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Conserved domains on  [gi|1034614398|ref|XP_016859737|]
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oxaloacetate tautomerase FAHD2A, mitochondrial isoform X4 [Homo sapiens]

Protein Classification

fumarylacetoacetate hydrolase family protein( domain architecture ID 1000357)

fumarylacetoacetate (FAA) hydrolase family protein belongs to the FAA hydrolase family which includes a large variety of metabolic enzymes, such as those with hydrolase functions involved in the breakdown of aromatic compounds, oxaloacetate decarboxylase, and enzymes associated with other catabolic pathways including decarboxylation of substrates other than oxaloacetate, hydration, isomerization and hydroxylation reactions

CATH:  2.30.30.370
EC:  3.7.-.-
Gene Ontology:  GO:0003824|GO:0016787
PubMed:  29487229
SCOP:  4002580

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
FAA_hydrolase super family cl46602
Fumarylacetoacetate (FAA) hydrolase family; This family consists of fumarylacetoacetate (FAA) ...
 100-173 2.38e-35

Fumarylacetoacetate (FAA) hydrolase family; This family consists of fumarylacetoacetate (FAA) hydrolase, or fumarylacetoacetate hydrolase (FAH) and it also includes HHDD isomerase/OPET decarboxylase from E. coli strain W. FAA is the last enzyme in the tyrosine catabolic pathway, it hydrolyses fumarylacetoacetate into fumarate and acetoacetate which then join the citric acid cycle. Mutations in FAA cause type I tyrosinemia in humans this is an inherited disorder mainly affecting the liver leading to liver cirrhosis, hepatocellular carcinoma, renal tubular damages and neurologic crises amongst other symptoms. The enzymatic defect causes the toxic accumulation of phenylalanine/tyrosine catabolites. The E. coli W enzyme HHDD isomerase/OPET decarboxylase contains two copies of this domain and functions in fourth and fifth steps of the homoprotocatechuate pathway; here it decarboxylates OPET to HHDD and isomerizes this to OHED. The final products of this pathway are pyruvic acid and succinic semialdehyde. This family also includes various hydratases and 4-oxalocrotonate decarboxylases which are involved in the bacterial meta-cleavage pathways for degradation of aromatic compounds. 2-hydroxypentadienoic acid hydratase encoded by mhpD in E. coli is involved in the phenylpropionic acid pathway of E. coli and catalyzes the conversion of 2-hydroxy pentadienoate to 4-hydroxy-2-keto-pentanoate and uses a Mn2+ co-factor. OHED hydratase encoded by hpcG in E. coli is involved in the homoprotocatechuic acid (HPC) catabolism. XylI in P. putida is a 4-Oxalocrotonate decarboxylase.


The actual alignment was detected with superfamily member COG0179:

Pssm-ID: 480942  Cd Length: 206  Bit Score: 122.48  E-value: 2.38e-35
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034614398 100 APVtRPDKVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIGKKGKHI 173
Cdd:COG0179     1 APV-PPGKIICVGLNYADHAAEMGNDVPEEPVLFLKPPSALVGPGDPIPLPAGSGKLDYEGELAVVIGKRARNV 73
 
Name Accession Description Interval E-value
YcgM COG0179
2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid hydratase (catechol pathway) ...
 100-173 2.38e-35

2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid hydratase (catechol pathway) [Secondary metabolites biosynthesis, transport and catabolism];


Pssm-ID: 439949  Cd Length: 206  Bit Score: 122.48  E-value: 2.38e-35
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034614398 100 APVtRPDKVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIGKKGKHI 173
Cdd:COG0179     1 APV-PPGKIICVGLNYADHAAEMGNDVPEEPVLFLKPPSALVGPGDPIPLPAGSGKLDYEGELAVVIGKRARNV 73
FAA_hydrolase pfam01557
Fumarylacetoacetate (FAA) hydrolase family; This family consists of fumarylacetoacetate (FAA) ...
 109-173 6.16e-21

Fumarylacetoacetate (FAA) hydrolase family; This family consists of fumarylacetoacetate (FAA) hydrolase, or fumarylacetoacetate hydrolase (FAH) and it also includes HHDD isomerase/OPET decarboxylase from E. coli strain W. FAA is the last enzyme in the tyrosine catabolic pathway, it hydrolyses fumarylacetoacetate into fumarate and acetoacetate which then join the citric acid cycle. Mutations in FAA cause type I tyrosinemia in humans this is an inherited disorder mainly affecting the liver leading to liver cirrhosis, hepatocellular carcinoma, renal tubular damages and neurologic crises amongst other symptoms. The enzymatic defect causes the toxic accumulation of phenylalanine/tyrosine catabolites. The E. coli W enzyme HHDD isomerase/OPET decarboxylase contains two copies of this domain and functions in fourth and fifth steps of the homoprotocatechuate pathway; here it decarboxylates OPET to HHDD and isomerizes this to OHED. The final products of this pathway are pyruvic acid and succinic semialdehyde. This family also includes various hydratases and 4-oxalocrotonate decarboxylases which are involved in the bacterial meta-cleavage pathways for degradation of aromatic compounds. 2-hydroxypentadienoic acid hydratase encoded by mhpD in E. coli is involved in the phenylpropionic acid pathway of E. coli and catalyzes the conversion of 2-hydroxy pentadienoate to 4-hydroxy-2-keto-pentanoate and uses a Mn2+ co-factor. OHED hydratase encoded by hpcG in E. coli is involved in the homoprotocatechuic acid (HPC) catabolism. XylI in P. putida is a 4-Oxalocrotonate decarboxylase.


Pssm-ID: 460252  Cd Length: 210  Bit Score: 85.41  E-value: 6.16e-21
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034614398 109 VCVGMNYVDHCKEQN--VPVPKEPI---IFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIGKKGKHI 173
Cdd:pfam01557   1 VCVGLNYAEHAREAGkaEPVPDFPIplvLFVKPPSSLIGPGDPIVRPAGVTKLDYEAELAVVIGRPARDV 70
HpaG-C-term TIGR02303
4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase, C-terminal subunit; ...
 83-174 7.92e-15

4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase, C-terminal subunit; This model represents one of two subunits/domains of the bifunctional isomerase/decarboxylase involved in 4-hydroxyphenylacetate degradation. In E. coli and some other species this enzyme is encoded by a single polypeptide containing both this domain and the closely related N-terminal domain (TIGR02305). In other species such as Pasteurella multocida these domains are found as two separate proteins (usually as tandem genes). Together, these domains carry out the decarboxylation of 5-oxopent-3-ene-1,2,5-tricarboxylic acid (OPET) to 2-hydroxy-2,4-diene-1,7-dioate (HHDD) and the subsequent isomerization to 2-oxohept-3-ene-1,7-dioate (OHED).


Pssm-ID: 131356 [Multi-domain]  Cd Length: 245  Bit Score: 69.84  E-value: 7.92e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034614398  83 ALAAQLPVLPRSEVTFLAPVTrPDKVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVEL 162
Cdd:TIGR02303  21 LLTEDGRALPPEQVTWLPPFE-PGTIFALGLNYADHASELGFSPPEEPLVFLKGNNTLTGHKGVTYRPKDVRFMHYECEL 99

                          90
                  ....*....|..
gi 1034614398 163 AVVIGKKGKHIK 174
Cdd:TIGR02303 100 AVVVGKTAKNVK 111
PRK10691 PRK10691
fumarylacetoacetate hydrolase family protein;
107-167 1.25e-10

fumarylacetoacetate hydrolase family protein;


Pssm-ID: 182650  Cd Length: 219  Bit Score: 57.79  E-value: 1.25e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034614398 107 KVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIG 167
Cdd:PRK10691   18 KVVCVGSNYAKHIKEMGSATPEEPVLFIKPETALCDLRQPLAIPKDFGSVHHEVELAVLIG 78
 
Name Accession Description Interval E-value
YcgM COG0179
2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid hydratase (catechol pathway) ...
 100-173 2.38e-35

2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid hydratase (catechol pathway) [Secondary metabolites biosynthesis, transport and catabolism];


Pssm-ID: 439949  Cd Length: 206  Bit Score: 122.48  E-value: 2.38e-35
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034614398 100 APVtRPDKVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIGKKGKHI 173
Cdd:COG0179     1 APV-PPGKIICVGLNYADHAAEMGNDVPEEPVLFLKPPSALVGPGDPIPLPAGSGKLDYEGELAVVIGKRARNV 73
FAA_hydrolase pfam01557
Fumarylacetoacetate (FAA) hydrolase family; This family consists of fumarylacetoacetate (FAA) ...
 109-173 6.16e-21

Fumarylacetoacetate (FAA) hydrolase family; This family consists of fumarylacetoacetate (FAA) hydrolase, or fumarylacetoacetate hydrolase (FAH) and it also includes HHDD isomerase/OPET decarboxylase from E. coli strain W. FAA is the last enzyme in the tyrosine catabolic pathway, it hydrolyses fumarylacetoacetate into fumarate and acetoacetate which then join the citric acid cycle. Mutations in FAA cause type I tyrosinemia in humans this is an inherited disorder mainly affecting the liver leading to liver cirrhosis, hepatocellular carcinoma, renal tubular damages and neurologic crises amongst other symptoms. The enzymatic defect causes the toxic accumulation of phenylalanine/tyrosine catabolites. The E. coli W enzyme HHDD isomerase/OPET decarboxylase contains two copies of this domain and functions in fourth and fifth steps of the homoprotocatechuate pathway; here it decarboxylates OPET to HHDD and isomerizes this to OHED. The final products of this pathway are pyruvic acid and succinic semialdehyde. This family also includes various hydratases and 4-oxalocrotonate decarboxylases which are involved in the bacterial meta-cleavage pathways for degradation of aromatic compounds. 2-hydroxypentadienoic acid hydratase encoded by mhpD in E. coli is involved in the phenylpropionic acid pathway of E. coli and catalyzes the conversion of 2-hydroxy pentadienoate to 4-hydroxy-2-keto-pentanoate and uses a Mn2+ co-factor. OHED hydratase encoded by hpcG in E. coli is involved in the homoprotocatechuic acid (HPC) catabolism. XylI in P. putida is a 4-Oxalocrotonate decarboxylase.


Pssm-ID: 460252  Cd Length: 210  Bit Score: 85.41  E-value: 6.16e-21
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034614398 109 VCVGMNYVDHCKEQN--VPVPKEPI---IFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIGKKGKHI 173
Cdd:pfam01557   1 VCVGLNYAEHAREAGkaEPVPDFPIplvLFVKPPSSLIGPGDPIVRPAGVTKLDYEAELAVVIGRPARDV 70
HpaG-C-term TIGR02303
4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase, C-terminal subunit; ...
 83-174 7.92e-15

4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase, C-terminal subunit; This model represents one of two subunits/domains of the bifunctional isomerase/decarboxylase involved in 4-hydroxyphenylacetate degradation. In E. coli and some other species this enzyme is encoded by a single polypeptide containing both this domain and the closely related N-terminal domain (TIGR02305). In other species such as Pasteurella multocida these domains are found as two separate proteins (usually as tandem genes). Together, these domains carry out the decarboxylation of 5-oxopent-3-ene-1,2,5-tricarboxylic acid (OPET) to 2-hydroxy-2,4-diene-1,7-dioate (HHDD) and the subsequent isomerization to 2-oxohept-3-ene-1,7-dioate (OHED).


Pssm-ID: 131356 [Multi-domain]  Cd Length: 245  Bit Score: 69.84  E-value: 7.92e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034614398  83 ALAAQLPVLPRSEVTFLAPVTrPDKVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVEL 162
Cdd:TIGR02303  21 LLTEDGRALPPEQVTWLPPFE-PGTIFALGLNYADHASELGFSPPEEPLVFLKGNNTLTGHKGVTYRPKDVRFMHYECEL 99

                          90
                  ....*....|..
gi 1034614398 163 AVVIGKKGKHIK 174
Cdd:TIGR02303 100 AVVVGKTAKNVK 111
PRK10691 PRK10691
fumarylacetoacetate hydrolase family protein;
107-167 1.25e-10

fumarylacetoacetate hydrolase family protein;


Pssm-ID: 182650  Cd Length: 219  Bit Score: 57.79  E-value: 1.25e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034614398 107 KVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIG 167
Cdd:PRK10691   18 KVVCVGSNYAKHIKEMGSATPEEPVLFIKPETALCDLRQPLAIPKDFGSVHHEVELAVLIG 78
PRK15203 PRK15203
4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase; Provisional
 70-173 2.52e-09

4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase; Provisional


Pssm-ID: 185125 [Multi-domain]  Cd Length: 429  Bit Score: 55.06  E-value: 2.52e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034614398  70 LEQGEATLSVARRALAAQLPVLPRSEV----TFLAPVTRPDKVVCVGMNYVDHCKEQNVPVPKEPIIFSKFASSIVGPYD 145
Cdd:PRK15203  183 IQPGDRVRVLAEGFPPLENPVVDEREVtthkSFPTPPHPHGTLFALGLNYADHASELEFKPPEEPLVFLKAPNTLTGDNQ 262

                          90       100
                  ....*....|....*....|....*...
gi 1034614398 146 EVVLPPQSQEVDWEVELAVVIGKKGKHI 173
Cdd:PRK15203  263 TSVRPNNIEYMHYEAELVVVIGKQARKV 290
PRK12764 PRK12764
fumarylacetoacetate hydrolase family protein;
88-176 1.14e-04

fumarylacetoacetate hydrolase family protein;


Pssm-ID: 237193 [Multi-domain]  Cd Length: 500  Bit Score: 41.66  E-value: 1.14e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034614398  88 LPVLPRSEVTFLAPVTRPDKVVCVGMNYVDHCKeQNVPVPKEPIIFSKFASSIVGPYDEVVLPPQSQEVDWEVELAVVIG 167
Cdd:PRK12764    4 APVPTVVAIVVAPLLARPGKVIAVHLNYPSRAA-QRGRTPAQPSYFLKPSSSLALSGGTVERPAGTELLAFEGEIALVIG 82


                  ....*....
gi 1034614398 168 KKGKHIKIH 176
Cdd:PRK12764   83 RPARRVSPE 91
 
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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