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Protein

Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A

Gene

Pde11a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

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

Cofactori

a divalent metal cationBy similarityNote: 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 regulationi

Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator.1 Publication

Kineticsi

  1. KM=3.9 µM for cAMP (isoform 1)1 Publication
  2. KM=1.6 µM for cGMP (isoform 1)1 Publication
  3. KM=4.0 µM for cAMP (isoform 2)1 Publication
  4. KM=1.6 µM for cGMP (isoform 2)1 Publication
  5. KM=2.2 µM for cAMP (isoform 3)1 Publication
  6. KM=1.3 µM for cGMP (isoform 3)1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei664 – 6641Proton donorBy similarity
    Metal bindingi668 – 6681Divalent metal cation 1By similarity
    Metal bindingi704 – 7041Divalent metal cation 1By similarity
    Metal bindingi705 – 7051Divalent metal cation 1By similarity
    Metal bindingi705 – 7051Divalent metal cation 2By similarity
    Metal bindingi708 – 7081Divalent metal cation 2By similarity
    Metal bindingi734 – 7341Divalent metal cation 2By similarity
    Metal bindingi816 – 8161Divalent metal cation 1By similarity
    Binding sitei869 – 8691cAMP or cGMPBy similarity

    GO - Molecular functioni

    • 3',5'-cyclic-GMP phosphodiesterase activity Source: UniProtKB-EC
    • cAMP binding Source: RGD
    • cGMP binding Source: RGD
    • cGMP-stimulated cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
    • cyclic-nucleotide phosphodiesterase activity Source: RGD
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    • cAMP catabolic process Source: RGD
    • cGMP catabolic process Source: RGD
    • signal transduction Source: InterPro
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, cGMP, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_287445. G alpha (s) signalling events.
    REACT_349609. cGMP effects.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:Pde11a
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494 Componenti: Chromosome 3

    Organism-specific databases

    RGDi621793. Pde11a.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB-SubCell
    • perikaryon Source: RGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 935935Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11APRO_0000247042Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei239 – 2391PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ8VID6.

    PTM databases

    PhosphoSiteiQ8VID6.

    Expressioni

    Tissue specificityi

    Isoform 1 is expressed in brain, heart, kidney and liver, but not in prostate. Isoform 2 is specifically expressed in testis. Isoform 3 is expressed in various tissues including brain, lung, skeletal muscle, spleen, testis and prostate.1 Publication

    Gene expression databases

    ExpressionAtlasiQ8VID6. baseline and differential.
    GenevisibleiQ8VID6. RN.

    Interactioni

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000008300.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8VID6.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini217 – 370154GAF 1Add
    BLAST
    Domaini402 – 558157GAF 2Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni640 – 905266CatalyticBy similarityAdd
    BLAST

    Domaini

    The tandem GAF domains bind cGMP, and regulate enzyme activity. The binding of cGMP stimulates enzyme activity (By similarity).By similarity

    Sequence similaritiesi

    Contains 2 GAF domains.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    GeneTreeiENSGT00760000119066.
    HOGENOMiHOG000007068.
    HOVERGENiHBG101207.
    InParanoidiQ8VID6.
    KOiK13298.
    PhylomeDBiQ8VID6.
    TreeFamiTF316499.

    Family and domain databases

    Gene3Di1.10.1300.10. 1 hit.
    3.30.450.40. 2 hits.
    InterProiIPR003018. GAF.
    IPR029016. GAF_dom_like.
    IPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view]
    PfamiPF01590. GAF. 2 hits.
    PF00233. PDEase_I. 1 hit.
    [Graphical view]
    PRINTSiPR00387. PDIESTERASE1.
    SMARTiSM00065. GAF. 2 hits.
    SM00471. HDc. 1 hit.
    [Graphical view]
    SUPFAMiSSF55781. SSF55781. 2 hits.
    PROSITEiPS00126. PDEASE_I. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q8VID6-1) [UniParc]FASTAAdd to basket

    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.

    « Hide

            10         20         30         40         50
    MAASRLDFGE VETFLDRHPE LFEDYLMRKG KQELVDKWLQ RHSSGQGASD
    60 70 80 90 100
    LRPALAGASS LAQSSARGST GIGGGAGPQG SANSHPASGG GESAGVPLSP
    110 120 130 140 150
    SWASGSRGDG NLQRRASQKE LRKSFARSKA IHVNRTYDEQ VTSRAQEPLS
    160 170 180 190 200
    SVRRRALLRK ASSLPPTTAH ILSALLESRV NLPQYPPTAI DYKCHLKKHN
    210 220 230 240 250
    ERQFFLELVK DISNDLDLTS LSYKILIFVC LMVDADRCSL FLVEGAAAGK
    260 270 280 290 300
    KTLVSKFFDV HAGTPLLPCS TTENSNEVQV PWGKGIIGYV GEHGETVNIP
    310 320 330 340 350
    DAYQDRRFND EIDKLTGYKT KSLLCMPIRN SDGEIIGVAQ AINKVPEGAP
    360 370 380 390 400
    FTEDDEKVMQ MYLPFCGIAI SNAQLFAASR KEYERSRALL EVVNDLFEEQ
    410 420 430 440 450
    TDLEKIVKKI MHRAQTLLKC ERCSVLLLED IESPVVKFTK SFELMSPKCS
    460 470 480 490 500
    ADAENSFKES VEKSSYSDWL INNSIAELVA STGLPVNVSD AYQDPRFDAE
    510 520 530 540 550
    ADQISGFHIR SVLCVPIWNS NHQIIGVAQV LNRLDGKPFD DADQRLFEAF
    560 570 580 590 600
    VIFCGLGINN TIMYDQVKKS WAKQSVALDV LSYHATCSKA EVDKFKAANI
    610 620 630 640 650
    PLVSELAIDD IHFDDFSLDV DAMITAALRM FMELGMVQKF KIDYETLCRW
    660 670 680 690 700
    LLTVRKNYRM VLYHNWRHAF NVCQLMFAML TTAGFQEILT EVEILAVIVG
    710 720 730 740 750
    CLCHDLDHRG TNNAFQAKSD SALAQLYGTS ATLEHHHFNH AVMILQSEGH
    760 770 780 790 800
    NIFANLSSKE YSDLMQLLKQ SILATDLTLY FERRTEFFEL VSKGAYDWSI
    810 820 830 840 850
    TSHRDVFRSM LMTACDLGAV TKPWEISRQV AELVTSEFFE QGDRERSELK
    860 870 880 890 900
    LTPSAIFDRN RKDELPRLQL EWIDSICMPL YQALVKVNAK LKPMLDSVAA
    910 920 930
    NRRKWEELHQ KRLQVSAASP VPSSPSPAVA GEDRL
    Length:935
    Mass (Da):104,571
    Last modified:March 1, 2002 - v1
    Checksum:iE80F1039770F8276
    GO
    Isoform 2 (identifier: Q8VID6-2) [UniParc]FASTAAdd to basket

    Also known as: PDE11A3

    The sequence of this isoform differs from the canonical sequence as follows:
         1-250: Missing.
         251-304: KTLVSKFFDV...ETVNIPDAYQ → MLKQARRFSF...FLTRMQTRTK

    Show »
    Length:685
    Mass (Da):78,067
    Checksum:i505E8748E9A6C21F
    GO
    Isoform 3 (identifier: Q8VID6-3) [UniParc]FASTAAdd to basket

    Also known as: PDE11A2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-354: Missing.
         355-357: DEK → MSW

    Show »
    Length:581
    Mass (Da):66,142
    Checksum:i2CA7C2F5DDB37D00
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 354354Missing in isoform 3. 1 PublicationVSP_019902Add
    BLAST
    Alternative sequencei1 – 250250Missing in isoform 2. 1 PublicationVSP_019903Add
    BLAST
    Alternative sequencei251 – 30454KTLVS…PDAYQ → MLKQARRFSFRNVRSATQWR KVGSTRQGQISGAFLAERLD KHQDFLTRMQTRTK in isoform 2. 1 PublicationVSP_019904Add
    BLAST
    Alternative sequencei355 – 3573DEK → MSW in isoform 3. 1 PublicationVSP_019905

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB059360 mRNA. Translation: BAB79627.1.
    AB059361 mRNA. Translation: BAB79628.1.
    AB059362 mRNA. Translation: BAB79629.1.
    RefSeqiNP_001120952.1. NM_001127480.1. [Q8VID6-2]
    NP_001120953.1. NM_001127481.2. [Q8VID6-3]
    NP_543169.1. NM_080893.1. [Q8VID6-1]
    UniGeneiRn.88630.

    Genome annotation databases

    EnsembliENSRNOT00000008301; ENSRNOP00000008300; ENSRNOG00000024457. [Q8VID6-1]
    ENSRNOT00000050355; ENSRNOP00000051289; ENSRNOG00000024457. [Q8VID6-2]
    GeneIDi140928.
    KEGGirno:140928.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB059360 mRNA. Translation: BAB79627.1.
    AB059361 mRNA. Translation: BAB79628.1.
    AB059362 mRNA. Translation: BAB79629.1.
    RefSeqiNP_001120952.1. NM_001127480.1. [Q8VID6-2]
    NP_001120953.1. NM_001127481.2. [Q8VID6-3]
    NP_543169.1. NM_080893.1. [Q8VID6-1]
    UniGeneiRn.88630.

    3D structure databases

    ProteinModelPortaliQ8VID6.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000008300.

    PTM databases

    PhosphoSiteiQ8VID6.

    Proteomic databases

    PRIDEiQ8VID6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000008301; ENSRNOP00000008300; ENSRNOG00000024457. [Q8VID6-1]
    ENSRNOT00000050355; ENSRNOP00000051289; ENSRNOG00000024457. [Q8VID6-2]
    GeneIDi140928.
    KEGGirno:140928.

    Organism-specific databases

    CTDi50940.
    RGDi621793. Pde11a.

    Phylogenomic databases

    GeneTreeiENSGT00760000119066.
    HOGENOMiHOG000007068.
    HOVERGENiHBG101207.
    InParanoidiQ8VID6.
    KOiK13298.
    PhylomeDBiQ8VID6.
    TreeFamiTF316499.

    Enzyme and pathway databases

    ReactomeiREACT_287445. G alpha (s) signalling events.
    REACT_349609. cGMP effects.

    Miscellaneous databases

    NextBioi620787.
    PROiQ8VID6.

    Gene expression databases

    ExpressionAtlasiQ8VID6. baseline and differential.
    GenevisibleiQ8VID6. RN.

    Family and domain databases

    Gene3Di1.10.1300.10. 1 hit.
    3.30.450.40. 2 hits.
    InterProiIPR003018. GAF.
    IPR029016. GAF_dom_like.
    IPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view]
    PfamiPF01590. GAF. 2 hits.
    PF00233. PDEase_I. 1 hit.
    [Graphical view]
    PRINTSiPR00387. PDIESTERASE1.
    SMARTiSM00065. GAF. 2 hits.
    SM00471. HDc. 1 hit.
    [Graphical view]
    SUPFAMiSSF55781. SSF55781. 2 hits.
    PROSITEiPS00126. PDEASE_I. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    1. "Identification of rat cyclic nucleotide phosphodiesterase 11A (PDE11A): comparison of rat and human PDE11A splicing variants."
      Yuasa K., Ohgaru T., Asahina M., Omori K.
      Eur. J. Biochem. 268:4440-4448(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiPDE11_RAT
    AccessioniPrimary (citable) accession number: Q8VID6
    Secondary accession number(s): Q8VID7, Q8VID8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 25, 2006
    Last sequence update: March 1, 2002
    Last modified: June 24, 2015
    This is version 88 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Allosteric enzyme, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.