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Q08499

- PDE4D_HUMAN

UniProt

Q08499 - PDE4D_HUMAN

Protein

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

Gene

PDE4D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 2 (01 Dec 2000)
      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.2 Publications

    Enzyme regulationi

    Inhibited by rolipram. Activated by phosphatidic acid.1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei462 – 4621Proton donorBy similarity
    Metal bindingi466 – 4661Divalent metal cation 1
    Metal bindingi502 – 5021Divalent metal cation 1
    Metal bindingi503 – 5031Divalent metal cation 1
    Metal bindingi503 – 5031Divalent metal cation 2
    Binding sitei503 – 5031cAMP2 Publications
    Metal bindingi620 – 6201Divalent metal cation 1
    Binding sitei620 – 6201cAMP2 Publications
    Sitei623 – 6231Binds AMP, but not cAMP
    Binding sitei671 – 6711cAMP2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi462 – 4665cAMP2 Publications

    GO - Molecular functioni

    1. 3',5'-cyclic-AMP phosphodiesterase activity Source: BHF-UCL
    2. 3',5'-cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
    3. ATPase binding Source: BHF-UCL
    4. beta-2 adrenergic receptor binding Source: BHF-UCL
    5. cAMP binding Source: BHF-UCL
    6. drug binding Source: UniProtKB
    7. enzyme binding Source: BHF-UCL
    8. ion channel binding Source: BHF-UCL
    9. metal ion binding Source: UniProtKB-KW
    10. protein binding Source: IntAct
    11. scaffold protein binding Source: BHF-UCL
    12. ubiquitin protein ligase binding Source: BHF-UCL

    GO - Biological processi

    1. adrenergic receptor signaling pathway Source: BHF-UCL
    2. adrenergic receptor signaling pathway involved in positive regulation of heart rate Source: BHF-UCL
    3. aging Source: Ensembl
    4. cAMP catabolic process Source: BHF-UCL
    5. cAMP-mediated signaling Source: BHF-UCL
    6. cellular response to cAMP Source: BHF-UCL
    7. cellular response to epinephrine stimulus Source: BHF-UCL
    8. cellular response to lipopolysaccharide Source: Ensembl
    9. establishment of endothelial barrier Source: UniProtKB
    10. multicellular organism growth Source: Ensembl
    11. negative regulation of heart contraction Source: BHF-UCL
    12. negative regulation of peptidyl-serine phosphorylation Source: BHF-UCL
    13. negative regulation of relaxation of cardiac muscle Source: BHF-UCL
    14. neutrophil chemotaxis Source: Ensembl
    15. positive regulation of interferon-gamma production Source: BHF-UCL
    16. positive regulation of interleukin-2 production Source: BHF-UCL
    17. positive regulation of interleukin-5 production Source: BHF-UCL
    18. regulation of cardiac muscle cell contraction Source: BHF-UCL
    19. regulation of cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
    20. regulation of heart rate Source: BHF-UCL
    21. regulation of receptor activity Source: BHF-UCL
    22. regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
    23. regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
    24. smooth muscle contraction Source: Ensembl
    25. T cell receptor signaling pathway Source: BHF-UCL

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    cAMP, Metal-binding

    Enzyme and pathway databases

    BRENDAi3.1.4.53. 2681.
    ReactomeiREACT_15334. DARPP-32 events.
    REACT_19327. G alpha (s) signalling events.
    SignaLinkiQ08499.
    UniPathwayiUPA00762; UER00747.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4D (EC:3.1.4.53)
    Alternative name(s):
    DPDE3
    PDE43
    Gene namesi
    Name:PDE4D
    Synonyms:DPDE3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:8783. PDE4D.

    Subcellular locationi

    Apical cell membrane 1 Publication. Cytoplasm By similarity. Membrane By similarity. Cytoplasmcytoskeleton By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
    Note: Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome By similarity. Colocalized with SHANK2 to the apical membrane of colonic crypt cells.By similarity

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB-SubCell
    2. calcium channel complex Source: BHF-UCL
    3. cytosol Source: BHF-UCL
    4. membrane Source: BHF-UCL
    5. microtubule organizing center Source: UniProtKB-SubCell
    6. voltage-gated calcium channel complex Source: Ensembl

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Cytoskeleton, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2) [MIM:614613]: A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti190 – 1901S → A in ACRDYS2. 1 Publication
    VAR_068242
    Natural varianti225 – 2251P → T in ACRDYS2. 2 Publications
    VAR_068243
    Natural varianti226 – 2261F → S in ACRDYS2. 1 Publication
    VAR_068244
    Natural varianti227 – 2271A → S in ACRDYS2. 1 Publication
    VAR_069448
    Natural varianti228 – 2281Q → E in ACRDYS2. 1 Publication
    VAR_069449
    Natural varianti301 – 3011S → T in ACRDYS2. 1 Publication
    VAR_069450
    Natural varianti304 – 3041A → V in ACRDYS2. 1 Publication
    VAR_069451
    Natural varianti329 – 3291V → A in ACRDYS2. 1 Publication
    VAR_069452
    Natural varianti587 – 5871T → P in ACRDYS2. 1 Publication
    VAR_068245
    Natural varianti590 – 5901E → A in ACRDYS2. 2 Publications
    VAR_069453
    Natural varianti673 – 6731G → D in ACRDYS2. 1 Publication
    VAR_069454
    Natural varianti678 – 6781I → T in ACRDYS2. 1 Publication
    VAR_069455

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi503 – 5031D → N: Abolishes catalytic activity.
    Mutagenesisi527 – 5271D → R: Abolishes homodimerization. 1 Publication
    Mutagenesisi563 – 5631R → D: Abolishes homodimerization. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi614613. phenotype.
    Orphaneti950. Acrodysostosis.
    280651. Acrodysostosis with multiple hormone resistance.
    PharmGKBiPA33130.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 809809cAMP-specific 3',5'-cyclic phosphodiesterase 4DPRO_0000198814Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei299 – 2991Phosphoserine2 Publications
    Modified residuei301 – 3011Phosphoserine2 Publications
    Cross-linki387 – 387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

    Post-translational modificationi

    Long isoforms that share a conserved PKA phosphorylation site in the N-terminus are activated by PKA through phosphorylation By similarity. Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.By similarity
    Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.1 Publication

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ08499.
    PaxDbiQ08499.
    PRIDEiQ08499.

    PTM databases

    PhosphoSiteiQ08499.

    Expressioni

    Tissue specificityi

    Expressed in colonic epithelial cells (at protein level). Widespread; most abundant in skeletal muscle. Isoform 6 is detected in brain. Isoform 8 is detected in brain, placenta, lung and kidney. Isoform 7 is detected in heart and skeletal muscle.2 Publications

    Gene expression databases

    ArrayExpressiQ08499.
    BgeeiQ08499.
    GenevestigatoriQ08499.

    Organism-specific databases

    HPAiHPA045895.

    Interactioni

    Subunit structurei

    Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) By similarity. Isoform 5, isoform N3 and isoform 12 bind GNB2L1 via their unique N-terminus. Binds ARRB2. Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.By similarity15 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Adcy2P267693EBI-8095525,EBI-1027877From a different organism.
    ZDHHC17Q8IUH52EBI-9090666,EBI-524753

    Protein-protein interaction databases

    BioGridi111170. 32 interactions.
    DIPiDIP-29709N.
    DIP-41115N.
    IntActiQ08499. 10 interactions.
    MINTiMINT-92262.

    Structurei

    Secondary structure

    1
    809
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi328 – 3369
    Beta strandi383 – 3864
    Helixi389 – 3979
    Helixi398 – 4003
    Helixi408 – 4147
    Helixi419 – 43012
    Helixi433 – 4364
    Helixi441 – 45313
    Beta strandi460 – 4634
    Helixi464 – 47815
    Helixi481 – 4833
    Turni484 – 4863
    Helixi489 – 50113
    Turni502 – 5054
    Helixi511 – 5166
    Helixi520 – 5256
    Helixi530 – 54112
    Helixi542 – 5443
    Turni545 – 5473
    Turni550 – 5534
    Helixi556 – 57116
    Helixi575 – 5773
    Helixi578 – 59013
    Beta strandi598 – 6003
    Helixi605 – 62016
    Helixi623 – 6253
    Helixi628 – 65225
    Turni658 – 6603
    Beta strandi662 – 6643
    Helixi667 – 67711
    Helixi679 – 68911
    Turni690 – 6945
    Helixi695 – 71016

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E9KNMR-A-[»]
    1MKDX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L388-715[»]
    1OYNX-ray2.00A/B/C/D381-740[»]
    1PTWX-ray2.30A/B/C/D381-740[»]
    1Q9MX-ray2.30A/B/C/D381-740[»]
    1TB7X-ray1.63A/B388-715[»]
    1TBBX-ray1.60A/B388-715[»]
    1XOMX-ray1.55A/B388-715[»]
    1XONX-ray1.72A/B388-715[»]
    1XOQX-ray1.83A/B388-715[»]
    1XORX-ray1.54A/B388-715[»]
    1Y2BX-ray1.40A/B388-715[»]
    1Y2CX-ray1.67A/B388-715[»]
    1Y2DX-ray1.70A/B388-715[»]
    1Y2EX-ray2.10A/B388-715[»]
    1Y2KX-ray1.36A/B388-715[»]
    1ZKNX-ray2.10A/B/C/D381-714[»]
    2FM0X-ray2.00A/B/C/D381-741[»]
    2FM5X-ray2.03A/B/C/D381-741[»]
    2PW3X-ray1.56A/B388-714[»]
    2QYNX-ray1.57A/B388-715[»]
    3G4GX-ray2.30A/B/C/D299-347[»]
    A/B/C/D360-714[»]
    3G4IX-ray1.90A/B/C/D380-753[»]
    3G4KX-ray1.95A/B/C/D380-753[»]
    3G4LX-ray2.50A/B/C/D380-753[»]
    3G58X-ray2.05A/B/C/D380-753[»]
    3IADX-ray2.65A/B/C/D326-339[»]
    A/B/C/D380-714[»]
    3IAKX-ray2.80A388-715[»]
    3K4SX-ray2.05A388-715[»]
    3SL3X-ray2.10A/B/C/D381-741[»]
    3SL4X-ray1.90A/B/C/D381-741[»]
    3SL5X-ray2.65A/B/C/D381-714[»]
    3SL6X-ray2.44A/B/C/D381-741[»]
    3SL8X-ray2.60A/B/C/D381-741[»]
    3V9BX-ray2.10A/B/C/D381-740[»]
    ProteinModelPortaliQ08499.
    SMRiQ08499. Positions 327-739.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ08499.

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi42 – 8847Pro-richAdd
    BLAST

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG122287.
    HOVERGENiHBG108239.
    InParanoidiQ08499.
    KOiK01120.
    OMAiYENSSAD.
    OrthoDBiEOG7HQNBC.
    PhylomeDBiQ08499.
    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 (12)i

    Sequence statusi: Complete.

    This entry describes 12 isoformsi produced by alternative splicing. Align

    Isoform 4 (identifier: Q08499-1) [UniParc]FASTAAdd to Basket

    Also known as: hPDE4D4

    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

    MEAEGSSAPA RAGSGEGSDS AGGATLKAPK HLWRHEQHHQ YPLRQPQFRL    50
    LHPHHHLPPP PPPSPQPQPQ CPLQPPPPPP LPPPPPPPGA ARGRYASSGA 100
    TGRVRHRGYS DTERYLYCRA MDRTSYAVET GHRPGLKKSR MSWPSSFQGL 150
    RRFDVDNGTS AGRSPLDPMT SPGSGLILQA NFVHSQRRES FLYRSDSDYD 200
    LSPKSMSRNS SIASDIHGDD LIVTPFAQVL ASLRTVRNNF AALTNLQDRA 250
    PSKRSPMCNQ PSINKATITE EAYQKLASET LEELDWCLDQ LETLQTRHSV 300
    SEMASNKFKR MLNRELTHLS EMSRSGNQVS EFISNTFLDK QHEVEIPSPT 350
    QKEKEKKKRP MSQISGVKKL MHSSSLTNSS IPRFGVKTEQ EDVLAKELED 400
    VNKWGLHVFR IAELSGNRPL TVIMHTIFQE RDLLKTFKIP VDTLITYLMT 450
    LEDHYHADVA YHNNIHAADV VQSTHVLLST PALEAVFTDL EILAAIFASA 500
    IHDVDHPGVS NQFLINTNSE LALMYNDSSV LENHHLAVGF KLLQEENCDI 550
    FQNLTKKQRQ SLRKMVIDIV LATDMSKHMN LLADLKTMVE TKKVTSSGVL 600
    LLDNYSDRIQ VLQNMVHCAD LSNPTKPLQL YRQWTDRIME EFFRQGDRER 650
    ERGMEISPMC DKHNASVEKS QVGFIDYIVH PLWETWADLV HPDAQDILDT 700
    LEDNREWYQS TIPQSPSPAP DDPEEGRQGQ TEKFQFELTL EEDGESDTEK 750
    DSGSQVEEDT SCSDSKTLCT QDSESTEIPL DEQVEEEAVG EEEESQPEAC 800
    VIDDRSPDT 809
    Length:809
    Mass (Da):91,115
    Last modified:December 1, 2000 - v2
    Checksum:i7A4773DD3A044F57
    GO
    Isoform 3 (identifier: Q08499-2) [UniParc]FASTAAdd to Basket

    Also known as: hPDE4D3

    The sequence of this isoform differs from the canonical sequence as follows:
         1-152: MEAEGSSAPA...WPSSFQGLRR → MMHVNNFPFRRHSWIC

    Note: Contains a phosphoserine at position 53. Activated by phosphorylation at Ser-53. Mutagenesis of Ser-53 abolishes activation.

    Show »
    Length:673
    Mass (Da):76,467
    Checksum:iBDC04171BA91A297
    GO
    Isoform 10 (identifier: Q08499-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-205: Missing.

    Show »
    Length:604
    Mass (Da):68,607
    Checksum:i446D0C31C86399AB
    GO
    Isoform 1 (identifier: Q08499-4) [UniParc]FASTAAdd to Basket

    Also known as: hPDE4D1

    The sequence of this isoform differs from the canonical sequence as follows:
         1-269: MEAEGSSAPA...QPSINKATIT → MKEQPSCAGT...TESPFPCLFA

    Show »
    Length:584
    Mass (Da):66,376
    Checksum:iC1761886FF962102
    GO
    Isoform 2 (identifier: Q08499-5) [UniParc]FASTAAdd to Basket

    Also known as: hPDE4D2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-302: Missing.

    Show »
    Length:507
    Mass (Da):57,792
    Checksum:i6C07C949952EE5DF
    GO
    Isoform 5 (identifier: Q08499-6) [UniParc]FASTAAdd to Basket

    Also known as: hPDE4D5

    The sequence of this isoform differs from the canonical sequence as follows:
         1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC

    Note: Contains a phosphoserine at position 59. Contains a phosphoserine at position 63.

    Show »
    Length:745
    Mass (Da):84,428
    Checksum:iD136AE2B7132DAAC
    GO
    Isoform N3 (identifier: Q08499-7) [UniParc]FASTAAdd to Basket

    Also known as: PDE4DN3

    The sequence of this isoform differs from the canonical sequence as follows:
         1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
         270-279: EEAYQKLASE → GLYNGIIAFL
         280-809: Missing.

    Note: Contains a phosphoserine at position 59. Contains a phosphoserine at position 63.

    Show »
    Length:215
    Mass (Da):23,839
    Checksum:i255EF7985DB75353
    GO
    Isoform 6 (identifier: Q08499-8) [UniParc]FASTAAdd to Basket

    Also known as: PDE4D6

    The sequence of this isoform differs from the canonical sequence as follows:
         1-291: Missing.
         292-306: ETLQTRHSVSEMASN → MPEANYLLSVSWGYI

    Show »
    Length:518
    Mass (Da):59,113
    Checksum:i069F18EB90BAAF4B
    GO
    Isoform 8 (identifier: Q08499-9) [UniParc]FASTAAdd to Basket

    Also known as: PDE4D8

    The sequence of this isoform differs from the canonical sequence as follows:
         1-122: Missing.
         123-152: RTSYAVETGHRPGLKKSRMSWPSSFQGLRR → MAFVWDPLGATVPGPSTRAKSRLRFSKSYS

    Show »
    Length:687
    Mass (Da):77,705
    Checksum:i90B1ED110D7ED77C
    GO
    Isoform 9 (identifier: Q08499-10) [UniParc]FASTAAdd to Basket

    Also known as: PDE4D9

    The sequence of this isoform differs from the canonical sequence as follows:
         1-130: Missing.
         131-152: GHRPGLKKSRMSWPSSFQGLRR → MSIIMKPRSRSTSSLRTAEAVC

    Show »
    Length:679
    Mass (Da):76,816
    Checksum:iD35B0A2D975C5705
    GO
    Isoform 7 (identifier: Q08499-11) [UniParc]FASTAAdd to Basket

    Also known as: PDE4D7

    The sequence of this isoform differs from the canonical sequence as follows:
         1-61: Missing.
         62-152: PPSPQPQPQC...WPSSFQGLRR → MKRNTCDLLS...IAITSAESSG

    Show »
    Length:748
    Mass (Da):84,662
    Checksum:iD10CF5036B1EA7C8
    GO
    Isoform 12 (identifier: Q08499-12) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
         270-283: EEAYQKLASETLEE → GSWMELNPYTLLDM
         284-809: Missing.

    Note: Contains a phosphoserine at position 59. Contains a phosphoserine at position 63.

    Show »
    Length:219
    Mass (Da):24,429
    Checksum:i04C84B400D6F7D2C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti510 – 5101S → F in AAH36319. (PubMed:15489334)Curated
    Sequence conflicti549 – 5491D → G in AAN10119. (PubMed:12834813)Curated
    Sequence conflicti644 – 6441R → P(PubMed:8797812)Curated
    Sequence conflicti769 – 7691C → R in AAA97890. (PubMed:8125310)Curated
    Sequence conflicti769 – 7691C → R in AAA97891. (PubMed:8125310)Curated
    Sequence conflicti769 – 7691C → R in AAA97892. (PubMed:8125310)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti190 – 1901S → A in ACRDYS2. 1 Publication
    VAR_068242
    Natural varianti225 – 2251P → T in ACRDYS2. 2 Publications
    VAR_068243
    Natural varianti226 – 2261F → S in ACRDYS2. 1 Publication
    VAR_068244
    Natural varianti227 – 2271A → S in ACRDYS2. 1 Publication
    VAR_069448
    Natural varianti228 – 2281Q → E in ACRDYS2. 1 Publication
    VAR_069449
    Natural varianti301 – 3011S → T in ACRDYS2. 1 Publication
    VAR_069450
    Natural varianti304 – 3041A → V in ACRDYS2. 1 Publication
    VAR_069451
    Natural varianti329 – 3291V → A in ACRDYS2. 1 Publication
    VAR_069452
    Natural varianti587 – 5871T → P in ACRDYS2. 1 Publication
    VAR_068245
    Natural varianti590 – 5901E → A in ACRDYS2. 2 Publications
    VAR_069453
    Natural varianti673 – 6731G → D in ACRDYS2. 1 Publication
    VAR_069454
    Natural varianti678 – 6781I → T in ACRDYS2. 1 Publication
    VAR_069455

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 302302Missing in isoform 2. 2 PublicationsVSP_004580Add
    BLAST
    Alternative sequencei1 – 291291Missing in isoform 6. 2 PublicationsVSP_012383Add
    BLAST
    Alternative sequencei1 – 269269MEAEG…KATIT → MKEQPSCAGTGHPMAGYGRM APFELASGPVKRLRTESPFP CLFA in isoform 1. 2 PublicationsVSP_004579Add
    BLAST
    Alternative sequencei1 – 205205Missing in isoform 10. 2 PublicationsVSP_004578Add
    BLAST
    Alternative sequencei1 – 152152MEAEG…QGLRR → MMHVNNFPFRRHSWIC in isoform 3. 2 PublicationsVSP_004577Add
    BLAST
    Alternative sequencei1 – 152152MEAEG…QGLRR → MAQQTSPDTLTVPEVDNPHC PNPWLNEDLVKSLRENLLQH EKSKTARKSVSPKLSPVISP RNSPRLLRRMLLSSNIPKQR RFTVAHTC in isoform 5, isoform N3 and isoform 12. 4 PublicationsVSP_012384Add
    BLAST
    Alternative sequencei1 – 130130Missing in isoform 9. 2 PublicationsVSP_012385Add
    BLAST
    Alternative sequencei1 – 122122Missing in isoform 8. 1 PublicationVSP_012386Add
    BLAST
    Alternative sequencei1 – 6161Missing in isoform 7. 2 PublicationsVSP_012387Add
    BLAST
    Alternative sequencei62 – 15291PPSPQ…QGLRR → MKRNTCDLLSRSKSASEETL HSSNEEEDPFRGMEPYLVRR LSCRNIQLPPLAFRQLEQAD LKSESENIQRPTSLPLKILP LIAITSAESSG in isoform 7. 2 PublicationsVSP_012388Add
    BLAST
    Alternative sequencei123 – 15230RTSYA…QGLRR → MAFVWDPLGATVPGPSTRAK SRLRFSKSYS in isoform 8. 1 PublicationVSP_012389Add
    BLAST
    Alternative sequencei131 – 15222GHRPG…QGLRR → MSIIMKPRSRSTSSLRTAEA VC in isoform 9. 2 PublicationsVSP_012390Add
    BLAST
    Alternative sequencei270 – 28314EEAYQ…ETLEE → GSWMELNPYTLLDM in isoform 12. 2 PublicationsVSP_023326Add
    BLAST
    Alternative sequencei270 – 27910EEAYQKLASE → GLYNGIIAFL in isoform N3. 1 PublicationVSP_012391
    Alternative sequencei280 – 809530Missing in isoform N3. 1 PublicationVSP_012392Add
    BLAST
    Alternative sequencei284 – 809526Missing in isoform 12. 2 PublicationsVSP_023327Add
    BLAST
    Alternative sequencei292 – 30615ETLQT…EMASN → MPEANYLLSVSWGYI in isoform 6. 2 PublicationsVSP_012393Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L20970 mRNA. Translation: AAA03592.1.
    L20969 mRNA. Translation: AAC00042.1.
    U02882 mRNA. Translation: AAC13745.1.
    U50157 mRNA. Translation: AAA97890.1.
    U50158 mRNA. Translation: AAA97891.1.
    U50159 mRNA. Translation: AAA97892.1.
    AF012074 mRNA. Translation: AAC00070.1.
    AF012073 mRNA. Translation: AAC00069.1.
    AJ250854 mRNA. Translation: CAC03757.1.
    AF536975 mRNA. Translation: AAN10117.1.
    AF536976 mRNA. Translation: AAN10118.1.
    AF536977 mRNA. Translation: AAN10119.1.
    AY388960 mRNA. Translation: AAQ90404.1.
    AY245866 mRNA. Translation: AAP75760.1.
    AY245867 mRNA. Translation: AAP75761.1.
    BT007398 mRNA. Translation: AAP36062.1.
    BC008390 mRNA. Translation: AAH08390.1.
    BC036319 mRNA. Translation: AAH36319.1.
    CCDSiCCDS47213.1. [Q08499-1]
    CCDS54858.1. [Q08499-2]
    CCDS54859.1. [Q08499-11]
    CCDS56369.1. [Q08499-8]
    CCDS56370.1. [Q08499-5]
    CCDS56371.1. [Q08499-10]
    CCDS56372.1. [Q08499-9]
    CCDS56373.1. [Q08499-6]
    PIRiI61358.
    RefSeqiNP_001098101.1. NM_001104631.1. [Q08499-1]
    NP_001159371.1. NM_001165899.1. [Q08499-11]
    NP_001184147.1. NM_001197218.1. [Q08499-6]
    NP_001184148.1. NM_001197219.1. [Q08499-9]
    NP_001184149.1. NM_001197220.1. [Q08499-10]
    NP_001184150.1. NM_001197221.1. [Q08499-5]
    NP_001184151.1. NM_001197222.1.
    NP_001184152.1. NM_001197223.1. [Q08499-8]
    NP_006194.2. NM_006203.4. [Q08499-2]
    XP_005248595.1. XM_005248538.2. [Q08499-2]
    XP_005248598.1. XM_005248541.2. [Q08499-5]
    UniGeneiHs.117545.

    Genome annotation databases

    GeneIDi5144.
    KEGGihsa:5144.
    UCSCiuc003jrs.2. human. [Q08499-8]
    uc003jrt.2. human. [Q08499-1]
    uc003jru.3. human. [Q08499-4]
    uc003jrv.2. human. [Q08499-10]
    uc003jrw.2. human. [Q08499-9]
    uc003jrz.3. human. [Q08499-6]
    uc003jsb.3. human. [Q08499-11]
    uc003jsc.3. human. [Q08499-12]

    Polymorphism databases

    DMDMi12644392.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) (PDE4D)

    Leiden Open Variation Database (LOVD)

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L20970 mRNA. Translation: AAA03592.1 .
    L20969 mRNA. Translation: AAC00042.1 .
    U02882 mRNA. Translation: AAC13745.1 .
    U50157 mRNA. Translation: AAA97890.1 .
    U50158 mRNA. Translation: AAA97891.1 .
    U50159 mRNA. Translation: AAA97892.1 .
    AF012074 mRNA. Translation: AAC00070.1 .
    AF012073 mRNA. Translation: AAC00069.1 .
    AJ250854 mRNA. Translation: CAC03757.1 .
    AF536975 mRNA. Translation: AAN10117.1 .
    AF536976 mRNA. Translation: AAN10118.1 .
    AF536977 mRNA. Translation: AAN10119.1 .
    AY388960 mRNA. Translation: AAQ90404.1 .
    AY245866 mRNA. Translation: AAP75760.1 .
    AY245867 mRNA. Translation: AAP75761.1 .
    BT007398 mRNA. Translation: AAP36062.1 .
    BC008390 mRNA. Translation: AAH08390.1 .
    BC036319 mRNA. Translation: AAH36319.1 .
    CCDSi CCDS47213.1. [Q08499-1 ]
    CCDS54858.1. [Q08499-2 ]
    CCDS54859.1. [Q08499-11 ]
    CCDS56369.1. [Q08499-8 ]
    CCDS56370.1. [Q08499-5 ]
    CCDS56371.1. [Q08499-10 ]
    CCDS56372.1. [Q08499-9 ]
    CCDS56373.1. [Q08499-6 ]
    PIRi I61358.
    RefSeqi NP_001098101.1. NM_001104631.1. [Q08499-1 ]
    NP_001159371.1. NM_001165899.1. [Q08499-11 ]
    NP_001184147.1. NM_001197218.1. [Q08499-6 ]
    NP_001184148.1. NM_001197219.1. [Q08499-9 ]
    NP_001184149.1. NM_001197220.1. [Q08499-10 ]
    NP_001184150.1. NM_001197221.1. [Q08499-5 ]
    NP_001184151.1. NM_001197222.1.
    NP_001184152.1. NM_001197223.1. [Q08499-8 ]
    NP_006194.2. NM_006203.4. [Q08499-2 ]
    XP_005248595.1. XM_005248538.2. [Q08499-2 ]
    XP_005248598.1. XM_005248541.2. [Q08499-5 ]
    UniGenei Hs.117545.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1E9K NMR - A - [» ]
    1MKD X-ray 2.90 A/B/C/D/E/F/G/H/I/J/K/L 388-715 [» ]
    1OYN X-ray 2.00 A/B/C/D 381-740 [» ]
    1PTW X-ray 2.30 A/B/C/D 381-740 [» ]
    1Q9M X-ray 2.30 A/B/C/D 381-740 [» ]
    1TB7 X-ray 1.63 A/B 388-715 [» ]
    1TBB X-ray 1.60 A/B 388-715 [» ]
    1XOM X-ray 1.55 A/B 388-715 [» ]
    1XON X-ray 1.72 A/B 388-715 [» ]
    1XOQ X-ray 1.83 A/B 388-715 [» ]
    1XOR X-ray 1.54 A/B 388-715 [» ]
    1Y2B X-ray 1.40 A/B 388-715 [» ]
    1Y2C X-ray 1.67 A/B 388-715 [» ]
    1Y2D X-ray 1.70 A/B 388-715 [» ]
    1Y2E X-ray 2.10 A/B 388-715 [» ]
    1Y2K X-ray 1.36 A/B 388-715 [» ]
    1ZKN X-ray 2.10 A/B/C/D 381-714 [» ]
    2FM0 X-ray 2.00 A/B/C/D 381-741 [» ]
    2FM5 X-ray 2.03 A/B/C/D 381-741 [» ]
    2PW3 X-ray 1.56 A/B 388-714 [» ]
    2QYN X-ray 1.57 A/B 388-715 [» ]
    3G4G X-ray 2.30 A/B/C/D 299-347 [» ]
    A/B/C/D 360-714 [» ]
    3G4I X-ray 1.90 A/B/C/D 380-753 [» ]
    3G4K X-ray 1.95 A/B/C/D 380-753 [» ]
    3G4L X-ray 2.50 A/B/C/D 380-753 [» ]
    3G58 X-ray 2.05 A/B/C/D 380-753 [» ]
    3IAD X-ray 2.65 A/B/C/D 326-339 [» ]
    A/B/C/D 380-714 [» ]
    3IAK X-ray 2.80 A 388-715 [» ]
    3K4S X-ray 2.05 A 388-715 [» ]
    3SL3 X-ray 2.10 A/B/C/D 381-741 [» ]
    3SL4 X-ray 1.90 A/B/C/D 381-741 [» ]
    3SL5 X-ray 2.65 A/B/C/D 381-714 [» ]
    3SL6 X-ray 2.44 A/B/C/D 381-741 [» ]
    3SL8 X-ray 2.60 A/B/C/D 381-741 [» ]
    3V9B X-ray 2.10 A/B/C/D 381-740 [» ]
    ProteinModelPortali Q08499.
    SMRi Q08499. Positions 327-739.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111170. 32 interactions.
    DIPi DIP-29709N.
    DIP-41115N.
    IntActi Q08499. 10 interactions.
    MINTi MINT-92262.

    Chemistry

    BindingDBi Q08499.
    ChEMBLi CHEMBL2111340.
    DrugBanki DB00131. Adenosine monophosphate.
    DB00651. Dyphylline.
    GuidetoPHARMACOLOGYi 1303.

    PTM databases

    PhosphoSitei Q08499.

    Polymorphism databases

    DMDMi 12644392.

    Proteomic databases

    MaxQBi Q08499.
    PaxDbi Q08499.
    PRIDEi Q08499.

    Protocols and materials databases

    DNASUi 5144.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 5144.
    KEGGi hsa:5144.
    UCSCi uc003jrs.2. human. [Q08499-8 ]
    uc003jrt.2. human. [Q08499-1 ]
    uc003jru.3. human. [Q08499-4 ]
    uc003jrv.2. human. [Q08499-10 ]
    uc003jrw.2. human. [Q08499-9 ]
    uc003jrz.3. human. [Q08499-6 ]
    uc003jsb.3. human. [Q08499-11 ]
    uc003jsc.3. human. [Q08499-12 ]

    Organism-specific databases

    CTDi 5144.
    GeneCardsi GC05M058302.
    HGNCi HGNC:8783. PDE4D.
    HPAi HPA045895.
    MIMi 600129. gene.
    614613. phenotype.
    neXtProti NX_Q08499.
    Orphaneti 950. Acrodysostosis.
    280651. Acrodysostosis with multiple hormone resistance.
    PharmGKBi PA33130.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG122287.
    HOVERGENi HBG108239.
    InParanoidi Q08499.
    KOi K01120.
    OMAi YENSSAD.
    OrthoDBi EOG7HQNBC.
    PhylomeDBi Q08499.
    TreeFami TF314638.

    Enzyme and pathway databases

    UniPathwayi UPA00762 ; UER00747 .
    BRENDAi 3.1.4.53. 2681.
    Reactomei REACT_15334. DARPP-32 events.
    REACT_19327. G alpha (s) signalling events.
    SignaLinki Q08499.

    Miscellaneous databases

    ChiTaRSi PDE4D. human.
    EvolutionaryTracei Q08499.
    GeneWikii PDE4D.
    GenomeRNAii 5144.
    NextBioi 19846.
    PROi Q08499.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q08499.
    Bgeei Q08499.
    Genevestigatori Q08499.

    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] (ISOFORMS 3 AND 4).
    2. "Identification of cyclic AMP-phosphodiesterase variants from the PDE4D gene expressed in human peripheral mononuclear cells."
      Nemoz G., Zhang R.B., Sette C., Conti M.
      FEBS Lett. 384:97-102(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4).
    3. "Isolation of a cDNA encoding a human rolipram-sensitive cyclic AMP phosphodiesterase (PDE IVD)."
      Baecker P.A., Obernolte R., Bach C., Yee C., Shelton E.R.
      Gene 138:253-256(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10).
      Tissue: Heart.
    4. "Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene."
      Bolger G.B., Erdogan S., Jones R.E., Loughney K., Scotland G., Hoffmann R., Wilkinson I., Farrell C., Houslay M.D.
      Biochem. J. 328:539-548(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 10), SEQUENCE REVISION (ISOFORM 1).
    5. "Phosphodiesterases 4D and 7A splice variants in the response of HUVEC cells to TNF-alpha1."
      Miro X., Casacuberta J.M., Gutierrez-Lopez M.D., Landazuri M.O., Puigdomenech P.
      Biochem. Biophys. Res. Commun. 274:415-421(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM N3), ALTERNATIVE SPLICING.
      Tissue: Umbilical vein endothelial cell.
    6. "Cloning and characterization of novel PDE4D isoforms PDE4D6 and PDE4D7."
      Wang D., Deng C., Bugaj-Gaweda B., Kwan M., Gunwaldsen C., Leonard C., Xin X., Hu Y., Unterbeck A., De Vivo M.
      Cell. Signal. 15:883-891(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6; 7; 8 AND 9), PHOSPHORYLATION, TISSUE SPECIFICITY.
    7. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 7 AND 9), INVOLVEMENT IN SUSCEPTIBILITY TO STROKE.
    8. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 12).
    9. "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] (ISOFORMS 6 AND 12).
      Tissue: Brain and Testis.
    10. "Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5."
      Bolger G.B., McCahill A., Yarwood S.J., Steele M.S., Warwicker J., Houslay M.D.
      BMC Biochem. 3:24-24(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GNB2L1.
    11. "The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with beta-arrestins."
      Bolger G.B., McCahill A., Huston E., Cheung Y.F., McSorley T., Baillie G.S., Houslay M.D.
      J. Biol. Chem. 278:49230-49238(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB2, SUBCELLULAR LOCATION.
    12. "The oligomerization state determines regulatory properties and inhibitor sensitivity of type 4 cAMP-specific phosphodiesterases."
      Richter W., Conti M.
      J. Biol. Chem. 279:30338-30348(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: HOMODIMERIZATION OF LONG ISOFORMS, ENZYME REGULATION BY ROLIPRAM AND PHOSPHATIDIC ACID, PHOSPHORYLATION AT SER-53 (ISOFORM 3).
    13. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    14. "Many hypotheses but no replication for the association between PDE4D and stroke."
      Rosand J., Bayley N., Rost N., de Bakker P.I.W.
      Nat. Genet. 38:1091-1092(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISCUSSION OF INVOLVEMENT IN STROKE.
    15. "Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors."
      Lee J.H., Richter W., Namkung W., Kim K.H., Kim E., Conti M., Lee M.G.
      J. Biol. Chem. 282:10414-10422(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SHANK2, TISSUE SPECIFICITY.
    16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Platelet.
    17. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59 AND SER-63 (ISOFORMS 12; 5 AND N3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    18. "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-387 BY PIAS4.
    19. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    20. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    21. "Crystal structure of phosphodiesterase 4D and inhibitor complex."
      Lee M.E., Markowitz J., Lee J.-O., Lee H.
      FEBS Lett. 530:53-58(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 388-715 IN COMPLEX WITH THE INHIBITOR ZARDAVERINE AND DIVALENT METAL IONS, MUTAGENESIS OF ASP-527 AND ARG-563.
    22. "The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis."
      Huai Q., Colicelli J., Ke H.
      Biochemistry 42:13220-13226(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 381-739 IN COMPLEX WITH CAMP AND DIVALENT METAL IONS.
    23. "Three-dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity."
      Huai Q., Wang H., Sun Y., Kim H.Y., Liu Y., Ke H.
      Structure 11:865-873(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 381-739 IN COMPLEX WITH INHIBITOR.
    24. "Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity."
      Huai Q., Liu Y., Francis S.H., Corbin J.D., Ke H.
      J. Biol. Chem. 279:13095-13101(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 381-714 IN COMPLEX WITH METAL IONS AND INHIBITOR.
    25. "Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram."
      Xu R.X., Rocque W.J., Lambert M.H., Vanderwall D.E., Luther M.A., Nolte R.T.
      J. Mol. Biol. 337:355-365(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 380-756 IN COMPLEX WITH AMP; METAL IONS AND THE INHIBITOR ROLIPRAM.
    26. Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 388-715 IN COMPLEX WITH AMP; METAL IONS AND THE INHIBITOR ROLIPRAM, FUNCTION, COFACTOR.
    27. Cited for: X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 388-715 IN COMPLEX WITH METAL IONS AND INHIBITORS, FUNCTION, COFACTOR.
    28. "A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design."
      Card G.L., Blasdel L., England B.P., Zhang C., Suzuki Y., Gillette S., Fong D., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.-H., Schlessinger J., Zhang K.Y.J.
      Nat. Biotechnol. 23:201-207(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.36 ANGSTROMS) OF 388-715 IN COMPLEX WITH METAL IONS AND INHIBITORS.
    29. "Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase."
      Huai Q., Sun Y., Wang H., Macdonald D., Aspiotis R., Robinson H., Huang Z., Ke H.
      J. Med. Chem. 49:1867-1873(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 381-741 IN COMPLEX WITH METAL IONS AND INHIBITORS.
    30. "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 (1.57 ANGSTROMS) OF 388-715 IN COMPLEX WITH METAL IONS AND THE INHIBITOR NVP.
    31. "1H NMR structural and functional characterisation of a cAMP-specific phosphodiesterase-4D5 (PDE4D5) N-terminal region peptide that disrupts PDE4D5 interaction with the signalling scaffold proteins, beta-arrestin and RACK1."
      Smith K.J., Baillie G.S., Hyde E.I., Li X., Houslay T.M., McCahill A., Dunlop A.J., Bolger G.B., Klussmann E., Adams D.R., Houslay M.D.
      Cell. Signal. 19:2612-2624(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF N-TERMINUS OF ISOFORM 5/N3/12, INTERACTION WITH GNB2L1.
    32. "The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10."
      Wang H., Robinson H., Ke H.
      J. Mol. Biol. 371:302-307(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 388-714 OF MUTANT ASN-503 IN COMPLEX WITH CAMP AND METAL IONS.
    33. Cited for: VARIANTS ACRDYS2 ALA-190; THR-225; SER-226 AND PRO-587.
    34. Cited for: VARIANTS ACRDYS2 GLU-228; ALA-590 AND ASP-673.
    35. Cited for: VARIANTS ACRDYS2 SER-227 AND ALA-590.
    36. Cited for: VARIANTS ACRDYS2 THR-225; THR-301; VAL-304; ALA-329 AND THR-678.

    Entry informationi

    Entry nameiPDE4D_HUMAN
    AccessioniPrimary (citable) accession number: Q08499
    Secondary accession number(s): O43433
    , Q13549, Q13550, Q13551, Q7Z2L8, Q8IV84, Q8IVA9, Q8IVD2, Q8IVD3, Q96HL4, Q9HCX7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: December 1, 2000
    Last modified: October 1, 2014
    This is version 160 of the entry and version 2 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 5
      Human chromosome 5: 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