Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.
Human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A) cDNAs were isolated. A 3.1-kb composite DNA sequence assembled from overlapping cDNAs encodes an 875-amino-acid protein with a predicted molecular mass of 100012 Da (PDE5A1). Extracts prepared from yeast expressing human PDE5A1 hydrolyzed cGMP. This activity was inhibited by the selective PDE5 inhibitors zaprinast and DMPPO. PDE5A mRNA is expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. A 5'-splice variant, PDE5A2, encodes an 833-amino-acid protein with eight unique amino acids at the amino terminus. PDE5A maps to chromosome 4q 25-27.
Loughney
K
K
ICOS Corporation, Bothell, WA 98021, USA. kloughney@icos.com
Hill
T R
TR
Florio
V A
VA
Uher
L
L
Rosman
G J
GJ
Wolda
S L
SL
Jones
B A
BA
Howard
M L
ML
McAllister-Lucas
L M
LM
Sonnenburg
W K
WK
Francis
S H
SH
Corbin
J D
JD
Beavo
J A
JA
Ferguson
K
K
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002417:Cattle; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification*; D015870:Gene Expression / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human