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Protein

High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A

Gene

PDE9A

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

Functioni

Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP (PubMed:9624146, PubMed:18757755, PubMed:21483814). Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart (PubMed:25799991). Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (Probable). In brain, involved in cognitive function, such as learning and long-term memory (By similarity).By similarityCurated4 Publications

Catalytic activityi

Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.3 Publications

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Inhibited by zaprinast; inhibitor is however not specific to PDE9A (PubMed:9624146). Specifically inhibited by BAY-73-6691 (1-(2-chlorophenyl)-6-((2R)-3,3,3- trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one) (PubMed:16150925). BAY-73-9961 has two enantiomers, (R) and (S), due to the presence of a chiral center, and both forms vary in their pattern of interaction (PubMed:20121115, PubMed:21483814). Specifically inhibited by PF-4181366 (4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1- cyclopentyl-1,5-dihydro-6-[(3S,4S)-4-methyl- 1-(6-quinoxalinylmethyl)-3-pyrrolidinyl]-one) (PubMed:19919087). Specifically inhibited by PF-4449613 ((R)-6-(1-(3-phenoxyazetidin-1-yl)ethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin- 4(5H)-one) (PubMed:25799991). Specifically inhibited by inhibitor 28 (2-((1-(2-Chlorophenyl)-4-hydroxy-1Hpyrazolo[ 3,4-d]pyrimidin-6-yl)amino)-N-(4- methoxyphenyl)propanamide): inhibitor forms a hydrogen bond with Tyr-484 and Gln-513 (PubMed:22985069). Specifically inhibited by 1-Cyclopentyl-6-[(1r)-1-(3-phenoxyazetidin- 1-Yl)ethyl]-1,5-dihydro-4h-pyrazolo[3,4-D] pyrimidin-4-one: inhibitor forms a hydrogen bond with Tyr-484 and Gln-513 (PubMed:23025719).1 Publication8 Publications

Kineticsi

kcat is 0.18 sec(-1) for cGMP. kcat is 2.37 sec(-1) for cAMP.1 Publication

Manual assertion based on experiment ini

  • Ref.20
    "Structural asymmetry of phosphodiesterase-9, potential protonation of a glutamic acid, and role of the invariant glutamine."
    Hou J., Xu J., Liu M., Zhao R., Luo H.B., Ke H.
    PLoS ONE 6:E18092-E18092(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTANT GLU-513 IN COMPLEX WITH MAGNESIUM; ZINC AND (S)-BAY-73-6691 INHIBITOR, ENZYME REGULATION, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-466 AND GLN-513.

  1. KM=0.113 µM for cGMP1 Publication
  2. KM=501 µM for cAMP1 Publication
  1. Vmax=0.285 µmol/min/mg enzyme with cGMP as substrate1 Publication
  2. Vmax=3.7 µmol/min/mg enzyme with cAMP as substrate1 Publication

Pathwayi: 3',5'-cyclic GMP degradation

This protein is involved in step 1 of the subpathway that synthesizes GMP from 3',5'-cyclic GMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (PDE9A), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A)
This subpathway is part of the pathway 3',5'-cyclic GMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes GMP from 3',5'-cyclic GMP, the pathway 3',5'-cyclic GMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei312Proton donor1 Publication1
Metal bindingi316Zinc; via tele nitrogenCombined sources6 Publications1
Metal bindingi352Zinc; via tele nitrogenCombined sources6 Publications1
Metal bindingi353MagnesiumCombined sources6 Publications1
Metal bindingi353ZincCombined sources6 Publications1
Binding sitei353cGMP1 Publication1
Metal bindingi462ZincCombined sources6 Publications1
Binding sitei462cGMP1 Publication1
Binding sitei484cGMP1 Publication1
Binding sitei484Inhibitor specific to PDE9A3 Publications1
Binding sitei513Inhibitor5 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi312 – 316cGMP1 Publication5
Nucleotide bindingi512 – 513cGMP1 Publication2

GO - Molecular functioni

  • 3',5'-cyclic-GMP phosphodiesterase activity Source: UniProtKB
  • 3',5'-cyclic-nucleotide phosphodiesterase activity Source: ProtInc
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cGMP catabolic process Source: UniProtKB
  • cGMP-mediated signaling Source: Ensembl
  • cGMP metabolic process Source: UniProtKB
  • positive regulation of cardiac muscle hypertrophy Source: UniProtKB
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cGMP, Magnesium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS08457-MONOMER.
BRENDAi3.1.4.35. 2681.
ReactomeiR-HSA-418457. cGMP effects.
UniPathwayiUPA00763; UER00748.

Names & Taxonomyi

Protein namesi
Recommended name:
High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9ACurated (EC:3.1.4.353 Publications)
Gene namesi
Name:PDE9AImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:8795. PDE9A.

Subcellular locationi

Isoform PDE9A1 :
Isoform PDE9A2 :
Isoform PDE9A3 :
  • Cytoplasm 1 Publication
  • Endoplasmic reticulum 1 Publication
Isoform PDE9A17 :
  • Cytoplasm 1 Publication
  • Endoplasmic reticulum 1 Publication

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB-SubCell
  • perikaryon Source: Ensembl
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • ruffle membrane Source: UniProtKB-SubCell
  • sarcolemma Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi312H → A: Completely abolishes catalytic activity. 1 Publication1
Mutagenesisi356H → A: Reduces catalytic activity, but has no effect on substrate affinity. 1 Publication1
Mutagenesisi425M → A: Induces a 2 fold change in inhibitory sensivity by BAY-73-9961. 1 Publication1
Mutagenesisi463I → A: Induces a 6-9 fold change in inhibitory sensivity by BAY-73-9961. 1 Publication1
Mutagenesisi466E → A: Decreased affinity and catalytic activity for cGMP and cAMP. 1 Publication1
Mutagenesisi480L → A: Induces a 6-9 fold change in inhibitory sensivity by BAY-73-9961. 1 Publication1
Mutagenesisi484Y → A: Induces a 6-9 fold change in inhibitory sensivity by BAY-73-9961. 1 Publication1
Mutagenesisi501F → A: Induces a 2 fold change in inhibitory sensivity by BAY-73-9961. 1 Publication1
Mutagenesisi513Q → A: Induces a dramatic change in inhibitory sensivity by BAY-73-9961. 1 Publication1
Mutagenesisi513Q → E: 2 fold decreased affinity and catalytic activity for cGMP. 8 fold decreased catalytic activity for cAMP without affecting the affinity for cAMP. 1 Publication1
Mutagenesisi516F → A: Induces a dramatic change in inhibitory sensivity by BAY-73-9961. 1 Publication1

Organism-specific databases

DisGeNETi5152.
OpenTargetsiENSG00000160191.
PharmGKBiPA33143.

Chemistry databases

ChEMBLiCHEMBL3535.
DrugBankiDB00201. Caffeine.
GuidetoPHARMACOLOGYi1309.

Polymorphism and mutation databases

BioMutaiPDE9A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988411 – 593High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AAdd BLAST593

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei379PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO76083.
PeptideAtlasiO76083.
PRIDEiO76083.

PTM databases

iPTMnetiO76083.
PhosphoSitePlusiO76083.

Expressioni

Tissue specificityi

Expressed in all tissues examined (testis, brain, small intestine, skeletal muscle, heart, lung, thymus, spleen, placenta, kidney, liver, pancreas, ovary and prostate) except blood (PubMed:9624146). Highest levels in brain, heart, kidney, spleen, prostate and colon. Isoform PDE9A12 is found in prostate (PubMed:12565835). In brain, present in the cortex, cerebellum, and subiculum (at protein level) (PubMed:22328573). In heart, primarily localizes to myocytes (PubMed:25799991).4 Publications

Inductioni

Up-regulated in left ventricular hypertrophy from aortic stenosis and following heart failure with preserved ejection fraction (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000160191.
ExpressionAtlasiO76083. baseline and differential.
GenevisibleiO76083. HS.

Organism-specific databases

HPAiHPA011380.

Interactioni

Subunit structurei

Homodimer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BAG3O958173EBI-742764,EBI-747185
C9orf106A2RU003EBI-742764,EBI-10173129
CLK1P497593EBI-742764,EBI-473775
CRY2Q49AN03EBI-742764,EBI-2212355
GORASP2Q9H8Y83EBI-742764,EBI-739467
KRTAP10-8P604103EBI-742764,EBI-10171774
KRTAP4-2Q9BYR53EBI-742764,EBI-10172511
KRTAP9-2Q9BYQ43EBI-742764,EBI-1044640
LAGE3Q146573EBI-742764,EBI-1052105
LMO2P257913EBI-742764,EBI-739696
NAA38Q9BRA03EBI-742764,EBI-9106509
NOTCH2NLQ7Z3S93EBI-742764,EBI-945833
PHYHIPLQ96FC7-23EBI-742764,EBI-10285660
SULT1E1P498883EBI-742764,EBI-712512
TRIM32Q130496EBI-742764,EBI-742790
TRPV6Q9Y2603EBI-742764,EBI-750052
UTP23Q9BRU93EBI-742764,EBI-5457544

Protein-protein interaction databases

BioGridi111178. 21 interactors.
IntActiO76083. 31 interactors.
MINTiMINT-1444906.
STRINGi9606.ENSP00000291539.

Chemistry databases

BindingDBiO76083.

Structurei

Secondary structure

1593
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi250 – 255Combined sources6
Helixi263 – 265Combined sources3
Helixi268 – 281Combined sources14
Helixi284 – 287Combined sources4
Helixi292 – 304Combined sources13
Beta strandi310 – 313Combined sources4
Helixi314 – 330Combined sources17
Helixi333 – 335Combined sources3
Helixi339 – 351Combined sources13
Turni352 – 355Combined sources4
Helixi361 – 366Combined sources6
Helixi370 – 374Combined sources5
Turni375 – 377Combined sources3
Helixi380 – 393Combined sources14
Helixi396 – 398Combined sources3
Turni400 – 403Combined sources4
Helixi406 – 421Combined sources16
Helixi425 – 427Combined sources3
Helixi428 – 438Combined sources11
Helixi439 – 441Combined sources3
Helixi447 – 462Combined sources16
Helixi465 – 467Combined sources3
Helixi470 – 492Combined sources23
Turni493 – 495Combined sources3
Helixi500 – 502Combined sources3
Turni504 – 506Combined sources3
Helixi509 – 519Combined sources11
Helixi521 – 531Combined sources11
Helixi535 – 538Combined sources4
Helixi540 – 562Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HD1X-ray2.23A/B241-566[»]
2YY2X-ray2.80A/B241-566[»]
3DY8X-ray2.15A/B242-566[»]
3DYLX-ray2.70A/B242-566[»]
3DYNX-ray2.10A/B242-566[»]
3DYQX-ray2.50A/B242-566[»]
3DYSX-ray2.30A/B242-566[»]
3JSIX-ray2.72A/B242-566[»]
3JSWX-ray2.30A/B242-566[»]
3K3EX-ray2.70A/B241-566[»]
3K3HX-ray2.50A/B241-566[»]
3N3ZX-ray2.75A/B241-566[»]
3QI3X-ray2.30A/B1-593[»]
3QI4X-ray2.50A/B1-593[»]
4E90X-ray2.50A/B242-566[»]
4G2JX-ray2.40A/B242-566[»]
4G2LX-ray3.00A/B242-566[»]
4GH6X-ray2.70A/B241-566[»]
4Y86X-ray2.01A/B1-593[»]
4Y87X-ray3.10A/B1-593[»]
4Y8CX-ray2.70A/B1-593[»]
ProteinModelPortaliO76083.
SMRiO76083.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO76083.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni288 – 550CatalyticBy similarityAdd BLAST263

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOVERGENiHBG053545.
KOiK13761.
OMAiPRAFKIN.
OrthoDBiEOG091G082I.
PhylomeDBiO76083.
TreeFamiTF314638.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequences (16)i

Sequence statusi: Complete.

This entry describes 16 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform PDE9A1 (identifier: O76083-1) [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
MGSGSSSYRP KAIYLDIDGR IQKVIFSKYC NSSDIMDLFC IATGLPRNTT
60 70 80 90 100
ISLLTTDDAM VSIDPTMPAN SERTPYKVRP VAIKQLSAGV EDKRTTSRGQ
110 120 130 140 150
SAERPLRDRR VVGLEQPRRE GAFESGQVEP RPREPQGCYQ EGQRIPPERE
160 170 180 190 200
ELIQSVLAQV AEQFSRAFKI NELKAEVANH LAVLEKRVEL EGLKVVEIEK
210 220 230 240 250
CKSDIKKMRE ELAARSSRTN CPCKYSFLDN HKKLTPRRDV PTYPKYLLSP
260 270 280 290 300
ETIEALRKPT FDVWLWEPNE MLSCLEHMYH DLGLVRDFSI NPVTLRRWLF
310 320 330 340 350
CVHDNYRNNP FHNFRHCFCV AQMMYSMVWL CSLQEKFSQT DILILMTAAI
360 370 380 390 400
CHDLDHPGYN NTYQINARTE LAVRYNDISP LENHHCAVAF QILAEPECNI
410 420 430 440 450
FSNIPPDGFK QIRQGMITLI LATDMARHAE IMDSFKEKME NFDYSNEEHM
460 470 480 490 500
TLLKMILIKC CDISNEVRPM EVAEPWVDCL LEEYFMQSDR EKSEGLPVAP
510 520 530 540 550
FMDRDKVTKA TAQIGFIKFV LIPMFETVTK LFPMVEEIML QPLWESRDRY
560 570 580 590
EELKRIDDAM KELQKKTDSL TSGATEKSRE RSRDVKNSEG DCA
Length:593
Mass (Da):68,493
Last modified:November 1, 1998 - v1
Checksum:iE2731C7C828C0994
GO
Isoform PDE9A2 (identifier: O76083-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     88-147: Missing.

Show »
Length:533
Mass (Da):61,709
Checksum:i728ADAAACE0E4D29
GO
Isoform PDE9A3 (identifier: O76083-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGSGSSSYRP...DPTMPANSER → MDAFRS
     88-147: Missing.

Show »
Length:466
Mass (Da):54,440
Checksum:iDE087DD09AAF4794
GO
Isoform PDE9A4 (identifier: O76083-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-165: VIFSKYCNSS...VLAQVAEQFS → HSVQSETCGHQATL

Show »
Length:465
Mass (Da):54,096
Checksum:iBDD6A8F85E591A67
GO
Isoform PDE9A5 (identifier: O76083-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     74-165: TPYKVRPVAI...VLAQVAEQFS → NELILYTSLR...SETCGHQATL

Show »
Length:540
Mass (Da):62,491
Checksum:i612A2ECEE7F656B4
GO
Isoform PDE9A6 (identifier: O76083-6) [UniParc]FASTAAdd to basket
Also known as: PDE9A5

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR
     88-147: Missing.

Show »
Length:492
Mass (Da):57,285
Checksum:i1FE4F709AD50C0E6
GO
Isoform PDE9A7 (identifier: O76083-7) [UniParc]FASTAAdd to basket
Also known as: PDE9A8, PDE9A14, PDE9A19, PDE9A20

The sequence of this isoform differs from the canonical sequence as follows:
     1-207: Missing.

Show »
Length:386
Mass (Da):45,290
Checksum:i4120AB778B9746B9
GO
Isoform PDE9A9 (identifier: O76083-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-73: Missing.
     88-147: Missing.

Show »
Length:507
Mass (Da):58,933
Checksum:iE211E0EB8B67F284
GO
Isoform PDE9A10 (identifier: O76083-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     161-165: AEQFS → MDAFR

Show »
Length:433
Mass (Da):50,713
Checksum:iD6036BB3CA9FB7B2
GO
Isoform PDE9A11 (identifier: O76083-10) [UniParc]FASTAAdd to basket
Also known as: PDE9A15

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.
     218-218: R → M

Show »
Length:376
Mass (Da):44,134
Checksum:iBF896546AED87831
GO
Isoform PDE9A12 (identifier: O76083-11) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR
     73-165: Missing.

Show »
Length:459
Mass (Da):53,489
Checksum:iE7DA06012931A850
GO
Isoform PDE9A13 (identifier: O76083-12) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-165: VIFSKYCNSS...VLAQVAEQFS → EHDHLPADHR...SETCGHQATL

Show »
Length:491
Mass (Da):57,350
Checksum:iCA53A1793F405CDB
GO
Isoform PDE9A16 (identifier: O76083-13) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGSGSSSYRP...DPTMPANSER → MDAFRS

Show »
Length:526
Mass (Da):61,223
Checksum:i02A36AE5185CEDF3
GO
Isoform PDE9A17 (identifier: O76083-14) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR

Show »
Length:552
Mass (Da):64,068
Checksum:iF10D41FE319A6D28
GO
Isoform PDE9A18 (identifier: O76083-15) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-73: Missing.

Show »
Length:567
Mass (Da):65,717
Checksum:i2DFEB16AFCA94F0D
GO
Isoform PDE9A21 (identifier: O76083-16) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGSGSSSYRP...DPTMPANSER → MSSFSIHHSVTCCFYLVRSHGRPTS
     88-147: Missing.

Show »
Length:485
Mass (Da):56,554
Checksum:i82275A46E46C4D83
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti79R → G in BAG57446 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0173021 – 217Missing in isoform PDE9A11. 1 PublicationAdd BLAST217
Alternative sequenceiVSP_0173031 – 207Missing in isoform PDE9A7. 1 PublicationAdd BLAST207
Alternative sequenceiVSP_0173041 – 160Missing in isoform PDE9A10. 1 PublicationAdd BLAST160
Alternative sequenceiVSP_0386471 – 73MGSGS…ANSER → MSSFSIHHSVTCCFYLVRSH GRPTS in isoform PDE9A21. 1 PublicationAdd BLAST73
Alternative sequenceiVSP_0045981 – 73MGSGS…ANSER → MDAFRS in isoform PDE9A3 and isoform PDE9A16. 3 PublicationsAdd BLAST73
Alternative sequenceiVSP_0173051 – 46MGSGS…ATGLP → MDAFR in isoform PDE9A6, isoform PDE9A12 and isoform PDE9A17. 2 PublicationsAdd BLAST46
Alternative sequenceiVSP_01730624 – 165VIFSK…AEQFS → EHDHLPADHRRRHGLHRPHH AREFRTHSVQSETCGHQATL in isoform PDE9A13. 1 PublicationAdd BLAST142
Alternative sequenceiVSP_00460024 – 165VIFSK…AEQFS → HSVQSETCGHQATL in isoform PDE9A4. 1 PublicationAdd BLAST142
Alternative sequenceiVSP_01730748 – 73Missing in isoform PDE9A9 and isoform PDE9A18. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_01730873 – 165Missing in isoform PDE9A12. 1 PublicationAdd BLAST93
Alternative sequenceiVSP_01730974 – 165TPYKV…AEQFS → NELILYTSLRNLLFLPSKES WASHQHSVQSETCGHQATL in isoform PDE9A5. 1 PublicationAdd BLAST92
Alternative sequenceiVSP_00459988 – 147Missing in isoform PDE9A2, isoform PDE9A3, isoform PDE9A6, isoform PDE9A9 and isoform PDE9A21. 7 PublicationsAdd BLAST60
Alternative sequenceiVSP_017310161 – 165AEQFS → MDAFR in isoform PDE9A10. 1 Publication5
Alternative sequenceiVSP_017311218R → M in isoform PDE9A11. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF048837 mRNA. Translation: AAC39778.1.
AB017602 Genomic DNA. Translation: BAA88847.1.
AF067223 mRNA. Translation: AAC26723.1.
AF067224 mRNA. Translation: AAC26724.1.
AF067225 mRNA. Translation: AAC26725.1.
AF067226 mRNA. Translation: AAC26726.1.
AY196299 mRNA. Translation: AAO34685.1.
AY196300 mRNA. Translation: AAO34686.1.
AY196301 mRNA. Translation: AAO34687.1.
AY196302 mRNA. Translation: AAO34688.1.
AY196303 mRNA. Translation: AAO34689.1.
AY196304 mRNA. Translation: AAO34690.1.
AY196305 mRNA. Translation: AAO34691.1.
AY196306 mRNA. Translation: AAO34692.1.
AY196307 mRNA. Translation: AAO34693.1.
AY196308 mRNA. Translation: AAO34694.1.
AY196309 mRNA. Translation: AAO34695.1.
AY196310 mRNA. Translation: AAO34696.1.
AY196311 mRNA. Translation: AAO34697.1.
AY196312 mRNA. Translation: AAO34698.1.
AY196313 mRNA. Translation: AAO34699.1.
AY196314 mRNA. Translation: AAO34700.1.
AY242121 mRNA. Translation: AAO88210.1.
AY701187 mRNA. Translation: AAV84271.1.
AK294112 mRNA. Translation: BAG57446.1.
AK314679 mRNA. Translation: BAG37232.1.
BT007016 mRNA. Translation: AAP35662.1.
AP001747 Genomic DNA. Translation: BAA95552.1.
CH471079 Genomic DNA. Translation: EAX09544.1.
CH471079 Genomic DNA. Translation: EAX09536.1.
CH471079 Genomic DNA. Translation: EAX09537.1.
CH471079 Genomic DNA. Translation: EAX09541.1.
CH471079 Genomic DNA. Translation: EAX09542.1.
CH471079 Genomic DNA. Translation: EAX09546.1.
CH471079 Genomic DNA. Translation: EAX09540.1.
CH471079 Genomic DNA. Translation: EAX09548.1.
CH471079 Genomic DNA. Translation: EAX09549.1.
BC009047 mRNA. Translation: AAH09047.1.
CCDSiCCDS13690.1. [O76083-1]
CCDS33567.1. [O76083-5]
CCDS33568.1. [O76083-2]
CCDS33569.1. [O76083-15]
CCDS33570.1. [O76083-12]
CCDS33571.1. [O76083-4]
CCDS42941.1. [O76083-8]
CCDS42942.1. [O76083-14]
CCDS42943.1. [O76083-6]
CCDS42944.1. [O76083-11]
CCDS42945.1. [O76083-13]
CCDS42946.1. [O76083-3]
CCDS42947.1. [O76083-9]
RefSeqiNP_001001567.1. NM_001001567.1. [O76083-2]
NP_001001568.1. NM_001001568.1. [O76083-3]
NP_001001569.1. NM_001001569.1. [O76083-4]
NP_001001570.1. NM_001001570.1. [O76083-5]
NP_001001571.1. NM_001001571.1. [O76083-6]
NP_001001572.1. NM_001001572.1. [O76083-7]
NP_001001573.1. NM_001001573.1. [O76083-7]
NP_001001574.1. NM_001001574.1. [O76083-8]
NP_001001575.1. NM_001001575.1. [O76083-9]
NP_001001576.1. NM_001001576.1. [O76083-10]
NP_001001577.1. NM_001001577.1. [O76083-11]
NP_001001578.1. NM_001001578.1. [O76083-12]
NP_001001579.1. NM_001001579.1. [O76083-7]
NP_001001580.1. NM_001001580.1. [O76083-10]
NP_001001581.1. NM_001001581.1. [O76083-13]
NP_001001582.1. NM_001001582.1. [O76083-14]
NP_001001583.1. NM_001001583.1. [O76083-15]
NP_001001584.1. NM_001001584.2. [O76083-7]
NP_001001585.1. NM_001001585.1. [O76083-7]
NP_001302462.1. NM_001315533.1. [O76083-16]
NP_002597.1. NM_002606.2. [O76083-1]
XP_016883855.1. XM_017028366.1. [O76083-7]
UniGeneiHs.473927.

Genome annotation databases

EnsembliENST00000291539; ENSP00000291539; ENSG00000160191. [O76083-1]
ENST00000328862; ENSP00000328699; ENSG00000160191. [O76083-15]
ENST00000335440; ENSP00000335365; ENSG00000160191. [O76083-12]
ENST00000335512; ENSP00000335242; ENSG00000160191. [O76083-2]
ENST00000349112; ENSP00000344730; ENSG00000160191. [O76083-4]
ENST00000380328; ENSP00000369685; ENSG00000160191. [O76083-5]
ENST00000398224; ENSP00000381280; ENSG00000160191. [O76083-3]
ENST00000398225; ENSP00000381281; ENSG00000160191. [O76083-14]
ENST00000398227; ENSP00000381283; ENSG00000160191. [O76083-9]
ENST00000398229; ENSP00000381285; ENSG00000160191. [O76083-11]
ENST00000398232; ENSP00000381287; ENSG00000160191. [O76083-13]
ENST00000398234; ENSP00000381289; ENSG00000160191. [O76083-6]
ENST00000398236; ENSP00000381291; ENSG00000160191. [O76083-8]
GeneIDi5152.
KEGGihsa:5152.
UCSCiuc002zbm.4. human. [O76083-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF048837 mRNA. Translation: AAC39778.1.
AB017602 Genomic DNA. Translation: BAA88847.1.
AF067223 mRNA. Translation: AAC26723.1.
AF067224 mRNA. Translation: AAC26724.1.
AF067225 mRNA. Translation: AAC26725.1.
AF067226 mRNA. Translation: AAC26726.1.
AY196299 mRNA. Translation: AAO34685.1.
AY196300 mRNA. Translation: AAO34686.1.
AY196301 mRNA. Translation: AAO34687.1.
AY196302 mRNA. Translation: AAO34688.1.
AY196303 mRNA. Translation: AAO34689.1.
AY196304 mRNA. Translation: AAO34690.1.
AY196305 mRNA. Translation: AAO34691.1.
AY196306 mRNA. Translation: AAO34692.1.
AY196307 mRNA. Translation: AAO34693.1.
AY196308 mRNA. Translation: AAO34694.1.
AY196309 mRNA. Translation: AAO34695.1.
AY196310 mRNA. Translation: AAO34696.1.
AY196311 mRNA. Translation: AAO34697.1.
AY196312 mRNA. Translation: AAO34698.1.
AY196313 mRNA. Translation: AAO34699.1.
AY196314 mRNA. Translation: AAO34700.1.
AY242121 mRNA. Translation: AAO88210.1.
AY701187 mRNA. Translation: AAV84271.1.
AK294112 mRNA. Translation: BAG57446.1.
AK314679 mRNA. Translation: BAG37232.1.
BT007016 mRNA. Translation: AAP35662.1.
AP001747 Genomic DNA. Translation: BAA95552.1.
CH471079 Genomic DNA. Translation: EAX09544.1.
CH471079 Genomic DNA. Translation: EAX09536.1.
CH471079 Genomic DNA. Translation: EAX09537.1.
CH471079 Genomic DNA. Translation: EAX09541.1.
CH471079 Genomic DNA. Translation: EAX09542.1.
CH471079 Genomic DNA. Translation: EAX09546.1.
CH471079 Genomic DNA. Translation: EAX09540.1.
CH471079 Genomic DNA. Translation: EAX09548.1.
CH471079 Genomic DNA. Translation: EAX09549.1.
BC009047 mRNA. Translation: AAH09047.1.
CCDSiCCDS13690.1. [O76083-1]
CCDS33567.1. [O76083-5]
CCDS33568.1. [O76083-2]
CCDS33569.1. [O76083-15]
CCDS33570.1. [O76083-12]
CCDS33571.1. [O76083-4]
CCDS42941.1. [O76083-8]
CCDS42942.1. [O76083-14]
CCDS42943.1. [O76083-6]
CCDS42944.1. [O76083-11]
CCDS42945.1. [O76083-13]
CCDS42946.1. [O76083-3]
CCDS42947.1. [O76083-9]
RefSeqiNP_001001567.1. NM_001001567.1. [O76083-2]
NP_001001568.1. NM_001001568.1. [O76083-3]
NP_001001569.1. NM_001001569.1. [O76083-4]
NP_001001570.1. NM_001001570.1. [O76083-5]
NP_001001571.1. NM_001001571.1. [O76083-6]
NP_001001572.1. NM_001001572.1. [O76083-7]
NP_001001573.1. NM_001001573.1. [O76083-7]
NP_001001574.1. NM_001001574.1. [O76083-8]
NP_001001575.1. NM_001001575.1. [O76083-9]
NP_001001576.1. NM_001001576.1. [O76083-10]
NP_001001577.1. NM_001001577.1. [O76083-11]
NP_001001578.1. NM_001001578.1. [O76083-12]
NP_001001579.1. NM_001001579.1. [O76083-7]
NP_001001580.1. NM_001001580.1. [O76083-10]
NP_001001581.1. NM_001001581.1. [O76083-13]
NP_001001582.1. NM_001001582.1. [O76083-14]
NP_001001583.1. NM_001001583.1. [O76083-15]
NP_001001584.1. NM_001001584.2. [O76083-7]
NP_001001585.1. NM_001001585.1. [O76083-7]
NP_001302462.1. NM_001315533.1. [O76083-16]
NP_002597.1. NM_002606.2. [O76083-1]
XP_016883855.1. XM_017028366.1. [O76083-7]
UniGeneiHs.473927.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HD1X-ray2.23A/B241-566[»]
2YY2X-ray2.80A/B241-566[»]
3DY8X-ray2.15A/B242-566[»]
3DYLX-ray2.70A/B242-566[»]
3DYNX-ray2.10A/B242-566[»]
3DYQX-ray2.50A/B242-566[»]
3DYSX-ray2.30A/B242-566[»]
3JSIX-ray2.72A/B242-566[»]
3JSWX-ray2.30A/B242-566[»]
3K3EX-ray2.70A/B241-566[»]
3K3HX-ray2.50A/B241-566[»]
3N3ZX-ray2.75A/B241-566[»]
3QI3X-ray2.30A/B1-593[»]
3QI4X-ray2.50A/B1-593[»]
4E90X-ray2.50A/B242-566[»]
4G2JX-ray2.40A/B242-566[»]
4G2LX-ray3.00A/B242-566[»]
4GH6X-ray2.70A/B241-566[»]
4Y86X-ray2.01A/B1-593[»]
4Y87X-ray3.10A/B1-593[»]
4Y8CX-ray2.70A/B1-593[»]
ProteinModelPortaliO76083.
SMRiO76083.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111178. 21 interactors.
IntActiO76083. 31 interactors.
MINTiMINT-1444906.
STRINGi9606.ENSP00000291539.

Chemistry databases

BindingDBiO76083.
ChEMBLiCHEMBL3535.
DrugBankiDB00201. Caffeine.
GuidetoPHARMACOLOGYi1309.

PTM databases

iPTMnetiO76083.
PhosphoSitePlusiO76083.

Polymorphism and mutation databases

BioMutaiPDE9A.

Proteomic databases

PaxDbiO76083.
PeptideAtlasiO76083.
PRIDEiO76083.

Protocols and materials databases

DNASUi5152.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000291539; ENSP00000291539; ENSG00000160191. [O76083-1]
ENST00000328862; ENSP00000328699; ENSG00000160191. [O76083-15]
ENST00000335440; ENSP00000335365; ENSG00000160191. [O76083-12]
ENST00000335512; ENSP00000335242; ENSG00000160191. [O76083-2]
ENST00000349112; ENSP00000344730; ENSG00000160191. [O76083-4]
ENST00000380328; ENSP00000369685; ENSG00000160191. [O76083-5]
ENST00000398224; ENSP00000381280; ENSG00000160191. [O76083-3]
ENST00000398225; ENSP00000381281; ENSG00000160191. [O76083-14]
ENST00000398227; ENSP00000381283; ENSG00000160191. [O76083-9]
ENST00000398229; ENSP00000381285; ENSG00000160191. [O76083-11]
ENST00000398232; ENSP00000381287; ENSG00000160191. [O76083-13]
ENST00000398234; ENSP00000381289; ENSG00000160191. [O76083-6]
ENST00000398236; ENSP00000381291; ENSG00000160191. [O76083-8]
GeneIDi5152.
KEGGihsa:5152.
UCSCiuc002zbm.4. human. [O76083-1]

Organism-specific databases

CTDi5152.
DisGeNETi5152.
GeneCardsiPDE9A.
HGNCiHGNC:8795. PDE9A.
HPAiHPA011380.
MIMi602973. gene.
neXtProtiNX_O76083.
OpenTargetsiENSG00000160191.
PharmGKBiPA33143.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOVERGENiHBG053545.
KOiK13761.
OMAiPRAFKIN.
OrthoDBiEOG091G082I.
PhylomeDBiO76083.
TreeFamiTF314638.

Enzyme and pathway databases

UniPathwayiUPA00763; UER00748.
BioCyciZFISH:HS08457-MONOMER.
BRENDAi3.1.4.35. 2681.
ReactomeiR-HSA-418457. cGMP effects.

Miscellaneous databases

ChiTaRSiPDE9A. human.
EvolutionaryTraceiO76083.
GeneWikiiPDE9A.
GenomeRNAii5152.
PROiO76083.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160191.
ExpressionAtlasiO76083. baseline and differential.
GenevisibleiO76083. HS.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDE9A_HUMAN
AccessioniPrimary (citable) accession number: O76083
Secondary accession number(s): B2RBI5
, B4DFI5, D3DSJ8, D3DSJ9, O75490, O75491, O95225, Q53Y40, Q5QD39, Q86SF7, Q86SI6, Q86SJ3, Q86WN3, Q86WN4, Q86WN5, Q86WN6, Q86WN7, Q86WN8, Q86WN9, Q86WP0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 161 of the entry and version 1 of the sequence. [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

Miscellaneous

PDE9A is a potential target for treatment of diseases such as stress-induced heart disease or long-term memory defects. Specific inhibitors, such as BAY-73-6691 or PF-4449613 are promising candidates for clinical tests.1 Publication1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.