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Reviewed, UniProtKB/Swiss-Prot P14270 (PDE4D_RAT)

Last modified June 16, 2009. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4D
    EC=3.1.4.17
Alternative name(s):
    DPDE3
Gene names
Name: Pde4d
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length803 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Regulates the levels of cAMP in the cell.

Catalytic activity

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

Cofactor

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 regulation

Inhibited by rolipram. Activated by phosphatidic acid By similarity.

Pathway

Purine metabolism; cAMP degradation; AMP from cAMP: step 1/1.

Subunit structure

Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Binds ARRB2. Isoform 1 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9 By similarity. Interacts with PDE4DIP.

Subcellular location

Cytoplasm. Membrane. Cytoplasmcytoskeleton. Centrosome. Note: Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome. Ref.11 Ref.13

Induction

Up-regulated by cAMP and follicle-stimulating hormone. Ref.1

Post-translational modification

Isoform 1 is rapidly activated by PKA through phosphorylation.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]
Isoform 5 (identifier: P14270-5)

Also known as: PDE4D4;

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.
Isoform 1 (identifier: P14270-1)

Also known as: PDE4D3; PDE3.3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-131: Missing.
     132-147: KKSRMSWPSSFQGLRR → MMHVNTFPFRRHSWIC
Isoform 2 (identifier: P14270-2)

Also known as: PDE3.1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-264: MEAEGSSVPA...QPSINKATIT → MKEQPSCAGT...TESPFPCLFA
Isoform 3 (identifier: P14270-3)

Also known as: PDE3.2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-297: Missing.
Isoform 4 (identifier: P14270-4)

Also known as: PDE4D7;

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.
     57-147: LPPPPPPSPQ...WPSSFQGLRR → MERNTCDVLS...IAVTSADSTG
Isoform 6 (identifier: P14270-6)

Also known as: PDE4D9;

The sequence of this isoform differs from the canonical sequence as follows:
     1-125: Missing.
     126-147: GHRPGLKKSRMSWPSSFQGLRR → MSIIMKPRSRSTSSLRTTEAVC
Isoform 7 (identifier: P14270-7)

Also known as: PDE4D6;

The sequence of this isoform differs from the canonical sequence as follows:
     1-286: Missing.
     287-301: ETLQTRHSVSEMASN → MPEANYLLSVSWGYI

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 803803cAMP-specific 3',5'-cyclic phosphodiesterase 4D
PRO_0000198816

Sites

Metal binding4611Divalent metal cation 1 By similarity
Metal binding4971Divalent metal cation 1 By similarity
Metal binding4981Divalent metal cation 1 By similarity
Metal binding4981Divalent metal cation 2 By similarity
Metal binding6151Divalent metal cation 1 By similarity
Binding site4571cAMP By similarity
Binding site6151cAMP By similarity
Binding site6181cAMP By similarity
Binding site6661cAMP By similarity

Amino acid modifications

Modified residue181Phosphoserine By similarity
Modified residue201Phosphoserine By similarity
Modified residue1921Phosphoserine By similarity
Modified residue1971Phosphoserine By similarity
Modified residue3431Phosphoserine By similarity

Natural variations

Alternative sequence1 – 297297Missing in isoform 3.
VSP_004582
Alternative sequence1 – 286286Missing in isoform 7.
VSP_012404
Alternative sequence1 – 264264MEAEG…KATIT → MKEQPSCAGTGHPSMAGYGR MAPFELAGGPVKRLRTESPF PCLFA in isoform 2.
VSP_004581
Alternative sequence1 – 131131Missing in isoform 1.
VSP_012398
Alternative sequence1 – 125125Missing in isoform 6.
VSP_012402
Alternative sequence1 – 5656Missing in isoform 4.
VSP_012400
Alternative sequence57 – 14791LPPPP…QGLRR → MERNTCDVLSRSKSASEETL HSCNDEEDPFRGMEPYLVRR LSSRSIQLPPLAFRQLEQTD LRSESENIPRPTSLPLKILP LIAVTSADSTG in isoform 4.
VSP_012401
Alternative sequence126 – 14722GHRPG…QGLRR → MSIIMKPRSRSTSSLRTTEA VC in isoform 6.
VSP_012403
Alternative sequence132 – 14716KKSRM…QGLRR → MMHVNTFPFRRHSWIC in isoform 1.
VSP_012399
Alternative sequence287 – 30115ETLQT…EMASN → MPEANYLLSVSWGYI in isoform 7.
VSP_012405

Experimental info

Sequence conflict2261A → N in AAA56857. Ref.4
Sequence conflict3571S → P in AAQ90405. Ref.9
Sequence conflict480 – 4867Missing Ref.5
Sequence conflict6411G → E in AAC26969. Ref.4
Sequence conflict7571C → Y in AAA56857. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 5 (PDE4D4) [UniParc].

Last modified January 4, 2005. Version 4.
Checksum: 13E28B257556496D

FASTA80390,552
        10         20         30         40         50         60 
MEAEGSSVPA RAGSHEGSDS SGGAALKAPK HLWRHEQHHQ YPLRQPQFRL LHPHHHLPPP 

        70         80         90        100        110        120 
PPPSPQPQLQ PPPPPPLPPP PPPPGATRGR YASSGASRVR HRGYSDTERY LYCRAMDRTS 

       130        140        150        160        170        180 
YAVETGHRPG LKKSRMSWPS SFQGLRRFDV DNGTSAGRSP LDPMTSPGSG LILQANFVHS 

       190        200        210        220        230        240 
QRRESFLYRS DSDYDLSPKS MSRNSSIASD IHGDDLIVTP FAQVLASLRT VRNNFAALTN 

       250        260        270        280        290        300 
LQDRAPSKRS PMCNQPSINK ATITEEAYQK LASETLEELD WCLDQLETLQ TRHSVSEMAS 

       310        320        330        340        350        360 
NKFKRMLNRE LTHLSEMSRS GNQVSEYISN TFLDKQHEVE IPSPTQKEKE KKKRPMSQIS 

       370        380        390        400        410        420 
GVKKLMHSSS LTNSCIPRFG VKTEQEDVLA KELEDVNKWG LHVFRIAELS GNRPLTVIMH 

       430        440        450        460        470        480 
TIFQERDLLK TFKIPVDTLI TYLMTLEDHY HADVAYHNNI HAADVVQSTH VLLSTPALEA 

       490        500        510        520        530        540 
VFTDLEILAA IFASAIHDVD HPGVSNQFLI NTNSELALMY NDSSVLENHH LAVGFKLLQE 

       550        560        570        580        590        600 
ENCDIFQNLT KKQRQSLRKM AIDIVLATDM SKHMNLLADL KTMVETKKVT SSGVLLLDNY 

       610        620        630        640        650        660 
SDRIQVLQNM VHCADLSNPT KPLQLYRQWT DRIMEEFFRQ GDRERERGME ISPMCDKHNA 

       670        680        690        700        710        720 
SVEKSQVGFI DYIVHPLWET WADLVHPDAQ DILDTLEDNR EWYQSTIPQS PSPAPDDQED 

       730        740        750        760        770        780 
GRQGQTEKFQ FELTLEEDGE SDTEKDSGSQ VEEDTSCSDS KTLCTQDSES TEIPLDEQVE 

       790        800 
EEAVAEEESQ PQTGVADDCC PDT 

« Hide

Isoform 1 (PDE4D3) (PDE3.3).

Checksum: 63CE38FA654A0BDD
Show »

FASTA67276,263
Isoform 2 (PDE3.1).

Checksum: 7C0DAEB75774F2F8
Show »

FASTA58466,243
Isoform 3 (PDE3.2).

Checksum: 7DCA5A564384FC34
Show »

FASTA50657,601
Isoform 4 (PDE4D7).

Checksum: D63B9EF50AA3EFC9
Show »

FASTA74784,430
Isoform 6 (PDE4D9).

Checksum: E3069D16ADEBEC6C
Show »

FASTA67876,656
Isoform 7 (PDE4D6).

Checksum: 251BF853D7CE6870
Show »

FASTA51758,923

References

[1]"The mRNA encoding a high-affinity cAMP phosphodiesterase is regulated by hormones and cAMP."
Swinnen J.V., Joseph D.R., Conti M.
Proc. Natl. Acad. Sci. U.S.A. 86:8197-8201(1989) [PubMed: 2554303] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION.
Tissue: Testis.
[2]"The ratPDE3/IVd phosphodiesterase gene codes for multiple proteins differentially activated by cAMP-dependent protein kinase."
Sette C., Vicini E., Conti M.
J. Biol. Chem. 269:18271-18274(1994) [PubMed: 8034568] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[3]Conti M.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 6.
[4]"Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases."
Bolger G.B., Rodgers L., Riggs M.
Gene 149:237-244(1994) [PubMed: 7958996] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 226-803 (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 253-803 (ISOFORM 2).
[5]"Structure of two rat genes coding for closely related rolipram-sensitive cAMP phosphodiesterases. Multiple mRNA variants originate from alternative splicing and multiple start sites."
Monaco L., Vicini E., Conti M.
J. Biol. Chem. 269:347-357(1994) [PubMed: 8276818] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 2 AND 3).
Strain: Wistar.
[6]Erratum
Monaco L., Vicini E., Conti M.
J. Biol. Chem. 269:20806-20806(1994)
[7]"Characterization of a cAMP-specific phosphodiesterase variant (PDE4D4) expressed in the rat brain."
Jin S.-L.C., Kuo W.-P., Conti M.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 5).
Strain: Sprague-Dawley.
Tissue: Brain.
[8]"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: 12834813] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 7).
Strain: Sprague-Dawley.
[9]"Novel PDE4D isoform, PDE4D9."
Gaweda B., De Vivo M., Wang D.
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 6).
[10]"Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes."
Swinnen J.V., Joseph D.R., Conti M.
Proc. Natl. Acad. Sci. U.S.A. 86:5325-5329(1989) [PubMed: 2546153] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 224-672.
Tissue: Testis.
[11]"Phosphorylation-mediated activation and translocation of the cyclic AMP-specific phosphodiesterase PDE4D3 by cyclic AMP-dependent protein kinase and mitogen-activated protein kinases. A potential mechanism allowing for the coordinated regulation of PDE4D activity and targeting."
Liu H., Maurice D.H.
J. Biol. Chem. 274:10557-10565(1999) [PubMed: 10187850] [Abstract]
Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[12]"Myomegalin is a novel protein of the Golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase."
Verde I., Pahlke G., Salanova M., Zhang G., Wang S., Coletti D., Onuffer J., Jin S.-L.C., Conti M.
J. Biol. Chem. 276:11189-11198(2001) [PubMed: 11134006] [Abstract]
Cited for: INTERACTION WITH PDE4DIP.
[13]"Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area."
Tasken K.A., Collas P., Kemmner W.A., Witczak O., Conti M., Tasken K.
J. Biol. Chem. 276:21999-22002(2001) [PubMed: 11285255] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH THE CENTROSOME (ISOFORM 1).
+Additional computationally mapped references.

Cross-references

Sequence databases

U09457 mRNA. Translation: AAB81869.1.
U09456 mRNA. Translation: AAA20393.1.
L27059 mRNA. Translation: AAA56857.1.
L27060 mRNA. Translation: AAC26969.1.
U01280 expand/collapse EMBL AC list , U01278, U01282, U01283, U01284, U01285, U01286, U01287, U01279 Unassigned DNA. Translation: AAA18925.1.
U01280 expand/collapse EMBL AC list , U01278, U01282, U01283, U01284, U01285, U01286, U01287, U01279 Unassigned DNA. Translation: AAA18924.1.
U09455 mRNA. Translation: AAA20401.1.
AF031373 mRNA. Translation: AAB95266.1.
AF536979 mRNA. Translation: AAN10121.1.
AY388961 mRNA. Translation: AAQ90405.1.
AF536974 mRNA. Translation: AAN10116.1.
IPIIPI00203378.
IPI00230929.
IPI00337259.
IPI00391626.
IPI00515793.
IPI00515813.
IPI00515827.
PIRB53109.
I61259.
RefSeqNP_001106799.1.
NP_001106800.1.
NP_058728.1.
UniGeneRn.163460
Rn.95959

3D structure databases

HSSPHSSP built from PDB template 1OYN based on UniProtKB Q08499.
SMRP14270. Positions 383-708.
ModBaseSearch...

PTM databases

PhosphoSiteP14270.

Proteomic databases

PRIDEP14270.

Genome annotation databases

GeneID24627.
KEGGrno:24627.

Organism-specific databases

RGD3281. Pde4d.

Phylogenomic databases

HOVERGENP14270.

Enzyme and pathway databases

BRENDA3.1.4.17. 248.

Family and domain databases

InterProIPR003607. Met-dep_phosphohydro_HD.
IPR002073. PDEase.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio603898.

Entry information

Entry namePDE4D_RAT
AccessionPrimary (citable) accession number: P14270
Secondary accession number(s): O35470 expand/collapse secondary AC list , Q6TRI0, Q8CG04, Q8CG06
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 4, 2005
Last modified: June 16, 2009
This is version 90 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents