINSQLDKVEGRKFFVSCNVqSVDEKTLYSEATSLFIKLNPAK 237
Cdd:COG2050  77 AVTIELNINFLRPARLGDRLTAEARVVRRGRRLAVVEVEV-TDEDGKLVATATGTFAVLPKRP 138
4HBT pfam03061
Thioesterase superfamily; This family contains a wide variety of enzymes, principally ...
 149-222 2.36e-12

Thioesterase superfamily; This family contains a wide variety of enzymes, principally thioesterases. This family includes 4HBT (EC 3.1.2.23) which catalyzes the final step in the biosynthesis of 4-hydroxybenzoate from 4-chlorobenzoate in the soil dwelling microbe Pseudomonas CBS-3. This family includes various cytosolic long-chain acyl-CoA thioester hydrolases. Long-chain acyl-CoA hydrolases hydrolyse palmitoyl-CoA to CoA and palmitate, they also catalyze the hydrolysis of other long chain fatty acyl-CoA thioesters.


Pssm-ID: 427116 [Multi-domain]  Cd Length: 79  Bit Score: 60.73  E-value: 2.36e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 76159293   149 GFIHGGAIATMIDATVGMCAMMAGG---IVMTANLNINYKRPIPLCSVVMINSQLDKVEGRKFFVSCNVQSVDEKTL 222
Cdd:pfam03061   2 GVVHGGVYLALADEAAGAAARRLGGsqqVVVVVELSIDFLRPARLGDRLTVEARVVRLGRTSAVVEVEVRDEDGRLV 78
hot_dog cd03440
The hotdog fold was initially identified in the E. coli FabA (beta-hydroxydecanoyl-acyl ...
 142-231 2.59e-09

The hotdog fold was initially identified in the E. coli FabA (beta-hydroxydecanoyl-acyl carrier protein (ACP)-dehydratase) structure and subsequently in 4HBT (4-hydroxybenzoyl-CoA thioesterase) from Pseudomonas. A number of other seemingly unrelated proteins also share the hotdog fold. These proteins have related, but distinct, catalytic activities that include metabolic roles such as thioester hydrolysis in fatty acid metabolism, and degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. This superfamily also includes the PaaI-like protein FapR, a non-catalytic bacterial homolog involved in transcriptional regulation of fatty acid biosynthesis.


Pssm-ID: 239524 [Multi-domain]  Cd Length: 100  Bit Score: 53.25  E-value: 2.59e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76159293 142 PYLEGPPGFIHGGAIATMIDATVGMCAMMAGG---IVMTANLNINYKRPIPLCSVVMINSQLDKVEGRKFFVSCNVqSVD 218
Cdd:cd03440   9 PEDIDGGGIVHGGLLLALADEAAGAAAARLGGrglGAVTLSLDVRFLRPVRPGDTLTVEAEVVRVGRSSVTVEVEV-RNE 87

                        90
                ....*....|...
gi 76159293 219 EKTLYSEATSLFI 231
Cdd:cd03440  88 DGKLVATATATFV 100
YciA COG1607
Acyl-CoA hydrolase [Lipid transport and metabolism];
147-206 1.87e-05

Acyl-CoA hydrolase [Lipid transport and metabolism];


Pssm-ID: 441215 [Multi-domain]  Cd Length: 146  Bit Score: 43.24  E-value: 1.87e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 76159293 147 PPGFIHGGAIATMIDATVGMCAM-MAGGIVMTANLN-INYKRPIPLCSVVMINSQLDKVeGR 206
Cdd:COG1607  20 HHGTLFGGWLLSWMDEAAAIAAArHARGRVVTASVDsVDFLRPVRVGDIVELYARVVRV-GR 80
BFIT_BACH cd03442
Brown fat-inducible thioesterase (BFIT). Brain acyl-CoA hydrolase (BACH). These enzymes ...
 142-221 3.33e-04

Brown fat-inducible thioesterase (BFIT). Brain acyl-CoA hydrolase (BACH). These enzymes deacylate long-chain fatty acids by hydrolyzing acyl-CoA thioesters to free fatty acids and CoA-SH. Eukaryotic members of this family are expressed in brain, testis, and brown adipose tissues. The archeal and eukaryotic members of this family have two tandem copies of the conserved hot dog fold, while most bacterial members have only one copy.


Pssm-ID: 239526 [Multi-domain]  Cd Length: 123  Bit Score: 39.47  E-value: 3.33e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76159293 142 PYLEGPPGFIHGGAIATMIDATVGMCAMM-AGGIVMTANLN-INYKRPIPLCSVVMINSQLDKVeGRKFF-VSCNVQSVD 218
Cdd:cd03442  16 PEDTNHHGTIFGGWLLEWMDELAGIAAYRhAGGRVVTASVDrIDFLKPVRVGDVVELSARVVYT-GRTSMeVGVEVEAED 94


                ...
gi 76159293 219 EKT 221
Cdd:cd03442  95 PLT 97
unchar_dom_1 TIGR00369
uncharacterized domain 1; Most proteins containing this domain consist almost entirely of a ...
 147-206 4.39e-04

uncharacterized domain 1; Most proteins containing this domain consist almost entirely of a single copy of this domain. A protein from C. elegans consists of two tandem copies of the domain. The domain is also found as the N-terminal region of an apparent initiation factor eIF-2B alpha subunit of Aquifex aeolicus. The function of the domain is unknown.


Pssm-ID: 161843 [Multi-domain]  Cd Length: 117  Bit Score: 38.87  E-value: 4.39e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 76159293   147 PPGFIHGGAIATMIDATVGMCAMM---AGGIVMTANLNINYKRP------IPLCSVVMINSQLDKVEGR 206
Cdd:TIGR00369  31 PFGSLHGGVSAALADTAGSAAGYLcnsGGQAVVGLELNANHLRParegkvRAIAQVVHLGRQTGVAEIE 99
 
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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