Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
112  structures 3508  species 3  interactions 10787  sequences 37  architectures

Family: FAA_hydrolase (PF01557)

Summary: Fumarylacetoacetate (FAA) hydrolase family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

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

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(95)
Full
(10787)
Representative proteomes NCBI
(8643)
Meta
(4023)
RP15
(912)
RP35
(2048)
RP55
(2900)
RP75
(3559)
Jalview View  View  View  View  View  View  View  View 
HTML View    View  View  View  View     
PP/heatmap 1   View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(95)
Full
(10787)
Representative proteomes NCBI
(8643)
Meta
(4023)
RP15
(912)
RP35
(2048)
RP55
(2900)
RP75
(3559)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(95)
Full
(10787)
Representative proteomes NCBI
(8643)
Meta
(4023)
RP15
(912)
RP35
(2048)
RP55
(2900)
RP75
(3559)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

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: 95
Number in full: 10787
Average length of the domain: 213.40 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 76.20 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -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 23.5
Model length: 218
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 3 interactions for this family. More...

FAA_hydrolase_N DUF2437 FAA_hydrolase

Structures

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 112 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.

Loading structure mapping...