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Protein

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

Gene

Pde4a

Organism
Rattus norvegicus (Rat)
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.

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 3',5'-cyclic phosphodiesterase 7A (Pde7a), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (Pde4b), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (Pde4a), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (Pde4c)
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 sitei419Proton donorBy similarity1
Metal bindingi423Divalent metal cation 1By similarity1
Metal bindingi459Divalent metal cation 1By similarity1
Metal bindingi460Divalent metal cation 1By similarity1
Metal bindingi460Divalent metal cation 2By similarity1
Binding sitei460cAMPBy similarity1
Metal bindingi577Divalent metal cation 1By similarity1
Binding sitei577cAMPBy similarity1
Sitei580Binds AMP, but not cAMPBy similarity1
Binding sitei628cAMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi419 – 423cAMPBy similarity5

GO - Molecular functioni

  • 3',5'-cyclic-AMP phosphodiesterase activity Source: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cAMP catabolic process Source: UniProtKB
  • response to drug Source: RGD
  • signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.53. 5301.
UniPathwayiUPA00762; UER00747.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC:3.1.4.53)
Alternative name(s):
DPDE2
Gene namesi
Name:Pde4a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3279. Pde4a.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • nucleus Source: RGD
  • perinuclear region of cytoplasm Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi147S → A: Abolishes phosphorylation by MAPKAPK2. 1 Publication1
Mutagenesisi161S → A: Does not affect phosphorylation by MAPKAPK2. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2094267.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988081 – 844cAMP-specific 3',5'-cyclic phosphodiesterase 4AAdd BLAST844

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphoserineBy similarity1
Modified residuei147Phosphoserine; by MAPKAPK2Combined sources1 Publication1
Modified residuei152PhosphoserineCombined sources1
Modified residuei160PhosphoserineBy similarity1
Modified residuei204PhosphoserineBy similarity1
Modified residuei333PhosphoserineBy similarity1
Cross-linki344Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei672PhosphoserineCombined sources1
Modified residuei674PhosphoserineCombined sources1

Post-translational modificationi

Proteolytically cleaved by caspase-3.By similarity
Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei69 – 70Cleavage; by caspase-3By similarity2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP54748.
PRIDEiP54748.

PTM databases

iPTMnetiP54748.
PhosphoSitePlusiP54748.

Miscellaneous databases

PMAP-CutDBP54748.

Expressioni

Tissue specificityi

Isoform 2 is testis specific.

Interactioni

Subunit structurei

Interacts with LYN and ARRB2.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000057815.

Structurei

Secondary structure

1844
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 9Combined sources7
Helixi16 – 19Combined sources4
Helixi20 – 23Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LOINMR-A1-25[»]
ProteinModelPortaliP54748.
SMRiP54748.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54748.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni317 – 710CatalyticBy similarityAdd BLAST394

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiP54748.
KOiK13293.
PhylomeDBiP54748.

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 (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P54748-1) [UniParc]FASTAAdd to basket

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
MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYPD
60 70 80 90 100
SAERSETERS PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS
110 120 130 140 150
RRLEAENGPT PSPGRSPLDS QASPGLVLHA GATTSQRRES FLYRSDSDYD
160 170 180 190 200
MSPKAVSRSS SVASEAHAED LIVTPFAQVL ASLRSVRSNF SLLTNVPIPS
210 220 230 240 250
NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL ETMQTYRSVS
260 270 280 290 300
EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ NEVEIPSPTP
310 320 330 340 350
RQRAFQQPPP SVLRQSQPMS QITGLKKLVH TGSLNTNVPR FGVKTDQEDL
360 370 380 390 400
LAQELENLSK WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT
410 420 430 440 450
MMMYMLTLED HYHADVAYHN SLHAADVLQS THVLLATPAL DAVFTDLEIL
460 470 480 490 500
AALFAAAIHD VDHPGVSNQF LINTNSELAL MYNDESVLEN HHLAVGFKLL
510 520 530 540 550
QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA DLKTMVETKK
560 570 580 590 600
VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF
610 620 630 640 650
QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD
660 670 680 690 700
AQDILDTLED NRDWYHSAIR QSPSPPLEEE PGGLGHPSLP DKFQFELTLE
710 720 730 740 750
EEEEEDSLEV PGLPTTEETF LAAEDARAQA VDWSKVKGPS TTVVEVAERL
760 770 780 790 800
KQETASAYGA PQESMEAVGC SFSPGTPILP DVRTLSSSEE APGLLGLPST
810 820 830 840
AAEVEAPRDH LAATRACSAC SGTSGDNSAI ISAPGRWGSG GDPA
Length:844
Mass (Da):93,439
Last modified:October 1, 1996 - v1
Checksum:i1A5F5101E4DBF1B6
GO
Isoform 2 (identifier: P54748-2) [UniParc]FASTAAdd to basket
Also known as: PDE4A8

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: MEPPAAPSER...TGTGGGSSRR → MPSRKRLTLPRIFIVRKNGNS

Show »
Length:763
Mass (Da):84,647
Checksum:i9E1E33481260566A
GO
Isoform 3 (identifier: P54748-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-234: Missing.
     235-256: WCLEQLETMQTYRSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ

Show »
Length:610
Mass (Da):68,161
Checksum:iFE439ACE95E1D1AC
GO
Isoform 4 (identifier: P54748-4) [UniParc]FASTAAdd to basket
Also known as: Medium

The sequence of this isoform differs from the canonical sequence as follows:
     1-259: Missing.

Show »
Length:585
Mass (Da):65,059
Checksum:i3A188A286A28E174
GO
Isoform 5 (identifier: P54748-5) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-318: Missing.
     354-386: Missing.

Show »
Length:493
Mass (Da):54,526
Checksum:i53735B34F1122F97
GO
Isoform 6 (identifier: P54748-6) [UniParc]FASTAAdd to basket
Also known as: PDE4A10

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: MEPPAAPSER...TGTGGGSSRR → ALPLGPESLTHFSFSEEDTLRHPPGRCVS

Note: Incomplete sequence.
Show »
Length:771
Mass (Da):85,344
Checksum:iC1DB345199B5D59C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti130A → R in AAF14352 (PubMed:11306681).Curated1
Sequence conflicti465 – 466GV → AL in AAA41848 (PubMed:2546153).Curated2
Sequence conflicti465 – 466GV → AL in AAA41823 (PubMed:2546153).Curated2
Sequence conflicti603 – 604GD → AH in AAA41848 (PubMed:2546153).Curated2
Sequence conflicti603 – 604GD → AH in AAA41823 (PubMed:2546153).Curated2
Sequence conflicti833A → T in AAC37699 (PubMed:2542942).Curated1
Sequence conflicti833A → T in AAA41101 (PubMed:2542942).Curated1
Sequence conflicti833A → T in AAA41102 (PubMed:2542942).Curated1
Sequence conflicti833A → T in AAF14352 (PubMed:11306681).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045691 – 318Missing in isoform 5. 2 PublicationsAdd BLAST318
Alternative sequenceiVSP_0045681 – 259Missing in isoform 4. 2 PublicationsAdd BLAST259
Alternative sequenceiVSP_0045661 – 234Missing in isoform 3. 2 PublicationsAdd BLAST234
Alternative sequenceiVSP_0045651 – 102MEPPA…GSSRR → MPSRKRLTLPRIFIVRKNGN S in isoform 2. 1 PublicationAdd BLAST102
Alternative sequenceiVSP_0381871 – 102MEPPA…GSSRR → ALPLGPESLTHFSFSEEDTL RHPPGRCVS in isoform 6. CuratedAdd BLAST102
Alternative sequenceiVSP_004567235 – 256WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 3. 2 PublicationsAdd BLAST22
Alternative sequenceiVSP_004570354 – 386Missing in isoform 5. 2 PublicationsAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27057 mRNA. Translation: AAC27098.1.
L36467 mRNA. Translation: AAB00357.1.
L27062 mRNA. Translation: AAA56859.1.
M25348 mRNA. Translation: AAA41848.1.
M28411 mRNA. Translation: AAA41823.1.
M26715 mRNA. Translation: AAC37699.1.
M26716 mRNA. Translation: AAA41101.1.
M26717 mRNA. Translation: AAA41102.1.
AF110461 mRNA. Translation: AAF14352.2.
PIRiI53865.
I67946.
RefSeqiNP_037233.3. NM_013101.3. [P54748-1]
UniGeneiRn.91357.

Genome annotation databases

GeneIDi25638.
KEGGirno:25638.
UCSCiRGD:3279. rat. [P54748-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27057 mRNA. Translation: AAC27098.1.
L36467 mRNA. Translation: AAB00357.1.
L27062 mRNA. Translation: AAA56859.1.
M25348 mRNA. Translation: AAA41848.1.
M28411 mRNA. Translation: AAA41823.1.
M26715 mRNA. Translation: AAC37699.1.
M26716 mRNA. Translation: AAA41101.1.
M26717 mRNA. Translation: AAA41102.1.
AF110461 mRNA. Translation: AAF14352.2.
PIRiI53865.
I67946.
RefSeqiNP_037233.3. NM_013101.3. [P54748-1]
UniGeneiRn.91357.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LOINMR-A1-25[»]
ProteinModelPortaliP54748.
SMRiP54748.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000057815.

Chemistry databases

ChEMBLiCHEMBL2094267.

PTM databases

iPTMnetiP54748.
PhosphoSitePlusiP54748.

Proteomic databases

PaxDbiP54748.
PRIDEiP54748.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25638.
KEGGirno:25638.
UCSCiRGD:3279. rat. [P54748-1]

Organism-specific databases

CTDi5141.
RGDi3279. Pde4a.

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
HOGENOMiHOG000236297.
HOVERGENiHBG108239.
InParanoidiP54748.
KOiK13293.
PhylomeDBiP54748.

Enzyme and pathway databases

UniPathwayiUPA00762; UER00747.
BRENDAi3.1.4.53. 5301.

Miscellaneous databases

EvolutionaryTraceiP54748.
PMAP-CutDBP54748.
PROiP54748.

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_RAT
AccessioniPrimary (citable) accession number: P54748
Secondary accession number(s): P14645, Q9EQR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.