PDE11_RAT
ID PDE11_RAT Reviewed; 935 AA.
AC Q8VID6; Q8VID7; Q8VID8;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A;
DE EC=3.1.4.35 {ECO:0000269|PubMed:11502204};
DE EC=3.1.4.53 {ECO:0000269|PubMed:11502204};
DE AltName: Full=cAMP and cGMP phosphodiesterase 11A {ECO:0000303|PubMed:11502204};
GN Name=Pde11a {ECO:0000303|PubMed:11502204, ECO:0000312|RGD:621793};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11502204; DOI=10.1046/j.1432-1327.2001.02366.x;
RA Yuasa K., Ohgaru T., Asahina M., Omori K.;
RT "Identification of rat cyclic nucleotide phosphodiesterase 11A (PDE11A):
RT comparison of rat and human PDE11A splicing variants.";
RL Eur. J. Biochem. 268:4440-4448(2001).
CC -!- FUNCTION: Plays a role in signal transduction by regulating the
CC intracellular concentration of cyclic nucleotides cAMP and cGMP
CC (PubMed:11502204). Catalyzes the hydrolysis of both cAMP and cGMP to
CC 5'-AMP and 5'-GMP, respectively (PubMed:11502204).
CC {ECO:0000269|PubMed:11502204}.
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:11502204};
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:11502204};
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 {ECO:0000269|PubMed:11502204}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.9 uM for cAMP (isoform 1) {ECO:0000269|PubMed:11502204};
CC KM=1.6 uM for cGMP (isoform 1) {ECO:0000269|PubMed:11502204};
CC KM=4.0 uM for cAMP (isoform 2) {ECO:0000269|PubMed:11502204};
CC KM=1.6 uM for cGMP (isoform 2) {ECO:0000269|PubMed:11502204};
CC KM=2.2 uM for cAMP (isoform 3) {ECO:0000269|PubMed:11502204};
CC KM=1.3 uM for cGMP (isoform 3) {ECO:0000269|PubMed:11502204};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9HCR9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=PDE11A4 {ECO:0000303|PubMed:11502204};
CC IsoId=Q8VID6-1; Sequence=Displayed;
CC Name=2; Synonyms=PDE11A3 {ECO:0000303|PubMed:11502204};
CC IsoId=Q8VID6-2; Sequence=VSP_019903, VSP_019904;
CC Name=3; Synonyms=PDE11A2 {ECO:0000303|PubMed:11502204};
CC IsoId=Q8VID6-3; Sequence=VSP_019902, VSP_019905;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in brain, heart, kidney and
CC liver, but not in prostate. Isoform 2 is specifically expressed in
CC testis. Isoform 3 is expressed in various tissues including brain,
CC lung, skeletal muscle, spleen, testis and prostate.
CC {ECO:0000269|PubMed:11502204}.
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 -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000305}.
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DR EMBL; AB059360; BAB79627.1; -; mRNA.
DR EMBL; AB059361; BAB79628.1; -; mRNA.
DR EMBL; AB059362; BAB79629.1; -; mRNA.
DR RefSeq; NP_001120952.1; NM_001127480.1. [Q8VID6-2]
DR RefSeq; NP_001120953.1; NM_001127481.2. [Q8VID6-3]
DR RefSeq; NP_543169.1; NM_080893.1. [Q8VID6-1]
DR AlphaFoldDB; Q8VID6; -.
DR SMR; Q8VID6; -.
DR BioGRID; 250862; 1.
DR STRING; 10116.ENSRNOP00000008300; -.
DR iPTMnet; Q8VID6; -.
DR PhosphoSitePlus; Q8VID6; -.
DR PaxDb; Q8VID6; -.
DR PRIDE; Q8VID6; -.
DR Ensembl; ENSRNOT00000045862; ENSRNOP00000048657; ENSRNOG00000024457. [Q8VID6-3]
DR Ensembl; ENSRNOT00000050355; ENSRNOP00000051289; ENSRNOG00000024457. [Q8VID6-2]
DR GeneID; 140928; -.
DR KEGG; rno:140928; -.
DR CTD; 50940; -.
DR RGD; 621793; Pde11a.
DR VEuPathDB; HostDB:ENSRNOG00000024457; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000162151; -.
DR HOGENOM; CLU_006980_0_1_1; -.
DR InParanoid; Q8VID6; -.
DR OMA; KGECDWN; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q8VID6; -.
DR TreeFam; TF316499; -.
DR Reactome; R-RNO-418457; cGMP effects.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR SABIO-RK; Q8VID6; -.
DR PRO; PR:Q8VID6; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000024457; Expressed in testis and 8 other tissues.
DR ExpressionAtlas; Q8VID6; baseline and differential.
DR Genevisible; Q8VID6; RN.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IDA:RGD.
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; Cytoplasm; Hydrolase;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..935
FT /note="Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase
FT 11A"
FT /id="PRO_0000247042"
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 41..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 915..935
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: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:0000250|UniProtKB:Q9HCR9"
FT VAR_SEQ 1..354
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11502204"
FT /id="VSP_019902"
FT VAR_SEQ 1..250
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11502204"
FT /id="VSP_019903"
FT VAR_SEQ 251..304
FT /note="KTLVSKFFDVHAGTPLLPCSTTENSNEVQVPWGKGIIGYVGEHGETVNIPDA
FT YQ -> MLKQARRFSFRNVRSATQWRKVGSTRQGQISGAFLAERLDKHQDFLTRMQTRT
FT K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11502204"
FT /id="VSP_019904"
FT VAR_SEQ 355..357
FT /note="DEK -> MSW (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11502204"
FT /id="VSP_019905"
SQ SEQUENCE 935 AA; 104571 MW; E80F1039770F8276 CRC64;
MAASRLDFGE VETFLDRHPE LFEDYLMRKG KQELVDKWLQ RHSSGQGASD LRPALAGASS
LAQSSARGST GIGGGAGPQG SANSHPASGG GESAGVPLSP SWASGSRGDG NLQRRASQKE
LRKSFARSKA IHVNRTYDEQ VTSRAQEPLS SVRRRALLRK ASSLPPTTAH ILSALLESRV
NLPQYPPTAI DYKCHLKKHN ERQFFLELVK DISNDLDLTS LSYKILIFVC LMVDADRCSL
FLVEGAAAGK KTLVSKFFDV HAGTPLLPCS TTENSNEVQV 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 VSKGAYDWSI TSHRDVFRSM LMTACDLGAV TKPWEISRQV AELVTSEFFE
QGDRERSELK LTPSAIFDRN RKDELPRLQL EWIDSICMPL YQALVKVNAK LKPMLDSVAA
NRRKWEELHQ KRLQVSAASP VPSSPSPAVA GEDRL
