Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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

    Pathwayi: 3',5'-cyclic AMP degradation

    This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
    Proteins known to be involved in this subpathway in this organism are:
    1. cAMP-specific 3',5'-cyclic phosphodiesterase 4C (PDE4C), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (PDE7A), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (PDE7B), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A)
    This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei433Proton donorBy similarity1
    Metal bindingi437Divalent metal cation 11
    Metal bindingi473Divalent metal cation 11
    Metal bindingi474Divalent metal cation 11
    Metal bindingi474Divalent metal cation 21
    Binding sitei474cAMPBy similarity1
    Metal bindingi591Divalent metal cation 11
    Binding sitei591cAMPBy similarity1
    Sitei594Binds AMP, but not cAMPBy similarity1
    Binding sitei642cAMPBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi433 – 437cAMPBy similarity5

    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

    BioCyciZFISH:HS00862-MONOMER.
    BRENDAi3.1.4.17. 2681.
    3.1.4.53. 2681.
    ReactomeiR-HSA-180024. DARPP-32 events.
    R-HSA-418555. 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
    Proteomesi
    • UP000005640 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

    DisGeNETi5141.
    OpenTargetsiENSG00000065989.
    PharmGKBiPA33128.

    Chemistry databases

    ChEMBLiCHEMBL254.
    DrugBankiDB05676. Apremilast.
    DB00201. 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.

    Polymorphism and mutation databases

    BioMutaiPDE4A.
    DMDMi116242706.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001988061 – 886cAMP-specific 3',5'-cyclic phosphodiesterase 4AAdd BLAST886

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei13PhosphoserineCombined sources1
    Modified residuei152Phosphoserine; by MAPKAPK2By similarity1
    Modified residuei157PhosphoserineBy similarity1
    Modified residuei165PhosphoserineCombined sources1
    Modified residuei209PhosphoserineCombined sources1
    Modified residuei346PhosphoserineCombined sources1
    Cross-linki358Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
    Modified residuei686Phosphoserine1 Publication1
    Modified residuei688Phosphoserine1 Publication1
    Isoform 2 (identifier: P27815-2)
    Modified residuei119Phosphoserine1 Publication1
    Isoform 7 (identifier: P27815-7)
    Modified residuei123Phosphoserine1 Publication1

    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.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei69 – 70Cleavage; by caspase-32

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiP27815.
    MaxQBiP27815.
    PaxDbiP27815.
    PeptideAtlasiP27815.
    PRIDEiP27815.

    PTM databases

    iPTMnetiP27815.
    PhosphoSitePlusiP27815.

    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

    BgeeiENSG00000065989.
    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. 8 interactors.
    IntActiP27815. 3 interactors.
    STRINGi9606.ENSP00000270474.

    Chemistry databases

    BindingDBiP27815.

    Structurei

    Secondary structure

    1886
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi362 – 368Combined sources7
    Helixi369 – 371Combined sources3
    Helixi379 – 385Combined sources7
    Turni386 – 388Combined sources3
    Helixi390 – 401Combined sources12
    Helixi404 – 407Combined sources4
    Helixi412 – 424Combined sources13
    Beta strandi430 – 434Combined sources5
    Helixi435 – 449Combined sources15
    Helixi452 – 454Combined sources3
    Turni455 – 457Combined sources3
    Helixi460 – 472Combined sources13
    Turni473 – 476Combined sources4
    Helixi482 – 487Combined sources6
    Helixi491 – 495Combined sources5
    Turni496 – 498Combined sources3
    Helixi501 – 512Combined sources12
    Helixi513 – 515Combined sources3
    Turni521 – 524Combined sources4
    Helixi527 – 542Combined sources16
    Helixi546 – 548Combined sources3
    Helixi549 – 561Combined sources13
    Beta strandi567 – 569Combined sources3
    Helixi576 – 591Combined sources16
    Helixi594 – 596Combined sources3
    Helixi599 – 622Combined sources24
    Turni633 – 635Combined sources3
    Helixi638 – 648Combined sources11
    Helixi650 – 660Combined sources11
    Turni661 – 665Combined sources5
    Helixi666 – 682Combined sources17

    3D structure databases

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

    Miscellaneous databases

    EvolutionaryTraceiP27815.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni330 – 723CatalyticAdd BLAST394

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG3689. Eukaryota.
    ENOG410XRI7. LUCA.
    GeneTreeiENSGT00760000118889.
    HOVERGENiHBG108239.
    KOiK13293.
    OMAiPSPTMKD.
    OrthoDBiEOG091G06CD.
    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

    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

    Show »
    Length:864
    Mass (Da):95,571
    Checksum:i1AB6019FC85E37E4
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_059544736A → E.2 PublicationsCorresponds to variant rs1051738dbSNPEnsembl.1
    Natural variantiVAR_059545808H → Y.Corresponds to variant rs2230190dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0045591 – 367MEPPT…ELLAQ → MVLPSDQGFKLLGNVLQGPE PYRLLTSGLRLHQ in isoform 5. 2 PublicationsAdd BLAST367
    Alternative sequenceiVSP_0045581 – 261MEPPT…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 4. 2 PublicationsAdd BLAST261
    Alternative sequenceiVSP_0045571 – 209MEPPT…SNKRS → MCPFPVTTV in isoform 3. 3 PublicationsAdd BLAST209
    Alternative sequenceiVSP_0045561 – 107MEPPT…GSSRR → MARPRGLGRIPELQLVAFPV AVAAEDEAFLPEPLAPRAPR RPRSPPSSPVFFASPSPTFR RRLRLLRSCQDLGRQAWAGA G in isoform 2. 2 PublicationsAdd BLAST107
    Alternative sequenceiVSP_0381851 – 107MEPPT…GSSRR → MRSGAAPRARPRPPALALPP TGPESLTHFPFSDEDTRRHP PGRSVS in isoform 6. 1 PublicationAdd BLAST107
    Alternative sequenceiVSP_0381861 – 107MEPPT…GSSRR → MKRSRSALSVAGTGDERSRE TPESDRANMLGADLRRPRRR LSSGPGLGWAQPEPSDPGVP LPPRPTTLPLLIPPRISITR AENDS in isoform 7. 1 PublicationAdd BLAST107
    Alternative sequenceiVSP_004560644 – 657GFIDY…LWETW → QARGIDGRAQGGFY in isoform 5. 2 PublicationsAdd BLAST14
    Alternative sequenceiVSP_004561658 – 886Missing in isoform 5. 2 PublicationsAdd BLAST229

    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]
    XP_011526356.1. XM_011528054.1. [P27815-7]
    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.3. human. [P27815-1]

    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]
    XP_011526356.1. XM_011528054.1. [P27815-7]
    UniGeneiHs.89901.

    3D structure databases

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

    Protein-protein interaction databases

    BioGridi111167. 8 interactors.
    IntActiP27815. 3 interactors.
    STRINGi9606.ENSP00000270474.

    Chemistry databases

    BindingDBiP27815.
    ChEMBLiCHEMBL254.
    DrugBankiDB05676. Apremilast.
    DB00201. 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

    iPTMnetiP27815.
    PhosphoSitePlusiP27815.

    Polymorphism and mutation databases

    BioMutaiPDE4A.
    DMDMi116242706.

    Proteomic databases

    EPDiP27815.
    MaxQBiP27815.
    PaxDbiP27815.
    PeptideAtlasiP27815.
    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.3. human. [P27815-1]

    Organism-specific databases

    CTDi5141.
    DisGeNETi5141.
    GeneCardsiPDE4A.
    HGNCiHGNC:8780. PDE4A.
    HPAiCAB017632.
    HPA043310.
    MIMi600126. gene.
    neXtProtiNX_P27815.
    OpenTargetsiENSG00000065989.
    PharmGKBiPA33128.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3689. Eukaryota.
    ENOG410XRI7. LUCA.
    GeneTreeiENSGT00760000118889.
    HOVERGENiHBG108239.
    KOiK13293.
    OMAiPSPTMKD.
    OrthoDBiEOG091G06CD.
    PhylomeDBiP27815.
    TreeFamiTF314638.

    Enzyme and pathway databases

    UniPathwayiUPA00762; UER00747.
    BioCyciZFISH:HS00862-MONOMER.
    BRENDAi3.1.4.17. 2681.
    3.1.4.53. 2681.
    ReactomeiR-HSA-180024. DARPP-32 events.
    R-HSA-418555. G alpha (s) signalling events.

    Miscellaneous databases

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

    Gene expression databases

    BgeeiENSG00000065989.
    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...

    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: November 30, 2016
    This is version 162 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

    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 one 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.