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Q9HCR9 (PDE11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A

EC=3.1.4.17
EC=3.1.4.35
Alternative name(s):
cAMP and cGMP phosphodiesterase 11A
Gene names
Name:PDE11A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length933 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively. Ref.1 Ref.2 Ref.3

Catalytic activity

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

Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate.

Cofactor

Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions By similarity.

Enzyme regulation

Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator. Weakly inhibited by Sildenafil (Viagra) and Tadalafil (Cialis); however, the fact that the protein is probably absent from testis, suggests that it is not biologically relevant and is not related with erectile dysfunction. Ref.2 Ref.3 Ref.8 Ref.9

Subcellular location

Cytoplasmcytosol Ref.1.

Tissue specificity

Isoform 1 is present in prostate, pituitary, heart and liver. It is however not present in testis nor in penis, suggesting that weak inhibition by Tadalafil (Cialis) is not relevant (at protein level). Isoform 2 may be expressed in testis. Isoform 4 is expressed in adrenal cortex. Ref.2 Ref.4 Ref.7 Ref.8 Ref.10

Domain

The tandem GAF domains bind cGMP, and regulate enzyme activity. The binding of cGMP stimulates enzyme activity. Ref.9

Involvement in disease

Primary pigmented nodular adrenocortical disease 2 (PPNAD2) [MIM:610475]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Contains 2 GAF domains.

Biophysicochemical properties

Kinetic parameters:

KM=3.0 µM for cAMP (isoform 1) Ref.1 Ref.2 Ref.3

KM=1.4 µM for cGMP (isoform 1)

KM=3.0 µM for cAMP (isoform 2)

KM=1.5 µM for cGMP (isoform 2)

KM=3.3 µM for cAMP (isoform 3)

KM=3.7 µM for cGMP (isoform 3)

KM=1.04 µM for cAMP (isoform 4)

KM=0.52 µM for cGMP (isoform 4)

Vmax=3.6 pmol/min/µg enzyme with cAMP as substrate (isoform 4)

Vmax=3.9 pmol/min/µg enzyme with cGMP as substrate (isoform 4)

Vmax=270 pmol/min/µg enzyme with cAMP as substrate (isoform 1)

Vmax=120 pmol/min/µg enzyme with cGMP as substrate (isoform 1)

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HCR9-1)

Also known as: PDE11A4;

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 2 (identifier: Q9HCR9-2)

Also known as: PDE11A3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-250: Missing.
     251-304: KTLVSKFFDV...ETVNIPDAYQ → MLKQARRPLF...FLIQRQTKTK
Isoform 3 (identifier: Q9HCR9-3)

Also known as: PDE11A2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-358: Missing.
Isoform 4 (identifier: Q9HCR9-4)

Also known as: PDE11A1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-444: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 933933Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A
PRO_0000247040

Regions

Domain217 – 370154GAF 1
Domain402 – 558157GAF 2
Region640 – 905266Catalytic By similarity

Sites

Active site6641Proton donor By similarity
Metal binding6681Divalent metal cation 1 By similarity
Metal binding7041Divalent metal cation 1 By similarity
Metal binding7051Divalent metal cation 1 By similarity
Metal binding7051Divalent metal cation 2 By similarity
Metal binding7081Divalent metal cation 2 By similarity
Metal binding7341Divalent metal cation 2 By similarity
Metal binding8161Divalent metal cation 1 By similarity
Binding site8691cAMP or cGMP By similarity

Amino acid modifications

Modified residue2391Phosphoserine Ref.11

Natural variations

Alternative sequence1 – 444444Missing in isoform 4.
VSP_019898
Alternative sequence1 – 358358Missing in isoform 3.
VSP_019899
Alternative sequence1 – 250250Missing in isoform 2.
VSP_019900
Alternative sequence251 – 30454KTLVS…PDAYQ → MLKQARRPLFRNVLSATQWK KVKITRLVQISGASLAEKQE KHQDFLIQRQTKTK in isoform 2.
VSP_019901
Natural variant8041R → H. Ref.10
Corresponds to variant rs75127279 [ dbSNP | Ensembl ].
VAR_027056
Natural variant8671R → G. Ref.10
Corresponds to variant rs61306957 [ dbSNP | Ensembl ].
VAR_027057

Experimental info

Mutagenesis3551D → A: Induces a decrease in enzyme activity due to the inability of cGMP to bind and stimulate enzyme activity. Ref.9
Sequence conflict1841R → Q in BAB16371. Ref.1
Sequence conflict1841R → Q in BAB62712. Ref.4
Sequence conflict1841R → Q in AAI12394. Ref.6
Sequence conflict1841R → Q in AAI14432. Ref.6
Sequence conflict9211S → SS in BAB16371. Ref.1
Sequence conflict9211S → SS in BAB16372. Ref.1
Sequence conflict9211S → SS in CAB82573. Ref.2
Sequence conflict9211S → SS in AAG32023. Ref.3
Sequence conflict9211S → SS in CAC15567. Ref.3
Sequence conflict9211S → SS in BAB62712. Ref.4
Sequence conflict9211S → SS in BAB62713. Ref.4
Sequence conflict9211S → SS in BAB62714. Ref.4
Sequence conflict9211S → SS in AAI12394. Ref.6
Sequence conflict9211S → SS in AAI14432. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PDE11A4) [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: B725AE6963D6E799

FASTA933104,752
        10         20         30         40         50         60 
MAASRLDFGE VETFLDRHPE LFEDYLMRKG KQEMVEKWLQ RHSQGQGALG PRPSLAGTSS 

        70         80         90        100        110        120 
LAHSTCRGGS SVGGGTGPNG SAHSQPLPGG GDCGGVPLSP SWAGGSRGDG NLQRRASQKE 

       130        140        150        160        170        180 
LRKSFARSKA IHVNRTYDEQ VTSRAQEPLS SVRRRALLRK ASSLPPTTAH ILSALLESRV 

       190        200        210        220        230        240 
NLPRYPPTAI DYKCHLKKHN ERQFFLELVK DISNDLDLTS LSYKILIFVC LMVDADRCSL 

       250        260        270        280        290        300 
FLVEGAAAGK KTLVSKFFDV HAGTPLLPCS STENSNEVQV PWGKGIIGYV GEHGETVNIP 

       310        320        330        340        350        360 
DAYQDRRFND EIDKLTGYKT KSLLCMPIRS SDGEIIGVAQ AINKIPEGAP FTEDDEKVMQ 

       370        380        390        400        410        420 
MYLPFCGIAI SNAQLFAASR KEYERSRALL EVVNDLFEEQ TDLEKIVKKI MHRAQTLLKC 

       430        440        450        460        470        480 
ERCSVLLLED IESPVVKFTK SFELMSPKCS ADAENSFKES MEKSSYSDWL INNSIAELVA 

       490        500        510        520        530        540 
STGLPVNISD AYQDPRFDAE ADQISGFHIR SVLCVPIWNS NHQIIGVAQV LNRLDGKPFD 

       550        560        570        580        590        600 
DADQRLFEAF VIFCGLGINN TIMYDQVKKS WAKQSVALDV LSYHATCSKA EVDKFKAANI 

       610        620        630        640        650        660 
PLVSELAIDD IHFDDFSLDV DAMITAALRM FMELGMVQKF KIDYETLCRW LLTVRKNYRM 

       670        680        690        700        710        720 
VLYHNWRHAF NVCQLMFAML TTAGFQDILT EVEILAVIVG CLCHDLDHRG TNNAFQAKSG 

       730        740        750        760        770        780 
SALAQLYGTS ATLEHHHFNH AVMILQSEGH NIFANLSSKE YSDLMQLLKQ SILATDLTLY 

       790        800        810        820        830        840 
FERRTEFFEL VSKGEYDWNI KNHRDIFRSM LMTACDLGAV TKPWEISRQV AELVTSEFFE 

       850        860        870        880        890        900 
QGDRERLELK LTPSAIFDRN RKDELPRLQL EWIDSICMPL YQALVKVNVK LKPMLDSVAT 

       910        920        930 
NRSKWEELHQ KRLLASTASS SPASVMVAKE DRN 

« Hide

Isoform 2 (PDE11A3) [UniParc].

Checksum: 82DD9BB77C941A1C
Show »

FASTA68378,047
Isoform 3 (PDE11A2) [UniParc].

Checksum: A1DDA7F4BAF43221
Show »

FASTA57565,679
Isoform 4 (PDE11A1) [UniParc].

Checksum: 3E6ED2AAE9CBF03C
Show »

FASTA48955,700

References

« Hide 'large scale' references
[1]"Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression."
Yuasa K., Kotera J., Fujishige K., Michibata H., Sasaki T., Omori K.
J. Biol. Chem. 275:31469-31479(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Prostate.
[2]"Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A."
Fawcett L., Baxendale R., Stacey P., McGrouther C., Harrow I., Soderling S., Hetman J., Beavo J.A., Phillips S.C.
Proc. Natl. Acad. Sci. U.S.A. 97:3702-3707(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, TISSUE SPECIFICITY.
Tissue: Skeletal muscle.
[3]"Cloning and characterisation of two splice variants of human phosphodiesterase 11A."
Hetman J.M., Robas N.M., Baxendale R., Fidock M., Phillips S.C., Soderling S.H., Beavo J.A.
Proc. Natl. Acad. Sci. U.S.A. 97:12891-12895(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[4]"Genomic organization of the human phosphodiesterase PDE11A gene: evolutionary relatedness with other PDEs containing GAF domains."
Yuasa K., Kanoh Y., Okumura K., Omori K.
Eur. J. Biochem. 268:168-178(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 4), TISSUE SPECIFICITY.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"3',5'-cyclic nucleotide phosphodiesterase 11A: localization in human tissues."
Loughney K., Taylor J., Florio V.A.
Int. J. Impot. Res. 17:320-325(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Phosphodiesterase 11 (PDE11): is it a player in human testicular function?"
Francis S.H.
Int. J. Impot. Res. 17:467-468(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, TISSUE SPECIFICITY.
[9]"cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10 and cGMP for the tandem GAF domain of phosphodiesterase 11."
Gross-Langenhoff M., Hofbauer K., Weber J., Schultz A., Schultz J.E.
J. Biol. Chem. 281:2841-2846(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, ENZYME REGULATION, MUTAGENESIS OF ASP-355.
[10]"A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia."
Horvath A., Boikos S., Giatzakis C., Robinson-White A., Groussin L., Griffin K.J., Stein E., Levine E., Delimpasi G., Hsiao H.P., Keil M., Heyerdahl S., Matyakhina L., Libe R., Fratticci A., Kirschner L.S., Cramer K., Gaillard R.C. expand/collapse author list , Bertagna X., Carney J.A., Bertherat J., Bossis I., Stratakis C.A.
Nat. Genet. 38:794-800(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PPNAD2, TISSUE SPECIFICITY, VARIANTS HIS-804 AND GLY-867.
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB036704 mRNA. Translation: BAB16371.1.
AB038041 mRNA. Translation: BAB16372.1.
AJ251509 mRNA. Translation: CAB82573.1.
AF281865 mRNA. Translation: AAG32023.1.
AJ278682 mRNA. Translation: CAC15567.1.
AB048423 Genomic DNA. Translation: BAB62712.1.
AB048423 Genomic DNA. Translation: BAB62713.2.
AB048423 Genomic DNA. Translation: BAB62714.1.
AC073834 Genomic DNA. No translation available.
AC073892 Genomic DNA. No translation available.
AC083824 Genomic DNA. No translation available.
AC011998 Genomic DNA. No translation available.
AC012499 Genomic DNA. Translation: AAY14803.1.
BC112393 mRNA. Translation: AAI12394.1.
BC114431 mRNA. Translation: AAI14432.1.
RefSeqNP_001070664.1. NM_001077196.1.
NP_001070665.1. NM_001077197.1.
NP_001070826.1. NM_001077358.1.
NP_058649.3. NM_016953.3.
UniGeneHs.570273.

3D structure databases

ProteinModelPortalQ9HCR9.
SMRQ9HCR9. Positions 205-911.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000286063.

Chemistry

ChEMBLCHEMBL2717.
GuidetoPHARMACOLOGY1311.

PTM databases

PhosphoSiteQ9HCR9.

Polymorphism databases

DMDM296439264.

Proteomic databases

PaxDbQ9HCR9.
PRIDEQ9HCR9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000286063; ENSP00000286063; ENSG00000128655. [Q9HCR9-1]
ENST00000358450; ENSP00000351232; ENSG00000128655. [Q9HCR9-2]
ENST00000389683; ENSP00000374333; ENSG00000128655. [Q9HCR9-4]
ENST00000409504; ENSP00000386539; ENSG00000128655. [Q9HCR9-3]
ENST00000449286; ENSP00000390599; ENSG00000128655. [Q9HCR9-3]
GeneID50940.
KEGGhsa:50940.
UCSCuc002ulp.3. human. [Q9HCR9-1]
uc002ulr.3. human. [Q9HCR9-2]

Organism-specific databases

CTD50940.
GeneCardsGC02M178487.
HGNCHGNC:8773. PDE11A.
HPAHPA034560.
MIM604961. gene.
610475. phenotype.
neXtProtNX_Q9HCR9.
Orphanet189439. Primary pigmented nodular adrenocortical disease.
PharmGKBPA33121.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG270709.
HOVERGENHBG101207.
InParanoidQ9HCR9.
KOK13298.
OMALLEDYLM.
OrthoDBEOG7RRF69.
PhylomeDBQ9HCR9.
TreeFamTF316499.

Enzyme and pathway databases

BRENDA3.1.4.17. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ9HCR9.
BgeeQ9HCR9.
CleanExHS_PDE11A.
GenevestigatorQ9HCR9.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003018. GAF.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPDE11A.
GenomeRNAi50940.
NextBio53391.
PROQ9HCR9.
SOURCESearch...

Entry information

Entry namePDE11_HUMAN
AccessionPrimary (citable) accession number: Q9HCR9
Secondary accession number(s): Q14CD1 expand/collapse secondary AC list , Q53T16, Q96S76, Q9GZY7, Q9HB46, Q9NY45
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM