PDE11_HUMAN
ID PDE11_HUMAN Reviewed; 933 AA.
AC Q9HCR9; Q14CD1; Q53T16; Q96S76; Q9GZY7; Q9HB46; Q9NY45;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A;
DE EC=3.1.4.35 {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148, ECO:0000269|PubMed:16330539};
DE EC=3.1.4.53 {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148, ECO:0000269|PubMed:16330539};
DE AltName: Full=cAMP and cGMP phosphodiesterase 11A {ECO:0000303|PubMed:10906126};
GN Name=PDE11A {ECO:0000303|PubMed:10906126, ECO:0000312|HGNC:HGNC:8773};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Prostate;
RX PubMed=10906126; DOI=10.1074/jbc.m003041200;
RA Yuasa K., Kotera J., Fujishige K., Michibata H., Sasaki T., Omori K.;
RT "Isolation and characterization of two novel phosphodiesterase PDE11A
RT variants showing unique structure and tissue-specific expression.";
RL J. Biol. Chem. 275:31469-31479(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=10725373; DOI=10.1073/pnas.97.7.3702;
RA Fawcett L., Baxendale R., Stacey P., McGrouther C., Harrow I.,
RA Soderling S., Hetman J., Beavo J.A., Phillips S.C.;
RT "Molecular cloning and characterization of a distinct human
RT phosphodiesterase gene family: PDE11A.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:3702-3707(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=11050148; DOI=10.1073/pnas.200355397;
RA Hetman J.M., Robas N.M., Baxendale R., Fidock M., Phillips S.C.,
RA Soderling S.H., Beavo J.A.;
RT "Cloning and characterisation of two splice variants of human
RT phosphodiesterase 11A.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:12891-12895(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND
RP 4), AND TISSUE SPECIFICITY.
RX PubMed=11121118; DOI=10.1046/j.1432-1327.2001.01866.x;
RA Yuasa K., Kanoh Y., Okumura K., Omori K.;
RT "Genomic organization of the human phosphodiesterase PDE11A gene:
RT evolutionary relatedness with other PDEs containing GAF domains.";
RL Eur. J. Biochem. 268:168-178(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=15800651; DOI=10.1038/sj.ijir.3901317;
RA Loughney K., Taylor J., Florio V.A.;
RT "3',5'-cyclic nucleotide phosphodiesterase 11A: localization in human
RT tissues.";
RL Int. J. Impot. Res. 17:320-325(2005).
RN [8]
RP ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=16079899; DOI=10.1038/sj.ijir.3901377;
RA Francis S.H.;
RT "Phosphodiesterase 11 (PDE11): is it a player in human testicular
RT function?";
RL Int. J. Impot. Res. 17:467-468(2005).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, ACTIVITY REGULATION, AND MUTAGENESIS
RP OF ASP-355.
RX PubMed=16330539; DOI=10.1074/jbc.m511468200;
RA Gross-Langenhoff M., Hofbauer K., Weber J., Schultz A., Schultz J.E.;
RT "cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10
RT and cGMP for the tandem GAF domain of phosphodiesterase 11.";
RL J. Biol. Chem. 281:2841-2846(2006).
RN [10]
RP INVOLVEMENT IN PPNAD2, TISSUE SPECIFICITY, AND VARIANTS HIS-804 AND
RP GLY-867.
RX PubMed=16767104; DOI=10.1038/ng1809;
RA Horvath A., Boikos S., Giatzakis C., Robinson-White A., Groussin L.,
RA Griffin K.J., Stein E., Levine E., Delimpasi G., Hsiao H.P., Keil M.,
RA Heyerdahl S., Matyakhina L., Libe R., Fratticci A., Kirschner L.S.,
RA Cramer K., Gaillard R.C., Bertagna X., Carney J.A., Bertherat J.,
RA Bossis I., Stratakis C.A.;
RT "A genome-wide scan identifies mutations in the gene encoding
RT phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical
RT hyperplasia.";
RL Nat. Genet. 38:794-800(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
CC -!- FUNCTION: Plays a role in signal transduction by regulating the
CC intracellular concentration of cyclic nucleotides cAMP and cGMP
CC (PubMed:10725373, PubMed:10906126, PubMed:11050148, PubMed:16330539).
CC Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP,
CC respectively (PubMed:10725373, PubMed:10906126, PubMed:11050148).
CC {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126,
CC ECO:0000269|PubMed:11050148, ECO:0000269|PubMed:16330539}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746,
CC ChEBI:CHEBI:58115; EC=3.1.4.35;
CC Evidence={ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126,
CC ECO:0000269|PubMed:11050148, ECO:0000269|PubMed:16330539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; EC=3.1.4.53;
CC Evidence={ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126,
CC ECO:0000269|PubMed:11050148, ECO:0000269|PubMed:16330539};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250|UniProtKB:O76083};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions, while site 2 has a preference for
CC magnesium and/or manganese ions. {ECO:0000250|UniProtKB:O76083};
CC -!- ACTIVITY REGULATION: Inhibited by 3-isobutyl-1-methylxanthine (IBMX),
CC zaprinast and dipyridamole. cGMP acts as an allosteric activator.
CC Weakly inhibited by Sildenafil (Viagra) and Tadalafil (Cialis);
CC however, the fact that the protein is probably absent from testis,
CC suggests that it is not biologically relevant and is not related with
CC erectile dysfunction. {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:11050148, ECO:0000269|PubMed:16079899,
CC ECO:0000269|PubMed:16330539}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.0 uM for cAMP (isoform 1) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC KM=1.4 uM for cGMP (isoform 1) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC KM=3.0 uM for cAMP (isoform 2) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC KM=1.5 uM for cGMP (isoform 2) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC KM=3.3 uM for cAMP (isoform 3) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC KM=3.7 uM for cGMP (isoform 3) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC KM=1.04 uM for cAMP (isoform 4) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC KM=0.52 uM for cGMP (isoform 4) {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:10906126, ECO:0000269|PubMed:11050148};
CC Vmax=3.6 pmol/min/ug enzyme with cAMP as substrate (isoform 4)
CC {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126,
CC ECO:0000269|PubMed:11050148};
CC Vmax=3.9 pmol/min/ug enzyme with cGMP as substrate (isoform 4)
CC {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126,
CC ECO:0000269|PubMed:11050148};
CC Vmax=270 pmol/min/ug enzyme with cAMP as substrate (isoform 1)
CC {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126,
CC ECO:0000269|PubMed:11050148};
CC Vmax=120 pmol/min/ug enzyme with cGMP as substrate (isoform 1)
CC {ECO:0000269|PubMed:10725373, ECO:0000269|PubMed:10906126,
CC ECO:0000269|PubMed:11050148};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10906126}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PDE11A4 {ECO:0000303|PubMed:11121118};
CC IsoId=Q9HCR9-1; Sequence=Displayed;
CC Name=2; Synonyms=PDE11A3 {ECO:0000303|PubMed:11121118};
CC IsoId=Q9HCR9-2; Sequence=VSP_019900, VSP_019901;
CC Name=3; Synonyms=PDE11A2 {ECO:0000303|PubMed:11121118};
CC IsoId=Q9HCR9-3; Sequence=VSP_019899;
CC Name=4; Synonyms=PDE11A1 {ECO:0000303|PubMed:11121118};
CC IsoId=Q9HCR9-4; Sequence=VSP_019898;
CC -!- TISSUE SPECIFICITY: Isoform 1 is present in prostate, pituitary, heart
CC and liver. It is however not present in testis nor in penis, suggesting
CC that weak inhibition by Tadalafil (Cialis) is not relevant (at protein
CC level). Isoform 2 may be expressed in testis. Isoform 4 is expressed in
CC adrenal cortex. {ECO:0000269|PubMed:10725373,
CC ECO:0000269|PubMed:11121118, ECO:0000269|PubMed:15800651,
CC ECO:0000269|PubMed:16079899, ECO:0000269|PubMed:16767104}.
CC -!- DOMAIN: The tandem GAF domains bind cGMP, and regulate enzyme activity.
CC The binding of cGMP stimulates enzyme activity.
CC {ECO:0000269|PubMed:16330539}.
CC -!- DISEASE: Primary pigmented nodular adrenocortical disease 2 (PPNAD2)
CC [MIM:610475]: A rare bilateral adrenal defect causing ACTH-independent
CC Cushing syndrome. Macroscopic appearance of the adrenals is
CC characteristic with small pigmented micronodules observed in the
CC cortex. Adrenal glands show overall normal size and weight, and
CC multiple small yellow-to-dark brown nodules surrounded by a cortex with
CC a uniform appearance. Microscopically, there are moderate diffuse
CC cortical hyperplasia with mostly nonpigmented nodules, multiple
CC capsular deficits and massive circumscribed and infiltrating extra-
CC adrenal cortical excrescences with micronodules. Clinical
CC manifestations of Cushing syndrome include facial and truncal obesity,
CC abdominal striae, muscular weakness, osteoporosis, arterial
CC hypertension, diabetes. {ECO:0000269|PubMed:16767104}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PDE11AID44448ch2q31.html";
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DR EMBL; AB036704; BAB16371.1; -; mRNA.
DR EMBL; AB038041; BAB16372.1; -; mRNA.
DR EMBL; AJ251509; CAB82573.1; -; mRNA.
DR EMBL; AF281865; AAG32023.1; -; mRNA.
DR EMBL; AJ278682; CAC15567.1; -; mRNA.
DR EMBL; AB048423; BAB62712.1; -; Genomic_DNA.
DR EMBL; AB048423; BAB62713.2; -; Genomic_DNA.
DR EMBL; AB048423; BAB62714.1; -; Genomic_DNA.
DR EMBL; AC073834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC083824; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011998; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012499; AAY14803.1; -; Genomic_DNA.
DR EMBL; BC112393; AAI12394.1; -; mRNA.
DR EMBL; BC114431; AAI14432.1; -; mRNA.
DR CCDS; CCDS33334.1; -. [Q9HCR9-1]
DR CCDS; CCDS42785.1; -. [Q9HCR9-2]
DR CCDS; CCDS42786.1; -. [Q9HCR9-4]
DR CCDS; CCDS46459.1; -. [Q9HCR9-3]
DR RefSeq; NP_001070664.1; NM_001077196.1. [Q9HCR9-4]
DR RefSeq; NP_001070665.1; NM_001077197.1. [Q9HCR9-2]
DR RefSeq; NP_001070826.1; NM_001077358.1. [Q9HCR9-3]
DR RefSeq; NP_058649.3; NM_016953.3. [Q9HCR9-1]
DR AlphaFoldDB; Q9HCR9; -.
DR SMR; Q9HCR9; -.
DR STRING; 9606.ENSP00000286063; -.
DR BindingDB; Q9HCR9; -.
DR ChEMBL; CHEMBL2717; -.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB00820; Tadalafil.
DR DrugBank; DB09283; Trapidil.
DR DrugCentral; Q9HCR9; -.
DR GuidetoPHARMACOLOGY; 1311; -.
DR iPTMnet; Q9HCR9; -.
DR PhosphoSitePlus; Q9HCR9; -.
DR BioMuta; PDE11A; -.
DR DMDM; 296439264; -.
DR jPOST; Q9HCR9; -.
DR MassIVE; Q9HCR9; -.
DR PaxDb; Q9HCR9; -.
DR PeptideAtlas; Q9HCR9; -.
DR PRIDE; Q9HCR9; -.
DR ProteomicsDB; 81789; -. [Q9HCR9-1]
DR ProteomicsDB; 81790; -. [Q9HCR9-2]
DR ProteomicsDB; 81791; -. [Q9HCR9-3]
DR ProteomicsDB; 81792; -. [Q9HCR9-4]
DR Antibodypedia; 19565; 293 antibodies from 31 providers.
DR DNASU; 50940; -.
DR Ensembl; ENST00000286063.11; ENSP00000286063.5; ENSG00000128655.19. [Q9HCR9-1]
DR Ensembl; ENST00000358450.8; ENSP00000351232.4; ENSG00000128655.19. [Q9HCR9-2]
DR Ensembl; ENST00000389683.7; ENSP00000374333.3; ENSG00000128655.19. [Q9HCR9-4]
DR Ensembl; ENST00000409504.5; ENSP00000386539.1; ENSG00000128655.19. [Q9HCR9-3]
DR GeneID; 50940; -.
DR KEGG; hsa:50940; -.
DR MANE-Select; ENST00000286063.11; ENSP00000286063.5; NM_016953.4; NP_058649.3.
DR UCSC; uc002ulp.4; human. [Q9HCR9-1]
DR CTD; 50940; -.
DR DisGeNET; 50940; -.
DR GeneCards; PDE11A; -.
DR HGNC; HGNC:8773; PDE11A.
DR HPA; ENSG00000128655; Tissue enhanced (liver, parathyroid gland).
DR MalaCards; PDE11A; -.
DR MIM; 604961; gene.
DR MIM; 610475; phenotype.
DR neXtProt; NX_Q9HCR9; -.
DR OpenTargets; ENSG00000128655; -.
DR Orphanet; 189439; Primary pigmented nodular adrenocortical disease.
DR PharmGKB; PA33121; -.
DR VEuPathDB; HostDB:ENSG00000128655; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000162151; -.
DR HOGENOM; CLU_006980_0_1_1; -.
DR OMA; SGERANI; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q9HCR9; -.
DR TreeFam; TF316499; -.
DR BRENDA; 3.1.4.17; 2681.
DR PathwayCommons; Q9HCR9; -.
DR Reactome; R-HSA-418457; cGMP effects.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR SABIO-RK; Q9HCR9; -.
DR SignaLink; Q9HCR9; -.
DR SIGNOR; Q9HCR9; -.
DR BioGRID-ORCS; 50940; 13 hits in 1078 CRISPR screens.
DR ChiTaRS; PDE11A; human.
DR GeneWiki; PDE11A; -.
DR GenomeRNAi; 50940; -.
DR Pharos; Q9HCR9; Tchem.
DR PRO; PR:Q9HCR9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HCR9; protein.
DR Bgee; ENSG00000128655; Expressed in deltoid and 116 other tissues.
DR ExpressionAtlas; Q9HCR9; baseline and differential.
DR Genevisible; Q9HCR9; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030553; F:cGMP binding; IDA:UniProtKB.
DR GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; NAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IBA:GO_Central.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR Gene3D; 3.30.450.40; -; 2.
DR InterPro; IPR003018; GAF.
DR InterPro; IPR029016; GAF-like_dom_sf.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF01590; GAF; 2.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00065; GAF; 2.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; Alternative splicing; cAMP; cGMP; Cushing syndrome;
KW Cytoplasm; Hydrolase; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..933
FT /note="Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase
FT 11A"
FT /id="PRO_0000247040"
FT DOMAIN 217..370
FT /note="GAF 1"
FT DOMAIN 402..558
FT /note="GAF 2"
FT DOMAIN 588..912
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 42..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 57..83
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 664
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 424
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250|UniProtKB:Q922S4"
FT BINDING 668
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 704
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 705
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 705
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 816
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0C1Q2"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0C1Q2"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 1..444
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10725373"
FT /id="VSP_019898"
FT VAR_SEQ 1..358
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11050148"
FT /id="VSP_019899"
FT VAR_SEQ 1..250
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10906126,
FT ECO:0000303|PubMed:11050148"
FT /id="VSP_019900"
FT VAR_SEQ 251..304
FT /note="KTLVSKFFDVHAGTPLLPCSSTENSNEVQVPWGKGIIGYVGEHGETVNIPDA
FT YQ -> MLKQARRPLFRNVLSATQWKKVKITRLVQISGASLAEKQEKHQDFLIQRQTKT
FT K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10906126,
FT ECO:0000303|PubMed:11050148"
FT /id="VSP_019901"
FT VARIANT 804
FT /note="R -> H (in dbSNP:rs75127279)"
FT /evidence="ECO:0000269|PubMed:16767104"
FT /id="VAR_027056"
FT VARIANT 867
FT /note="R -> G (in dbSNP:rs61306957)"
FT /evidence="ECO:0000269|PubMed:16767104"
FT /id="VAR_027057"
FT MUTAGEN 355
FT /note="D->A: Induces a decrease in enzyme activity due to
FT the inability of cGMP to bind and stimulate enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:16330539"
FT CONFLICT 184
FT /note="R -> Q (in Ref. 1; BAB16371, 4; BAB62712 and 6;
FT AAI12394/AAI14432)"
FT /evidence="ECO:0000305"
FT CONFLICT 921
FT /note="S -> SS (in Ref. 1; BAB16371/BAB16372, 2; CAB82573,
FT 3; AAG32023/CAC15567, 4; BAB62712/BAB62713/BAB62714 and 6;
FT AAI12394/AAI14432)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 933 AA; 104752 MW; B725AE6963D6E799 CRC64;
MAASRLDFGE VETFLDRHPE LFEDYLMRKG KQEMVEKWLQ RHSQGQGALG PRPSLAGTSS
LAHSTCRGGS SVGGGTGPNG SAHSQPLPGG GDCGGVPLSP SWAGGSRGDG NLQRRASQKE
LRKSFARSKA IHVNRTYDEQ VTSRAQEPLS SVRRRALLRK ASSLPPTTAH ILSALLESRV
NLPRYPPTAI DYKCHLKKHN ERQFFLELVK DISNDLDLTS LSYKILIFVC LMVDADRCSL
FLVEGAAAGK KTLVSKFFDV HAGTPLLPCS STENSNEVQV PWGKGIIGYV GEHGETVNIP
DAYQDRRFND EIDKLTGYKT KSLLCMPIRS SDGEIIGVAQ AINKIPEGAP FTEDDEKVMQ
MYLPFCGIAI SNAQLFAASR KEYERSRALL EVVNDLFEEQ TDLEKIVKKI MHRAQTLLKC
ERCSVLLLED IESPVVKFTK SFELMSPKCS ADAENSFKES MEKSSYSDWL INNSIAELVA
STGLPVNISD AYQDPRFDAE ADQISGFHIR SVLCVPIWNS NHQIIGVAQV LNRLDGKPFD
DADQRLFEAF VIFCGLGINN TIMYDQVKKS WAKQSVALDV LSYHATCSKA EVDKFKAANI
PLVSELAIDD IHFDDFSLDV DAMITAALRM FMELGMVQKF KIDYETLCRW LLTVRKNYRM
VLYHNWRHAF NVCQLMFAML TTAGFQDILT EVEILAVIVG CLCHDLDHRG TNNAFQAKSG
SALAQLYGTS ATLEHHHFNH AVMILQSEGH NIFANLSSKE YSDLMQLLKQ SILATDLTLY
FERRTEFFEL VSKGEYDWNI KNHRDIFRSM LMTACDLGAV TKPWEISRQV AELVTSEFFE
QGDRERLELK LTPSAIFDRN RKDELPRLQL EWIDSICMPL YQALVKVNVK LKPMLDSVAT
NRSKWEELHQ KRLLASTASS SPASVMVAKE DRN
