ID   PDE11_MOUSE             Reviewed;         933 AA.
AC   P0C1Q2; A2AKR2;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   25-JUL-2006, sequence version 1.
DT   24-JAN-2024, entry version 117.
DE   RecName: Full=Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A;
DE            EC=3.1.4.35 {ECO:0000250|UniProtKB:Q9HCR9};
DE            EC=3.1.4.53 {ECO:0000250|UniProtKB:Q9HCR9};
DE   AltName: Full=cAMP and cGMP phosphodiesterase 11A;
GN   Name=Pde11a;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   TISSUE SPECIFICITY, FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=15800654; DOI=10.1038/sj.ijir.3901307;
RA   Wayman C., Phillips S., Lunny C., Webb T., Fawcett L., Baxendale R.,
RA   Burgess G.;
RT   "Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology.";
RL   Int. J. Impot. Res. 17:216-223(2005).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162 AND SER-163, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Plays a role in signal transduction by regulating the
CC       intracellular concentration of cyclic nucleotides cAMP and cGMP
CC       (PubMed:15800654). Catalyzes the hydrolysis of both cAMP and cGMP to
CC       5'-AMP and 5'-GMP, respectively (By similarity).
CC       {ECO:0000250|UniProtKB:Q9HCR9, ECO:0000269|PubMed:15800654}.
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:0000250|UniProtKB:Q9HCR9};
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:0000250|UniProtKB:Q9HCR9};
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 (By
CC       similarity). {ECO:0000250|UniProtKB:Q9HCR9}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q9HCR9}.
CC   -!- TISSUE SPECIFICITY: Expressed in testis and developing spermatoza.
CC       {ECO:0000269|PubMed:15800654}.
CC   -!- DOMAIN: The tandem GAF domains bind cGMP, and regulate enzyme activity.
CC       The binding of cGMP stimulates enzyme activity.
CC       {ECO:0000250|UniProtKB:Q9HCR9}.
CC   -!- DISRUPTION PHENOTYPE: Mice live well and have no impaired fertility.
CC       They do however display reduced sperm concentration, rate of forward
CC       progression and percentage of live spermatozoa. Pre-ejaculated sperm
CC       display increased premature/spontaneous capacitance.
CC       {ECO:0000269|PubMed:15800654}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       {ECO:0000305}.
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DR   EMBL; AL772341; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL845373; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL929133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL929589; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS38152.1; -.
DR   RefSeq; NP_001074502.1; NM_001081033.1.
DR   AlphaFoldDB; P0C1Q2; -.
DR   SMR; P0C1Q2; -.
DR   BioGRID; 232315; 1.
DR   STRING; 10090.ENSMUSP00000097572; -.
DR   ChEMBL; CHEMBL4295711; -.
DR   iPTMnet; P0C1Q2; -.
DR   PhosphoSitePlus; P0C1Q2; -.
DR   SwissPalm; P0C1Q2; -.
DR   MaxQB; P0C1Q2; -.
DR   PaxDb; 10090-ENSMUSP00000097572; -.
DR   ProteomicsDB; 287803; -.
DR   Ensembl; ENSMUST00000099992.10; ENSMUSP00000097572.4; ENSMUSG00000075270.12.
DR   GeneID; 241489; -.
DR   KEGG; mmu:241489; -.
DR   UCSC; uc008kex.1; mouse.
DR   AGR; MGI:3036251; -.
DR   CTD; 50940; -.
DR   MGI; MGI:3036251; Pde11a.
DR   VEuPathDB; HostDB:ENSMUSG00000075270; -.
DR   eggNOG; KOG3689; Eukaryota.
DR   GeneTree; ENSGT00940000162151; -.
DR   HOGENOM; CLU_006980_0_1_1; -.
DR   InParanoid; P0C1Q2; -.
DR   OMA; HHDANEE; -.
DR   OrthoDB; 5479253at2759; -.
DR   PhylomeDB; P0C1Q2; -.
DR   TreeFam; TF316499; -.
DR   Reactome; R-MMU-418457; cGMP effects.
DR   Reactome; R-MMU-418555; G alpha (s) signalling events.
DR   BioGRID-ORCS; 241489; 1 hit in 76 CRISPR screens.
DR   PRO; PR:P0C1Q2; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; P0C1Q2; Protein.
DR   Bgee; ENSMUSG00000075270; Expressed in Ammon's horn and 46 other cell types or tissues.
DR   ExpressionAtlas; P0C1Q2; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0043204; C:perikaryon; ISO:MGI.
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:0030553; F:cGMP binding; ISS:UniProtKB.
DR   GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; ISS:UniProtKB.
DR   GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; ISO:MGI.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd00077; HDc; 1.
DR   Gene3D; 3.30.450.40; -; 2.
DR   Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1.
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   PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR   PANTHER; PTHR11347:SF130; DUAL 3',5'-CYCLIC-AMP AND -GMP PHOSPHODIESTERASE 11A; 1.
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   SUPFAM; SSF55781; GAF domain-like; 2.
DR   SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR   PROSITE; PS00126; PDEASE_I_1; 1.
DR   PROSITE; PS51845; PDEASE_I_2; 1.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; cAMP; cGMP; Cytoplasm; Hydrolase; Metal-binding;
KW   Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN           1..933
FT                   /note="Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase
FT                   11A"
FT                   /id="PRO_0000247041"
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..121
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          913..933
FT                   /note="Disordered"
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:0007744|PubMed:21183079"
FT   MOD_RES         163
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         239
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HCR9"
SQ   SEQUENCE   933 AA;  104563 MW;  07B7CA1E4F905755 CRC64;
     MAASRLDFGE VETFLDRHPE LFEDYLMRKG KQELVDKWLQ RHTSGQGASS LRPALAGASS
     LAQSNAKGSP GIGGGAGPQG SAHSHPTPGG GESAGVPLSP SWASGSRGDG SLQRRASQKE
     LRKSFARSKA IHVNRTYDEQ VTSRAQEPLS SVRRRALLRK ASSLPPTTAH ILSALLESRV
     NLPQYPPTAI DYKCHLKKHN ERQFFLELVK DISNDLDLTS LSYKILIFVC LMVDADRCSL
     FLVEGAAAGK KTLVSKFFDV HAGTPLLPCS STENSNEVQV PWGKGIIGYV GEHGETVNIP
     DAYQDRRFND EIDKLTGYKT KSLLCMPIRN SDGEIIGVAQ AINKVPEGAP FTEDDEKVMQ
     MYLPFCGIAI SNAQLFAASR KEYERSRALL EVVNDLFEEQ TDLEKIVKKI MHRAQTLLKC
     ERCSVLLLED IESPVVKFTK SFELMSPKCS ADAENSFKES VEKSSYSDWL INNSIAELVA
     STGLPVNVSD AYQDPRFDAE ADQISGFHIR SVLCVPIWNS NHQIIGVAQV LNRLDGKPFD
     DADQRLFEAF VIFCGLGINN TIMYDQVKKS WAKQSVALDV LSYHATCSKA EVDKFKAANI
     PLVSELAIDD IHFDDFSLDV DAMITAALRM FMELGMVQKF KIDYETLCRW LLTVRKNYRM
     VLYHNWRHAF NVCQLMFAML TTAGFQEILT EVEILAVIVG CLCHDLDHRG TNNAFQAKSD
     SALAQLYGTS ATLEHHHFNH AVMILQSEGH NIFANLSSKE YSDLMQLLKQ SILATDLTLY
     FERRTEFFEL VRKGDYDWSI TSHRDVFRSM LMTACDLGAV TKPWEISRQV AELVTSEFFE
     QGDRERSELK LTPSAIFDRN RKDELPRLQL EWIDSICMPL YQALVKVNAK LKPMLDSVAA
     NRRKWEELHQ KRLQVSAASP DPASPMVAGE DRL
//