Reviewed,
UniProtKB/Swiss-Prot P16930 (FAAA_HUMAN)
Last modified
November 3, 2009.
Version 103.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Fumarylacetoacetase Short name=FAA EC=3.7.1.2 Alternative name(s): Fumarylacetoacetate hydrolase Beta-diketonase | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 419 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Catalytic activity | 4-fumarylacetoacetate + H2O = acetoacetate + fumarate. |
| Cofactor | Calcium By similarity. Magnesium By similarity. |
| Pathway | |
| Subunit structure | Homodimer. |
| Tissue specificity | Mainly in liver and kidney. Lower levels are also detected in many other tissues. |
| Involvement in disease | Defects in FAH are the cause of tyrosinemia type 1 (TYRO1) [MIM:276700]. TYRO1 is an inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and hepatorenal manifestations. Typical features include hepatic necrosis, renal tubular injury, episodic weakness, self-mutilation, and seizures. Renal tubular dysfunction is associated with phosphate loss and hypophosphataemic rickets. Progressive liver disease can lead to the development of hepatocellular carcinoma. Dietary treatment with restriction of tyrosine and phenylalanine alleviates the rickets, but liver transplantation has so far been the only definite treatment. TYRO1 is a rare condition, except in the Saguenay-lac-St-Jean region (province of Quebec, Canada) where the frequency is high as the result of a founder effect. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 |
| Sequence similarities | Belongs to the FAH family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Phenylalanine catabolism Tyrosine catabolism |
| Disease | Disease mutation |
| Ligand | Calcium Magnesium Metal-binding |
| Molecular function | Hydrolase |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | L-phenylalanine catabolic process Inferred from electronic annotation. Source: UniProtKB-KW tyrosine catabolic processTraceable author statement. Source: ProtInc |
| Cellular component | cytosol Ref.11 Inferred from Experiment. Source: Reactome |
| Molecular function | calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW fumarylacetoacetase activity Ref.1 Ref.11Inferred from Experiment. Source: Reactome magnesium ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 419 | 419 | Fumarylacetoacetase | PRO_0000156825 | |||||
Sites | |||||||||
| Active site | 133 | 1 | Proton acceptor Probable | ||||||
| Metal binding | 126 | 1 | Calcium By similarity | ||||||
| Metal binding | 199 | 1 | Calcium By similarity | ||||||
| Metal binding | 201 | 1 | Calcium By similarity | ||||||
| Metal binding | 233 | 1 | Calcium By similarity | ||||||
| Metal binding | 233 | 1 | Magnesium By similarity | ||||||
| Metal binding | 253 | 1 | Magnesium By similarity | ||||||
| Metal binding | 257 | 1 | Magnesium By similarity | ||||||
| Binding site | 128 | 1 | Substrate By similarity | ||||||
| Binding site | 142 | 1 | Substrate By similarity | ||||||
| Binding site | 240 | 1 | Substrate By similarity | ||||||
| Binding site | 244 | 1 | Substrate By similarity | ||||||
| Binding site | 350 | 1 | Substrate By similarity | ||||||
Natural variations | |||||||||
| Natural variant | 16 | 1 | N → I in TYRO1; loss of activity. Ref.10 | VAR_005205 | |||||
| Natural variant | 62 | 1 | F → C in TYRO1; loss of activity. | VAR_005206 | |||||
| Natural variant | 64 | 1 | Q → H in TYRO1; many patients of Pakistani origin. | VAR_005207 | |||||
| Natural variant | 134 | 1 | A → D in TYRO1; chronic; loss of activity. Ref.11 Ref.15 | VAR_005208 | |||||
| Natural variant | 158 | 1 | G → D in TYRO1. Ref.19 | VAR_005209 | |||||
| Natural variant | 166 | 1 | V → G in TYRO1. Ref.12 | VAR_005210 | |||||
| Natural variant | 193 | 1 | C → R in TYRO1; loss of activity. Ref.18 | VAR_005211 | |||||
| Natural variant | 207 | 1 | G → D in TYRO1. | VAR_005212 | |||||
| Natural variant | 233 | 1 | D → V in TYRO1; loss of activity; many patients of Turkish origin. Ref.13 | VAR_005213 | |||||
| Natural variant | 234 | 1 | W → G in TYRO1; loss of activity. Ref.17 | VAR_005214 | |||||
| Natural variant | 249 | 1 | P → T in TYRO1. | VAR_005215 | |||||
| Natural variant | 261 | 1 | P → L in TYRO1. Ref.19 | VAR_005216 | |||||
| Natural variant | 294 | 1 | T → P in TYRO1. | VAR_005217 | |||||
| Natural variant | 337 | 1 | G → S in TYRO1. Ref.16 | VAR_005218 | |||||
| Natural variant | 341 | 1 | R → W in TYRO1 and FAH pseudodeficiency; lower activity. dbSNP rs11555096. Ref.14 | VAR_005219 | |||||
| Natural variant | 342 | 1 | P → L in TYRO1; chronic; loss of activity. Ref.15 | VAR_005220 | |||||
| Natural variant | 366 | 1 | Missing in TYRO1. | VAR_005221 | |||||
| Natural variant | 369 | 1 | G → V in TYRO1. Ref.18 | VAR_005222 | |||||
| Natural variant | 381 | 1 | R → G in TYRO1; loss of activity. Ref.16 | VAR_005223 | |||||
| Natural variant | 405 | 1 | F → H in TYRO1; requires 2 nucleotide substitutions. Ref.19 | VAR_005224 | |||||
Experimental info | |||||||||
| Mutagenesis | 279 | 1 | Q → R: Lower activity. Ref.7 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning and expression of the cDNA encoding human fumarylacetoacetate hydrolase, the enzyme deficient in hereditary tyrosinemia: assignment of the gene to chromosome 15." Phaneuf D., Labelle Y., Berube D., Arden K., Cavenee W., Gagne R., Tanguay R.M. Am. J. Hum. Genet. 48:525-535(1991) [PubMed: 1998338] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta. |
| [6] | "Nucleotide sequence of cDNA encoding human fumarylacetoacetase." Agsteribbe E., van Faassen H., Hartog M.V., Reversma T., Taanman J.-W., Pannekoek H., Evers R.F., Welling G.M., Berger R. Nucleic Acids Res. 18:1887-1887(1990) [PubMed: 2336361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 71-419. Tissue: Liver. |
| [7] | "Structural and functional analysis of missense mutations in fumarylacetoacetate hydrolase, the gene deficient in hereditary tyrosinemia type 1." Bergeron A., D'Astous M., Timm D.E., Tanguay R.M. J. Biol. Chem. 276:15225-15231(2001) [PubMed: 11278491] [Abstract] Cited for: MUTAGENESIS OF ASN-16; PHE-62; ALA-134; CYS-193; ASP-233; TRP-234; GLN-279 AND ARG-341. |
| [8] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [9] | "Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview." St Louis M., Tanguay R.M. Hum. Mutat. 9:291-299(1997) [PubMed: 9101289] [Abstract] Cited for: REVIEW ON VARIANTS. |
| [10] | "Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient." Phaneuf D., Lambert M., Laframboise R., Mitchell G., Lettre F., Tanguay R.M. J. Clin. Invest. 90:1185-1192(1992) [PubMed: 1401056] [Abstract] Cited for: VARIANT TYRO1 ILE-16. |
| [11] | "Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity." Labelle Y., Phaneuf D., Leclerc B., Tanguay R.M. Hum. Mol. Genet. 2:941-946(1993) [PubMed: 8364576] [Abstract] Cited for: VARIANT TYRO1 ASP-134. |
| [12] | "Mutations of the fumarylacetoacetate hydrolase gene in four patients with tyrosinemia, type I." Grompe M., Al-Dhalimy M. Hum. Mutat. 2:85-93(1993) [PubMed: 8318997] [Abstract] Cited for: VARIANT TYRO1 GLY-166. |
| [13] | "Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1." Rootwelt H., Berger R., Gray G., Kelly D.A., Coskun T., Kvittingen E.A. Am. J. Hum. Genet. 55:653-658(1994) [PubMed: 7942842] [Abstract] Cited for: VARIANT TYRO1 VAL-233. |
| [14] | "Identification of a frequent pseudodeficiency mutation in the fumarylacetoacetase gene, with implications for diagnosis of tyrosinemia type I." Rootwelt H., Brodtkorb E., Kvittingen E.A. Am. J. Hum. Genet. 55:1122-1127(1994) [PubMed: 7977370] [Abstract] Cited for: VARIANT TYRO1 TRP-341. |
| [15] | "Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase." Rootwelt H., Chou J., Gahl W.A., Berger R., Coskun T., Brodtkorb E., Kvittingen E.A. Hum. Genet. 93:615-619(1994) [PubMed: 8005583] [Abstract] Cited for: VARIANTS TYRO1 ASP-134 AND LEU-342. |
| [16] | "Two novel mutations involved in hereditary tyrosinemia type I." St Louis M., Poudrier J., Phaneuf D., Leclerc B., Laframboise R., Tanguay R.M. Hum. Mol. Genet. 4:319-320(1995) [PubMed: 7757089] [Abstract] Cited for: VARIANTS TYRO1 SER-337 AND GLY-381. |
| [17] | "Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1." Hahn S.H., Krasnewich D., Brantly M., Kvittingen E.A., Gahl W.A. Hum. Mutat. 6:66-73(1995) [PubMed: 7550234] [Abstract] Cited for: VARIANT TYRO1 GLY-234. |
| [18] | "Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship." Ploos van Amstel J.K., Bergman A.J.I.W., van Beurden E.A.C.M., Roijers J.F.M., Peelen T., van den Berg I.E.T., Poll-The B.T., Kvittingen E.A., Berger R. Hum. Genet. 97:51-59(1996) [PubMed: 8557261] [Abstract] Cited for: VARIANTS TYRO1 ARG-193 AND VAL-369. |
| [19] | "Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries." Bergman A.J.I.W., van den Berg I.E.T., Brink W., Poll-The B.T., Ploos van Amstel J.K., Berger R. Hum. Mutat. 12:19-26(1998) [PubMed: 9633815] [Abstract] Cited for: VARIANTS TYRO1 ASP-158; LEU-261; SER-366 DEL AND HIS-405. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| M55150 mRNA. Translation: AAA52422.1. BT007160 mRNA. Translation: AAP35824.1. AK313951 mRNA. Translation: BAG36668.1. CH471136 Genomic DNA. Translation: EAW99120.1. BC002527 mRNA. Translation: AAH02527.1. X51728 mRNA. Translation: CAA36016.1. | |
| IPI | IPI00031708. |
| PIR | A37926. |
| RefSeq | NP_000128.1. |
| UniGene | Hs.73875 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1HYO based on UniProtKB P35505. |
| SMR | P16930. Positions 1-416. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P16930. |
PTM databases | |
| PhosphoSite | P16930. |
2-D gel databases | |
| OGP | P16930. |
| REPRODUCTION-2DPAGE | IPI00031708. |
Proteomic databases | |
| PeptideAtlas | P16930. |
| PRIDE | P16930. |
Genome annotation databases | |
| Ensembl | ENST00000261755; ENSP00000261755; ENSG00000103876; Homo sapiens. [Genome view] ENST00000407106; ENSP00000385080; ENSG00000103876; Homo sapiens. [Genome view] |
| GeneID | 2184. |
| KEGG | hsa:2184. |
| UCSC | uc002bfj.1. human. |
Organism-specific databases | |
| CTD | 2184. |
| GeneCards | GC15P078232. |
| H-InvDB | HIX0012491. |
| HGNC | HGNC:3579. FAH. |
| MIM | 276700. gene+phenotype. |
| Orphanet | 882. Tyrosinemia type 1. |
| PharmGKB | PA27977. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P16930. |
| HOVERGEN | P16930. |
| OMA | DFELEMA. |
Enzyme and pathway databases | |
| BioCyc | MetaCyc:MON-12049. |
| BRENDA | 3.7.1.2. 247. |
| Reactome | REACT_13. Metabolism of amino acids. |
Gene expression databases | |
| ArrayExpress | P16930. |
| Bgee | P16930. |
| CleanEx | HS_FAH. |
| Genevestigator | P16930. |
| GermOnline | ENSG00000103876. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR005959. Fumarylacetoacetase. IPR002529. Fumarylacetoacetase_C-like. IPR011234. Fumarylacetoacetase_C-rel. IPR015377. Fumarylacetoacetase_N. [Graphical view] |
| Gene3D | G3DSA:3.90.850.10. Fumarylacetoacetase_C-rel. 1 hit. G3DSA:2.30.30.230. Fumarylacetoacetase_N. 1 hit. |
| PANTHER | PTHR11820:SF1. Fum_ac_acetase. 1 hit. |
| Pfam | PF09298. DUF1969. 1 hit. PF01557. FAA_hydrolase. 1 hit. [Graphical view] |
| TIGRFAMs | TIGR01266. fum_ac_acetase. 1 hit. |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 8817. |
| SOURCE | Search... |
Entry information
| Entry name | FAAA_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P16930 Secondary accession number(s): B2R9X1 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 15 Human chromosome 15: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |

Clusters with


