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

Preferred order of sections

Names and origin

Protein names

Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
EC=3.1.4.17

Gene names

Name:

Pde4a

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	844 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes By similarity.
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 and diazepam. Ref.2
Pathway	Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Subunit structure	Interacts with LYN and ARRB2 By similarity.
Subcellular location	Cytoplasm › perinuclear region By similarity.
Post-translational modification	Proteolytically cleaved by caspase-3 By similarity. Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation By similarity.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Sequence caution	The sequence AAH27224.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding cAMP
Molecular function	Hydrolase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cAMP catabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway cellular response to drug Inferred from direct assay Ref.2. Source: MGI regulation of cAMP-mediated signaling Inferred from mutant phenotype PubMed 18923023. Source: MGI regulation of protein kinase A signaling cascade Inferred from mutant phenotype PubMed 18923023. Source: MGI sensory perception of smell Inferred from genetic interaction PubMed 19305400. Source: MGI signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay PubMed 19305400. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	3',5'-cyclic-AMP phosphodiesterase activity Inferred from sequence or structural similarity PubMed 10213096. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] Note: Additional isoforms seem to exist.

Isoform 1 (identifier: O89084-1) 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 2 (identifier: O89084-2) The sequence of this isoform differs from the canonical sequence as follows: 1-234: Missing. 235-256: WCLEQLETMQTYRSVSEMASHK → MPLVDFFCETCSKPWLVGWWDQ

Isoform 3 (identifier: O89084-3) The sequence of this isoform differs from the canonical sequence as follows: 1-102: MEPPAAPSER...TGTGGGSSRR → MRSSAAPRAR...LRHPPGRCVS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 844

844

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

PRO_0000198807

Regions

Nucleotide binding

419 – 423

5

cAMP By similarity

Region

317 – 710

394

Catalytic By similarity

Sites

Active site

419

1

Proton donor By similarity

Metal binding

423

1

Divalent metal cation 1 By similarity

Metal binding

459

1

Divalent metal cation 1 By similarity

Metal binding

460

1

Divalent metal cation 1 By similarity

Metal binding

460

1

Divalent metal cation 2 By similarity

Metal binding

577

1

Divalent metal cation 1 By similarity

Binding site

460

1

cAMP By similarity

Binding site

577

1

cAMP By similarity

Binding site

628

1

cAMP By similarity

Site

69 – 70

2

Cleavage; by caspase-3 By similarity

Site

580

1

Binds AMP, but not cAMP By similarity

Amino acid modifications

Modified residue

147

1

Phosphoserine; by MAPKAPK2 By similarity

Modified residue

160

1

Phosphoserine By similarity

Cross-link

344

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence

1 – 234

234

Missing in isoform 2.

VSP_004563

Alternative sequence

1 – 102

102

MEPPA…GSSRR → MRSSAAPRARPRPPALALPL GPESLTHFSFSEEDTLRHPP GRCVS in isoform 3.

VSP_004562

Alternative sequence

235 – 256

22

WCLEQ…MASHK → MPLVDFFCETCSKPWLVGWW DQ in isoform 2.

VSP_004564

Experimental info

Sequence conflict

516

1

R → K in AAF19201. Ref.2

Sequence conflict

685

1

S → G in AAH27224. Ref.3

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified March 1, 2002. Version 2. Checksum: 632396C9F70E0F61 Show »	FASTA	844	93,558
10 20 30 40 50 60 MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD SAERSEPERS 70 80 90 100 110 120 PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS RRLEAENGPT PSPGRSPLDS 130 140 150 160 170 180 QASPGLMLHA GAATSQRRES FLYRSDSDYD MSPKTMSRNS SVASEAHGED LIVTPFAQVL 190 200 210 220 230 240 ASLRNVRSNF SLLTNVPIPS NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL 250 260 270 280 290 300 ETMQTYRSVS EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTP 310 320 330 340 350 360 RQRPFQQPPP AAVQQAQPMS QITGLKKLVH TGSLNINVPR FGVKTDQEDL LAQELENLSK 370 380 390 400 410 420 WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT MMTYMLTLED HYHADVAYHN 430 440 450 460 470 480 SLHAADVLQS THVLLATPAL DAVFTDLEIL AALFAAAIHD VDHPGVSNQF LINTNSELAL 490 500 510 520 530 540 MYNDESVLEN HHLAVGFKLL QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA 550 560 570 580 590 600 DLKTMVETKK VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF 610 620 630 640 650 660 QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD AQDILDTLED 670 680 690 700 710 720 NRDWYHSAIR QSPSPTLEEE PGVLSDPALP DKFQFELTLE EEDEEDSLEV PGLPCTEETL 730 740 750 760 770 780 LAPHDTRAQA MEQSKVKGQS PAVVEVAESL KQETASAHGA PEESAEAVGH SFSLETSILP 790 800 810 820 830 840 DLRTLSPSEE AQGLLGLPSM AAEVEAPRDH LAAMRACSAC SGTSGDNSAV ISAPGRWGSG GDPA « Hide
Isoform 2 [UniParc]. Checksum: 280D59FE2DFD67A5 Show »	FASTA	610	68,190
10 20 30 40 50 60 MPLVDFFCET CSKPWLVGWW DQFKRMLNRE LTHLSEMSRS GNQVSEYISN TFLDKQHEVE 70 80 90 100 110 120 IPSPTPRQRP FQQPPPAAVQ QAQPMSQITG LKKLVHTGSL NINVPRFGVK TDQEDLLAQE 130 140 150 160 170 180 LENLSKWGLN IFCVSEYAGG RSLSCIMYTI FQERDLLKKF HIPVDTMMTY MLTLEDHYHA 190 200 210 220 230 240 DVAYHNSLHA ADVLQSTHVL LATPALDAVF TDLEILAALF AAAIHDVDHP GVSNQFLINT 250 260 270 280 290 300 NSELALMYND ESVLENHHLA VGFKLLQEEN CDIFQNLSKR QRQSLRKMVI DMVLATDMSK 310 320 330 340 350 360 HMTLLADLKT MVETKKVTSS GVLLLDNYSD RIQVLRNMVH CADLSNPTKP LELYRQWTDR 370 380 390 400 410 420 IMAEFFQQGD RERERGMEIS PMCDKHTASV EKSQVGFIDY IVHPLWETWA DLVHPDAQDI 430 440 450 460 470 480 LDTLEDNRDW YHSAIRQSPS PTLEEEPGVL SDPALPDKFQ FELTLEEEDE EDSLEVPGLP 490 500 510 520 530 540 CTEETLLAPH DTRAQAMEQS KVKGQSPAVV EVAESLKQET ASAHGAPEES AEAVGHSFSL 550 560 570 580 590 600 ETSILPDLRT LSPSEEAQGL LGLPSMAAEV EAPRDHLAAM RACSACSGTS GDNSAVISAP 610 GRWGSGGDPA « Hide
Isoform 3 [UniParc]. Checksum: 703D813F13AB5E03 Show »	FASTA	787	87,193
10 20 30 40 50 60 MRSSAAPRAR PRPPALALPL GPESLTHFSF SEEDTLRHPP GRCVSLEAEN GPTPSPGRSP 70 80 90 100 110 120 LDSQASPGLM LHAGAATSQR RESFLYRSDS DYDMSPKTMS RNSSVASEAH GEDLIVTPFA 130 140 150 160 170 180 QVLASLRNVR SNFSLLTNVP IPSNKRSPLG GPPSVCKATL SEETCQQLAR ETLEELDWCL 190 200 210 220 230 240 EQLETMQTYR SVSEMASHKF KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQHEVEIPS 250 260 270 280 290 300 PTPRQRPFQQ PPPAAVQQAQ PMSQITGLKK LVHTGSLNIN VPRFGVKTDQ EDLLAQELEN 310 320 330 340 350 360 LSKWGLNIFC VSEYAGGRSL SCIMYTIFQE RDLLKKFHIP VDTMMTYMLT LEDHYHADVA 370 380 390 400 410 420 YHNSLHAADV LQSTHVLLAT PALDAVFTDL EILAALFAAA IHDVDHPGVS NQFLINTNSE 430 440 450 460 470 480 LALMYNDESV LENHHLAVGF KLLQEENCDI FQNLSKRQRQ SLRKMVIDMV LATDMSKHMT 490 500 510 520 530 540 LLADLKTMVE TKKVTSSGVL LLDNYSDRIQ VLRNMVHCAD LSNPTKPLEL YRQWTDRIMA 550 560 570 580 590 600 EFFQQGDRER ERGMEISPMC DKHTASVEKS QVGFIDYIVH PLWETWADLV HPDAQDILDT 610 620 630 640 650 660 LEDNRDWYHS AIRQSPSPTL EEEPGVLSDP ALPDKFQFEL TLEEEDEEDS LEVPGLPCTE 670 680 690 700 710 720 ETLLAPHDTR AQAMEQSKVK GQSPAVVEVA ESLKQETASA HGAPEESAEA VGHSFSLETS 730 740 750 760 770 780 ILPDLRTLSP SEEAQGLLGL PSMAAEVEAP RDHLAAMRAC SACSGTSGDN SAVISAPGRW GSGGDPA « Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Physical mapping and promoter structure of the murine cAMP-specific phosphodiesterase pde4a gene." Olsen A.E., Bolger G.B. Mamm. Genome 11:41-45(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING. Tissue: Embryonic stem cell.
[2]	"Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse." Cherry J.A., Thompson B.E., Pho V. Biochim. Biophys. Acta 1518:27-35(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ENZYME REGULATION. Strain: Swiss Webster. Tissue: Brain.
[3]	"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 3). Strain: FVB/N. Tissue: Salivary gland.
[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 [MRNA] OF 248-355 (ISOFORM 2). Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF142646 , AF142643, AF142644, AF142645 Genomic DNA. Translation: AAF14519.1. AF142646, AF142644, AF142645 Genomic DNA. Translation: AAF14520.1. AF208021 mRNA. Translation: AAF19201.2. AJ297396 mRNA. Translation: CAB96769.1. BC027224 mRNA. Translation: AAH27224.2. Different initiation. U97586 mRNA. Translation: AAC25681.1.
IPI	IPI00130881. IPI00228051. IPI00316902.
RefSeq	NP_062772.3. NM_019798.5. NP_899668.1. NM_183408.3.
UniGene	Mm.191749.
3D structure databases
ProteinModelPortal	O89084.
SMR	O89084. Positions 254-696.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4996302.
PTM databases
PhosphoSite	O89084.
Proteomic databases
PaxDb	O89084.
PRIDE	O89084.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000003395; ENSMUSP00000003395; ENSMUSG00000032177. ENSMUST00000039413; ENSMUSP00000037025; ENSMUSG00000032177. ENSMUST00000115458; ENSMUSP00000111118; ENSMUSG00000032177.
GeneID	18577.
KEGG	mmu:18577.
UCSC	uc009oki.2. mouse. uc009okl.2. mouse. uc009okm.2. mouse.
Organism-specific databases
CTD	5141.
MGI	MGI:99558. Pde4a.
Phylogenomic databases
eggNOG	NOG122287.
GeneTree	ENSGT00690000101692.
HOGENOM	HOG000236297.
HOVERGEN	HBG108239.
InParanoid	O89084.
KO	K01120.
OMA	HIPVDTM.
OrthoDB	EOG402WRM.
Enzyme and pathway databases
UniPathway	UPA00762; UER00747.
Gene expression databases
ArrayExpress	O89084.
Bgee	O89084.
CleanEx	MM_PDE4A.
Genevestigator	O89084.
GermOnline	ENSMUSG00000032177. Mus musculus.
Family and domain databases
Gene3D	1.10.1300.10. 1 hit.
InterPro	IPR003607. HD/PDEase_dom. IPR023088. PDEase. IPR002073. PDEase_catalytic_dom. IPR023174. PDEase_CS. [Graphical view]
Pfam	PF00233. PDEase_I. 1 hit. [Graphical view]
PRINTS	PR00387. PDIESTERASE1.
SMART	SM00471. HDc. 1 hit. [Graphical view]
PROSITE	PS00126. PDEASE_I. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O89084.
ChEMBL	CHEMBL2698.
NextBio	294438.
SOURCE	Search...

Entry information

Entry name

PDE4A_MOUSE

Accession

Primary (citable) accession number: O89084
Secondary accession number(s): Q8R078

Q9QXI8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	March 1, 2002
Last modified:	May 29, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents