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P16930 (FAAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fumarylacetoacetase

Short name=FAA
EC=3.7.1.2
Alternative name(s):
Beta-diketonase
Fumarylacetoacetate hydrolase
Gene names
Name:FAH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length419 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

4-fumarylacetoacetate + H2O = acetoacetate + fumarate.

Cofactor

Calcium By similarity.

Magnesium By similarity.

Pathway

Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 6/6.

Subunit structure

Homodimer.

Tissue specificity

Mainly expressed in liver and kidney. Lower levels are also detected in many other tissues.

Involvement in disease

Tyrosinemia 1 (TYRO1) [MIM:276700]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23

Sequence similarities

Belongs to the FAH family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6
Chain2 – 419418Fumarylacetoacetase
PRO_0000156825

Sites

Active site1331Proton acceptor Probable
Metal binding1261Calcium By similarity
Metal binding1991Calcium By similarity
Metal binding2011Calcium By similarity
Metal binding2331Calcium By similarity
Metal binding2331Magnesium By similarity
Metal binding2531Magnesium By similarity
Metal binding2571Magnesium By similarity
Binding site1281Substrate By similarity
Binding site1421Substrate By similarity
Binding site2401Substrate By similarity
Binding site2441Substrate By similarity
Binding site3501Substrate By similarity

Amino acid modifications

Modified residue21N-acetylserine Ref.6

Natural variations

Natural variant161N → I in TYRO1; loss of activity. Ref.10 Ref.22
VAR_005205
Natural variant351A → T in TYRO1; atypical mild phenotype. Ref.23
VAR_065454
Natural variant621F → C in TYRO1; loss of activity. Ref.22
VAR_005206
Natural variant641Q → H in TYRO1.
VAR_005207
Natural variant1341A → D in TYRO1; loss of activity. Ref.11 Ref.15 Ref.22
VAR_005208
Natural variant1581G → D in TYRO1. Ref.19
VAR_005209
Natural variant1661V → G in TYRO1. Ref.12
VAR_005210
Natural variant1931C → R in TYRO1; loss of activity. Ref.18 Ref.22
VAR_005211
Natural variant2071G → D in TYRO1.
VAR_005212
Natural variant2331D → V in TYRO1; loss of activity. Ref.13 Ref.22
VAR_005213
Natural variant2341W → G in TYRO1; loss of activity. Ref.17 Ref.22
VAR_005214
Natural variant2491P → T in TYRO1.
VAR_005215
Natural variant2611P → L in TYRO1. Ref.19
VAR_005216
Natural variant2791Q → R in TYRO1; may affect splicing resulting in skipping of exon 8 alone or together with exon 9; lower activity as compared to wild type. Ref.20 Ref.21 Ref.22
VAR_065455
Natural variant2941T → P in TYRO1.
VAR_005217
Natural variant3371G → S in TYRO1. Ref.16
VAR_005218
Natural variant3411R → W in TYRO1; pseudo-deficient phenotype; lower activity. Ref.14 Ref.22
Corresponds to variant rs11555096 [ dbSNP | Ensembl ].
VAR_005219
Natural variant3421P → L in TYRO1; loss of activity. Ref.15
VAR_005220
Natural variant3661Missing in TYRO1. Ref.19
VAR_005221
Natural variant3691G → V in TYRO1. Ref.18
VAR_005222
Natural variant3811R → G in TYRO1; loss of activity. Ref.16
VAR_005223
Natural variant4051F → H in TYRO1; requires 2 nucleotide substitutions. Ref.19
VAR_005224

Sequences

Sequence LengthMass (Da)Tools
P16930 [UniParc].

Last modified August 1, 1992. Version 2.
Checksum: 12EA8D8074C55BB2

FASTA41946,374
        10         20         30         40         50         60 
MSFIPVAEDS DFPIHNLPYG VFSTRGDPRP RIGVAIGDQI LDLSIIKHLF TGPVLSKHQD 

        70         80         90        100        110        120 
VFNQPTLNSF MGLGQAAWKE ARVFLQNLLS VSQARLRDDT ELRKCAFISQ ASATMHLPAT 

       130        140        150        160        170        180 
IGDYTDFYSS RQHATNVGIM FRDKENALMP NWLHLPVGYH GRASSVVVSG TPIRRPMGQM 

       190        200        210        220        230        240 
KPDDSKPPVY GACKLLDMEL EMAFFVGPGN RLGEPIPISK AHEHIFGMVL MNDWSARDIQ 

       250        260        270        280        290        300 
KWEYVPLGPF LGKSFGTTVS PWVVPMDALM PFAVPNPKQD PRPLPYLCHD EPYTFDINLS 

       310        320        330        340        350        360 
VNLKGEGMSQ AATICKSNFK YMYWTMLQQL THHSVNGCNL RPGDLLASGT ISGPEPENFG 

       370        380        390        400        410 
SMLELSWKGT KPIDLGNGQT RKFLLDGDEV IITGYCQGDG YRIGFGQCAG KVLPALLPS 

« Hide

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] [Europe PMC] [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. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [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. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[6]Bienvenut W.V.
Submitted (JAN-2010) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-25; 32-47; 83-95 AND 195-211, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Ovarian carcinoma.
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 71-419.
Tissue: Liver.
[8]"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] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANTS TYRO1 ASP-158; LEU-261; SER-366 DEL AND HIS-405.
[20]"Hepatocellular carcinoma despite long-term survival in chronic tyrosinaemia I."
Kim S.Z., Kupke K.G., Ierardi-Curto L., Holme E., Greter J., Tanguay R.M., Poudrier J., D'Astous M., Lettre F., Hahn S.H., Levy H.L.
J. Inherit. Metab. Dis. 23:791-804(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYRO1 ARG-279.
[21]"A missense mutation (Q279R) in the fumarylacetoacetate hydrolase gene, responsible for hereditary tyrosinemia, acts as a splicing mutation."
Dreumont N., Poudrier J.A., Bergeron A., Levy H.L., Baklouti F., Tanguay R.M.
BMC Genet. 2:9-9(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYRO1 ARG-279.
[22]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS TYRO1 ILE-16; CYS-62; ASP-134; ARG-193; VAL-233; GLY-234; ARG-279 AND TRP-341.
[23]"A novel mutation causing mild, atypical fumarylacetoacetase deficiency (Tyrosinemia type I): a case report."
Cassiman D., Zeevaert R., Holme E., Kvittingen E.A., Jaeken J.
Orphanet J. Rare Dis. 4:28-28(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYRO1 THR-35.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M55150 mRNA. Translation: AAA52422.1.
BT007160 mRNA. Translation: AAP35824.1.
AK313951 mRNA. Translation: BAG36668.1.
CH471136 Genomic DNA. Translation: EAW99120.1.
CH471136 Genomic DNA. Translation: EAW99121.1.
BC002527 mRNA. Translation: AAH02527.1.
X51728 mRNA. Translation: CAA36016.1.
PIRA37926.
RefSeqNP_000128.1. NM_000137.2.
UniGeneHs.73875.

3D structure databases

ProteinModelPortalP16930.
SMRP16930. Positions 1-416.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108479. 2 interactions.
IntActP16930. 1 interaction.
STRING9606.ENSP00000261755.

PTM databases

PhosphoSiteP16930.

Polymorphism databases

DMDM119778.

2D gel databases

OGPP16930.
REPRODUCTION-2DPAGEIPI00031708.

Proteomic databases

PaxDbP16930.
PeptideAtlasP16930.
PRIDEP16930.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261755; ENSP00000261755; ENSG00000103876.
ENST00000407106; ENSP00000385080; ENSG00000103876.
ENST00000561421; ENSP00000453347; ENSG00000103876.
GeneID2184.
KEGGhsa:2184.
UCSCuc002bfm.2. human.

Organism-specific databases

CTD2184.
GeneCardsGC15P080445.
HGNCHGNC:3579. FAH.
HPAHPA041370.
HPA044093.
MIM276700. phenotype.
613871. gene.
neXtProtNX_P16930.
Orphanet882. Tyrosinemia type 1.
PharmGKBPA27977.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0179.
HOGENOMHOG000256845.
HOVERGENHBG001919.
InParanoidP16930.
KOK01555.
OMALSWKGTK.
PhylomeDBP16930.
TreeFamTF315211.

Enzyme and pathway databases

BioCycMetaCyc:HS02536-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00139; UER00341.

Gene expression databases

ArrayExpressP16930.
BgeeP16930.
CleanExHS_FAH.
GenevestigatorP16930.

Family and domain databases

Gene3D2.30.30.230. 1 hit.
3.90.850.10. 1 hit.
InterProIPR005959. Fumarylacetoacetase.
IPR002529. Fumarylacetoacetase_C.
IPR011234. Fumarylacetoacetase_C-rel.
IPR015377. Fumarylacetoacetase_N.
[Graphical view]
PANTHERPTHR11820:SF1. PTHR11820:SF1. 1 hit.
PfamPF01557. FAA_hydrolase. 1 hit.
PF09298. FAA_hydrolase_N. 1 hit.
[Graphical view]
SUPFAMSSF56529. SSF56529. 1 hit.
SSF63433. SSF63433. 1 hit.
TIGRFAMsTIGR01266. fum_ac_acetase. 1 hit.
ProtoNetSearch...

Other

ChiTaRSFAH. human.
GeneWikiFumarylacetoacetate_hydrolase.
GenomeRNAi2184.
NextBio8817.
PROP16930.
SOURCESearch...

Entry information

Entry nameFAAA_HUMAN
AccessionPrimary (citable) accession number: P16930
Secondary accession number(s): B2R9X1, D3DW95
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1992
Last modified: April 16, 2014
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM