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P27815

- PDE4A_HUMAN

UniProt

P27815 - PDE4A_HUMAN

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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

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

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

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
Complete GO annotation...

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. cell projection Source: UniProtKB-KW
  2. cytosol Source: Reactome
  3. membrane Source: ProtInc
  4. perinuclear region of cytoplasm Source: UniProtKB
  5. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

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

BgeeiP27815.
CleanExiHS_PDE4A.
ExpressionAtlasiP27815. baseline and differential.
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 – 3687Combined sources
Helixi369 – 3713Combined sources
Helixi379 – 3857Combined sources
Turni386 – 3883Combined sources
Helixi390 – 40112Combined sources
Helixi404 – 4074Combined sources
Helixi412 – 42413Combined sources
Beta strandi430 – 4345Combined sources
Helixi435 – 44915Combined sources
Helixi452 – 4543Combined sources
Turni455 – 4573Combined sources
Helixi460 – 47213Combined sources
Turni473 – 4764Combined sources
Helixi482 – 4876Combined sources
Helixi491 – 4955Combined sources
Turni496 – 4983Combined sources
Helixi501 – 51212Combined sources
Helixi513 – 5153Combined sources
Turni521 – 5244Combined sources
Helixi527 – 54216Combined sources
Helixi546 – 5483Combined sources
Helixi549 – 56113Combined sources
Beta strandi567 – 5693Combined sources
Helixi576 – 59116Combined sources
Helixi594 – 5963Combined sources
Helixi599 – 62224Combined sources
Turni633 – 6353Combined sources
Helixi638 – 64811Combined sources
Helixi650 – 66011Combined sources
Turni661 – 6655Combined sources
Helixi666 – 68217Combined sources

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP27815.

Family & Domainsi

Region

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG122287.
GeneTreeiENSGT00760000118889.
HOVERGENiHBG108239.
KOiK13293.
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

        10         20         30         40         50
MEPPTVPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD
60 70 80 90 100
SAERAERERQ PHRPIERADA MDTSDRPGLR TTRMSWPSSF HGTGTGSGGA
110 120 130 140 150
GGGSSRRFEA ENGPTPSPGR SPLDSQASPG LVLHAGAATS QRRESFLYRS
160 170 180 190 200
DSDYDMSPKT MSRNSSVTSE AHAEDLIVTP FAQVLASLRS VRSNFSLLTN
210 220 230 240 250
VPVPSNKRSP LGGPTPVCKA TLSEETCQQL ARETLEELDW CLEQLETMQT
260 270 280 290 300
YRSVSEMASH KFKRMLNREL THLSEMSRSG NQVSEYISTT FLDKQNEVEI
310 320 330 340 350
PSPTMKEREK QQAPRPRPSQ PPPPPVPHLQ PMSQITGLKK LMHSNSLNNS
360 370 380 390 400
NIPRFGVKTD QEELLAQELE NLNKWGLNIF CVSDYAGGRS LTCIMYMIFQ
410 420 430 440 450
ERDLLKKFRI PVDTMVTYML TLEDHYHADV AYHNSLHAAD VLQSTHVLLA
460 470 480 490 500
TPALDAVFTD LEILAALFAA AIHDVDHPGV SNQFLINTNS ELALMYNDES
510 520 530 540 550
VLENHHLAVG FKLLQEDNCD IFQNLSKRQR QSLRKMVIDM VLATDMSKHM
560 570 580 590 600
TLLADLKTMV ETKKVTSSGV LLLDNYSDRI QVLRNMVHCA DLSNPTKPLE
610 620 630 640 650
LYRQWTDRIM AEFFQQGDRE RERGMEISPM CDKHTASVEK SQVGFIDYIV
660 670 680 690 700
HPLWETWADL VHPDAQEILD TLEDNRDWYY SAIRQSPSPP PEEESRGPGH
710 720 730 740 750
PPLPDKFQFE LTLEEEEEEE ISMAQIPCTA QEALTAQGLS GVEEALDATI
760 770 780 790 800
AWEASPAQES LEVMAQEASL EAELEAVYLT QQAQSTGSAP VAPDEFSSRE
810 820 830 840 850
EFVVAVSHSS PSALALQSPL LPAWRTLSVS EHAPGLPGLP STAAEVEAQR
860 870 880
EHQAAKRACS ACAGTFGEDT SALPAPGGGG SGGDPT
Length:886
Mass (Da):98,143
Last modified:October 17, 2006 - v3
Checksum:i92BB9B98BED711E7
GO
Isoform 2 (identifier: P27815-2) [UniParc]FASTAAdd to Basket

Also known as: TM3, PDE4A11

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

Note: Contains a phosphoserine at position 119.

Show »
Length:860
Mass (Da):95,236
Checksum:i6A4FC32E8AF7559D
GO
Isoform 3 (identifier: P27815-3) [UniParc]FASTAAdd to Basket

Also known as: PDE4A7, PDE4A6

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

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

Also known as: PDE4A1, RD1

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

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

Also known as: PDE4A8A, 2EL

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

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Probably represents a non-functional splice isoform.

Show »
Length:323
Mass (Da):36,706
Checksum:i14D0EEF3D6CD4BEE
GO
Isoform 6 (identifier: P27815-6) [UniParc]FASTAAdd to Basket

Also known as: PDE4A10

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

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

Also known as: PDE4A8

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

Note: Contains a phosphoserine at position 123.

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

Natural variant

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

Alternative sequence

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

Sequence databases

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

Genome annotation databases

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

Polymorphism databases

DMDMi116242706.

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 .
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:
PDBei
RCSB PDBi
PDBji
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 CHEMBL2363066.
DrugBanki 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.
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 . [P27815-1 ]
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.
GeneTreei ENSGT00760000118889.
HOVERGENi HBG108239.
KOi K13293.
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

Bgeei P27815.
CleanExi HS_PDE4A.
ExpressionAtlasi P27815. baseline and differential.
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.
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Publicationsi

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  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: November 26, 2014
This is version 142 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