k"::/ 1990 Oxford University Press
Nucleic Acids Research, Vol. 18, No. 7 1887
Nucleotide sequence of cDNA encoding human fumarylacetoacetase E.Agsteribbel,
H. van Faassen2, M.V.1Hartog1, T.Reversma1, J.-W.Taanman1, H.Pannekoek3, R.F.Evers3, G.M.Welling4 and R.Berger5 1Laboratory of Physiological Chemistry, University of Groningen, 2Department of Pediatrics, University of Groningen, 3Department of Molecular Biology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, 4Laboratory of Medical Microbiology, University of Groningen and 5Laboratory of Metabolic Diseases, Wilhelmina Children's Hospital, Utrecht, The Netherlands EMBL accession no. X51728
Submitted March 7, 1990
Fumarylacetoacetase (FAA) (EC 3.7.1.2) is a dimeric enzyme, apparent MW 82 kD, that catalyses the last step in the metabolism of tyrosine, the conversion of fumarylacetoacetate into fumarate and acetoacetate (1). FAA is deficient in tissue of patients suffering from hereditary type I tyrosinemia (2, 3). cDNA clones encoding FAA were isolated from a human liver cDNA library using antibodies raised against beef FAA. Nucleotide (nt) 14noer seuecngrvele open readingnrae frame encoding a revealed a 1047-nt sequencing protein with a MW of 40 kD. Proof for cloning the correct cDNA is the complete identity between the amino acid (aa) sequence e
g
a
deduced from the nt sequence and a sequence of a tryptic peptide generated froom the purified protein (4). REFERENCES 1. Ravdin,R.G. and Crandle,D.J. (1951) J. Bio. Chem. 189, 137. 2. Kvittingen,E.A., Jellum,E. and Stokke,O. (1981) Clin. Chim. Acta 115, 311.
Vries,S.A., 3. Berger,R., Smit,G.P.A., Chim. Acta 114, 37.Duran,M., Ketting,D. and (1981) Clin.Stoker-de
Wadman,S.K.
4. van Faassen,H., van Berg,J.E.T. and Berger,R. (1990) J. Biochem. Biophys. Meth. in press.
1 CCTCC eCAAGACCGAGGATAGGTGTGGCCATTGGCGACCAGATCCTGGACCTCAGCATCATCAAGCACCTCTTTACTGGTCCTGTCCTCTCCAAACA
101 CCAGGATGTCTTCAATCAGCCTACACTCAACAGCTTCATGGGCCTGGGTCAGGCTGCCTGGAAGGAGGCGAGAGTGTTCTTGCAGAACTTGCTGTCTGTG M G L G Q A A W K E A R V F L Q N L L S V 201 AGCCAAGCCAGGCTCAGAGATGACACCGAACTTCGGAAGTGTGCATTCATCTCCCAGGCTTCTGCCACGATGCACCTTCCAGCCACCATAGGAGACTACA S Q A R L R D D T E L R K C A F I S Q A S A T M H L P A T I G D Y 301 CAGACTTCTATTCCTCTCGGCAGCATGCTACCAACGTCGGAATCATGTTCAGGGACAAGGAGAATGCGTTGATGCCAAATTGGCTGCACTTACCAGTGGG T D F Y S S R Q H A T N V G I M F R D K E N A L M P N W L H L P V G 401 CTACCATGGCCGTGCCTCCTCTGTCGTGGTGTCTGGCACCCCAATCCGAAGGCCCATGGGACAGATGAAACCTGATGACTCTAAGCCTCCCGTATATGGT Y H G R A S S V V V S G T P I R R P M G Q M K P D D S K P P V Y G
501 GCCTGCAAGCTCTTGGACATGGAGCTGGAAATGGCTTTTTTTGTAGGCCCTGGAAACAGATTGGGAGAGCCGATCCCCA=CCAAGGCCCATGAGCACA A C K L L D M E L E M A F F V G P G N R L G E P I P I S K A H E H 601 TTTTTGGAATGGTCCTTATGAACGACTGGAGTGCACGAGACAITCAGAAGTGGGAGTATGTCCCTCTCGGGCCATTCCTTGGGAAGAGl I F G M V L M N D W S A R D I Q K W E Y V P L G P F L G K S
-GGGACCAC F
G
T
T
701 TGTCTCTCCGTGGGTGGTGCCCATGGATGCTCTCATGCCCTTTGCTGTGCCCAACCCGAAGCAGGACCCCAGGCCCCTGCCGTATCTGTGCCATGACGAG V S P W V V P M D A L M P F A V P N P K Q D P R P L P Y L C H D E 801 CCCTACACATTTGACATCAACCTCTCTGTTAACCTGAAAGGAGAAGGAATGAGCCAGGCGGCTACCATATGCAAGTCCAATTTTAAGTACATGTACTGGA P Y T F D I N L S V N L K G E G M S Q A A T I C K S N F K Y M Y W
901 CGATGCTGCAGCAGCTCACTCACCACTCTGTCAACGGCTGCAACCTGCGGCCGGGGGACCTCCTGGCTTCTGGGACCATCAGCGGGCCGGAGCCAGAAAA T M L Q Q L T H H S V N G C N L R P G D L L A S G T I S G P E P E N 1001 CTTCGGCTCCATGTTGGAACTGTCGTGGAAGGGAACGAAGCCCATAGACCTGGGGAATGGTCAGACCAGGAAGTTTCTGCTGGACGGGGATGAAGTCATC F G S M L E L S W K G T K P I D L G N G Q T R K F L L D G D E V I
1101 ATAACAGGGTACTGCCAGGGGGATGGTTACCGCATCGGCTTTGGCCAGTGTGCTGGAAAAGTGCTGCCTGCTCTCCTGCCATCATGAGAT-llCTCTGCT I T G Y C Q G D G .Y R I G F G Q C A G K V L P A L L P S 1201 CTTCTGGAAACAAAGGGCTCAAGCACCCCTTTCAACCCTGTGACTGGGGTCCTCCCTCGGGCTGTAGGCCTGGTCCGCTATTCAGTGACAAATAAAGCCA 1301 TTGTGCTCTGAAAAAAAAAAA
0I: in frame stopcodon upstream of ATG, -, confirmed by aa sequence determination (Eurosequence B.V., Groningen, The Netherlands).
Nucleic Acids Research, Vol. 18, No. 7 1887
Nucleotide sequence of cDNA encoding human fumarylacetoacetase E.Agsteribbel,
H. van Faassen2, M.V.1Hartog1, T.Reversma1, J.-W.Taanman1, H.Pannekoek3, R.F.Evers3, G.M.Welling4 and R.Berger5 1Laboratory of Physiological Chemistry, University of Groningen, 2Department of Pediatrics, University of Groningen, 3Department of Molecular Biology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, 4Laboratory of Medical Microbiology, University of Groningen and 5Laboratory of Metabolic Diseases, Wilhelmina Children's Hospital, Utrecht, The Netherlands EMBL accession no. X51728
Submitted March 7, 1990
Fumarylacetoacetase (FAA) (EC 3.7.1.2) is a dimeric enzyme, apparent MW 82 kD, that catalyses the last step in the metabolism of tyrosine, the conversion of fumarylacetoacetate into fumarate and acetoacetate (1). FAA is deficient in tissue of patients suffering from hereditary type I tyrosinemia (2, 3). cDNA clones encoding FAA were isolated from a human liver cDNA library using antibodies raised against beef FAA. Nucleotide (nt) 14noer seuecngrvele open readingnrae frame encoding a revealed a 1047-nt sequencing protein with a MW of 40 kD. Proof for cloning the correct cDNA is the complete identity between the amino acid (aa) sequence e
g
a
deduced from the nt sequence and a sequence of a tryptic peptide generated froom the purified protein (4). REFERENCES 1. Ravdin,R.G. and Crandle,D.J. (1951) J. Bio. Chem. 189, 137. 2. Kvittingen,E.A., Jellum,E. and Stokke,O. (1981) Clin. Chim. Acta 115, 311.
Vries,S.A., 3. Berger,R., Smit,G.P.A., Chim. Acta 114, 37.Duran,M., Ketting,D. and (1981) Clin.Stoker-de
Wadman,S.K.
4. van Faassen,H., van Berg,J.E.T. and Berger,R. (1990) J. Biochem. Biophys. Meth. in press.
1 CCTCC eCAAGACCGAGGATAGGTGTGGCCATTGGCGACCAGATCCTGGACCTCAGCATCATCAAGCACCTCTTTACTGGTCCTGTCCTCTCCAAACA
101 CCAGGATGTCTTCAATCAGCCTACACTCAACAGCTTCATGGGCCTGGGTCAGGCTGCCTGGAAGGAGGCGAGAGTGTTCTTGCAGAACTTGCTGTCTGTG M G L G Q A A W K E A R V F L Q N L L S V 201 AGCCAAGCCAGGCTCAGAGATGACACCGAACTTCGGAAGTGTGCATTCATCTCCCAGGCTTCTGCCACGATGCACCTTCCAGCCACCATAGGAGACTACA S Q A R L R D D T E L R K C A F I S Q A S A T M H L P A T I G D Y 301 CAGACTTCTATTCCTCTCGGCAGCATGCTACCAACGTCGGAATCATGTTCAGGGACAAGGAGAATGCGTTGATGCCAAATTGGCTGCACTTACCAGTGGG T D F Y S S R Q H A T N V G I M F R D K E N A L M P N W L H L P V G 401 CTACCATGGCCGTGCCTCCTCTGTCGTGGTGTCTGGCACCCCAATCCGAAGGCCCATGGGACAGATGAAACCTGATGACTCTAAGCCTCCCGTATATGGT Y H G R A S S V V V S G T P I R R P M G Q M K P D D S K P P V Y G
501 GCCTGCAAGCTCTTGGACATGGAGCTGGAAATGGCTTTTTTTGTAGGCCCTGGAAACAGATTGGGAGAGCCGATCCCCA=CCAAGGCCCATGAGCACA A C K L L D M E L E M A F F V G P G N R L G E P I P I S K A H E H 601 TTTTTGGAATGGTCCTTATGAACGACTGGAGTGCACGAGACAITCAGAAGTGGGAGTATGTCCCTCTCGGGCCATTCCTTGGGAAGAGl I F G M V L M N D W S A R D I Q K W E Y V P L G P F L G K S
-GGGACCAC F
G
T
T
701 TGTCTCTCCGTGGGTGGTGCCCATGGATGCTCTCATGCCCTTTGCTGTGCCCAACCCGAAGCAGGACCCCAGGCCCCTGCCGTATCTGTGCCATGACGAG V S P W V V P M D A L M P F A V P N P K Q D P R P L P Y L C H D E 801 CCCTACACATTTGACATCAACCTCTCTGTTAACCTGAAAGGAGAAGGAATGAGCCAGGCGGCTACCATATGCAAGTCCAATTTTAAGTACATGTACTGGA P Y T F D I N L S V N L K G E G M S Q A A T I C K S N F K Y M Y W
901 CGATGCTGCAGCAGCTCACTCACCACTCTGTCAACGGCTGCAACCTGCGGCCGGGGGACCTCCTGGCTTCTGGGACCATCAGCGGGCCGGAGCCAGAAAA T M L Q Q L T H H S V N G C N L R P G D L L A S G T I S G P E P E N 1001 CTTCGGCTCCATGTTGGAACTGTCGTGGAAGGGAACGAAGCCCATAGACCTGGGGAATGGTCAGACCAGGAAGTTTCTGCTGGACGGGGATGAAGTCATC F G S M L E L S W K G T K P I D L G N G Q T R K F L L D G D E V I
1101 ATAACAGGGTACTGCCAGGGGGATGGTTACCGCATCGGCTTTGGCCAGTGTGCTGGAAAAGTGCTGCCTGCTCTCCTGCCATCATGAGAT-llCTCTGCT I T G Y C Q G D G .Y R I G F G Q C A G K V L P A L L P S 1201 CTTCTGGAAACAAAGGGCTCAAGCACCCCTTTCAACCCTGTGACTGGGGTCCTCCCTCGGGCTGTAGGCCTGGTCCGCTATTCAGTGACAAATAAAGCCA 1301 TTGTGCTCTGAAAAAAAAAAA
0I: in frame stopcodon upstream of ATG, -, confirmed by aa sequence determination (Eurosequence B.V., Groningen, The Netherlands).
