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Protein

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

Gene

Pde4d

Organism
Mus musculus (Mouse)
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.By similarity

Catalytic activityi

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

Cofactori

a divalent metal cationBy similarityNote: 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.By similarity

Enzyme regulationi

Inhibited by rolipram. Activated by phosphatidic acid (By similarity).By similarity

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. High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (Pde8b), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (Pde4a), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (Pde4c), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (Pde8a), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (Pde7a), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (Pde7b)
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 sitei401Proton donorBy similarity1
Metal bindingi405Divalent metal cation 1By similarity1
Metal bindingi441Divalent metal cation 1By similarity1
Metal bindingi442Divalent metal cation 1By similarity1
Metal bindingi442Divalent metal cation 2By similarity1
Binding sitei442cAMPBy similarity1
Metal bindingi559Divalent metal cation 1By similarity1
Sitei562Binds AMP, but not cAMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi401 – 405cAMPBy similarity5

GO - Molecular functioni

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

GO - Biological processi

  • aging Source: MGI
  • cAMP catabolic process Source: BHF-UCL
  • cellular response to epinephrine stimulus Source: BHF-UCL
  • cellular response to lipopolysaccharide Source: MGI
  • establishment of endothelial barrier Source: UniProtKB
  • leukocyte migration Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of heart contraction Source: BHF-UCL
  • negative regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  • negative regulation of relaxation of cardiac muscle Source: BHF-UCL
  • neutrophil chemotaxis Source: MGI
  • positive regulation of interferon-gamma production Source: Ensembl
  • positive regulation of interleukin-2 production Source: Ensembl
  • positive regulation of interleukin-5 production Source: Ensembl
  • regulation of cAMP metabolic process Source: CACAO
  • regulation of cardiac muscle cell contraction Source: BHF-UCL
  • regulation of cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
  • regulation of heart rate Source: BHF-UCL
  • regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
  • regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
  • smooth muscle contraction Source: MGI
  • T cell receptor signaling pathway Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.53. 3474.
ReactomeiR-MMU-180024. DARPP-32 events.
R-MMU-418555. G alpha (s) signalling events.
UniPathwayiUPA00762; UER00747.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4D (EC:3.1.4.53)
Alternative name(s):
DPDE3
Gene namesi
Name:Pde4d
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:99555. Pde4d.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • calcium channel complex Source: BHF-UCL
  • centrosome Source: MGI
  • cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2111373.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988151 – 747cAMP-specific 3',5'-cyclic phosphodiesterase 4DAdd BLAST747

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei238PhosphoserineBy similarity1
Modified residuei240PhosphoserineBy similarity1
Modified residuei287PhosphoserineBy similarity1
Modified residuei314PhosphoserineBy similarity1
Cross-linki326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ01063.
PaxDbiQ01063.
PRIDEiQ01063.

PTM databases

iPTMnetiQ01063.
PhosphoSitePlusiQ01063.

Expressioni

Tissue specificityi

Expressed in brain (at protein level). Isoform 7 is detected in heart, brain, lung, kidney and testis.2 Publications

Inductioni

Up-regulated by cAMP and follicle-stimulating hormone.By similarity

Gene expression databases

BgeeiENSMUSG00000021699.
CleanExiMM_PDE4D.
ExpressionAtlasiQ01063. baseline and differential.

Interactioni

Subunit structurei

Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Binds ARRB2. Interacts with PDE4DIP (By similarity). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Adrb1P349713EBI-7764239,EBI-7764182

GO - Molecular functioni

  • ATPase binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi232023. 2 interactors.
DIPiDIP-29706N.
IntActiQ01063. 2 interactors.
STRINGi10090.ENSMUSP00000113488.

Structurei

3D structure databases

ProteinModelPortaliQ01063.
SMRiQ01063.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiQ01063.
KOiK13293.
OMAiPLDPMAS.
PhylomeDBiQ01063.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 7 (identifier: Q01063-1) [UniParc]FASTAAdd to basket
Also known as: PDE4D7

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
MERDTCDVLS RSKSASEETL HSCNEEEDPF RGMEPYLVRR LSSRSIQLPP
60 70 80 90 100
LAFRQLEQAD LRSESENIPR PTSLPLKILP LIAVTSADSS GFDVDNGTSA
110 120 130 140 150
GRSPLDPMTS PGSGLILQAN FVHSQRRESF LYRSDSDYDL SPKSMSRNSS
160 170 180 190 200
IASDIHGDDL IVTPFAQVLA SLRTVRNNFA ALTNLQDRAP SKRSPMCNQP
210 220 230 240 250
SINKATITEE AYQKLASETL EELDWCLDQL ETLQTRHSVS EMASNKFKRM
260 270 280 290 300
LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTQ KEKEKKKRPM
310 320 330 340 350
SQISGVKKLM HSSSLTNSCI PRFGVKTEQE DVLAKELEDV NKWGLHVFRI
360 370 380 390 400
AELSGNRPLT VIMHTIFQER DLLKTFKIPV DTLITYLMTL EDHYHADVAY
410 420 430 440 450
HNNIHAADVV QSTHVLLSTP ALEAVFTDLE ILAAIFASAI HDVDHPGVSN
460 470 480 490 500
QFLINTNSEL ALMYNDSSVL ENHHLAVGFK LLQEENCDIF QNLTKKQRQS
510 520 530 540 550
LRKMVIDIVL ATDMSKHMNL LADLKTMVET KKVTSSGVLL LDNYSDRIQV
560 570 580 590 600
LQNMVHCADL SNPTKPLQLY RQWTDRIMEE FFRQGDRERE RGMEISPMCD
610 620 630 640 650
KHNASVEKSQ VGFIDYIVHP LWETWADLVH PDAQDILDTL EDNREWYQST
660 670 680 690 700
IPQSPSPAPD DQEEGRQGQT EKFQFELTLE EDCESDTEKD SGSQVEEDTS
710 720 730 740
CSDSKTLCTQ DSESTEIPLD EQVEEEAVAE EESQPETCVP DDCCPDT
Length:747
Mass (Da):84,563
Last modified:January 4, 2005 - v2
Checksum:i68402163664B3676
GO
Isoform 9 (identifier: Q01063-2) [UniParc]FASTAAdd to basket
Also known as: PDE4D9

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.
     70-91: RPTSLPLKILPLIAVTSADSSG → MSIIMKPRSRSTSSLRTTEAVC

Show »
Length:678
Mass (Da):76,817
Checksum:i51D44F3467C9B71A
GO
Isoform 3 (identifier: Q01063-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: Missing.
     164-208: PFAQVLASLR...QPSINKATIT → MKEQPSCAGT...TESSFPCLFA

Show »
Length:584
Mass (Da):66,394
Checksum:iCEDFA3A57387798E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti403 – 404NI → SR in AAA37368 (PubMed:1326532).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0123941 – 163Missing in isoform 3. 1 PublicationAdd BLAST163
Alternative sequenceiVSP_0123951 – 69Missing in isoform 9. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_01239670 – 91RPTSL…ADSSG → MSIIMKPRSRSTSSLRTTEA VC in isoform 9. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_012397164 – 208PFAQV…KATIT → MKEQPSCAGTGHPSMAGYGR MAPFELAGGPVKRLRTESSF PCLFA in isoform 3. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF536978 mRNA. Translation: AAN10120.1.
AY388962 mRNA. Translation: AAQ90406.1.
AK081466 mRNA. Translation: BAC38226.1.
CT025605, AC161585, AC163650 Genomic DNA. Translation: CAQ51656.1.
M94541 mRNA. Translation: AAA37368.1. Different termination.
CCDSiCCDS49359.1. [Q01063-1]
RefSeqiNP_035186.1. NM_011056.3. [Q01063-1]
XP_006517710.1. XM_006517647.2. [Q01063-2]
UniGeneiMm.434429.

Genome annotation databases

EnsembliENSMUST00000074103; ENSMUSP00000073742; ENSMUSG00000021699. [Q01063-2]
ENSMUST00000120664; ENSMUSP00000113024; ENSMUSG00000021699. [Q01063-3]
ENSMUST00000122041; ENSMUSP00000113488; ENSMUSG00000021699. [Q01063-1]
ENSMUST00000177907; ENSMUSP00000136485; ENSMUSG00000021699. [Q01063-1]
GeneIDi238871.
KEGGimmu:238871.
UCSCiuc007rvg.2. mouse. [Q01063-1]
uc007rvj.2. mouse. [Q01063-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF536978 mRNA. Translation: AAN10120.1.
AY388962 mRNA. Translation: AAQ90406.1.
AK081466 mRNA. Translation: BAC38226.1.
CT025605, AC161585, AC163650 Genomic DNA. Translation: CAQ51656.1.
M94541 mRNA. Translation: AAA37368.1. Different termination.
CCDSiCCDS49359.1. [Q01063-1]
RefSeqiNP_035186.1. NM_011056.3. [Q01063-1]
XP_006517710.1. XM_006517647.2. [Q01063-2]
UniGeneiMm.434429.

3D structure databases

ProteinModelPortaliQ01063.
SMRiQ01063.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi232023. 2 interactors.
DIPiDIP-29706N.
IntActiQ01063. 2 interactors.
STRINGi10090.ENSMUSP00000113488.

Chemistry databases

ChEMBLiCHEMBL2111373.

PTM databases

iPTMnetiQ01063.
PhosphoSitePlusiQ01063.

Proteomic databases

MaxQBiQ01063.
PaxDbiQ01063.
PRIDEiQ01063.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000074103; ENSMUSP00000073742; ENSMUSG00000021699. [Q01063-2]
ENSMUST00000120664; ENSMUSP00000113024; ENSMUSG00000021699. [Q01063-3]
ENSMUST00000122041; ENSMUSP00000113488; ENSMUSG00000021699. [Q01063-1]
ENSMUST00000177907; ENSMUSP00000136485; ENSMUSG00000021699. [Q01063-1]
GeneIDi238871.
KEGGimmu:238871.
UCSCiuc007rvg.2. mouse. [Q01063-1]
uc007rvj.2. mouse. [Q01063-2]

Organism-specific databases

CTDi5144.
MGIiMGI:99555. Pde4d.

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiQ01063.
KOiK13293.
OMAiPLDPMAS.
PhylomeDBiQ01063.

Enzyme and pathway databases

UniPathwayiUPA00762; UER00747.
BRENDAi3.1.4.53. 3474.
ReactomeiR-MMU-180024. DARPP-32 events.
R-MMU-418555. G alpha (s) signalling events.

Miscellaneous databases

PROiQ01063.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021699.
CleanExiMM_PDE4D.
ExpressionAtlasiQ01063. baseline and differential.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDE4D_MOUSE
AccessioniPrimary (citable) accession number: Q01063
Secondary accession number(s): B2KF58
, Q6TRH9, Q8C4Q7, Q8CG05
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 4, 2005
Last modified: November 2, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.