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124  structures 15898  species 4  interactions 43389  sequences 71  architectures

Family: FAA_hydrolase (PF01557)

Summary: Fumarylacetoacetate (FAA) hydrolase family

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Fumarylacetoacetate (FAA) hydrolase family Provide feedback

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 [1]. 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 [1]. The enzymatic defect causes the toxic accumulation of phenylalanine/tyrosine catabolites [3]. 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 isomerises 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 P77608 is involved in the phenylpropionic acid pathway of E. coli and catalyses the conversion of 2-hydroxy pentadienoate to 4-hydroxy-2-keto-pentanoate and uses a Mn2+ co-factor [5]. OHED hydratase encoded by hpcG in E. coli P42270 is involved in the homoprotocatechuic acid (HPC) catabolism [6]. XylI in P. putida P49155 is a 4-Oxalocrotonate decarboxylase [7].

Literature references

  1. St-Louis M, Tanguay RM; , Hum Mutat 1997;9:291-299.: Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview. PUBMED:9101289 EPMC:9101289

  2. Prieto MA, Diaz E, Garcia JL; , J Bacteriol 1996;178:111-120.: Molecular characterization of the 4-hydroxyphenylacetate catabolic pathway of Escherichia coli W: engineering a mobile aromatic degradative cluster. PUBMED:8550403 EPMC:8550403

  3. Fernandez-Canon JM, Penalva MA; , Proc Natl Acad Sci U S A 1995;92:9132-9136.: Fungal metabolic model for human type I hereditary tyrosinaemia. PUBMED:7568087 EPMC:7568087

  4. Roper DI, Cooper RA; , Eur J Biochem 1993;217:575-580.: Purification, nucleotide sequence and some properties of a bifunctional isomerase/decarboxylase from the homoprotocatechuate degradative pathway of Escherichia coli C. PUBMED:8223600 EPMC:8223600

  5. Pollard JR, Bugg TD; , Eur J Biochem 1998;251:98-106.: Purification, characterisation and reaction mechanism of monofunctional 2-hydroxypentadienoic acid hydratase from Escherichia coli. PUBMED:9492273 EPMC:9492273

  6. Roper DI, Stringfellow JM, Cooper RA; , Gene 1995;156:47-51.: Sequence of the hpcC and hpcG genes of the meta-fission homoprotocatechuic acid pathway of Escherichia coli C: nearly 40% amino- acid identity with the analogous enzymes of the catechol pathway. PUBMED:7737515 EPMC:7737515

  7. Harayama S, Rekik M; , Mol Gen Genet 1993;239:81-89.: Comparison of the nucleotide sequences of the meta-cleavage pathway genes of TOL plasmid pWW0 from Pseudomonas putida with other meta- cleavage genes suggests that both single and multiple nucleotide substitutions contribute to enzyme evolution. PUBMED:8510667 EPMC:8510667

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002529

Fumarylacetoacetase (EC; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation [PUBMED:11154690]. This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders [PUBMED:9101289, PUBMED:16602095]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole [PUBMED:10508789]. FAH folds into two domains: an N-terminal domain SH3-like beta-barrel, and a C-terminal with an unusual fold consisting of three layers of beta-sheet structures [PUBMED:10508789].

This entry represents the C-terminal domain of fumarylacetoacetase, as well as other domains that share a homologous sequence, including:

  • 5-carboxymethyl-2-hydroxymuconate delta-isomerase (CHM isomerase; EC), which catalyses the conversion of 5-carboxymethyl-2-hydroxymuconate to 5-carboxy-2-oxohept-3-enedioate [PUBMED:2194841].
  • 5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (OPET decarboxylase; EC), which catalyses the conversion of 5-oxopent-3-ene-1,2,5-tricarboxylate to 2-oxohept-3-enedioate and carbon dioxide.
  • Bifunctional enzyme HpcE (OPET decarboxylase EC/HHDD isomerase EC), which is a duplication consisting of a tandem repeat of two FAH C-terminal-like domains. This enzyme is responsible for the degradation of 4-hydroxyphenylacetate, a product of tyrosine and phenylalanine metabolism also released by lignin catabolism [PUBMED:11863436].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan FAH (CL0377), which has the following description:

Superfamily contains fumarylacetoacetate hydrolase and related enzymes,

The clan contains the following 2 members:

DUF2848 FAA_hydrolase


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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_641 (release 4.0) & Pfam-B_1228 (release 4.1)
Previous IDs: none
Type: Family
Author: Bashton M, Bateman A
Number in seed: 53
Number in full: 43389
Average length of the domain: 208.90 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 72.99 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.9 23.9
Trusted cut-off 23.9 23.9
Noise cut-off 23.8 23.8
Model length: 218
Family (HMM) version: 14
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Species distribution

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There are 4 interactions for this family. More...

FAA_hydrolase FAA_hydrolase_N DUF2437 DUF2437


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the FAA_hydrolase domain has been found. There are 124 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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