PDE11_MOUSE
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 03-AUG-2022, entry version 110.
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 MaxQB; P0C1Q2; -.
DR PaxDb; P0C1Q2; -.
DR PRIDE; P0C1Q2; -.
DR ProteomicsDB; 287803; -.
DR Ensembl; ENSMUST00000099992; ENSMUSP00000097572; ENSMUSG00000075270.
DR GeneID; 241489; -.
DR KEGG; mmu:241489; -.
DR UCSC; uc008kex.1; mouse.
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; SGERANI; -.
DR OrthoDB; 904682at2759; -.
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 71 CRISPR screens.
DR PRO; PR:P0C1Q2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P0C1Q2; protein.
DR Bgee; ENSMUSG00000075270; Expressed in Ammon's horn and 45 other 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:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
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; 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; 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
