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UniProtKB - O76083 (PDE9A_HUMAN)

Protein

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

Gene

PDE9A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:

Activity 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
  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. cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (PDE9A), cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A)
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
  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase
LigandcGMP, Magnesium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.1.4.35 2681
ReactomeiR-HSA-418457 cGMP effects
SABIO-RKiO76083
UniPathwayi
UPA00763;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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000160191.17
HGNCiHGNC:8795 PDE9A
MIMi602973 gene
neXtProtiNX_O76083

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 sensitivity by BAY-73-9961. 1 Publication1
Mutagenesisi463I → A: Induces a 6-9 fold change in inhibitory sensitivity 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 sensitivity by BAY-73-9961. 1 Publication1
Mutagenesisi484Y → A: Induces a 6-9 fold change in inhibitory sensitivity by BAY-73-9961. 1 Publication1
Mutagenesisi501F → A: Induces a 2 fold change in inhibitory sensitivity by BAY-73-9961. 1 Publication1
Mutagenesisi513Q → A: Induces a dramatic change in inhibitory sensitivity 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 sensitivity by BAY-73-9961. 1 Publication1

Organism-specific databases

DisGeNETi5152
OpenTargetsiENSG00000160191
PharmGKBiPA33143

Chemistry databases

ChEMBLiCHEMBL3535
DrugBankiDB07954 3-isobutyl-1-methyl-7H-xanthine
DB00201 Caffeine
DB03597 Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine
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

EPDiO76083
PaxDbiO76083
PeptideAtlasiO76083
PRIDEiO76083
ProteomicsDBi50391
50392 [O76083-10]
50393 [O76083-11]
50394 [O76083-12]
50395 [O76083-13]
50396 [O76083-14]
50397 [O76083-15]
50398 [O76083-16]
50399 [O76083-2]
50400 [O76083-3]
50401 [O76083-4]
50402 [O76083-5]
50403 [O76083-6]
50404 [O76083-7]
50405 [O76083-8]
50406 [O76083-9]

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 Expressed in 179 organ(s), highest expression level in mucosa of transverse colon
ExpressionAtlasiO76083 baseline and differential
GenevisibleiO76083 HS

Organism-specific databases

HPAiHPA011380

Interactioni

Subunit structurei

Homodimer.2 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111178, 33 interactors
IntActiO76083, 34 interactors
STRINGi9606.ENSP00000291539

Chemistry databases

BindingDBiO76083

Structurei

Secondary structure

1593
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO76083
SMRiO76083
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO76083

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini236 – 557PDEasePROSITE-ProRule annotationAdd BLAST322

Sequence similaritiesi

Belongs to the cyclic nucleotide phosphodiesterase family. PDE9 subfamily.Curated

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000119066
HOVERGENiHBG053545
KOiK13761
OMAiSNEEHMT
OrthoDBiEOG091G082I
PhylomeDBiO76083
TreeFamiTF314638

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

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

Similar proteinsi

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, 33 interactors
IntActiO76083, 34 interactors
STRINGi9606.ENSP00000291539

Chemistry databases

BindingDBiO76083
ChEMBLiCHEMBL3535
DrugBankiDB07954 3-isobutyl-1-methyl-7H-xanthine
DB00201 Caffeine
DB03597 Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine
GuidetoPHARMACOLOGYi1309

PTM databases

iPTMnetiO76083
PhosphoSitePlusiO76083

Polymorphism and mutation databases

BioMutaiPDE9A

Proteomic databases

EPDiO76083
PaxDbiO76083
PeptideAtlasiO76083
PRIDEiO76083
ProteomicsDBi50391
50392 [O76083-10]
50393 [O76083-11]
50394 [O76083-12]
50395 [O76083-13]
50396 [O76083-14]
50397 [O76083-15]
50398 [O76083-16]
50399 [O76083-2]
50400 [O76083-3]
50401 [O76083-4]
50402 [O76083-5]
50403 [O76083-6]
50404 [O76083-7]
50405 [O76083-8]
50406 [O76083-9]

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
EuPathDBiHostDB:ENSG00000160191.17
GeneCardsiPDE9A
HGNCiHGNC:8795 PDE9A
HPAiHPA011380
MIMi602973 gene
neXtProtiNX_O76083
OpenTargetsiENSG00000160191
PharmGKBiPA33143
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000119066
HOVERGENiHBG053545
KOiK13761
OMAiSNEEHMT
OrthoDBiEOG091G082I
PhylomeDBiO76083
TreeFamiTF314638

Enzyme and pathway databases

UniPathwayi
UPA00763;UER00748

BRENDAi3.1.4.35 2681
ReactomeiR-HSA-418457 cGMP effects
SABIO-RKiO76083

Miscellaneous databases

ChiTaRSiPDE9A human
EvolutionaryTraceiO76083
GeneWikiiPDE9A
GenomeRNAii5152
PROiPR:O76083
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160191 Expressed in 179 organ(s), highest expression level in mucosa of transverse colon
ExpressionAtlasiO76083 baseline and differential
GenevisibleiO76083 HS

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: September 12, 2018
This is version 176 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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