P35505 (FAAA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fumarylacetoacetase
Short name=FAA
EC=3.7.1.2

Alternative name(s):
Beta-diketonase
Fumarylacetoacetate hydrolase

Gene names

Name:

Fah

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	419 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	4-fumarylacetoacetate + H2O = acetoacetate + fumarate.
Cofactor	Calcium. Magnesium.
Pathway	Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 6/6.
Subunit structure	Homodimer.
Tissue specificity	Mainly in liver and kidney.
Sequence similarities	Belongs to the FAH family.

Ontologies

Keywords
Biological process	Phenylalanine catabolism Tyrosine catabolism
Ligand	Calcium Magnesium Metal-binding
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	L-phenylalanine catabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway arginine catabolic process Inferred from mutant phenotype Ref.6. Source: MGI tyrosine catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	fumarylacetoacetase activity Inferred from mutant phenotype Ref.6. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 419

418

Fumarylacetoacetase

PRO_0000156826

Sites

Active site

133

1

Proton acceptor Probable

Metal binding

126

1

Calcium

Metal binding

199

1

Calcium

Metal binding

201

1

Calcium

Metal binding

233

1

Calcium

Metal binding

233

1

Magnesium

Metal binding

253

1

Magnesium

Metal binding

257

1

Magnesium

Binding site

128

1

Substrate

Binding site

142

1

Substrate

Binding site

240

1

Substrate

Binding site

244

1

Substrate

Binding site

350

1

Substrate

Amino acid modifications

Modified residue

2

1

N-acetylserine By similarity

Experimental info

Mutagenesis

201

1

E → G: Decrease in activity. Ref.6

Sequence conflict

129 – 130

2

SS → PF in CAA77819. Ref.2

Sequence conflict

307

1

G → R no nucleotide entry Ref.3

Sequence conflict

376

1

E → G in AAA37591. Ref.1

Sequence conflict

376

1

E → G in AAH10767. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

419

Helix Strand Turn

Details...

Beta strand

2 – 4

3

Turn

14 – 16

3

Beta strand

19 – 23

5

Beta strand

31 – 36

6

Beta strand

39 – 42

4

Turn

43 – 46

4

Helix

47 – 49

3

Turn

53 – 57

5

Helix

59 – 63

5

Beta strand

64 – 67

4

Helix

68 – 73

6

Helix

75 – 89

15

Turn

90 – 94

5

Helix

95 – 98

4

Helix

100 – 106

7

Beta strand

107 – 110

4

Beta strand

114 – 116

3

Beta strand

124 – 127

4

Helix

131 – 142

12

Helix

144 – 146

3

Turn

150 – 154

5

Beta strand

158 – 160

3

Beta strand

166 – 168

3

Beta strand

177 – 180

4

Beta strand

189 – 192

4

Beta strand

199 – 206

8

Helix

218 – 221

4

Helix

222 – 224

3

Beta strand

225 – 232

8

Helix

237 – 243

7

Turn

245 – 247

3

Helix

251 – 254

4

Beta strand

257 – 259

3

Beta strand

263 – 265

3

Helix

266 – 269

4

Helix

270 – 272

3

Helix

285 – 287

3

Beta strand

298 – 304

7

Beta strand

312 – 318

7

Helix

319 – 321

3

Helix

326 – 334

9

Beta strand

345 – 347

3

Helix

356 – 358

3

Helix

362 – 365

4

Turn

366 – 370

5

Beta strand

373 – 376

4

Beta strand

380 – 383

4

Beta strand

389 – 397

9

Beta strand

402 – 413

12

Sequences

	Sequence		Length	Mass (Da)
	P35505 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 771C247377B59102	FASTA	419	46,176
	10 20 30 40 50 60 MSFIPVAEDS DFPIQNLPYG VFSTQSNPKP RIGVAIGDQI LDLSVIKHLF TGPALSKHQH 70 80 90 100 110 120 VFDETTLNNF MGLGQAAWKE ARASLQNLLS ASQARLRDDK ELRQRAFTSQ ASATMHLPAT 130 140 150 160 170 180 IGDYTDFYSS RQHATNVGIM FRGKENALLP NWLHLPVGYH GRASSIVVSG TPIRRPMGQM 190 200 210 220 230 240 RPDNSKPPVY GACRLLDMEL EMAFFVGPGN RFGEPIPISK AHEHIFGMVL MNDWSARDIQ 250 260 270 280 290 300 QWEYVPLGPF LGKSFGTTIS PWVVPMDALM PFVVPNPKQD PKPLPYLCHS QPYTFDINLS 310 320 330 340 350 360 VSLKGEGMSQ AATICRSNFK HMYWTMLQQL THHSVNGCNL RPGDLLASGT ISGSDPESFG 370 380 390 400 410 SMLELSWKGT KAIDVEQGQT RTFLLDGDEV IITGHCQGDG YRVGFGQCAG KVLPALSPA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Murine fumarylacetoacetate hydrolase (Fah) gene is disrupted by a neonatally lethal albino deletion that defines the hepatocyte-specific developmental regulation 1 (hsdr-1) locus." Klebig M.L., Russell L.B., Rinchik E.M. Proc. Natl. Acad. Sci. U.S.A. 89:1363-1367(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Nucleotide sequence of a cDNA encoding murine fumarylacetoacetate hydrolase." Grompe M., Al-Dhalimy M. Biochem. Med. Metab. Biol. 48:26-31(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6. Tissue: Liver.
[3]	"Deficiency of an enzyme of tyrosine metabolism underlies altered gene expression in newborn liver of lethal albino mice." Ruppert S., Kelsey G., Schedl A., Schmid E., Thies E., Schutz G. Genes Dev. 6:1430-1443(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Spleen and Visual cortex.
[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]. Strain: FVB/N. Tissue: Kidney.
[6]	"Point mutations in the murine fumarylacetoacetate hydrolase gene: animal models for the human genetic disorder hereditary tyrosinemia type 1." Aponte J.L., Sega G.A., Hauser L.J., Dhar M.S., Withrow C.M., Carpenter D.A., Rinchik E.M., Culiat C.T., Johnson D.K. Proc. Natl. Acad. Sci. U.S.A. 98:641-645(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLU-201.
[7]	"Crystal structure and mechanism of a carbon-carbon bond hydrolase." Timm D.E., Mueller H.A., Bhanumoorthy P., Harp J.M., Bunick G.J. Structure 7:1023-1033(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH PRODUCTS AND DIVALENT METAL CATIONS.
[8]	"Mechanistic inferences from the crystal structure of fumarylacetoacetate hydrolase with a bound phosphorus-based inhibitor." Bateman R.L., Bhanumoorthy P., Witte J.F., McClard R.W., Grompe M., Timm D.E. J. Biol. Chem. 276:15284-15291(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND METAL IONS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M84145 mRNA. Translation: AAA37591.1.
Z11774 mRNA. Translation: CAA77819.1.
AK143759 mRNA. Translation: BAE25527.1.
AK158808 mRNA. Translation: BAE34676.1.
BC010767 mRNA. Translation: AAH10767.1.

IPI

IPI00310035.

PIR

A40219.
A56825.

RefSeq

NP_034306.2. NM_010176.4.

UniGene

Mm.3798.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HYO	X-ray	1.30	A/B	1-419	[»]
1QCN	X-ray	1.90	A/B	1-419	[»]
1QCO	X-ray	1.90	A/B	1-419	[»]
1QQJ	X-ray	1.55	A/B	1-419	[»]
2HZY	X-ray	1.35	A/B	1-419	[»]

ProteinModelPortal

P35505.

SMR

P35505. Positions 1-417.

ModBase

Search...

Protein-protein interaction databases

IntAct

P35505. 1 interaction.

STRING

10090.ENSMUSP00000032865.

PTM databases

PhosphoSite

P35505.

2D gel databases

SWISS-2DPAGE

P35505.

Proteomic databases

PaxDb

P35505.

PRIDE

P35505.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000032865; ENSMUSP00000032865; ENSMUSG00000030630.

GeneID

14085.

KEGG

mmu:14085.

Organism-specific databases

CTD

2184.

MGI

MGI:95482. Fah.

Phylogenomic databases

eggNOG

COG0179.

GeneTree

ENSGT00390000008646.

HOGENOM

HOG000256845.

HOVERGEN

HBG001919.

InParanoid

Q3TY87.

KO

K01555.

OMA

MLELSWK.

OrthoDB

EOG4Q2DFM.

Enzyme and pathway databases

UniPathway

UPA00139; UER00341.

Gene expression databases

ArrayExpress

P35505.

Bgee

P35505.

CleanEx

MM_FAH.

Genevestigator

P35505.

GermOnline

ENSMUSG00000030630. Mus musculus.

Family and domain databases

Gene3D

2.30.30.230. 1 hit.
3.90.850.10. 1 hit.

InterPro

IPR005959. Fumarylacetoacetase.
IPR002529. Fumarylacetoacetase_C.
IPR011234. Fumarylacetoacetase_C-rel.
IPR015377. Fumarylacetoacetase_N.
[Graphical view]

PANTHER

PTHR11820:SF1. PTHR11820:SF1. 1 hit.

Pfam

PF09298. DUF1969. 1 hit.
PF01557. FAA_hydrolase. 1 hit.
[Graphical view]

SUPFAM

SSF56529. Fumarylacetoacetase_C-rel. 1 hit.
SSF63433. Fumarylacetoacetase_N. 1 hit.

TIGRFAMs

TIGR01266. fum_ac_acetase. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P35505.

NextBio

285108.

SOURCE

Search...

Entry information

Entry name

FAAA_MOUSE

Accession

Primary (citable) accession number: P35505
Secondary accession number(s): Q3TY87, Q9QW65

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	July 27, 2011
Last modified:	April 3, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program