Q08499 (PDE4D_HUMAN) 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
PDE43

Gene names

Name:	PDE4D
Synonyms:	DPDE3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	809 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. Ref.26 Ref.27
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. Ref.26 Ref.27
Enzyme regulation	Inhibited by rolipram. Activated by phosphatidic acid. Ref.13
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. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) By similarity. Isoform 5, isoform N3 and isoform 12 bind GNB2L1 via their unique N-terminus. Binds ARRB2. Ref.11 Ref.12 Ref.13 Ref.31
Subcellular location	Cytoplasm By similarity. Membrane By similarity. Cytoplasm › cytoskeleton By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Note: Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome By similarity. Ref.12
Tissue specificity	Widespread; most abundant in skeletal muscle. Isoform 6 is detected in brain. Isoform 8 is detected in brain, placenta, lung and kidney. Isoform 7 is detected in heart and skeletal muscle. Ref.6
Post-translational modification	Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59. Ref.6 Ref.13 Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation. Ref.18
Involvement in disease	Genetic variations in PDE4D might be associated with susceptibility to stroke. Ref.15 states that association with stroke has to be considered with caution. Acrodysostosis 2, with or without hormone resistance (ACRDYS2) [MIM:614613]: A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.33
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	Metal-binding cAMP
Molecular function	Hydrolase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cAMP catabolic process Inferred from mutant phenotype PubMed 19252089. Source: UniProtKB cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara establishment of endothelial barrier Inferred from sequence or structural similarity. Source: UniProtKB multicellular organism growth Inferred from electronic annotation. Source: Compara neutrophil chemotaxis Inferred from electronic annotation. Source: Compara signal transduction Inferred from electronic annotation. Source: InterPro smooth muscle contraction Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	3',5'-cyclic-AMP phosphodiesterase activity Traceable author statement Ref.4. Source: ProtInc cAMP binding Inferred from direct assay PubMed 15938621. Source: UniProtKB drug binding Inferred from physical interaction PubMed 15938621. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 12 isoforms produced by alternative splicing. [Align] [Select]

Isoform 4 (identifier: Q08499-1)

Also known as: hPDE4D4;

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 3 (identifier: Q08499-2)

Also known as: hPDE4D3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MMHVNNFFRRHSWIC

Note: Activated by phosphorylation at Ser-53. Mutagenesis of Ser-53 abolishes activation.

Isoform 10 (identifier: Q08499-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-205: Missing.

Isoform 1 (identifier: Q08499-4)

Also known as: hPDE4D1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-269: MEAEGSSAPA...QPSINKATIT → MKEQPSCAGT...TESPFPCLFA

Isoform 2 (identifier: Q08499-5)

Also known as: hPDE4D2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-302: Missing.

Isoform 5 (identifier: Q08499-6)

Also known as: hPDE4D5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC

Note: Contains a phosphoserine at position 59. Contains a phosphoserine at position 63.

Isoform N3 (identifier: Q08499-7)

Also known as: PDE4DN3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
     270-279: EEAYQKLASE → GLYNGIIAFL
     280-809: Missing.

Note: Contains a phosphoserine at position 59. Contains a phosphoserine at position 63.

Isoform 6 (identifier: Q08499-8)

Also known as: PDE4D6;

The sequence of this isoform differs from the canonical sequence as follows:
     1-291: Missing.
     292-306: ETLQTRHSVSEMASN → MPEANYLLSVSWGYI

Isoform 8 (identifier: Q08499-9)

Also known as: PDE4D8;

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.
     123-152: RTSYAVETGHRPGLKKSRMSWPSSFQGLRR → MAFVWDPLGATVPGPSTRAKSRLRFSKSYS

Isoform 9 (identifier: Q08499-10)

Also known as: PDE4D9;

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.
     131-152: GHRPGLKKSRMSWPSSFQGLRR → MSIIMKPRSRSTSSLRTAEAVC

Isoform 7 (identifier: Q08499-11)

Also known as: PDE4D7;

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.
     62-152: PPSPQPQPQC...WPSSFQGLRR → MKRNTCDLLS...IAITSAESSG

Isoform 12 (identifier: Q08499-12)

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
     270-283: EEAYQKLASETLEE → GSWMELNPYTLLDM
     284-809: Missing.

Note: Contains a phosphoserine at position 59. Contains a phosphoserine at position 63.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 809

809

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

PRO_0000198814

Regions

Nucleotide binding

462 – 466

5

cAMP

Compositional bias

42 – 88

47

Pro-rich

Sites

Active site

462

1

Proton donor By similarity

Metal binding

466

1

Divalent metal cation 1

Metal binding

502

1

Divalent metal cation 1

Metal binding

503

1

Divalent metal cation 1

Metal binding

503

1

Divalent metal cation 2

Metal binding

620

1

Divalent metal cation 1

Binding site

503

1

cAMP

Binding site

620

1

cAMP

Binding site

671

1

cAMP

Site

623

1

Binds AMP, but not cAMP

Amino acid modifications

Modified residue

190

1

Phosphoserine By similarity

Modified residue

299

1

Phosphoserine Ref.20

Modified residue

301

1

Phosphoserine Ref.20

Cross-link

387

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.18

Natural variations

Alternative sequence

1 – 302

302

Missing in isoform 2.

VSP_004580

Alternative sequence

1 – 291

291

Missing in isoform 6.

VSP_012383

Alternative sequence

1 – 269

269

MEAEG…KATIT → MKEQPSCAGTGHPMAGYGRM APFELASGPVKRLRTESPFP CLFA in isoform 1.

VSP_004579

Alternative sequence

1 – 205

205

Missing in isoform 10.

VSP_004578

Alternative sequence

1 – 152

152

MEAEG…QGLRR → MMHVNNFFRRHSWIC in isoform 3.

VSP_004577

Alternative sequence

1 – 152

152

MEAEG…QGLRR → MAQQTSPDTLTVPEVDNPHC PNPWLNEDLVKSLRENLLQH EKSKTARKSVSPKLSPVISP RNSPRLLRRMLLSSNIPKQR RFTVAHTC in isoform 5, isoform N3 and isoform 12.

VSP_012384

Alternative sequence

1 – 130

130

Missing in isoform 9.

VSP_012385

Alternative sequence

1 – 122

122

Missing in isoform 8.

VSP_012386

Alternative sequence

1 – 61

61

Missing in isoform 7.

VSP_012387

Alternative sequence

62 – 152

91

PPSPQ…QGLRR → MKRNTCDLLSRSKSASEETL HSSNEEEDPFRGMEPYLVRR LSCRNIQLPPLAFRQLEQAD LKSESENIQRPTSLPLKILP LIAITSAESSG in isoform 7.

VSP_012388

Alternative sequence

123 – 152

30

RTSYA…QGLRR → MAFVWDPLGATVPGPSTRAK SRLRFSKSYS in isoform 8.

VSP_012389

Alternative sequence

131 – 152

22

GHRPG…QGLRR → MSIIMKPRSRSTSSLRTAEA VC in isoform 9.

VSP_012390

Alternative sequence

270 – 283

14

EEAYQ…ETLEE → GSWMELNPYTLLDM in isoform 12.

VSP_023326

Alternative sequence

270 – 279

10

EEAYQKLASE → GLYNGIIAFL in isoform N3.

VSP_012391

Alternative sequence

280 – 809

530

Missing in isoform N3.

VSP_012392

Alternative sequence

284 – 809

526

Missing in isoform 12.

VSP_023327

Alternative sequence

292 – 306

15

ETLQT…EMASN → MPEANYLLSVSWGYI in isoform 6.

VSP_012393

Natural variant

190

1

S → A in ACRDYS2. Ref.33

VAR_068242

Natural variant

225

1

P → T in ACRDYS2. Ref.33

VAR_068243

Natural variant

226

1

F → S in ACRDYS2. Ref.33

VAR_068244

Natural variant

587

1

T → P in ACRDYS2. Ref.33

VAR_068245

Experimental info

Mutagenesis

503

1

D → N: Abolishes catalytic activity.

Mutagenesis

527

1

D → R: Abolishes homodimerization. Ref.21

Mutagenesis

563

1

R → D: Abolishes homodimerization. Ref.21

Sequence conflict

510

1

S → F in AAH36319. Ref.10

Sequence conflict

549

1

D → G in AAN10119. Ref.6

Sequence conflict

644

1

R → P Ref.2

Sequence conflict

769

1

C → R in AAA97890. Ref.3

Sequence conflict

769

1

C → R in AAA97891. Ref.3

Sequence conflict

769

1

C → R in AAA97892. Ref.3

Secondary structure

1

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809

Helix Strand Turn

Details...

Helix

328 – 336

9

Beta strand

383 – 386

4

Helix

389 – 397

9

Helix

398 – 400

3

Helix

408 – 414

7

Helix

419 – 430

12

Helix

433 – 436

4

Helix

441 – 453

13

Beta strand

460 – 463

4

Helix

464 – 478

15

Helix

481 – 483

3

Turn

484 – 486

3

Helix

489 – 501

13

Turn

502 – 505

4

Helix

511 – 516

6

Helix

520 – 525

6

Helix

530 – 541

12

Helix

542 – 544

3

Turn

545 – 547

3

Turn

550 – 553

4

Helix

556 – 571

16

Helix

575 – 577

3

Helix

578 – 590

13

Beta strand

598 – 600

3

Helix

605 – 620

16

Helix

623 – 625

3

Helix

628 – 652

25

Turn

658 – 660

3

Beta strand

662 – 664

3

Helix

667 – 677

11

Helix

679 – 689

11

Turn

690 – 694

5

Helix

695 – 710

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 4 (hPDE4D4) [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 7A4773DD3A044F57	FASTA	809	91,115
	10 20 30 40 50 60 MEAEGSSAPA RAGSGEGSDS AGGATLKAPK HLWRHEQHHQ YPLRQPQFRL LHPHHHLPPP 70 80 90 100 110 120 PPPSPQPQPQ CPLQPPPPPP LPPPPPPPGA ARGRYASSGA TGRVRHRGYS DTERYLYCRA 130 140 150 160 170 180 MDRTSYAVET GHRPGLKKSR MSWPSSFQGL RRFDVDNGTS AGRSPLDPMT SPGSGLILQA 190 200 210 220 230 240 NFVHSQRRES FLYRSDSDYD LSPKSMSRNS SIASDIHGDD LIVTPFAQVL ASLRTVRNNF 250 260 270 280 290 300 AALTNLQDRA PSKRSPMCNQ PSINKATITE EAYQKLASET LEELDWCLDQ LETLQTRHSV 310 320 330 340 350 360 SEMASNKFKR MLNRELTHLS EMSRSGNQVS EFISNTFLDK QHEVEIPSPT QKEKEKKKRP 370 380 390 400 410 420 MSQISGVKKL MHSSSLTNSS IPRFGVKTEQ EDVLAKELED VNKWGLHVFR IAELSGNRPL 430 440 450 460 470 480 TVIMHTIFQE RDLLKTFKIP VDTLITYLMT LEDHYHADVA YHNNIHAADV VQSTHVLLST 490 500 510 520 530 540 PALEAVFTDL EILAAIFASA IHDVDHPGVS NQFLINTNSE LALMYNDSSV LENHHLAVGF 550 560 570 580 590 600 KLLQEENCDI FQNLTKKQRQ SLRKMVIDIV LATDMSKHMN LLADLKTMVE TKKVTSSGVL 610 620 630 640 650 660 LLDNYSDRIQ VLQNMVHCAD LSNPTKPLQL YRQWTDRIME EFFRQGDRER ERGMEISPMC 670 680 690 700 710 720 DKHNASVEKS QVGFIDYIVH PLWETWADLV HPDAQDILDT LEDNREWYQS TIPQSPSPAP 730 740 750 760 770 780 DDPEEGRQGQ TEKFQFELTL EEDGESDTEK DSGSQVEEDT SCSDSKTLCT QDSESTEIPL 790 800 DEQVEEEAVG EEEESQPEAC VIDDRSPDT
	Isoform 3 (hPDE4D3) [UniParc]. Checksum: 24174F02715A412A	FASTA	672	76,369
	10 20 30 40 50 60 MMHVNNFFRR HSWICFDVDN GTSAGRSPLD PMTSPGSGLI LQANFVHSQR RESFLYRSDS 70 80 90 100 110 120 DYDLSPKSMS RNSSIASDIH GDDLIVTPFA QVLASLRTVR NNFAALTNLQ DRAPSKRSPM 130 140 150 160 170 180 CNQPSINKAT ITEEAYQKLA SETLEELDWC LDQLETLQTR HSVSEMASNK FKRMLNRELT 190 200 210 220 230 240 HLSEMSRSGN QVSEFISNTF LDKQHEVEIP SPTQKEKEKK KRPMSQISGV KKLMHSSSLT 250 260 270 280 290 300 NSSIPRFGVK TEQEDVLAKE LEDVNKWGLH VFRIAELSGN RPLTVIMHTI FQERDLLKTF 310 320 330 340 350 360 KIPVDTLITY LMTLEDHYHA DVAYHNNIHA ADVVQSTHVL LSTPALEAVF TDLEILAAIF 370 380 390 400 410 420 ASAIHDVDHP GVSNQFLINT NSELALMYND SSVLENHHLA VGFKLLQEEN CDIFQNLTKK 430 440 450 460 470 480 QRQSLRKMVI DIVLATDMSK HMNLLADLKT MVETKKVTSS GVLLLDNYSD RIQVLQNMVH 490 500 510 520 530 540 CADLSNPTKP LQLYRQWTDR IMEEFFRQGD RERERGMEIS PMCDKHNASV EKSQVGFIDY 550 560 570 580 590 600 IVHPLWETWA DLVHPDAQDI LDTLEDNREW YQSTIPQSPS PAPDDPEEGR QGQTEKFQFE 610 620 630 640 650 660 LTLEEDGESD TEKDSGSQVE EDTSCSDSKT LCTQDSESTE IPLDEQVEEE AVGEEEESQP 670 EACVIDDRSP DT
	Isoform 10 [UniParc]. Checksum: 446D0C31C86399AB	FASTA	604	68,607
	10 20 30 40 50 60 MSRNSSIASD IHGDDLIVTP FAQVLASLRT VRNNFAALTN LQDRAPSKRS PMCNQPSINK 70 80 90 100 110 120 ATITEEAYQK LASETLEELD WCLDQLETLQ TRHSVSEMAS NKFKRMLNRE LTHLSEMSRS 130 140 150 160 170 180 GNQVSEFISN TFLDKQHEVE IPSPTQKEKE KKKRPMSQIS GVKKLMHSSS LTNSSIPRFG 190 200 210 220 230 240 VKTEQEDVLA KELEDVNKWG LHVFRIAELS GNRPLTVIMH TIFQERDLLK TFKIPVDTLI 250 260 270 280 290 300 TYLMTLEDHY HADVAYHNNI HAADVVQSTH VLLSTPALEA VFTDLEILAA IFASAIHDVD 310 320 330 340 350 360 HPGVSNQFLI NTNSELALMY NDSSVLENHH LAVGFKLLQE ENCDIFQNLT KKQRQSLRKM 370 380 390 400 410 420 VIDIVLATDM SKHMNLLADL KTMVETKKVT SSGVLLLDNY SDRIQVLQNM VHCADLSNPT 430 440 450 460 470 480 KPLQLYRQWT DRIMEEFFRQ GDRERERGME ISPMCDKHNA SVEKSQVGFI DYIVHPLWET 490 500 510 520 530 540 WADLVHPDAQ DILDTLEDNR EWYQSTIPQS PSPAPDDPEE GRQGQTEKFQ FELTLEEDGE 550 560 570 580 590 600 SDTEKDSGSQ VEEDTSCSDS KTLCTQDSES TEIPLDEQVE EEAVGEEEES QPEACVIDDR SPDT
	Isoform 1 (hPDE4D1) [UniParc]. Checksum: C1761886FF962102	FASTA	584	66,376
	10 20 30 40 50 60 MKEQPSCAGT GHPMAGYGRM APFELASGPV KRLRTESPFP CLFAEEAYQK LASETLEELD 70 80 90 100 110 120 WCLDQLETLQ TRHSVSEMAS NKFKRMLNRE LTHLSEMSRS GNQVSEFISN TFLDKQHEVE 130 140 150 160 170 180 IPSPTQKEKE KKKRPMSQIS GVKKLMHSSS LTNSSIPRFG VKTEQEDVLA KELEDVNKWG 190 200 210 220 230 240 LHVFRIAELS GNRPLTVIMH TIFQERDLLK TFKIPVDTLI TYLMTLEDHY HADVAYHNNI 250 260 270 280 290 300 HAADVVQSTH VLLSTPALEA VFTDLEILAA IFASAIHDVD HPGVSNQFLI NTNSELALMY 310 320 330 340 350 360 NDSSVLENHH LAVGFKLLQE ENCDIFQNLT KKQRQSLRKM VIDIVLATDM SKHMNLLADL 370 380 390 400 410 420 KTMVETKKVT SSGVLLLDNY SDRIQVLQNM VHCADLSNPT KPLQLYRQWT DRIMEEFFRQ 430 440 450 460 470 480 GDRERERGME ISPMCDKHNA SVEKSQVGFI DYIVHPLWET WADLVHPDAQ DILDTLEDNR 490 500 510 520 530 540 EWYQSTIPQS PSPAPDDPEE GRQGQTEKFQ FELTLEEDGE SDTEKDSGSQ VEEDTSCSDS 550 560 570 580 KTLCTQDSES TEIPLDEQVE EEAVGEEEES QPEACVIDDR SPDT
	Isoform 2 (hPDE4D2) [UniParc]. Checksum: 6C07C949952EE5DF	FASTA	507	57,792
	10 20 30 40 50 60 MASNKFKRML NRELTHLSEM SRSGNQVSEF ISNTFLDKQH EVEIPSPTQK EKEKKKRPMS 70 80 90 100 110 120 QISGVKKLMH SSSLTNSSIP RFGVKTEQED VLAKELEDVN KWGLHVFRIA ELSGNRPLTV 130 140 150 160 170 180 IMHTIFQERD LLKTFKIPVD TLITYLMTLE DHYHADVAYH NNIHAADVVQ STHVLLSTPA 190 200 210 220 230 240 LEAVFTDLEI LAAIFASAIH DVDHPGVSNQ FLINTNSELA LMYNDSSVLE NHHLAVGFKL 250 260 270 280 290 300 LQEENCDIFQ NLTKKQRQSL RKMVIDIVLA TDMSKHMNLL ADLKTMVETK KVTSSGVLLL 310 320 330 340 350 360 DNYSDRIQVL QNMVHCADLS NPTKPLQLYR QWTDRIMEEF FRQGDRERER GMEISPMCDK 370 380 390 400 410 420 HNASVEKSQV GFIDYIVHPL WETWADLVHP DAQDILDTLE DNREWYQSTI PQSPSPAPDD 430 440 450 460 470 480 PEEGRQGQTE KFQFELTLEE DGESDTEKDS GSQVEEDTSC SDSKTLCTQD SESTEIPLDE 490 500 QVEEEAVGEE EESQPEACVI DDRSPDT
	Isoform 5 (hPDE4D5) [UniParc]. Checksum: D136AE2B7132DAAC	FASTA	745	84,428
	10 20 30 40 50 60 MAQQTSPDTL TVPEVDNPHC PNPWLNEDLV KSLRENLLQH EKSKTARKSV SPKLSPVISP 70 80 90 100 110 120 RNSPRLLRRM LLSSNIPKQR RFTVAHTCFD VDNGTSAGRS PLDPMTSPGS GLILQANFVH 130 140 150 160 170 180 SQRRESFLYR SDSDYDLSPK SMSRNSSIAS DIHGDDLIVT PFAQVLASLR TVRNNFAALT 190 200 210 220 230 240 NLQDRAPSKR SPMCNQPSIN KATITEEAYQ KLASETLEEL DWCLDQLETL QTRHSVSEMA 250 260 270 280 290 300 SNKFKRMLNR ELTHLSEMSR SGNQVSEFIS NTFLDKQHEV EIPSPTQKEK EKKKRPMSQI 310 320 330 340 350 360 SGVKKLMHSS SLTNSSIPRF GVKTEQEDVL AKELEDVNKW GLHVFRIAEL SGNRPLTVIM 370 380 390 400 410 420 HTIFQERDLL KTFKIPVDTL ITYLMTLEDH YHADVAYHNN IHAADVVQST HVLLSTPALE 430 440 450 460 470 480 AVFTDLEILA AIFASAIHDV DHPGVSNQFL INTNSELALM YNDSSVLENH HLAVGFKLLQ 490 500 510 520 530 540 EENCDIFQNL TKKQRQSLRK MVIDIVLATD MSKHMNLLAD LKTMVETKKV TSSGVLLLDN 550 560 570 580 590 600 YSDRIQVLQN MVHCADLSNP TKPLQLYRQW TDRIMEEFFR QGDRERERGM EISPMCDKHN 610 620 630 640 650 660 ASVEKSQVGF IDYIVHPLWE TWADLVHPDA QDILDTLEDN REWYQSTIPQ SPSPAPDDPE 670 680 690 700 710 720 EGRQGQTEKF QFELTLEEDG ESDTEKDSGS QVEEDTSCSD SKTLCTQDSE STEIPLDEQV 730 740 EEEAVGEEEE SQPEACVIDD RSPDT
	Isoform N3 (PDE4DN3) [UniParc]. Checksum: 255EF7985DB75353	FASTA	215	23,839
	10 20 30 40 50 60 MAQQTSPDTL TVPEVDNPHC PNPWLNEDLV KSLRENLLQH EKSKTARKSV SPKLSPVISP 70 80 90 100 110 120 RNSPRLLRRM LLSSNIPKQR RFTVAHTCFD VDNGTSAGRS PLDPMTSPGS GLILQANFVH 130 140 150 160 170 180 SQRRESFLYR SDSDYDLSPK SMSRNSSIAS DIHGDDLIVT PFAQVLASLR TVRNNFAALT 190 200 210 NLQDRAPSKR SPMCNQPSIN KATITGLYNG IIAFL
	Isoform 6 (PDE4D6) [UniParc]. Checksum: 069F18EB90BAAF4B	FASTA	518	59,113
	10 20 30 40 50 60 MPEANYLLSV SWGYIKFKRM LNRELTHLSE MSRSGNQVSE FISNTFLDKQ HEVEIPSPTQ 70 80 90 100 110 120 KEKEKKKRPM SQISGVKKLM HSSSLTNSSI PRFGVKTEQE DVLAKELEDV NKWGLHVFRI 130 140 150 160 170 180 AELSGNRPLT VIMHTIFQER DLLKTFKIPV DTLITYLMTL EDHYHADVAY HNNIHAADVV 190 200 210 220 230 240 QSTHVLLSTP ALEAVFTDLE ILAAIFASAI HDVDHPGVSN QFLINTNSEL ALMYNDSSVL 250 260 270 280 290 300 ENHHLAVGFK LLQEENCDIF QNLTKKQRQS LRKMVIDIVL ATDMSKHMNL LADLKTMVET 310 320 330 340 350 360 KKVTSSGVLL LDNYSDRIQV LQNMVHCADL SNPTKPLQLY RQWTDRIMEE FFRQGDRERE 370 380 390 400 410 420 RGMEISPMCD KHNASVEKSQ VGFIDYIVHP LWETWADLVH PDAQDILDTL EDNREWYQST 430 440 450 460 470 480 IPQSPSPAPD DPEEGRQGQT EKFQFELTLE EDGESDTEKD SGSQVEEDTS CSDSKTLCTQ 490 500 510 DSESTEIPLD EQVEEEAVGE EEESQPEACV IDDRSPDT
	Isoform 8 (PDE4D8) [UniParc]. Checksum: 90B1ED110D7ED77C	FASTA	687	77,705
	10 20 30 40 50 60 MAFVWDPLGA TVPGPSTRAK SRLRFSKSYS FDVDNGTSAG RSPLDPMTSP GSGLILQANF 70 80 90 100 110 120 VHSQRRESFL YRSDSDYDLS PKSMSRNSSI ASDIHGDDLI VTPFAQVLAS LRTVRNNFAA 130 140 150 160 170 180 LTNLQDRAPS KRSPMCNQPS INKATITEEA YQKLASETLE ELDWCLDQLE TLQTRHSVSE 190 200 210 220 230 240 MASNKFKRML NRELTHLSEM SRSGNQVSEF ISNTFLDKQH EVEIPSPTQK EKEKKKRPMS 250 260 270 280 290 300 QISGVKKLMH SSSLTNSSIP RFGVKTEQED VLAKELEDVN KWGLHVFRIA ELSGNRPLTV 310 320 330 340 350 360 IMHTIFQERD LLKTFKIPVD TLITYLMTLE DHYHADVAYH NNIHAADVVQ STHVLLSTPA 370 380 390 400 410 420 LEAVFTDLEI LAAIFASAIH DVDHPGVSNQ FLINTNSELA LMYNDSSVLE NHHLAVGFKL 430 440 450 460 470 480 LQEENCDIFQ NLTKKQRQSL RKMVIDIVLA TDMSKHMNLL ADLKTMVETK KVTSSGVLLL 490 500 510 520 530 540 DNYSDRIQVL QNMVHCADLS NPTKPLQLYR QWTDRIMEEF FRQGDRERER GMEISPMCDK 550 560 570 580 590 600 HNASVEKSQV GFIDYIVHPL WETWADLVHP DAQDILDTLE DNREWYQSTI PQSPSPAPDD 610 620 630 640 650 660 PEEGRQGQTE KFQFELTLEE DGESDTEKDS GSQVEEDTSC SDSKTLCTQD SESTEIPLDE 670 680 QVEEEAVGEE EESQPEACVI DDRSPDT
	Isoform 9 (PDE4D9) [UniParc]. Checksum: D35B0A2D975C5705	FASTA	679	76,816
	10 20 30 40 50 60 MSIIMKPRSR STSSLRTAEA 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 EFISNTFLDK QHEVEIPSPT QKEKEKKKRP MSQISGVKKL 250 260 270 280 290 300 MHSSSLTNSS 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 DDPEEGRQGQ 610 620 630 640 650 660 TEKFQFELTL EEDGESDTEK DSGSQVEEDT SCSDSKTLCT QDSESTEIPL DEQVEEEAVG 670 EEEESQPEAC VIDDRSPDT
	Isoform 7 (PDE4D7) [UniParc]. Checksum: D10CF5036B1EA7C8	FASTA	748	84,662
	10 20 30 40 50 60 MKRNTCDLLS RSKSASEETL HSSNEEEDPF RGMEPYLVRR LSCRNIQLPP LAFRQLEQAD 70 80 90 100 110 120 LKSESENIQR PTSLPLKILP LIAITSAESS 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 FISNTFLDKQ HEVEIPSPTQ KEKEKKKRPM 310 320 330 340 350 360 SQISGVKKLM HSSSLTNSSI 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 DPEEGRQGQT EKFQFELTLE EDGESDTEKD SGSQVEEDTS CSDSKTLCTQ DSESTEIPLD 730 740 EQVEEEAVGE EEESQPEACV IDDRSPDT
	Isoform 12 [UniParc]. Checksum: 04C84B400D6F7D2C	FASTA	219	24,429
	10 20 30 40 50 60 MAQQTSPDTL TVPEVDNPHC PNPWLNEDLV KSLRENLLQH EKSKTARKSV SPKLSPVISP 70 80 90 100 110 120 RNSPRLLRRM LLSSNIPKQR RFTVAHTCFD VDNGTSAGRS PLDPMTSPGS GLILQANFVH 130 140 150 160 170 180 SQRRESFLYR SDSDYDLSPK SMSRNSSIAS DIHGDDLIVT PFAQVLASLR TVRNNFAALT 190 200 210 NLQDRAPSKR SPMCNQPSIN KATITGSWME LNPYTLLDM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs." Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., Riggs M., Wigler M., Ferguson K. Mol. Cell. Biol. 13:6558-6571(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
[2]	"Identification of cyclic AMP-phosphodiesterase variants from the PDE4D gene expressed in human peripheral mononuclear cells." Nemoz G., Zhang R.B., Sette C., Conti M. FEBS Lett. 384:97-102(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4).
[3]	"Isolation of a cDNA encoding a human rolipram-sensitive cyclic AMP phosphodiesterase (PDE IVD)." Baecker P.A., Obernolte R., Bach C., Yee C., Shelton E.R. Gene 138:253-256(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10). Tissue: Heart.
[4]	"Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene." Bolger G.B., Erdogan S., Jones R.E., Loughney K., Scotland G., Hoffmann R., Wilkinson I., Farrell C., Houslay M.D. Biochem. J. 328:539-548(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 10), SEQUENCE REVISION (ISOFORM 1).
[5]	"Phosphodiesterases 4D and 7A splice variants in the response of HUVEC cells to TNF-alpha1." Miro X., Casacuberta J.M., Gutierrez-Lopez M.D., Landazuri M.O., Puigdomenech P. Biochem. Biophys. Res. Commun. 274:415-421(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM N3), ALTERNATIVE SPLICING. Tissue: Umbilical vein endothelial cell.
[6]	"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] (ISOFORMS 6; 7; 8 AND 9), PHOSPHORYLATION, TISSUE SPECIFICITY.
[7]	"The gene encoding phosphodiesterase 4D confers risk of ischemic stroke." Gretarsdottir S., Thorleifsson G., Reynisdottir S.T., Manolescu A., Jonsdottir S., Jonsdottir T., Gudmundsdottir T., Bjarnadottir S.M., Einarsson O.B., Gudjonsdottir H.M., Hawkins M., Gudmundsson G., Gudmundsdottir H., Andrason H., Gudmundsdottir A.S., Sigurdardottir M., Chou T.T., Nahmias J. , Goss S., Sveinbjoernsdottir S., Valdimarsson E.M., Jakobsson F., Agnarsson U., Gudnason V., Thorgeirsson G., Fingerle J., Gurney M., Gudbjartsson D., Frigge M.L., Kong A., Stefansson K., Gulcher J.R. Nat. Genet. 35:131-138(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 7 AND 9), INVOLVEMENT IN SUSCEPTIBILITY TO STROKE.
[8]	Erratum Gretarsdottir S., Thorleifsson G., Reynisdottir S.T., Manolescu A., Jonsdottir S., Jonsdottir T., Gudmundsdottir T., Bjarnadottir S.M., Einarsson O.B., Gudjonsdottir H.M., Hawkins M., Gudmundsson G., Gudmundsdottir H., Andrason H., Gudmundsdottir A.S., Sigurdardottir M., Chou T.T., Nahmias J. , Goss S., Sveinbjoernsdottir S., Valdimarsson E.M., Jakobsson F., Agnarsson U., Gudnason V., Thorgeirsson G., Fingerle J., Gurney M., Gudbjartsson D., Frigge M.L., Kong A., Stefansson K., Gulcher J.R. Nat. Genet. 37:555-555(2005)
[9]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 12).
[10]	"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] (ISOFORMS 6 AND 12). Tissue: Brain and Testis.
[11]	"Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5." Bolger G.B., McCahill A., Yarwood S.J., Steele M.S., Warwicker J., Houslay M.D. BMC Biochem. 3:24-24(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GNB2L1.
[12]	"The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with beta-arrestins." Bolger G.B., McCahill A., Huston E., Cheung Y.F., McSorley T., Baillie G.S., Houslay M.D. J. Biol. Chem. 278:49230-49238(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB2, SUBCELLULAR LOCATION.
[13]	"The oligomerization state determines regulatory properties and inhibitor sensitivity of type 4 cAMP-specific phosphodiesterases." Richter W., Conti M. J. Biol. Chem. 279:30338-30348(2004) [PubMed] [Europe PMC] [Abstract] Cited for: HOMODIMERIZATION OF LONG ISOFORMS, ENZYME REGULATION BY ROLIPRAM AND PHOSPHATIDIC ACID, PHOSPHORYLATION AT SER-53 (ISOFORM 3).
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[15]	"Many hypotheses but no replication for the association between PDE4D and stroke." Rosand J., Bayley N., Rost N., de Bakker P.I.W. Nat. Genet. 38:1091-1092(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DISCUSSION OF INVOLVEMENT IN STROKE.
[16]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Platelet.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59 AND SER-63 (ISOFORMS 12; 5 AND N3), MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK." Li X., Vadrevu S., Dunlop A., Day J., Advant N., Troeger J., Klussmann E., Jaffrey E., Hay R.T., Adams D.R., Houslay M.D., Baillie G.S. Biochem. J. 428:55-65(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-387 BY PIAS4.
[19]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[20]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-301, MASS SPECTROMETRY.
[21]	"Crystal structure of phosphodiesterase 4D and inhibitor complex." Lee M.E., Markowitz J., Lee J.-O., Lee H. FEBS Lett. 530:53-58(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 388-715 IN COMPLEX WITH THE INHIBITOR ZARDAVERINE AND DIVALENT METAL IONS, MUTAGENESIS OF ASP-527 AND ARG-563.
[22]	"The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis." Huai Q., Colicelli J., Ke H. Biochemistry 42:13220-13226(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 381-739 IN COMPLEX WITH CAMP AND DIVALENT METAL IONS.
[23]	"Three-dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity." Huai Q., Wang H., Sun Y., Kim H.Y., Liu Y., Ke H. Structure 11:865-873(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 381-739 IN COMPLEX WITH INHIBITOR.
[24]	"Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity." Huai Q., Liu Y., Francis S.H., Corbin J.D., Ke H. J. Biol. Chem. 279:13095-13101(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 381-714 IN COMPLEX WITH METAL IONS AND INHIBITOR.
[25]	"Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram." Xu R.X., Rocque W.J., Lambert M.H., Vanderwall D.E., Luther M.A., Nolte R.T. J. Mol. Biol. 337:355-365(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 380-756 IN COMPLEX WITH AMP; METAL IONS AND THE INHIBITOR ROLIPRAM.
[26]	"A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases." Zhang K.Y.J., Card G.L., Suzuki Y., Artis D.R., Fong D., Gillette S., Hsieh D., Neiman J., West B.L., Zhang C., Milburn M.V., Kim S.-H., Schlessinger J., Bollag G. Mol. Cell 15:279-286(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 388-715 IN COMPLEX WITH AMP; METAL IONS AND THE INHIBITOR ROLIPRAM, FUNCTION, COFACTOR.
[27]	"Structural basis for the activity of drugs that inhibit phosphodiesterases." Card G.L., England B.P., Suzuki Y., Fong D., Powell B., Lee B., Luu C., Tabrizizad M., Gillette S., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.-H., Schlessinger J., Zhang K.Y.J. Structure 12:2233-2247(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 388-715 IN COMPLEX WITH METAL IONS AND INHIBITORS, FUNCTION, COFACTOR.
[28]	"A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design." Card G.L., Blasdel L., England B.P., Zhang C., Suzuki Y., Gillette S., Fong D., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.-H., Schlessinger J., Zhang K.Y.J. Nat. Biotechnol. 23:201-207(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.36 ANGSTROMS) OF 388-715 IN COMPLEX WITH METAL IONS AND INHIBITORS.
[29]	"Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase." Huai Q., Sun Y., Wang H., Macdonald D., Aspiotis R., Robinson H., Huang Z., Ke H. J. Med. Chem. 49:1867-1873(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 381-741 IN COMPLEX WITH METAL IONS AND INHIBITORS.
[30]	"Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors." Wang H., Peng M.-S., Chen Y., Geng J., Robinson H., Houslay M.D., Cai J., Ke H. Biochem. J. 408:193-201(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 388-715 IN COMPLEX WITH METAL IONS AND THE INHIBITOR NVP.
[31]	"1H NMR structural and functional characterisation of a cAMP-specific phosphodiesterase-4D5 (PDE4D5) N-terminal region peptide that disrupts PDE4D5 interaction with the signalling scaffold proteins, beta-arrestin and RACK1." Smith K.J., Baillie G.S., Hyde E.I., Li X., Houslay T.M., McCahill A., Dunlop A.J., Bolger G.B., Klussmann E., Adams D.R., Houslay M.D. Cell. Signal. 19:2612-2624(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF N-TERMINUS OF ISOFORM 5/N3/12, INTERACTION WITH GNB2L1.
[32]	"The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10." Wang H., Robinson H., Ke H. J. Mol. Biol. 371:302-307(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 388-714 OF MUTANT ASN-503 IN COMPLEX WITH CAMP AND METAL IONS.
[33]	"Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis." Michot C., Le Goff C., Goldenberg A., Abhyankar A., Klein C., Kinning E., Guerrot A.M., Flahaut P., Duncombe A., Baujat G., Lyonnet S., Thalassinos C., Nitschke P., Casanova J.L., Le Merrer M., Munnich A., Cormier-Daire V. Am. J. Hum. Genet. 90:740-745(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ACRDYS2 ALA-190; THR-225; SER-226 AND PRO-587.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L20970 mRNA. Translation: AAA03592.1.
L20969 mRNA. Translation: AAC00042.1.
U02882 mRNA. Translation: AAC13745.1.
U50157 mRNA. Translation: AAA97890.1.
U50158 mRNA. Translation: AAA97891.1.
U50159 mRNA. Translation: AAA97892.1.
AF012074 mRNA. Translation: AAC00070.1.
AF012073 mRNA. Translation: AAC00069.1.
AJ250854 mRNA. Translation: CAC03757.1.
AF536975 mRNA. Translation: AAN10117.1.
AF536976 mRNA. Translation: AAN10118.1.
AF536977 mRNA. Translation: AAN10119.1.
AY388960 mRNA. Translation: AAQ90404.1.
AY245866 mRNA. Translation: AAP75760.1.
AY245867 mRNA. Translation: AAP75761.1.
BT007398 mRNA. Translation: AAP36062.1.
BC008390 mRNA. Translation: AAH08390.1.
BC036319 mRNA. Translation: AAH36319.1.

IPI

IPI00002449.
IPI00217565.
IPI00217567.
IPI00375235.
IPI00375236.
IPI00386765.
IPI00478370.
IPI00514112.
IPI00514183.
IPI00514643.
IPI00828158.
IPI00963973.

PIR

I61358.

RefSeq

NP_001098101.1. NM_001104631.1.
NP_001159371.1. NM_001165899.1.
NP_001184147.1. NM_001197218.1.
NP_001184148.1. NM_001197219.1.
NP_001184149.1. NM_001197220.1.
NP_001184150.1. NM_001197221.1.
NP_001184151.1. NM_001197222.1.
NP_001184152.1. NM_001197223.1.
NP_006194.2. NM_006203.4.

UniGene

Hs.117545.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E9K	NMR	-	A	-	[»]
1MKD	X-ray	2.90	A/B/C/D/E/F/G/H/I/J/K/L	388-715	[»]
1OYN	X-ray	2.00	A/B/C/D	381-740	[»]
1PTW	X-ray	2.30	A/B/C/D	381-740	[»]
1Q9M	X-ray	2.30	A/B/C/D	381-740	[»]
1TB7	X-ray	1.63	A/B	388-715	[»]
1TBB	X-ray	1.60	A/B	388-715	[»]
1XOM	X-ray	1.55	A/B	388-715	[»]
1XON	X-ray	1.72	A/B	388-715	[»]
1XOQ	X-ray	1.83	A/B	388-715	[»]
1XOR	X-ray	1.54	A/B	388-715	[»]
1Y2B	X-ray	1.40	A/B	388-715	[»]
1Y2C	X-ray	1.67	A/B	388-715	[»]
1Y2D	X-ray	1.70	A/B	388-715	[»]
1Y2E	X-ray	2.10	A/B	388-715	[»]
1Y2K	X-ray	1.36	A/B	388-715	[»]
1ZKN	X-ray	2.10	A/B/C/D	381-714	[»]
2FM0	X-ray	2.00	A/B/C/D	381-741	[»]
2FM5	X-ray	2.03	A/B/C/D	381-741	[»]
2PW3	X-ray	1.56	A/B	388-714	[»]
2QYN	X-ray	1.57	A/B	388-715	[»]
3G4G	X-ray	2.30	A/B/C/D	299-714	[»]
3G4I	X-ray	1.90	A/B/C/D	380-753	[»]
3G4K	X-ray	1.95	A/B/C/D	380-753	[»]
3G4L	X-ray	2.50	A/B/C/D	380-753	[»]
3G58	X-ray	2.05	A/B/C/D	380-753	[»]
3IAD	X-ray	2.65	A/B/C/D	326-714	[»]
3IAK	X-ray	2.80	A	388-715	[»]
3K4S	X-ray	2.05	A	388-715	[»]
3SL3	X-ray	2.10	A/B/C/D	381-741	[»]
3SL4	X-ray	1.90	A/B/C/D	381-741	[»]
3SL5	X-ray	2.65	A/B/C/D	381-734	[»]
3SL6	X-ray	2.44	A/B/C/D	381-741	[»]
3SL8	X-ray	2.60	A/B/C/D	381-741	[»]
3V9B	X-ray	2.10	A/B/C/D	381-740	[»]

ProteinModelPortal

Q08499.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29709N.
DIP-41115N.

IntAct

Q08499. 3 interactions.

MINT

MINT-92262.

PTM databases

PhosphoSite

Q08499.

Polymorphism databases

DMDM

12644392.

Proteomic databases

PaxDb

Q08499.

PRIDE

Q08499.

Protocols and materials databases

DNASU

5144.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309641; ENSP00000308485; ENSG00000113448.
ENST00000317118; ENSP00000321739; ENSG00000113448.
ENST00000340635; ENSP00000345502; ENSG00000113448.
ENST00000358923; ENSP00000351800; ENSG00000113448.
ENST00000360047; ENSP00000353152; ENSG00000113448.
ENST00000405755; ENSP00000384806; ENSG00000113448.
ENST00000502484; ENSP00000423094; ENSG00000113448.
ENST00000502575; ENSP00000425917; ENSG00000113448.
ENST00000503258; ENSP00000425605; ENSG00000113448.
ENST00000507116; ENSP00000424852; ENSG00000113448.
ENST00000546160; ENSP00000442734; ENSG00000113448.

GeneID

5144.

KEGG

hsa:5144.

UCSC

uc003jrs.2. human.
uc003jrt.2. human.
uc003jru.3. human.
uc003jrv.2. human.
uc003jrw.2. human.
uc003jrz.3. human.
uc003jsb.3. human.
uc003jsc.3. human.

Organism-specific databases

CTD

5144.

GeneCards

GC05M058302.

HGNC

HGNC:8783. PDE4D.

HPA

HPA045895.

MIM

600129. gene.
614613. phenotype.

neXtProt

NX_Q08499.

Orphanet

950. Acrodysostosis.
280651. Acrodysostosis with multiple hormone resistance.

PharmGKB

PA33130.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG122287.

HOVERGEN

HBG108239.

InParanoid

Q08499.

KO

K01120.

OMA

QHEVEMP.

OrthoDB

EOG4ZGPBT.

PhylomeDB

Q08499.

Enzyme and pathway databases

BRENDA

3.1.4.53. 2681.

Reactome

REACT_111102. Signal Transduction.

SignaLink

Q08499.

UniPathway

UPA00762; UER00747.

Gene expression databases

ArrayExpress

Q08499.

Bgee

Q08499.

Genevestigator

Q08499.

GermOnline

ENSG00000113448. Homo sapiens.

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

Q08499.

ChEMBL

CHEMBL288.

ChiTaRS

PDE4D. human.

DrugBank

DB00131. Adenosine monophosphate.
DB00651. Dyphylline.

EvolutionaryTrace

Q08499.

GenomeRNAi

5144.

NextBio

19846.

SOURCE

Search...

Entry information

Entry name

PDE4D_HUMAN

Accession

Primary (citable) accession number: Q08499
Secondary accession number(s): O43433 , Q13549, Q13550, Q13551, Q7Z2L8, Q8IV84, Q8IVA9, Q8IVD2, Q8IVD3, Q96HL4, Q9HCX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	December 1, 2000
Last modified:	May 29, 2013
This is version 146 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.