Fumarylacetoacetase (FAH)
The protein contains 419 amino acids for an estimated molecular weight of 46374 Da.
No function (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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The reference OMIM entry for this protein is 276700
Tyrosinemia, type i; tyrsn1
Hepatorenal tyrosinemia
Fumarylacetoacetase deficiency
Fah deficiency
A number sign (#) is used with this entry because tyrosinemia type I (TYRSN1) is caused by homozygous or compound heterozygous mutation in the FAH gene (613871), encoding fumarylacetoacetate hydrolase, on chromosome 15q25.
DESCRIPTION
Hereditary tyrosinemia type I is an autosomal recessive disorder caused by deficiency of fumarylacetoacetase (FAH), the last enzyme of tyrosine degradation. The disorder is characterized by progressive liver disease and a secondary renal tubular dysfunction leading to hypophosphatemic rickets. Onset varies from infancy to adolescence. In the most acute form patients present with severe liver failure within weeks after birth, whereas rickets may be the major symptom in chronic tyrosinemia. Untreated, patients die from cirrhosis or hepatocellular carcinoma at a young age (summary by Bliksrud et al., 2005). - Genetic Heterogeneity of Hereditary Tyrosinemia Tyrosinemia type II (TYRSN2; 276600), also known as Richner-Hanhart syndrome, is caused by mutation in the TAT gene (613018) on chromosome 16q22. Tyrosinemia type III (TYRNS3; 276710) is caused by mutation in the HPD gene (609695) on chromosome 12q24.CLINICAL FEATURES
Among the children of first-cousin parents, Lelong et al. (1963) observed 2 sons with cirrhosis, Fanconi renotubular syndrome, and marked increase in plasma tyrosine. In the sib most extensively observed, hepatosplenomegaly was discovered at 3 months of age and rickets at 18 months. Malignant changes developed in the liver, and death from pulmonary metastases occurred shortly before his 5th birthday. The author suggested that the basic defect concerns an enzyme involved with tyrosine metabolism. Earlier, Himsworth (1950) described a similar case. Zetterstrom (1963) studied 7 cases coming from an isolated area of southwestern Sweden. Halvorsen et al. (1966) gave details on 6 cases from Norway. Perry et al. (1965) described 3 sibs (2 females and a male) in 1 sibship who died in the third month after an illness characterized by irritability and progressive somnolence, and terminally by a tendency to bleed and hypoglycemia. A peculiar odor was noted. Pathologic changes included hepatic cirrhosis, renal tubular dilatation, and pancreatic islet hypertrophy. Biochemical studies showed generalized amino aciduria, marked elevation of methionine in the serum, and a disproportionately high urinary excretion of methionine. Alpha-keto-gamma-methiolbutyric acid was present in the urine and may account for the peculiar odor. The hypertrophy of the islets of Langerhans was probably due to stimulation by methionine or one of its metabolites. It seems likely that the disorder in the patients of Perry et al. (1965) was tyrosinemia since hypermethioninemia occurs secondary to liver failure in that condition (Scriver et al., 1967; Gaull et al., 1970). Gentz et al. (1965) described 7 patients in 4 families with multiple renal tubular defects like those of the de Toni-Debre-Fanconi syndrome, nodular cirrhosis of the liver, and impaired tyrosine metabolism. In the urine, p-hydroxyphenyllactic acid was excreted in unusually large amounts. A total lack of liver p-hydroxyphenylpyruvate oxidase activity was demonstrated. Tyrosine-alpha-ketoglutarate transaminase was normal. Scriver et al. (1967) identified the disease in 35 French Canadian infants, of whom 16 were sibs (i.e., 2 or more in each of several families). Marked tyrosinemia and tyrosyluria were present. The urine contained parahydroxyphen ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 276700 was added.