Q01063 (PDE4D_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
DPDE3

Gene names

Name:

Pde4d

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	747 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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. Activated by phosphatidic acid By similarity.
Pathway	Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Subunit structure	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). Ref.7
Subcellular location	Cytoplasm. Membrane. Cytoplasm › cytoskeleton. Cytoplasm › cytoskeleton › centrosome. Note: Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome.
Tissue specificity	Isoform 7 is detected in heart, brain, lung, kidney and testis. Ref.1
Induction	Up-regulated by cAMP and follicle-stimulating hormone By similarity.
Post-translational modification	Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation By similarity.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Membrane
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	aging Inferred from mutant phenotype PubMed 10518565. Source: MGI cAMP catabolic process Inferred from mutant phenotype PubMed 14519662. Source: MGI cellular response to lipopolysaccharide Inferred from mutant phenotype PubMed 15585880. Source: MGI establishment of endothelial barrier Inferred from sequence or structural similarity. Source: UniProtKB multicellular organism growth Inferred from mutant phenotype PubMed 10518565. Source: MGI neutrophil chemotaxis Inferred from mutant phenotype PubMed 15585880. Source: MGI signal transduction Inferred from electronic annotation. Source: InterPro smooth muscle contraction Inferred from mutant phenotype PubMed 14519662. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	3',5'-cyclic-nucleotide phosphodiesterase activity Inferred from electronic annotation. Source: EC cAMP binding Inferred from electronic annotation. Source: Compara drug binding Inferred from electronic annotation. Source: Compara 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]

Isoform 7 (identifier: Q01063-1)

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.

Isoform 9 (identifier: Q01063-2)

Also known as: PDE4D9;

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

Isoform 3 (identifier: Q01063-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 747	747	cAMP-specific 3',5'-cyclic phosphodiesterase 4D		PRO_0000198815
Regions
	Nucleotide binding	401 – 405	5	cAMP By similarity
Sites
	Active site	401	1	Proton donor By similarity
	Metal binding	405	1	Divalent metal cation 1 By similarity
	Metal binding	441	1	Divalent metal cation 1 By similarity
	Metal binding	442	1	Divalent metal cation 1 By similarity
	Metal binding	442	1	Divalent metal cation 2 By similarity
	Metal binding	559	1	Divalent metal cation 1 By similarity
	Binding site	442	1	cAMP By similarity
	Site	562	1	Binds AMP, but not cAMP By similarity
Amino acid modifications
	Modified residue	129	1	Phosphoserine Ref.6
	Modified residue	238	1	Phosphoserine By similarity
	Modified residue	240	1	Phosphoserine By similarity
	Cross-link	326		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Alternative sequence	1 – 163	163	Missing in isoform 3.		VSP_012394
	Alternative sequence	1 – 69	69	Missing in isoform 9.		VSP_012395
	Alternative sequence	70 – 91	22	RPTSL…ADSSG → MSIIMKPRSRSTSSLRTTEA VC in isoform 9.		VSP_012396
	Alternative sequence	164 – 208	45	PFAQV…KATIT → MKEQPSCAGTGHPSMAGYGR MAPFELAGGPVKRLRTESSF PCLFA in isoform 3.		VSP_012397
Experimental info
	Sequence conflict	403 – 404	2	NI → SR in AAA37368. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 7 (PDE4D7) [UniParc]. Last modified January 4, 2005. Version 2. Checksum: 68402163664B3676	FASTA	747	84,563
	10 20 30 40 50 60 MERDTCDVLS RSKSASEETL HSCNEEEDPF RGMEPYLVRR LSSRSIQLPP LAFRQLEQAD 70 80 90 100 110 120 LRSESENIPR PTSLPLKILP LIAVTSADSS GFDVDNGTSA GRSPLDPMTS PGSGLILQAN 130 140 150 160 170 180 FVHSQRRESF LYRSDSDYDL SPKSMSRNSS IASDIHGDDL IVTPFAQVLA SLRTVRNNFA 190 200 210 220 230 240 ALTNLQDRAP SKRSPMCNQP SINKATITEE AYQKLASETL EELDWCLDQL ETLQTRHSVS 250 260 270 280 290 300 EMASNKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTQ KEKEKKKRPM 310 320 330 340 350 360 SQISGVKKLM HSSSLTNSCI PRFGVKTEQE DVLAKELEDV NKWGLHVFRI AELSGNRPLT 370 380 390 400 410 420 VIMHTIFQER DLLKTFKIPV DTLITYLMTL EDHYHADVAY HNNIHAADVV QSTHVLLSTP 430 440 450 460 470 480 ALEAVFTDLE ILAAIFASAI HDVDHPGVSN QFLINTNSEL ALMYNDSSVL ENHHLAVGFK 490 500 510 520 530 540 LLQEENCDIF QNLTKKQRQS LRKMVIDIVL ATDMSKHMNL LADLKTMVET KKVTSSGVLL 550 560 570 580 590 600 LDNYSDRIQV LQNMVHCADL SNPTKPLQLY RQWTDRIMEE FFRQGDRERE RGMEISPMCD 610 620 630 640 650 660 KHNASVEKSQ VGFIDYIVHP LWETWADLVH PDAQDILDTL EDNREWYQST IPQSPSPAPD 670 680 690 700 710 720 DQEEGRQGQT EKFQFELTLE EDCESDTEKD SGSQVEEDTS CSDSKTLCTQ DSESTEIPLD 730 740 EQVEEEAVAE EESQPETCVP DDCCPDT
	Isoform 9 (PDE4D9) [UniParc]. Checksum: 51D44F3467C9B71A	FASTA	678	76,817
	10 20 30 40 50 60 MSIIMKPRSR STSSLRTTEA VCFDVDNGTS AGRSPLDPMT SPGSGLILQA NFVHSQRRES 70 80 90 100 110 120 FLYRSDSDYD LSPKSMSRNS SIASDIHGDD LIVTPFAQVL ASLRTVRNNF AALTNLQDRA 130 140 150 160 170 180 PSKRSPMCNQ PSINKATITE EAYQKLASET LEELDWCLDQ LETLQTRHSV SEMASNKFKR 190 200 210 220 230 240 MLNRELTHLS EMSRSGNQVS EYISNTFLDK QHEVEIPSPT QKEKEKKKRP MSQISGVKKL 250 260 270 280 290 300 MHSSSLTNSC IPRFGVKTEQ EDVLAKELED VNKWGLHVFR IAELSGNRPL TVIMHTIFQE 310 320 330 340 350 360 RDLLKTFKIP VDTLITYLMT LEDHYHADVA YHNNIHAADV VQSTHVLLST PALEAVFTDL 370 380 390 400 410 420 EILAAIFASA IHDVDHPGVS NQFLINTNSE LALMYNDSSV LENHHLAVGF KLLQEENCDI 430 440 450 460 470 480 FQNLTKKQRQ SLRKMVIDIV LATDMSKHMN LLADLKTMVE TKKVTSSGVL LLDNYSDRIQ 490 500 510 520 530 540 VLQNMVHCAD LSNPTKPLQL YRQWTDRIME EFFRQGDRER ERGMEISPMC DKHNASVEKS 550 560 570 580 590 600 QVGFIDYIVH PLWETWADLV HPDAQDILDT LEDNREWYQS TIPQSPSPAP DDQEEGRQGQ 610 620 630 640 650 660 TEKFQFELTL EEDCESDTEK DSGSQVEEDT SCSDSKTLCT QDSESTEIPL DEQVEEEAVA 670 EEESQPETCV PDDCCPDT
	Isoform 3 [UniParc]. Checksum: CEDFA3A57387798E	FASTA	584	66,394
	10 20 30 40 50 60 MKEQPSCAGT GHPSMAGYGR MAPFELAGGP VKRLRTESSF PCLFAEEAYQ KLASETLEEL 70 80 90 100 110 120 DWCLDQLETL QTRHSVSEMA SNKFKRMLNR ELTHLSEMSR SGNQVSEYIS NTFLDKQHEV 130 140 150 160 170 180 EIPSPTQKEK EKKKRPMSQI SGVKKLMHSS SLTNSCIPRF GVKTEQEDVL AKELEDVNKW 190 200 210 220 230 240 GLHVFRIAEL SGNRPLTVIM HTIFQERDLL KTFKIPVDTL ITYLMTLEDH YHADVAYHNN 250 260 270 280 290 300 IHAADVVQST HVLLSTPALE AVFTDLEILA AIFASAIHDV DHPGVSNQFL INTNSELALM 310 320 330 340 350 360 YNDSSVLENH HLAVGFKLLQ EENCDIFQNL TKKQRQSLRK MVIDIVLATD MSKHMNLLAD 370 380 390 400 410 420 LKTMVETKKV TSSGVLLLDN YSDRIQVLQN MVHCADLSNP TKPLQLYRQW TDRIMEEFFR 430 440 450 460 470 480 QGDRERERGM EISPMCDKHN ASVEKSQVGF IDYIVHPLWE TWADLVHPDA QDILDTLEDN 490 500 510 520 530 540 REWYQSTIPQ SPSPAPDDQE EGRQGQTEKF QFELTLEEDC ESDTEKDSGS QVEEDTSCSD 550 560 570 580 SKTLCTQDSE STEIPLDEQV EEEAVAEEES QPETCVPDDC CPDT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), TISSUE SPECIFICITY. Strain: BALB/c.
[2]	Chai H., Gaweda B., De Vivo M., Wang D. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9).
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Strain: C57BL/6J. Tissue: Head.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning of the cDNA encoding the 63-kDa calmodulin-dependent phosphodiesterase." Repaske D.R., Swinnen J.V., Jin S.-L.C., van Wyk J.J., Conti M. J. Biol. Chem. 267:18683-18688(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 400-514.
[6]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, MASS SPECTROMETRY. Tissue: Melanoma.
[7]	"Remodeling of ryanodine receptor complex causes 'leaky' channels: a molecular mechanism for decreased exercise capacity." Bellinger A.M., Reiken S., Dura M., Murphy P.W., Deng S.X., Landry D.W., Nieman D., Lehnart S.E., Samaru M., LaCampagne A., Marks A.R. Proc. Natl. Acad. Sci. U.S.A. 105:2198-2202(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH RYR1; FKBP1A; PKA AND PP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00344583. IPI00466648. IPI00515366.
RefSeq	NP_035186.1. NM_011056.3.
UniGene	Mm.434429.
3D structure databases
ProteinModelPortal	Q01063.
SMR	Q01063. Positions 244-678.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29706N.
PTM databases
PhosphoSite	Q01063.
Proteomic databases
PaxDb	Q01063.
PRIDE	Q01063.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000074103; ENSMUSP00000073742; ENSMUSG00000021699. ENSMUST00000120664; ENSMUSP00000113024; ENSMUSG00000021699. ENSMUST00000122041; ENSMUSP00000113488; ENSMUSG00000021699. ENSMUST00000177907; ENSMUSP00000136485; ENSMUSG00000021699.
GeneID	238871.
KEGG	mmu:238871.
UCSC	uc007rvj.2. mouse.
Organism-specific databases
CTD	5144.
MGI	MGI:99555. Pde4d.
Phylogenomic databases
eggNOG	NOG122287.
GeneTree	ENSGT00690000101692.
HOGENOM	HOG000236297.
HOVERGEN	HBG108239.
KO	K01120.
OMA	QHEVEMP.
OrthoDB	EOG4ZGPBT.
Enzyme and pathway databases
UniPathway	UPA00762; UER00747.
Gene expression databases
ArrayExpress	Q01063.
Bgee	Q01063.
CleanEx	MM_PDE4D.
Genevestigator	Q01063.
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	Q01063.
ChEMBL	CHEMBL3846.
DrugBank	DB00131. Adenosine monophosphate.
NextBio	383911.
SOURCE	Search...

Entry information

Entry name

PDE4D_MOUSE

Accession

Primary (citable) accession number: Q01063
Secondary accession number(s): B2KF58 , Q6TRH9, Q8C4Q7, Q8CG05

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 4, 2005
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program