Descriptions

PDE5A plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. PDE5A contains a catalytic domain that hydrolyzes cGMP and a regulatory (R) domain (1-539) that contains two GAFs, a and b. The R domain binds cGMP allosterically, provides for dimerization, and is phosphorylated at a site regulated by allosteric cGMP binding. The sequence containing GAF b and its flanking amino acids (403-539) autoinhibits GAF a cGMP-binding affinity.

Autoinhibitory domains (AIDs)

Target domain

154-314 (GAF a domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for O77746

Entry ID Method Resolution Chain Position Source
AF-O77746-F1 Predicted AlphaFoldDB

No variants for O77746

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for O77746

No associated diseases with O77746

4 regional properties for O77746

Type Name Position InterPro Accession
domain 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain 526 - 850 IPR002073
domain GAF domain 154 - 314 IPR003018-1
domain GAF domain 336 - 503 IPR003018-2
domain HD/PDEase domain 600 - 777 IPR003607

Functions

Description
EC Number 3.1.4.35 Phosphoric diester hydrolases
Subcellular Localization
  • Cytoplasm
  • Cytoplasm, cytosol
  • PDE5A1 and PDE5A2 are located mostly to soluble cellular fractions and some to particulate cellular fractions
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

1 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.

4 GO annotations of molecular function

Name Definition
3',5'-cyclic-GMP phosphodiesterase activity Catalysis of the reaction: 3',5'-cyclic GMP + H2O = GMP + H+.
3',5'-cyclic-nucleotide phosphodiesterase activity Catalysis of the reaction: a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate.
cGMP binding Binding to cGMP, the nucleotide cyclic GMP (guanosine 3',5'-cyclophosphate).
metal ion binding Binding to a metal ion.

2 GO annotations of biological process

Name Definition
cGMP catabolic process The chemical reactions and pathways resulting in the breakdown of cyclic GMP, guanosine 3',5'-phosphate.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

6 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q28156 PDE5A cGMP-specific 3',5'-cyclic phosphodiesterase Bos taurus (Bovine) SS
P33726 PDE6B Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Canis lupus familiaris (Dog) (Canis familiaris) PR
Q9VJ79 Pde11 Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11 Drosophila melanogaster (Fruit fly) SS
O76074 PDE5A cGMP-specific 3',5'-cyclic phosphodiesterase Homo sapiens (Human) EV
Q8CG03 Pde5a cGMP-specific 3',5'-cyclic phosphodiesterase Mus musculus (Mouse) SS
O54735 Pde5a cGMP-specific 3',5'-cyclic phosphodiesterase Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MERGSPGAGA ARLPRDQDSV EAWLDDHRDF TFSYFVKKAT REMVNAWFAE RVHTIPVCKE
70 80 90 100 110 120
GIRGHAESCS CSSQQSSRAD SSAPGTPTRK ISASEFDRPL RPIVVKDSEG TVSFLADSEK
130 140 150 160 170 180
KEQMPLTPPR FDNDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI SADRYSLFLV
190 200 210 220 230 240
CEDSSNDKFL ISRLFDVAEG STLEEASNNC IRLEWNKGIV GHVAALGEPL NIKDAYEDPR
250 260 270 280 290 300
FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE KDFAAYLAFC
310 320 330 340 350 360
GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS FMQVQKCTIF
370 380 390 400 410 420
IVDEDCSDSF SSVFHMECEE LEKLPDTLTR ERDANRINYM YAQYVKNTME PLNIPDVSKD
430 440 450 460 470 480
KRFPWTNENT GNVNQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK VKPFNRNDEQ
490 500 510 520 530 540
FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETKEL QSLAAAVVPS
550 560 570 580 590 600
AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL SVKKNYRKNV
610 620 630 640 650 660
AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV NNSYIQRSEH
670 680 690 700 710 720
PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK TTLKIIKQAI LATDLALYIK
730 740 750 760 770 780
RRGEFFELIR KNQFNLEDPH QKELFLAMLM TACDLSAITK PWPIQQRIAE LVATEFFDQG
790 800 810 820 830 840
DRERKELNIE PADLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF PLLDGCRKNR
850 860
QKWQALAEQQ EKTLINGESS QAKRN