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Protein

cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Gene

PDE4A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.2 Publications

Catalytic activityi

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

Cofactori

a divalent metal cation1 PublicationNote: 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.1 Publication

Enzyme regulationi

Isoform 1, isoform 2, isoform 6 and isoform 7 are inhibited by rolipram and cilomilast. Isoform 1, isoform 2 and isoform 6 are inhibited by 4-[(3-butoxy-4-methoxyphenyl)-methyl]-2-imidazolidinone (Ro 20-1724), roflumilast and denbufylline.3 Publications

Kineticsi

  1. KM=4.0 µM for cAMP (isoform 2)2 Publications
  2. KM=3 µM for cAMP (isoform 6)2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei69 – 702Cleavage; by caspase-3
    Active sitei433 – 4331Proton donorBy similarity
    Metal bindingi437 – 4371Divalent metal cation 1
    Metal bindingi473 – 4731Divalent metal cation 1
    Metal bindingi474 – 4741Divalent metal cation 1
    Metal bindingi474 – 4741Divalent metal cation 2
    Binding sitei474 – 4741cAMPBy similarity
    Metal bindingi591 – 5911Divalent metal cation 1
    Binding sitei591 – 5911cAMPBy similarity
    Sitei594 – 5941Binds AMP, but not cAMPBy similarity
    Binding sitei642 – 6421cAMPBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi433 – 4375cAMPBy similarity

    GO - Molecular functioni

    • 3',5'-cyclic-AMP phosphodiesterase activity Source: BHF-UCL
    • cAMP binding Source: BHF-UCL
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    • cAMP catabolic process Source: UniProtKB
    • cellular response to drug Source: Ensembl
    • regulation of cAMP-mediated signaling Source: Ensembl
    • regulation of protein kinase A signaling Source: Ensembl
    • sensory perception of smell Source: Ensembl
    • signal transduction Source: ProtInc
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, Metal-binding

    Enzyme and pathway databases

    BRENDAi3.1.4.17. 2681.
    3.1.4.53. 2681.
    ReactomeiREACT_15334. DARPP-32 events.
    REACT_19327. G alpha (s) signalling events.
    UniPathwayiUPA00762; UER00747.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC:3.1.4.53)
    Alternative name(s):
    DPDE2
    PDE46
    Gene namesi
    Name:PDE4A
    Synonyms:DPDE2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:8780. PDE4A.

    Subcellular locationi

    Isoform 4 :
    Isoform 7 :

    GO - Cellular componenti

    • cytosol Source: Reactome
    • membrane Source: ProtInc
    • perinuclear region of cytoplasm Source: UniProtKB
    • ruffle membrane Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasm, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA33128.

    Chemistry

    DrugBankiDB00201. Caffeine.
    DB00975. Dipyridamole.
    DB06751. Drotaverine.
    DB00651. Dyphylline.
    DB00824. Enprofylline.
    DB05266. Ibudilast.
    DB01088. Iloprost.
    DB00920. Ketotifen.
    DB01303. Oxtriphylline.
    DB00806. Pentoxifylline.
    DB01656. Roflumilast.
    DB00277. Theophylline.
    DB08811. Tofisopam.

    Polymorphism and mutation databases

    BioMutaiPDE4A.
    DMDMi116242706.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 886886cAMP-specific 3',5'-cyclic phosphodiesterase 4APRO_0000198806Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei152 – 1521Phosphoserine; by MAPKAPK2By similarity
    Modified residuei165 – 1651Phosphoserine1 Publication
    Cross-linki358 – 358Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
    Modified residuei686 – 6861Phosphoserine1 Publication
    Modified residuei688 – 6881Phosphoserine1 Publication

    Post-translational modificationi

    Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation (By similarity). Phosphorylated at Ser-686 and Ser-688 when expressed in S.frugiperda cells. Isoform 2 and isoform 7 are activated by phosphorylation at Ser-119 and Ser-123 respectively by PKA.By similarity1 Publication
    Proteolytically cleaved by caspase-3.

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP27815.
    PaxDbiP27815.
    PRIDEiP27815.

    PTM databases

    PhosphoSiteiP27815.

    Expressioni

    Tissue specificityi

    Isoform 1 is widely expressed. Isoform 2 is abundant in liver, stomach, testis, thyroid and adrenal glands. It is also found in placenta, kidney, pancreas, ovary, uterus, skin, monocytes, mast cells, macrophages, as well as in bronchial smooth muscle. Isoform 6 is expressed at high levels in the heart and small intestine. It is also found in the brain, kidney, spleen, colon, salivary gland, ovary and peripheral blood lymphocytes. Isoform 7 is expressed predominantly in skeletal muscle and brain and at lower levels in the testis. Isoform 7 is expressed in the brain. Found in specific neuronal subpopulations in cortex, spinal cord and cerebellum (at protein level).3 Publications

    Gene expression databases

    BgeeiP27815.
    CleanExiHS_PDE4A.
    ExpressionAtlasiP27815. baseline and differential.
    GenevisibleiP27815. HS.

    Organism-specific databases

    HPAiCAB017632.
    HPA043310.

    Interactioni

    Subunit structurei

    Isoform 1 interacts with LYN. Isoform 2 and isoform 6 interact weakly with LYN. Isoform 1, isoform 2 and isoform 6 interact with ARRB2.4 Publications

    Protein-protein interaction databases

    BioGridi111167. 7 interactions.
    IntActiP27815. 1 interaction.

    Structurei

    Secondary structure

    1
    886
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi362 – 3687Combined sources
    Helixi369 – 3713Combined sources
    Helixi379 – 3857Combined sources
    Turni386 – 3883Combined sources
    Helixi390 – 40112Combined sources
    Helixi404 – 4074Combined sources
    Helixi412 – 42413Combined sources
    Beta strandi430 – 4345Combined sources
    Helixi435 – 44915Combined sources
    Helixi452 – 4543Combined sources
    Turni455 – 4573Combined sources
    Helixi460 – 47213Combined sources
    Turni473 – 4764Combined sources
    Helixi482 – 4876Combined sources
    Helixi491 – 4955Combined sources
    Turni496 – 4983Combined sources
    Helixi501 – 51212Combined sources
    Helixi513 – 5153Combined sources
    Turni521 – 5244Combined sources
    Helixi527 – 54216Combined sources
    Helixi546 – 5483Combined sources
    Helixi549 – 56113Combined sources
    Beta strandi567 – 5693Combined sources
    Helixi576 – 59116Combined sources
    Helixi594 – 5963Combined sources
    Helixi599 – 62224Combined sources
    Turni633 – 6353Combined sources
    Helixi638 – 64811Combined sources
    Helixi650 – 66011Combined sources
    Turni661 – 6655Combined sources
    Helixi666 – 68217Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2QYKX-ray2.10A/B351-683[»]
    3I8VX-ray2.25A/B351-683[»]
    3TVXX-ray2.84A/B351-683[»]
    ProteinModelPortaliP27815.
    SMRiP27815. Positions 259-293, 328-710.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP27815.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni330 – 723394CatalyticAdd
    BLAST

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG122287.
    GeneTreeiENSGT00760000118889.
    HOVERGENiHBG108239.
    KOiK13293.
    OMAiNIFCVSE.
    OrthoDBiEOG7HQNBC.
    PhylomeDBiP27815.
    TreeFamiTF314638.

    Family and domain databases

    Gene3Di1.10.1300.10. 1 hit.
    InterProiIPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view]
    PfamiPF00233. PDEase_I. 1 hit.
    [Graphical view]
    PRINTSiPR00387. PDIESTERASE1.
    SMARTiSM00471. HDc. 1 hit.
    [Graphical view]
    PROSITEiPS00126. PDEASE_I. 1 hit.
    [Graphical view]

    Sequences (7)i

    Sequence statusi: Complete.

    This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P27815-1) [UniParc]FASTAAdd to basket

    Also known as: PDE4A4, PDE4A4B, PDE46

    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
    MEPPTVPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD
    60 70 80 90 100
    SAERAERERQ PHRPIERADA MDTSDRPGLR TTRMSWPSSF HGTGTGSGGA
    110 120 130 140 150
    GGGSSRRFEA ENGPTPSPGR SPLDSQASPG LVLHAGAATS QRRESFLYRS
    160 170 180 190 200
    DSDYDMSPKT MSRNSSVTSE AHAEDLIVTP FAQVLASLRS VRSNFSLLTN
    210 220 230 240 250
    VPVPSNKRSP LGGPTPVCKA TLSEETCQQL ARETLEELDW CLEQLETMQT
    260 270 280 290 300
    YRSVSEMASH KFKRMLNREL THLSEMSRSG NQVSEYISTT FLDKQNEVEI
    310 320 330 340 350
    PSPTMKEREK QQAPRPRPSQ PPPPPVPHLQ PMSQITGLKK LMHSNSLNNS
    360 370 380 390 400
    NIPRFGVKTD QEELLAQELE NLNKWGLNIF CVSDYAGGRS LTCIMYMIFQ
    410 420 430 440 450
    ERDLLKKFRI PVDTMVTYML TLEDHYHADV AYHNSLHAAD VLQSTHVLLA
    460 470 480 490 500
    TPALDAVFTD LEILAALFAA AIHDVDHPGV SNQFLINTNS ELALMYNDES
    510 520 530 540 550
    VLENHHLAVG FKLLQEDNCD IFQNLSKRQR QSLRKMVIDM VLATDMSKHM
    560 570 580 590 600
    TLLADLKTMV ETKKVTSSGV LLLDNYSDRI QVLRNMVHCA DLSNPTKPLE
    610 620 630 640 650
    LYRQWTDRIM AEFFQQGDRE RERGMEISPM CDKHTASVEK SQVGFIDYIV
    660 670 680 690 700
    HPLWETWADL VHPDAQEILD TLEDNRDWYY SAIRQSPSPP PEEESRGPGH
    710 720 730 740 750
    PPLPDKFQFE LTLEEEEEEE ISMAQIPCTA QEALTAQGLS GVEEALDATI
    760 770 780 790 800
    AWEASPAQES LEVMAQEASL EAELEAVYLT QQAQSTGSAP VAPDEFSSRE
    810 820 830 840 850
    EFVVAVSHSS PSALALQSPL LPAWRTLSVS EHAPGLPGLP STAAEVEAQR
    860 870 880
    EHQAAKRACS ACAGTFGEDT SALPAPGGGG SGGDPT
    Length:886
    Mass (Da):98,143
    Last modified:October 17, 2006 - v3
    Checksum:i92BB9B98BED711E7
    GO
    Isoform 2 (identifier: P27815-2) [UniParc]FASTAAdd to basket

    Also known as: TM3, PDE4A11

    The sequence of this isoform differs from the canonical sequence as follows:
         1-107: MEPPTVPSER...GGAGGGSSRR → MARPRGLGRI...LGRQAWAGAG

    Note: Contains a phosphoserine at position 119.
    Show »
    Length:860
    Mass (Da):95,236
    Checksum:i6A4FC32E8AF7559D
    GO
    Isoform 3 (identifier: P27815-3) [UniParc]FASTAAdd to basket

    Also known as: PDE4A7, PDE4A6

    The sequence of this isoform differs from the canonical sequence as follows:
         1-209: MEPPTVPSER...NVPVPSNKRS → MCPFPVTTV

    Show »
    Length:686
    Mass (Da):76,380
    Checksum:i35F0A712804410AF
    GO
    Isoform 4 (identifier: P27815-4) [UniParc]FASTAAdd to basket

    Also known as: PDE4A1, RD1

    The sequence of this isoform differs from the canonical sequence as follows:
         1-261: MEPPTVPSER...RSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ

    Show »
    Length:647
    Mass (Da):72,222
    Checksum:i622A0BA91B7AC938
    GO
    Isoform 5 (identifier: P27815-5) [UniParc]FASTAAdd to basket

    Also known as: PDE4A8A, 2EL

    The sequence of this isoform differs from the canonical sequence as follows:
         1-367: MEPPTVPSER...KTDQEELLAQ → MVLPSDQGFKLLGNVLQGPEPYRLLTSGLRLHQ
         644-657: GFIDYIVHPLWETW → QARGIDGRAQGGFY
         658-886: Missing.

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Probably represents a non-functional splice isoform.
    Show »
    Length:323
    Mass (Da):36,706
    Checksum:i14D0EEF3D6CD4BEE
    GO
    Isoform 6 (identifier: P27815-6) [UniParc]FASTAAdd to basket

    Also known as: PDE4A10

    The sequence of this isoform differs from the canonical sequence as follows:
         1-107: MEPPTVPSER...GGAGGGSSRR → MRSGAAPRAR...RRHPPGRSVS

    Show »
    Length:825
    Mass (Da):91,323
    Checksum:iB50A342801E605FB
    GO
    Isoform 7 (identifier: P27815-7) [UniParc]FASTAAdd to basket

    Also known as: PDE4A8

    The sequence of this isoform differs from the canonical sequence as follows:
         1-107: MEPPTVPSER...GGAGGGSSRR → MKRSRSALSV...ISITRAENDS

    Note: Contains a phosphoserine at position 123.
    Show »
    Length:864
    Mass (Da):95,571
    Checksum:i1AB6019FC85E37E4
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti736 – 7361A → E.2 Publications
    Corresponds to variant rs1051738 [ dbSNP | Ensembl ].
    VAR_059544
    Natural varianti808 – 8081H → Y.
    Corresponds to variant rs2230190 [ dbSNP | Ensembl ].
    VAR_059545

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 367367MEPPT…ELLAQ → MVLPSDQGFKLLGNVLQGPE PYRLLTSGLRLHQ in isoform 5. 2 PublicationsVSP_004559Add
    BLAST
    Alternative sequencei1 – 261261MEPPT…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 4. 2 PublicationsVSP_004558Add
    BLAST
    Alternative sequencei1 – 209209MEPPT…SNKRS → MCPFPVTTV in isoform 3. 3 PublicationsVSP_004557Add
    BLAST
    Alternative sequencei1 – 107107MEPPT…GSSRR → MARPRGLGRIPELQLVAFPV AVAAEDEAFLPEPLAPRAPR RPRSPPSSPVFFASPSPTFR RRLRLLRSCQDLGRQAWAGA G in isoform 2. 2 PublicationsVSP_004556Add
    BLAST
    Alternative sequencei1 – 107107MEPPT…GSSRR → MRSGAAPRARPRPPALALPP TGPESLTHFPFSDEDTRRHP PGRSVS in isoform 6. 1 PublicationVSP_038185Add
    BLAST
    Alternative sequencei1 – 107107MEPPT…GSSRR → MKRSRSALSVAGTGDERSRE TPESDRANMLGADLRRPRRR LSSGPGLGWAQPEPSDPGVP LPPRPTTLPLLIPPRISITR AENDS in isoform 7. 1 PublicationVSP_038186Add
    BLAST
    Alternative sequencei644 – 65714GFIDY…LWETW → QARGIDGRAQGGFY in isoform 5. 2 PublicationsVSP_004560Add
    BLAST
    Alternative sequencei658 – 886229Missing in isoform 5. 2 PublicationsVSP_004561Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L20965 mRNA. Translation: AAA03588.1.
    S75213 mRNA. Translation: AAB33798.1.
    U18087 mRNA. Translation: AAC50458.1.
    U18088 mRNA. Translation: AAA98540.1.
    AF069491
    , AF069487, AF069489, AF069490 Genomic DNA. Translation: AAC35012.1.
    AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35013.1.
    AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35014.1.
    AF069491
    , AF069488, AF069489, AF069490 Genomic DNA. Translation: AAC35015.1.
    U68532 mRNA. Translation: AAC63832.1.
    U97584 mRNA. Translation: AAC25679.1.
    AF073745 mRNA. Translation: AAD34217.2.
    AY618547 mRNA. Translation: AAU82096.1.
    AY593872 mRNA. Translation: AAT00628.1.
    AC011548 Genomic DNA. No translation available.
    AC011529 Genomic DNA. No translation available.
    AC011461 Genomic DNA. No translation available.
    CH471106 Genomic DNA. Translation: EAW84104.1.
    CH471106 Genomic DNA. Translation: EAW84105.1.
    CH471106 Genomic DNA. Translation: EAW84108.1.
    BC019864 mRNA. Translation: AAH19864.1.
    BC038234 mRNA. Translation: AAH38234.1.
    M37744 mRNA. Translation: AAA69697.1.
    CCDSiCCDS12238.1. [P27815-4]
    CCDS45961.1. [P27815-1]
    CCDS45962.1. [P27815-2]
    CCDS45963.1. [P27815-6]
    CCDS58649.1. [P27815-7]
    PIRiA54442.
    S55348.
    RefSeqiNP_001104777.1. NM_001111307.1. [P27815-1]
    NP_001104778.1. NM_001111308.1. [P27815-2]
    NP_001104779.1. NM_001111309.1. [P27815-6]
    NP_001230050.1. NM_001243121.1. [P27815-7]
    NP_006193.1. NM_006202.2. [P27815-4]
    UniGeneiHs.89901.

    Genome annotation databases

    EnsembliENST00000293683; ENSP00000293683; ENSG00000065989. [P27815-2]
    ENST00000344979; ENSP00000341007; ENSG00000065989. [P27815-4]
    ENST00000380702; ENSP00000370078; ENSG00000065989. [P27815-1]
    ENST00000440014; ENSP00000394754; ENSG00000065989. [P27815-6]
    ENST00000592685; ENSP00000468507; ENSG00000065989. [P27815-7]
    GeneIDi5141.
    KEGGihsa:5141.
    UCSCiuc002moj.2. human. [P27815-1]
    uc002mok.2. human. [P27815-2]
    uc002mol.2. human. [P27815-6]
    uc002mom.2. human. [P27815-4]
    uc002moo.2. human. [P27815-5]
    uc021uow.1. human. [P27815-7]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L20965 mRNA. Translation: AAA03588.1.
    S75213 mRNA. Translation: AAB33798.1.
    U18087 mRNA. Translation: AAC50458.1.
    U18088 mRNA. Translation: AAA98540.1.
    AF069491
    , AF069487, AF069489, AF069490 Genomic DNA. Translation: AAC35012.1.
    AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35013.1.
    AF069491, AF069489, AF069490 Genomic DNA. Translation: AAC35014.1.
    AF069491
    , AF069488, AF069489, AF069490 Genomic DNA. Translation: AAC35015.1.
    U68532 mRNA. Translation: AAC63832.1.
    U97584 mRNA. Translation: AAC25679.1.
    AF073745 mRNA. Translation: AAD34217.2.
    AY618547 mRNA. Translation: AAU82096.1.
    AY593872 mRNA. Translation: AAT00628.1.
    AC011548 Genomic DNA. No translation available.
    AC011529 Genomic DNA. No translation available.
    AC011461 Genomic DNA. No translation available.
    CH471106 Genomic DNA. Translation: EAW84104.1.
    CH471106 Genomic DNA. Translation: EAW84105.1.
    CH471106 Genomic DNA. Translation: EAW84108.1.
    BC019864 mRNA. Translation: AAH19864.1.
    BC038234 mRNA. Translation: AAH38234.1.
    M37744 mRNA. Translation: AAA69697.1.
    CCDSiCCDS12238.1. [P27815-4]
    CCDS45961.1. [P27815-1]
    CCDS45962.1. [P27815-2]
    CCDS45963.1. [P27815-6]
    CCDS58649.1. [P27815-7]
    PIRiA54442.
    S55348.
    RefSeqiNP_001104777.1. NM_001111307.1. [P27815-1]
    NP_001104778.1. NM_001111308.1. [P27815-2]
    NP_001104779.1. NM_001111309.1. [P27815-6]
    NP_001230050.1. NM_001243121.1. [P27815-7]
    NP_006193.1. NM_006202.2. [P27815-4]
    UniGeneiHs.89901.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2QYKX-ray2.10A/B351-683[»]
    3I8VX-ray2.25A/B351-683[»]
    3TVXX-ray2.84A/B351-683[»]
    ProteinModelPortaliP27815.
    SMRiP27815. Positions 259-293, 328-710.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi111167. 7 interactions.
    IntActiP27815. 1 interaction.

    Chemistry

    BindingDBiP27815.
    ChEMBLiCHEMBL2093863.
    DrugBankiDB00201. Caffeine.
    DB00975. Dipyridamole.
    DB06751. Drotaverine.
    DB00651. Dyphylline.
    DB00824. Enprofylline.
    DB05266. Ibudilast.
    DB01088. Iloprost.
    DB00920. Ketotifen.
    DB01303. Oxtriphylline.
    DB00806. Pentoxifylline.
    DB01656. Roflumilast.
    DB00277. Theophylline.
    DB08811. Tofisopam.
    GuidetoPHARMACOLOGYi1300.

    PTM databases

    PhosphoSiteiP27815.

    Polymorphism and mutation databases

    BioMutaiPDE4A.
    DMDMi116242706.

    Proteomic databases

    MaxQBiP27815.
    PaxDbiP27815.
    PRIDEiP27815.

    Protocols and materials databases

    DNASUi5141.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000293683; ENSP00000293683; ENSG00000065989. [P27815-2]
    ENST00000344979; ENSP00000341007; ENSG00000065989. [P27815-4]
    ENST00000380702; ENSP00000370078; ENSG00000065989. [P27815-1]
    ENST00000440014; ENSP00000394754; ENSG00000065989. [P27815-6]
    ENST00000592685; ENSP00000468507; ENSG00000065989. [P27815-7]
    GeneIDi5141.
    KEGGihsa:5141.
    UCSCiuc002moj.2. human. [P27815-1]
    uc002mok.2. human. [P27815-2]
    uc002mol.2. human. [P27815-6]
    uc002mom.2. human. [P27815-4]
    uc002moo.2. human. [P27815-5]
    uc021uow.1. human. [P27815-7]

    Organism-specific databases

    CTDi5141.
    GeneCardsiGC19P010527.
    HGNCiHGNC:8780. PDE4A.
    HPAiCAB017632.
    HPA043310.
    MIMi600126. gene.
    neXtProtiNX_P27815.
    PharmGKBiPA33128.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiNOG122287.
    GeneTreeiENSGT00760000118889.
    HOVERGENiHBG108239.
    KOiK13293.
    OMAiNIFCVSE.
    OrthoDBiEOG7HQNBC.
    PhylomeDBiP27815.
    TreeFamiTF314638.

    Enzyme and pathway databases

    UniPathwayiUPA00762; UER00747.
    BRENDAi3.1.4.17. 2681.
    3.1.4.53. 2681.
    ReactomeiREACT_15334. DARPP-32 events.
    REACT_19327. G alpha (s) signalling events.

    Miscellaneous databases

    ChiTaRSiPDE4A. human.
    EvolutionaryTraceiP27815.
    GeneWikiiPDE4A.
    GenomeRNAii5141.
    NextBioi19824.
    PROiP27815.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP27815.
    CleanExiHS_PDE4A.
    ExpressionAtlasiP27815. baseline and differential.
    GenevisibleiP27815. HS.

    Family and domain databases

    Gene3Di1.10.1300.10. 1 hit.
    InterProiIPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view]
    PfamiPF00233. PDEase_I. 1 hit.
    [Graphical view]
    PRINTSiPR00387. PDIESTERASE1.
    SMARTiSM00471. HDc. 1 hit.
    [Graphical view]
    PROSITEiPS00126. PDEASE_I. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs."
      Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., Riggs M., Wigler M., Ferguson K.
      Mol. Cell. Biol. 13:6558-6571(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)."
      Sullivan M., Egerton M., Shakur Y., Marquardsen A., Houslay M.D.
      Cell. Signal. 6:793-812(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    3. "Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19."
      Horton Y.M., Sullivan M., Houslay M.D.
      Biochem. J. 308:683-691(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5), VARIANT GLU-736.
    4. "Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase 4A variant RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2."
      Sullivan M., Rena G., Begg F., Gordon L., Olsen A.S., Houslay M.D.
      Biochem. J. 333:693-703(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
      Tissue: Brain.
    5. "Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic AMP-specific phosphodiesterase PDE4A10."
      Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L., Huston E., Sullivan M., Houslay M.D.
      Mol. Pharmacol. 59:996-1011(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, TISSUE SPECIFICITY, INTERACTION WITH LYN.
      Tissue: Brain.
    6. "Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene."
      Wallace D.A., Johnston L.A., Huston E., Macmaster D., Houslay T.M., Cheung Y.-F., Campbell L., Millen J.E., Smith R.A., Gall I., Knowles R.G., Sullivan M., Houslay M.D.
      Mol. Pharmacol. 67:1920-1934(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PHOSPHORYLATION AT SER-119 (ISOFORM 2), CLEAVAGE BY CASPASE-3 (ISOFORM 1), INTERACTION WITH LYN AND ARRB2.
    7. "Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change."
      Mackenzie K.F., Topping E.C., Bugaj-Gaweda B., Deng C., Cheung Y.-F., Olsen A.E., Stockard C.R., High Mitchell L., Baillie G.S., Grizzle W.E., De Vivo M., Houslay M.D., Wang D., Bolger G.B.
      Biochem. J. 411:361-369(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-123 (ISOFORM 7).
    8. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    10. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
      Tissue: Brain.
    11. "Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase."
      Livi G.P., Kmetz P., McHale M.M., Cieslinski L.B., Sathe G.M., Taylor D.P., Davis R.L., Torphy T.J., Balcarek J.M.
      Mol. Cell. Biol. 10:2678-2686(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-886, VARIANT GLU-736.
      Tissue: Monocyte.
    12. McLaughlin M.M.
      Submitted (JAN-1991) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    13. "Purification and characterization of the human pde4a catalytic domain (pde4a(330-723)) expressed in sf9 cells."
      Lario P.I., Bobechko B., Bateman K., Kelly J., Vrielink A., Huang Z.
      Arch. Biochem. Biophys. 394:54-60(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT SER-686 AND SER-688, IDENTIFICATION BY MASS SPECTROMETRY.
    14. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
    15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    16. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    17. "Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK."
      Li X., Vadrevu S., Dunlop A., Day J., Advant N., Troeger J., Klussmann E., Jaffrey E., Hay R.T., Adams D.R., Houslay M.D., Baillie G.S.
      Biochem. J. 428:55-65(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION AT LYS-358 BY PIAS4.
    18. "Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors."
      Wang H., Peng M.-S., Chen Y., Geng J., Robinson H., Houslay M.D., Cai J., Ke H.
      Biochem. J. 408:193-201(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 351-683 IN COMPLEX WITH METAL IONS AND THE INHIBITOR NVP, FUNCTION, COFACTOR.
    19. "Crystal structure of human PDE4a with 4-(3-butoxy-4-methoxyphenyl)methyl-2-imidazolidone."
      Cheng R.K.Y., Crawley L., Barker J., Wood M., Felicetti B., Whittaker M.
      Submitted (JUL-2009) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 351-683 IN COMPLEX WITH METAL IONS AND INHIBITOR.

    Entry informationi

    Entry nameiPDE4A_HUMAN
    AccessioniPrimary (citable) accession number: P27815
    Secondary accession number(s): O75522
    , O76092, Q16255, Q16691, Q5DM53, Q6PMT2, Q8IVA7, Q8WUQ3, Q9H3H2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: October 17, 2006
    Last modified: June 24, 2015
    This is version 148 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. 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.