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Reviewed, UniProtKB/Swiss-Prot O76083 (PDE9A_HUMAN)

Last modified June 16, 2009. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
    EC=3.1.4.35
Gene names
Name: PDE9A
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length593 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase has a high affinity for cGMP.

Catalytic activity

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

Cofactor

Divalent cations. Preferably manganese.

Enzyme regulation

Inhibited by zaprinast.

Tissue specificity

Expressed in all tissues examined (testis, brain, small intestine, skeletal muscle, heart, lung, thymus, spleen, placenta, kidney, liver, pancreas, ovary and prostate) except blood. Highest levels in brain, heart, kidney, spleen, prostate and colon. Isoform PDE9A12 is found in prostate. Ref.3

Domain

Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.

Involvement in disease

May be involved in affective bipolar disorder.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
   LigandManganese
Metal-binding
cGMP
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Gene Ontology (GO)
   Biological processsignal transduction Ref.2

Traceable author statement. Source: ProtInc

   Cellular componentcytosol

Inferred from direct assay. Source: UniProtKB

   Molecular function3',5'-cyclic-GMP phosphodiesterase activity

Inferred from electronic annotation. Source: EC

manganese ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 15 isoforms produced by alternative splicing. [Align] [Select]
Isoform PDE9A1 (identifier: O76083-1)

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.
Isoform PDE9A2 (identifier: O76083-2)

The sequence of this isoform differs from the canonical sequence as follows:
     88-147: Missing.
Isoform PDE9A3 (identifier: O76083-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGSGSSSYRP...DPTMPANSER → MDAFRS
     88-147: Missing.
Isoform PDE9A4 (identifier: O76083-4)

The sequence of this isoform differs from the canonical sequence as follows:
     24-165: VIFSKYCNSS...VLAQVAEQFS → HSVQSETCGHQATL
Isoform PDE9A5 (identifier: O76083-5)

The sequence of this isoform differs from the canonical sequence as follows:
     74-165: TPYKVRPVAI...VLAQVAEQFS → NELILYTSLR...SETCGHQATL
Isoform PDE9A6 (identifier: O76083-6)

Also known as: PDE9A5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR
     88-147: Missing.
Isoform PDE9A7/A8/A14/A19/A20 (identifier: O76083-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-207: Missing.
Isoform PDE9A9 (identifier: O76083-8)

The sequence of this isoform differs from the canonical sequence as follows:
     48-73: Missing.
     88-147: Missing.
Isoform PDE9A10 (identifier: O76083-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     161-165: AEQFS → MDAFR
Isoform PDE9A11/A15 (identifier: O76083-10)

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.
     218-218: R → M
Isoform PDE9A12 (identifier: O76083-11)

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR
     73-165: Missing.
Isoform PDE9A13 (identifier: O76083-12)

The sequence of this isoform differs from the canonical sequence as follows:
     24-165: VIFSKYCNSS...VLAQVAEQFS → EHDHLPADHR...SETCGHQATL
Isoform PDE9A16 (identifier: O76083-13)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGSGSSSYRP...DPTMPANSER → MDAFRS
Isoform PDE9A17 (identifier: O76083-14)

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR
Isoform PDE9A18 (identifier: O76083-15)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 593593High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
PRO_0000198841

Regions

Region288 – 550263Catalytic By similarity

Sites

Metal binding3121Manganese 1 Potential
Metal binding3161Manganese 1 Potential
Metal binding3411Manganese 1 Potential
Metal binding3521Manganese 2 Potential
Metal binding3561Manganese 2 Potential
Metal binding3821Manganese 2 Potential

Amino acid modifications

Modified residue291Phosphotyrosine Ref.7

Natural variations

Alternative sequence1 – 217217Missing in isoform PDE9A11/A15.
VSP_017302
Alternative sequence1 – 207207Missing in isoform PDE9A7/A8/A14/A19/A20.
VSP_017303
Alternative sequence1 – 160160Missing in isoform PDE9A10.
VSP_017304
Alternative sequence1 – 7373MGSGS…ANSER → MDAFRS in isoform PDE9A3 and isoform PDE9A16.
VSP_004598
Alternative sequence1 – 4646MGSGS…ATGLP → MDAFR in isoform PDE9A6, isoform PDE9A12 and isoform PDE9A17.
VSP_017305
Alternative sequence24 – 165142VIFSK…AEQFS → EHDHLPADHRRRHGLHRPHH AREFRTHSVQSETCGHQATL in isoform PDE9A13.
VSP_017306
Alternative sequence24 – 165142VIFSK…AEQFS → HSVQSETCGHQATL in isoform PDE9A4.
VSP_004600
Alternative sequence48 – 7326Missing in isoform PDE9A9 and isoform PDE9A18.
VSP_017307
Alternative sequence73 – 16593Missing in isoform PDE9A12.
VSP_017308
Alternative sequence74 – 16592TPYKV…AEQFS → NELILYTSLRNLLFLPSKES WASHQHSVQSETCGHQATL in isoform PDE9A5.
VSP_017309
Alternative sequence88 – 14760Missing in isoform PDE9A2, isoform PDE9A3, isoform PDE9A6 and isoform PDE9A9.
VSP_004599
Alternative sequence161 – 1655AEQFS → MDAFR in isoform PDE9A10.
VSP_017310
Alternative sequence2181R → M in isoform PDE9A11/A15.
VSP_017311

Secondary structure

.................................................. 593
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform PDE9A1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: E2731C7C828C0994

FASTA59368,493
        10         20         30         40         50         60 
MGSGSSSYRP KAIYLDIDGR IQKVIFSKYC NSSDIMDLFC IATGLPRNTT ISLLTTDDAM 

        70         80         90        100        110        120 
VSIDPTMPAN SERTPYKVRP VAIKQLSAGV EDKRTTSRGQ SAERPLRDRR VVGLEQPRRE 

       130        140        150        160        170        180 
GAFESGQVEP RPREPQGCYQ EGQRIPPERE ELIQSVLAQV AEQFSRAFKI NELKAEVANH 

       190        200        210        220        230        240 
LAVLEKRVEL EGLKVVEIEK CKSDIKKMRE ELAARSSRTN CPCKYSFLDN HKKLTPRRDV 

       250        260        270        280        290        300 
PTYPKYLLSP ETIEALRKPT FDVWLWEPNE MLSCLEHMYH DLGLVRDFSI NPVTLRRWLF 

       310        320        330        340        350        360 
CVHDNYRNNP FHNFRHCFCV AQMMYSMVWL CSLQEKFSQT DILILMTAAI CHDLDHPGYN 

       370        380        390        400        410        420 
NTYQINARTE LAVRYNDISP LENHHCAVAF QILAEPECNI FSNIPPDGFK QIRQGMITLI 

       430        440        450        460        470        480 
LATDMARHAE IMDSFKEKME NFDYSNEEHM TLLKMILIKC CDISNEVRPM EVAEPWVDCL 

       490        500        510        520        530        540 
LEEYFMQSDR EKSEGLPVAP FMDRDKVTKA TAQIGFIKFV LIPMFETVTK LFPMVEEIML 

       550        560        570        580        590 
QPLWESRDRY EELKRIDDAM KELQKKTDSL TSGATEKSRE RSRDVKNSEG DCA 

« Hide

Isoform PDE9A2.

Checksum: 728ADAAACE0E4D29
Show »

FASTA53361,709
Isoform PDE9A3.

Checksum: DE087DD09AAF4794
Show »

FASTA46654,440
Isoform PDE9A4.

Checksum: BDD6A8F85E591A67
Show »

FASTA46554,096
Isoform PDE9A5.

Checksum: 612A2ECEE7F656B4
Show »

FASTA54062,491
Isoform PDE9A6 (PDE9A5).

Checksum: 1FE4F709AD50C0E6
Show »

FASTA49257,285
Isoform PDE9A7/A8/A14/A19/A20.

Checksum: 4120AB778B9746B9
Show »

FASTA38645,290
Isoform PDE9A9.

Checksum: E211E0EB8B67F284
Show »

FASTA50758,933
Isoform PDE9A10.

Checksum: D6036BB3CA9FB7B2
Show »

FASTA43350,713
Isoform PDE9A11/A15.

Checksum: BF896546AED87831
Show »

FASTA37644,134
Isoform PDE9A12.

Checksum: E7DA06012931A850
Show »

FASTA45953,489
Isoform PDE9A13.

Checksum: CA53A1793F405CDB
Show »

FASTA49157,350
Isoform PDE9A16.

Checksum: 02A36AE5185CEDF3
Show »

FASTA52661,223
Isoform PDE9A17.

Checksum: F10D41FE319A6D28
Show »

FASTA55264,068
Isoform PDE9A18.

Checksum: 2DFEB16AFCA94F0D
Show »

FASTA56765,717

References

« Hide 'large scale' references
[1]"Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase."
Fisher D.A., Smith J.F., Pillar J.S., St Denis S.H., Cheng J.B.
J. Biol. Chem. 273:15559-15564(1998) [PubMed: 9624146] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE9A1).
Tissue: Brain, Prostate and Testis.
[2]"Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: alternative splicing of mRNA transcripts, genomic structure and sequence."
Guipponi M., Scott H.S., Kudoh J., Kawasaki K., Shibuya K., Shintani A., Asakawa S., Chen H., Lalioti M.D., Rossier C., Minoshima S., Shimizu N., Antonarakis S.E.
Hum. Genet. 103:386-392(1998) [PubMed: 9856478] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE9A1; PDE9A2; PDE9A3 AND PDE9A4).
Tissue: Fetal brain.
[3]"Identification and distribution of different mRNA variants produced by differential splicing in the human phosphodiesterase 9A gene."
Rentero C., Monfort A., Puigdomenech P.
Biochem. Biophys. Res. Commun. 301:686-692(2003) [PubMed: 12565835] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE9A5; PDE9A6; PDE9A7/A8/A14/A19/A20; PDE9A9; PDE9A10; PDE9A11/A15; PDE9A13; PDE9A16; PDE9A17 AND PDE9A18), TISSUE SPECIFICITY.
[4]"Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants."
Wang P., Wu P., Egan R.W., Billah M.M.
Gene 314:15-27(2003) [PubMed: 14527714] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE9A6).
Tissue: Brain, Small intestine and Spleen.
[5]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed: 10830953] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE9A2).
Tissue: Eye.
[7]"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling."
Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z.
EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-29, MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF048837 mRNA. Translation: AAC39778.1.
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.
AB017602 Genomic DNA. Translation: BAA88847.1.
AP001747 Genomic DNA. Translation: BAA95552.1.
BC009047 mRNA. Translation: AAH09047.1.
IPIIPI00008806.
IPI00221058.
IPI00221059.
IPI00221060.
IPI00384465.
IPI00384467.
IPI00418691.
IPI00418692.
IPI00418694.
IPI00419056.
IPI00419057.
IPI00419058.
IPI00419059.
IPI00419063.
IPI00873811.
RefSeqNP_001001567.1.
NP_001001568.1.
NP_001001569.1.
NP_001001570.1.
NP_001001571.1.
NP_001001572.1.
NP_001001573.1.
NP_001001574.1.
NP_001001575.1.
NP_001001576.1.
NP_001001577.1.
NP_001001578.1.
NP_001001579.1.
NP_001001580.1.
NP_001001581.1.
NP_001001582.1.
NP_001001583.1.
NP_001001584.1.
NP_001001585.1.
NP_002597.1.
UniGeneHs.473927

3D structure databases

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[»]
ModBaseSearch...

Protein-protein interaction databases

IntActO76083. 3 interactions.

PTM databases

PhosphoSiteO76083.

Proteomic databases

PRIDEO76083.

Genome annotation databases

EnsemblENSG00000160191. Homo sapiens. [Contig view]
GeneID5152.
KEGGhsa:5152.

Organism-specific databases

GeneCardsGC21P042946.
H-InvDBHIX0016144.
HGNCHGNC:8795. PDE9A.
HPAHPA011380.
MIM602973. gene.
PharmGKBPA33143.
GenAtlasSearch...

Phylogenomic databases

HOVERGENO76083.
OMAO76083. ILVLMTA.

Enzyme and pathway databases

BRENDA3.1.4.35. 247.
Pathway_Interaction_DBar_tf_pathway. Regulation of Androgen receptor activity.

Gene expression databases

ArrayExpressO76083.
BgeeO76083.
GermOnlineENSG00000160191. Homo sapiens.

Family and domain databases

InterProIPR003607. Met-dep_phosphohydro_HD.
IPR002073. PDEase.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

BindingDBO76083.
NextBio19884.
SOURCESearch...

Entry information

Entry namePDE9A_HUMAN
AccessionPrimary (citable) accession number: O76083
Secondary accession number(s): O75490 expand/collapse secondary AC list , O75491, O95225, Q86SF7, Q86SI6, Q86SJ3, Q86WN3, Q86WN4, Q86WN5, Q86WN6, Q86WN7, Q86WN8, Q86WN9, Q86WP0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: June 16, 2009
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents