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Protein

Fumarylacetoacetase

Gene

FAH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

4-fumarylacetoacetate + H2O = acetoacetate + fumarate.By similarity

Cofactori

Protein has several cofactor binding sites:
  • Ca2+By similarity
  • Mg2+By similarity

Pathwayi: L-phenylalanine degradation

This protein is involved in step 6 of the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine.
Proteins known to be involved in the 6 steps of the subpathway in this organism are:
  1. Phenylalanine-4-hydroxylase (PAH)
  2. Tyrosine aminotransferase (TAT)
  3. 4-hydroxyphenylpyruvate dioxygenase (HPD)
  4. Homogentisate 1,2-dioxygenase (HGD)
  5. Maleylacetoacetate isomerase (GSTZ1)
  6. Fumarylacetoacetase (FAH)
This subpathway is part of the pathway L-phenylalanine degradation, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine, the pathway L-phenylalanine degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi126CalciumBy similarity1
Binding sitei128SubstrateBy similarity1
Active sitei133Proton acceptorCurated1
Binding sitei142SubstrateBy similarity1
Metal bindingi199CalciumBy similarity1
Metal bindingi201CalciumBy similarity1
Metal bindingi233CalciumBy similarity1
Metal bindingi233MagnesiumBy similarity1
Binding sitei240SubstrateBy similarity1
Binding sitei244SubstrateBy similarity1
Metal bindingi253MagnesiumBy similarity1
Metal bindingi257MagnesiumBy similarity1
Binding sitei350SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • arginine catabolic process Source: Ensembl
  • L-phenylalanine catabolic process Source: Reactome
  • tyrosine catabolic process Source: ProtInc

Keywordsi

Molecular functionHydrolase
Biological processPhenylalanine catabolism, Tyrosine catabolism
LigandCalcium, Magnesium, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02536-MONOMER.
ReactomeiR-HSA-71182. Phenylalanine and tyrosine catabolism.
UniPathwayiUPA00139; UER00341.

Names & Taxonomyi

Protein namesi
Recommended name:
Fumarylacetoacetase (EC:3.7.1.2By similarity)
Short name:
FAA
Alternative name(s):
Beta-diketonase
Fumarylacetoacetate hydrolase
Gene namesi
Name:FAH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000103876.11.
HGNCiHGNC:3579. FAH.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Tyrosinemia 1 (TYRSN1)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:276700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00520516N → I in TYRSN1; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121965073Ensembl.1
Natural variantiVAR_06545435A → T in TYRSN1; atypical mild phenotype. 1 Publication1
Natural variantiVAR_00520662F → C in TYRSN1; loss of activity. 1 Publication1
Natural variantiVAR_00520764Q → H in TYRSN1. Corresponds to variant dbSNP:rs80338894Ensembl.1
Natural variantiVAR_005208134A → D in TYRSN1; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs121965074Ensembl.1
Natural variantiVAR_005209158G → D in TYRSN1. 1 Publication1
Natural variantiVAR_005210166V → G in TYRSN1. 1 PublicationCorresponds to variant dbSNP:rs778387055Ensembl.1
Natural variantiVAR_005211193C → R in TYRSN1; loss of activity. 2 Publications1
Natural variantiVAR_005212207G → D in TYRSN1. Corresponds to variant dbSNP:rs754196530Ensembl.1
Natural variantiVAR_005213233D → V in TYRSN1; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs80338897Ensembl.1
Natural variantiVAR_005214234W → G in TYRSN1; loss of activity. 2 Publications1
Natural variantiVAR_005215249P → T in TYRSN1. 1
Natural variantiVAR_005216261P → L in TYRSN1. 1 PublicationCorresponds to variant dbSNP:rs80338898Ensembl.1
Natural variantiVAR_065455279Q → R in TYRSN1; may affect splicing resulting in skipping of exon 8 alone or together with exon 9; lower activity as compared to wild type. 3 PublicationsCorresponds to variant dbSNP:rs121965078Ensembl.1
Natural variantiVAR_005217294T → P in TYRSN1. Corresponds to variant dbSNP:rs370634385Ensembl.1
Natural variantiVAR_005218337G → S in TYRSN1. 1 PublicationCorresponds to variant dbSNP:rs80338900Ensembl.1
Natural variantiVAR_005220342P → L in TYRSN1; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs779040832Ensembl.1
Natural variantiVAR_005221366Missing in TYRSN1. 1 Publication1
Natural variantiVAR_005222369G → V in TYRSN1. 1 Publication1
Natural variantiVAR_005223381R → G in TYRSN1; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121965077Ensembl.1
Natural variantiVAR_005224405F → H in TYRSN1; requires 2 nucleotide substitutions. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2184.
MalaCardsiFAH.
MIMi276700. phenotype.
OpenTargetsiENSG00000103876.
Orphaneti882. Tyrosinemia type 1.
PharmGKBiPA27977.

Chemistry databases

DrugBankiDB01832. 4-[Hydroxy-[Methyl-Phosphinoyl]]-3-Oxo-Butanoic Acid.
DB01762. Acetoacetic Acid.
DB01677. Fumarate.

Polymorphism and mutation databases

BioMutaiFAH.
DMDMi119778.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001568252 – 419FumarylacetoacetaseAdd BLAST418

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei92PhosphoserineBy similarity1
Modified residuei309PhosphoserineCombined sources1
Modified residuei395PhosphotyrosineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP16930.
MaxQBiP16930.
PaxDbiP16930.
PeptideAtlasiP16930.
PRIDEiP16930.

2D gel databases

OGPiP16930.
REPRODUCTION-2DPAGEiIPI00031708.

PTM databases

iPTMnetiP16930.
PhosphoSitePlusiP16930.
SwissPalmiP16930.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000103876.
CleanExiHS_FAH.
ExpressionAtlasiP16930. baseline and differential.
GenevisibleiP16930. HS.

Organism-specific databases

HPAiHPA041370.
HPA044093.

Interactioni

Subunit structurei

Homodimer.By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi108479. 11 interactors.
IntActiP16930. 6 interactors.
STRINGi9606.ENSP00000261755.

Structurei

3D structure databases

ProteinModelPortaliP16930.
SMRiP16930.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the FAH family.Curated

Phylogenomic databases

eggNOGiKOG2843. Eukaryota.
COG0179. LUCA.
GeneTreeiENSGT00390000008646.
HOGENOMiHOG000256845.
HOVERGENiHBG001919.
InParanoidiP16930.
KOiK01555.
OMAiPNWLHIP.
OrthoDBiEOG091G00CM.
PhylomeDBiP16930.
TreeFamiTF315211.

Family and domain databases

Gene3Di2.30.30.230. 1 hit.
3.90.850.10. 1 hit.
InterProiView protein in InterPro
IPR005959. Fumarylacetoacetase.
IPR011234. Fumarylacetoacetase_C-rel.
IPR015377. Fumarylacetoacetase_N.
PANTHERiPTHR43069. PTHR43069. 1 hit.
PfamiView protein in Pfam
PF01557. FAA_hydrolase. 1 hit.
PF09298. FAA_hydrolase_N. 1 hit.
SUPFAMiSSF56529. SSF56529. 1 hit.
SSF63433. SSF63433. 1 hit.
TIGRFAMsiTIGR01266. fum_ac_acetase. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16930-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSFIPVAEDS DFPIHNLPYG VFSTRGDPRP RIGVAIGDQI LDLSIIKHLF
60 70 80 90 100
TGPVLSKHQD VFNQPTLNSF MGLGQAAWKE ARVFLQNLLS VSQARLRDDT
110 120 130 140 150
ELRKCAFISQ ASATMHLPAT IGDYTDFYSS RQHATNVGIM FRDKENALMP
160 170 180 190 200
NWLHLPVGYH GRASSVVVSG TPIRRPMGQM KPDDSKPPVY GACKLLDMEL
210 220 230 240 250
EMAFFVGPGN RLGEPIPISK AHEHIFGMVL MNDWSARDIQ KWEYVPLGPF
260 270 280 290 300
LGKSFGTTVS PWVVPMDALM PFAVPNPKQD PRPLPYLCHD EPYTFDINLS
310 320 330 340 350
VNLKGEGMSQ AATICKSNFK YMYWTMLQQL THHSVNGCNL RPGDLLASGT
360 370 380 390 400
ISGPEPENFG SMLELSWKGT KPIDLGNGQT RKFLLDGDEV IITGYCQGDG
410
YRIGFGQCAG KVLPALLPS
Length:419
Mass (Da):46,374
Last modified:August 1, 1992 - v2
Checksum:i12EA8D8074C55BB2
GO
Isoform 2 (identifier: P16930-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.

Note: No experimental confirmation available.
Show »
Length:349
Mass (Da):38,614
Checksum:i76484AD16731BE21
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00520516N → I in TYRSN1; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121965073Ensembl.1
Natural variantiVAR_06545435A → T in TYRSN1; atypical mild phenotype. 1 Publication1
Natural variantiVAR_00520662F → C in TYRSN1; loss of activity. 1 Publication1
Natural variantiVAR_00520764Q → H in TYRSN1. Corresponds to variant dbSNP:rs80338894Ensembl.1
Natural variantiVAR_005208134A → D in TYRSN1; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs121965074Ensembl.1
Natural variantiVAR_005209158G → D in TYRSN1. 1 Publication1
Natural variantiVAR_005210166V → G in TYRSN1. 1 PublicationCorresponds to variant dbSNP:rs778387055Ensembl.1
Natural variantiVAR_005211193C → R in TYRSN1; loss of activity. 2 Publications1
Natural variantiVAR_005212207G → D in TYRSN1. Corresponds to variant dbSNP:rs754196530Ensembl.1
Natural variantiVAR_005213233D → V in TYRSN1; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs80338897Ensembl.1
Natural variantiVAR_005214234W → G in TYRSN1; loss of activity. 2 Publications1
Natural variantiVAR_005215249P → T in TYRSN1. 1
Natural variantiVAR_005216261P → L in TYRSN1. 1 PublicationCorresponds to variant dbSNP:rs80338898Ensembl.1
Natural variantiVAR_065455279Q → R in TYRSN1; may affect splicing resulting in skipping of exon 8 alone or together with exon 9; lower activity as compared to wild type. 3 PublicationsCorresponds to variant dbSNP:rs121965078Ensembl.1
Natural variantiVAR_005217294T → P in TYRSN1. Corresponds to variant dbSNP:rs370634385Ensembl.1
Natural variantiVAR_005218337G → S in TYRSN1. 1 PublicationCorresponds to variant dbSNP:rs80338900Ensembl.1
Natural variantiVAR_005219341R → W Functional polymorphism; does not cause a clinically relevant phenotype; results in lower enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs11555096Ensembl.1
Natural variantiVAR_005220342P → L in TYRSN1; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs779040832Ensembl.1
Natural variantiVAR_005221366Missing in TYRSN1. 1 Publication1
Natural variantiVAR_005222369G → V in TYRSN1. 1 Publication1
Natural variantiVAR_005223381R → G in TYRSN1; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121965077Ensembl.1
Natural variantiVAR_005224405F → H in TYRSN1; requires 2 nucleotide substitutions. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0554911 – 70Missing in isoform 2. 1 PublicationAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55150 mRNA. Translation: AAA52422.1.
BT007160 mRNA. Translation: AAP35824.1.
AK313951 mRNA. Translation: BAG36668.1.
BX537608 mRNA. Translation: CAD97795.1.
AC087761 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99120.1.
CH471136 Genomic DNA. Translation: EAW99121.1.
BC002527 mRNA. Translation: AAH02527.1.
X51728 mRNA. Translation: CAA36016.1.
CCDSiCCDS10314.1. [P16930-1]
PIRiA37926.
RefSeqiNP_000128.1. NM_000137.2. [P16930-1]
UniGeneiHs.73875.

Genome annotation databases

EnsembliENST00000261755; ENSP00000261755; ENSG00000103876. [P16930-1]
ENST00000407106; ENSP00000385080; ENSG00000103876. [P16930-1]
ENST00000539156; ENSP00000454271; ENSG00000103876. [P16930-2]
ENST00000561421; ENSP00000453347; ENSG00000103876. [P16930-1]
GeneIDi2184.
KEGGihsa:2184.
UCSCiuc002bfm.3. human. [P16930-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFAAA_HUMAN
AccessioniPrimary (citable) accession number: P16930
Secondary accession number(s): B2R9X1, D3DW95, Q53XA7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1992
Last modified: September 27, 2017
This is version 175 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families