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P27815

- PDE4A_HUMAN

UniProt

P27815 - PDE4A_HUMAN

Protein

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

Gene

PDE4A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 3 (17 Oct 2006)
      Previous versions | rss
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    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

    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

    Pathwayi

    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

    1. 3',5'-cyclic-AMP phosphodiesterase activity Source: BHF-UCL
    2. cAMP binding Source: BHF-UCL
    3. metal ion binding Source: UniProtKB-KW
    4. protein binding Source: UniProtKB

    GO - Biological processi

    1. cAMP catabolic process Source: UniProtKB
    2. cellular response to drug Source: Ensembl
    3. regulation of cAMP-mediated signaling Source: Ensembl
    4. regulation of protein kinase A signaling Source: Ensembl
    5. sensory perception of smell Source: Ensembl
    6. signal transduction Source: ProtInc

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, Metal-binding

    Enzyme and pathway databases

    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: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:8780. PDE4A.

    Subcellular locationi

    Isoform 4 : Membrane; Peripheral membrane protein
    Note: Isoform 4 has propensity for association with membranes.
    Isoform 7 : Cytoplasm. Membrane
    Note: Predominantly cytoplasmic.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. membrane Source: ProtInc
    3. perinuclear region of cytoplasm Source: UniProtKB
    4. ruffle membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasm, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA33128.

    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 similarity2 Publications
    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

    ArrayExpressiP27815.
    BgeeiP27815.
    CleanExiHS_PDE4A.
    GenevestigatoriP27815.

    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 – 3687
    Helixi369 – 3713
    Helixi379 – 3857
    Turni386 – 3883
    Helixi390 – 40112
    Helixi404 – 4074
    Helixi412 – 42413
    Beta strandi430 – 4345
    Helixi435 – 44915
    Helixi452 – 4543
    Turni455 – 4573
    Helixi460 – 47213
    Turni473 – 4764
    Helixi482 – 4876
    Helixi491 – 4955
    Turni496 – 4983
    Helixi501 – 51212
    Helixi513 – 5153
    Turni521 – 5244
    Helixi527 – 54216
    Helixi546 – 5483
    Helixi549 – 56113
    Beta strandi567 – 5693
    Helixi576 – 59116
    Helixi594 – 5963
    Helixi599 – 62224
    Turni633 – 6353
    Helixi638 – 64811
    Helixi650 – 66011
    Turni661 – 6655
    Helixi666 – 68217

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOVERGENiHBG108239.
    InParanoidiP27815.
    KOiK01120.
    OMAiPSPTMKD.
    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. Align

    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

    MEPPTVPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD    50
    SAERAERERQ PHRPIERADA MDTSDRPGLR TTRMSWPSSF HGTGTGSGGA 100
    GGGSSRRFEA ENGPTPSPGR SPLDSQASPG LVLHAGAATS QRRESFLYRS 150
    DSDYDMSPKT MSRNSSVTSE AHAEDLIVTP FAQVLASLRS VRSNFSLLTN 200
    VPVPSNKRSP LGGPTPVCKA TLSEETCQQL ARETLEELDW CLEQLETMQT 250
    YRSVSEMASH KFKRMLNREL THLSEMSRSG NQVSEYISTT FLDKQNEVEI 300
    PSPTMKEREK QQAPRPRPSQ PPPPPVPHLQ PMSQITGLKK LMHSNSLNNS 350
    NIPRFGVKTD QEELLAQELE NLNKWGLNIF CVSDYAGGRS LTCIMYMIFQ 400
    ERDLLKKFRI PVDTMVTYML TLEDHYHADV AYHNSLHAAD VLQSTHVLLA 450
    TPALDAVFTD LEILAALFAA AIHDVDHPGV SNQFLINTNS ELALMYNDES 500
    VLENHHLAVG FKLLQEDNCD IFQNLSKRQR QSLRKMVIDM VLATDMSKHM 550
    TLLADLKTMV ETKKVTSSGV LLLDNYSDRI QVLRNMVHCA DLSNPTKPLE 600
    LYRQWTDRIM AEFFQQGDRE RERGMEISPM CDKHTASVEK SQVGFIDYIV 650
    HPLWETWADL VHPDAQEILD TLEDNRDWYY SAIRQSPSPP PEEESRGPGH 700
    PPLPDKFQFE LTLEEEEEEE ISMAQIPCTA QEALTAQGLS GVEEALDATI 750
    AWEASPAQES LEVMAQEASL EAELEAVYLT QQAQSTGSAP VAPDEFSSRE 800
    EFVVAVSHSS PSALALQSPL LPAWRTLSVS EHAPGLPGLP STAAEVEAQR 850
    EHQAAKRACS ACAGTFGEDT SALPAPGGGG SGGDPT 886
    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:
    EMBL
    GenBank
    DDBJ
    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. [P27815-7]
    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]

    Polymorphism databases

    DMDMi116242706.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS12238.1. [P27815-4 ]
    CCDS45961.1. [P27815-1 ]
    CCDS45962.1. [P27815-2 ]
    CCDS45963.1. [P27815-6 ]
    CCDS58649.1. [P27815-7 ]
    PIRi A54442.
    S55348.
    RefSeqi NP_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 ]
    UniGenei Hs.89901.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2QYK X-ray 2.10 A/B 351-683 [» ]
    3I8V X-ray 2.25 A/B 351-683 [» ]
    3TVX X-ray 2.84 A/B 351-683 [» ]
    ProteinModelPortali P27815.
    SMRi P27815. Positions 259-293, 328-710.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111167. 7 interactions.
    IntActi P27815. 1 interaction.

    Chemistry

    BindingDBi P27815.
    ChEMBLi CHEMBL2111340.
    DrugBanki DB01166. Cilostazol.
    DB00975. Dipyridamole.
    DB00651. Dyphylline.
    DB00824. Enprofylline.
    DB01088. Iloprost.
    DB00235. Milrinone.
    DB00806. Pentoxifylline.
    DB00692. Phentolamine.
    DB00820. Tadalafil.
    DB00277. Theophylline.
    GuidetoPHARMACOLOGYi 1300.

    PTM databases

    PhosphoSitei P27815.

    Polymorphism databases

    DMDMi 116242706.

    Proteomic databases

    MaxQBi P27815.
    PaxDbi P27815.
    PRIDEi P27815.

    Protocols and materials databases

    DNASUi 5141.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000293683 ; ENSP00000293683 ; ENSG00000065989 . [P27815-2 ]
    ENST00000344979 ; ENSP00000341007 ; ENSG00000065989 . [P27815-4 ]
    ENST00000380702 ; ENSP00000370078 ; ENSG00000065989 . [P27815-7 ]
    ENST00000440014 ; ENSP00000394754 ; ENSG00000065989 . [P27815-6 ]
    ENST00000592685 ; ENSP00000468507 ; ENSG00000065989 . [P27815-7 ]
    GeneIDi 5141.
    KEGGi hsa:5141.
    UCSCi uc002moj.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

    CTDi 5141.
    GeneCardsi GC19P010527.
    HGNCi HGNC:8780. PDE4A.
    HPAi CAB017632.
    HPA043310.
    MIMi 600126. gene.
    neXtProti NX_P27815.
    PharmGKBi PA33128.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG122287.
    HOVERGENi HBG108239.
    InParanoidi P27815.
    KOi K01120.
    OMAi PSPTMKD.
    OrthoDBi EOG7HQNBC.
    PhylomeDBi P27815.
    TreeFami TF314638.

    Enzyme and pathway databases

    UniPathwayi UPA00762 ; UER00747 .
    Reactomei REACT_15334. DARPP-32 events.
    REACT_19327. G alpha (s) signalling events.

    Miscellaneous databases

    ChiTaRSi PDE4A. human.
    EvolutionaryTracei P27815.
    GeneWikii PDE4A.
    GenomeRNAii 5141.
    NextBioi 19824.
    PROi P27815.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P27815.
    Bgeei P27815.
    CleanExi HS_PDE4A.
    Genevestigatori P27815.

    Family and domain databases

    Gene3Di 1.10.1300.10. 1 hit.
    InterProi IPR003607. HD/PDEase_dom.
    IPR023088. PDEase.
    IPR002073. PDEase_catalytic_dom.
    IPR023174. PDEase_CS.
    [Graphical view ]
    Pfami PF00233. PDEase_I. 1 hit.
    [Graphical view ]
    PRINTSi PR00387. PDIESTERASE1.
    SMARTi SM00471. HDc. 1 hit.
    [Graphical view ]
    PROSITEi PS00126. PDEASE_I. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 140 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