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Protein

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

Gene

PDE4D

Organism
Homo sapiens (Human)
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.2 Publications

Catalytic activityi

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

Cofactori

a divalent metal cation2 PublicationsNote: 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.2 Publications

Enzyme regulationi

Inhibited by rolipram. Activated by phosphatidic acid.1 Publication

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. cAMP-specific 3',5'-cyclic phosphodiesterase 4C (PDE4C), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (PDE7B), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (PDE7A), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A)
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 sitei462Proton donorBy similarity1
Metal bindingi466Divalent metal cation 11
Metal bindingi502Divalent metal cation 11
Metal bindingi503Divalent metal cation 11
Metal bindingi503Divalent metal cation 21
Binding sitei503cAMP2 Publications1
Metal bindingi620Divalent metal cation 11
Binding sitei620cAMP2 Publications1
Sitei623Binds AMP, but not cAMP1
Binding sitei671cAMP2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi462 – 466cAMP2 Publications5

GO - Molecular functioni

  • 3',5'-cyclic-AMP phosphodiesterase activity Source: BHF-UCL
  • 3',5'-cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
  • ATPase binding Source: BHF-UCL
  • beta-2 adrenergic receptor binding Source: BHF-UCL
  • cAMP binding Source: BHF-UCL
  • drug binding Source: UniProtKB
  • enzyme binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • scaffold protein binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: BHF-UCL

GO - Biological processi

  • adrenergic receptor signaling pathway Source: BHF-UCL
  • adrenergic receptor signaling pathway involved in positive regulation of heart rate Source: BHF-UCL
  • aging Source: Ensembl
  • cAMP catabolic process Source: BHF-UCL
  • cAMP-mediated signaling Source: BHF-UCL
  • cellular response to cAMP Source: BHF-UCL
  • cellular response to epinephrine stimulus Source: BHF-UCL
  • cellular response to lipopolysaccharide Source: Ensembl
  • establishment of endothelial barrier Source: UniProtKB
  • multicellular organism growth Source: Ensembl
  • negative regulation of heart contraction Source: BHF-UCL
  • negative regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  • negative regulation of relaxation of cardiac muscle Source: BHF-UCL
  • neutrophil chemotaxis Source: Ensembl
  • positive regulation of interferon-gamma production Source: BHF-UCL
  • positive regulation of interleukin-2 production Source: BHF-UCL
  • positive regulation of interleukin-5 production Source: BHF-UCL
  • regulation of cAMP metabolic process Source: Ensembl
  • regulation of cardiac muscle cell contraction Source: BHF-UCL
  • regulation of cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
  • regulation of heart rate Source: BHF-UCL
  • regulation of receptor activity Source: BHF-UCL
  • regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
  • regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
  • smooth muscle contraction Source: Ensembl
  • T cell receptor signaling pathway Source: BHF-UCL

Keywordsi

Molecular functionHydrolase
LigandcAMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.53. 2681.
ReactomeiR-HSA-180024. DARPP-32 events.
R-HSA-418555. G alpha (s) signalling events.
SignaLinkiQ08499.
SIGNORiQ08499.
UniPathwayiUPA00762; UER00747.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4D (EC:3.1.4.53)
Alternative name(s):
DPDE3
PDE43
Gene namesi
Name:PDE4D
Synonyms:DPDE3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:8783. PDE4D.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • calcium channel complex Source: BHF-UCL
  • centrosome Source: Ensembl
  • cytosol Source: BHF-UCL
  • membrane Source: BHF-UCL
  • nuclear membrane Source: HPA
  • plasma membrane Source: HPA
  • voltage-gated calcium channel complex Source: Ensembl

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.1 Publication
Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614613
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068242190S → A in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514466Ensembl.1
Natural variantiVAR_068243225P → T in ACRDYS2. 2 PublicationsCorresponds to variant dbSNP:rs397514464Ensembl.1
Natural variantiVAR_068244226F → S in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514465Ensembl.1
Natural variantiVAR_069448227A → S in ACRDYS2. 1 Publication1
Natural variantiVAR_069449228Q → E in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514468Ensembl.1
Natural variantiVAR_069450301S → T in ACRDYS2. 1 Publication1
Natural variantiVAR_069451304A → V in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397515433Ensembl.1
Natural variantiVAR_069452329V → A in ACRDYS2. 1 Publication1
Natural variantiVAR_068245587T → P in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514467Ensembl.1
Natural variantiVAR_069453590E → A in ACRDYS2. 2 Publications1
Natural variantiVAR_069454673G → D in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514469Ensembl.1
Natural variantiVAR_069455678I → T in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs587777188Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi503D → N: Abolishes catalytic activity. 1
Mutagenesisi527D → R: Abolishes homodimerization. 1 Publication1
Mutagenesisi563R → D: Abolishes homodimerization. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5144.
MalaCardsiPDE4D.
MIMi614613. phenotype.
OpenTargetsiENSG00000113448.
Orphaneti950. Acrodysostosis.
280651. Acrodysostosis with multiple hormone resistance.
PharmGKBiPA33130.

Chemistry databases

ChEMBLiCHEMBL288.
DrugBankiDB06842. (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one.
DB04149. (R)-Rolipram.
DB03606. (S)-Rolipram.
DB07954. 3-isobutyl-1-methyl-7H-xanthine.
DB02918. 6-(4-Difluoromethoxy-3-Methoxy-Phenyl)-2h-Pyridazin-3-One.
DB00131. Adenosine monophosphate.
DB05676. Apremilast.
DB00201. Caffeine.
DB03849. Cilomilast.
DB05219. Crisaborole.
DB00651. Dyphylline.
DB05266. Ibudilast.
DB01088. Iloprost.
DB05298. OPC-6535.
DB01791. Piclamilast.
DB01656. Roflumilast.
DB01954. Rolipram.
GuidetoPHARMACOLOGYi1303.

Polymorphism and mutation databases

BioMutaiPDE4D.
DMDMi12644392.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988141 – 809cAMP-specific 3',5'-cyclic phosphodiesterase 4DAdd BLAST809

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei142PhosphoserineBy similarity1
Modified residuei299PhosphoserineCombined sources1
Modified residuei301PhosphoserineCombined sources1
Modified residuei348PhosphoserineCombined sources1
Modified residuei375PhosphoserineCombined sources1
Cross-linki387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Isoform 3 (identifier: Q08499-2)
Modified residuei53Phosphoserine1 Publication1
Isoform 5 (identifier: Q08499-6)
Modified residuei59PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1
Isoform N3 (identifier: Q08499-7)
Modified residuei59PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1
Isoform 12 (identifier: Q08499-12)
Modified residuei59PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1

Post-translational modificationi

Long isoforms that share a conserved PKA phosphorylation site in the N-terminus are activated by PKA through phosphorylation (By similarity). 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.By similarity
Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ08499.
PaxDbiQ08499.
PeptideAtlasiQ08499.
PRIDEiQ08499.

PTM databases

iPTMnetiQ08499.
PhosphoSitePlusiQ08499.

Expressioni

Tissue specificityi

Expressed in colonic epithelial cells (at protein level). 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.2 Publications

Gene expression databases

BgeeiENSG00000113448.
ExpressionAtlasiQ08499. baseline and differential.
GenevisibleiQ08499. HS.

Organism-specific databases

HPAiHPA045895.

Interactioni

Subunit structurei

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 RACK1 via their unique N-terminus. Binds ARRB2. Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.By similarity15 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ATPase binding Source: BHF-UCL
  • beta-2 adrenergic receptor binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • scaffold protein binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi111170. 48 interactors.
DIPiDIP-29709N.
DIP-41115N.
IntActiQ08499. 24 interactors.
MINTiMINT-92262.
STRINGi9606.ENSP00000345502.

Chemistry databases

BindingDBiQ08499.

Structurei

Secondary structure

1809
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi328 – 336Combined sources9
Beta strandi383 – 386Combined sources4
Helixi389 – 397Combined sources9
Helixi398 – 400Combined sources3
Helixi408 – 414Combined sources7
Helixi419 – 430Combined sources12
Helixi433 – 436Combined sources4
Helixi441 – 453Combined sources13
Beta strandi460 – 463Combined sources4
Helixi464 – 478Combined sources15
Helixi481 – 483Combined sources3
Turni484 – 486Combined sources3
Helixi489 – 501Combined sources13
Turni502 – 505Combined sources4
Helixi511 – 516Combined sources6
Helixi520 – 525Combined sources6
Helixi530 – 541Combined sources12
Helixi542 – 544Combined sources3
Turni545 – 547Combined sources3
Turni550 – 553Combined sources4
Helixi556 – 571Combined sources16
Helixi575 – 577Combined sources3
Helixi578 – 590Combined sources13
Beta strandi598 – 600Combined sources3
Helixi605 – 620Combined sources16
Helixi623 – 625Combined sources3
Helixi628 – 652Combined sources25
Turni658 – 660Combined sources3
Beta strandi662 – 664Combined sources3
Helixi667 – 677Combined sources11
Helixi679 – 689Combined sources11
Turni690 – 694Combined sources5
Helixi695 – 710Combined sources16
Helixi730 – 734Combined sources5
Turni735 – 738Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1E9KNMR-A-[»]
1MKDX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L388-715[»]
1OYNX-ray2.00A/B/C/D381-740[»]
1PTWX-ray2.30A/B/C/D381-740[»]
1Q9MX-ray2.30A/B/C/D381-740[»]
1TB7X-ray1.63A/B388-715[»]
1TBBX-ray1.60A/B388-715[»]
1XOMX-ray1.55A/B388-715[»]
1XONX-ray1.72A/B388-715[»]
1XOQX-ray1.83A/B388-715[»]
1XORX-ray1.54A/B388-715[»]
1Y2BX-ray1.40A/B388-715[»]
1Y2CX-ray1.67A/B388-715[»]
1Y2DX-ray1.70A/B388-715[»]
1Y2EX-ray2.10A/B388-715[»]
1Y2KX-ray1.36A/B388-715[»]
1ZKNX-ray2.10A/B/C/D381-714[»]
2FM0X-ray2.00A/B/C/D381-741[»]
2FM5X-ray2.03A/B/C/D381-741[»]
2PW3X-ray1.56A/B388-714[»]
2QYNX-ray1.57A/B388-715[»]
3G4GX-ray2.30A/B/C/D299-347[»]
A/B/C/D360-714[»]
3G4IX-ray1.90A/B/C/D380-753[»]
3G4KX-ray1.95A/B/C/D380-753[»]
3G4LX-ray2.50A/B/C/D380-753[»]
3G58X-ray2.05A/B/C/D380-753[»]
3IADX-ray2.65A/B/C/D326-339[»]
A/B/C/D380-714[»]
3IAKX-ray2.80A388-715[»]
3K4SX-ray2.05A388-715[»]
3SL3X-ray2.10A/B/C/D381-741[»]
3SL4X-ray1.90A/B/C/D381-741[»]
3SL5X-ray2.65A/B/C/D381-714[»]
3SL6X-ray2.44A/B/C/D381-741[»]
3SL8X-ray2.60A/B/C/D381-741[»]
3V9BX-ray2.10A/B/C/D381-740[»]
4OGBX-ray2.03A/B/C/D381-741[»]
4W1OX-ray2.20A/B/C/D381-739[»]
4WCUX-ray2.35A/B/C/D381-739[»]
5K1IX-ray2.61A/B/C/D/E/F/G/H388-713[»]
5K32X-ray1.99A/B390-713[»]
5TKBX-ray2.16A/B/C/D380-753[»]
5WQAX-ray2.30A/B381-714[»]
ProteinModelPortaliQ08499.
SMRiQ08499.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ08499.

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi42 – 88Pro-richAdd BLAST47

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOVERGENiHBG108239.
KOiK13293.
OMAiQHEVEMP.
OrthoDBiEOG091G06CD.
PhylomeDBiQ08499.
TreeFamiTF314638.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiView protein in InterPro
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
PfamiView protein in Pfam
PF00233. PDEase_I. 1 hit.
PRINTSiPR00387. PDIESTERASE1.
PROSITEiView protein in PROSITE
PS00126. PDEASE_I. 1 hit.

Sequences (12)i

Sequence statusi: Complete.

This entry describes 12 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 4 (identifier: Q08499-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MEAEGSSAPA RAGSGEGSDS AGGATLKAPK HLWRHEQHHQ YPLRQPQFRL
60 70 80 90 100
LHPHHHLPPP PPPSPQPQPQ CPLQPPPPPP LPPPPPPPGA ARGRYASSGA
110 120 130 140 150
TGRVRHRGYS DTERYLYCRA MDRTSYAVET GHRPGLKKSR MSWPSSFQGL
160 170 180 190 200
RRFDVDNGTS AGRSPLDPMT SPGSGLILQA NFVHSQRRES FLYRSDSDYD
210 220 230 240 250
LSPKSMSRNS SIASDIHGDD LIVTPFAQVL ASLRTVRNNF AALTNLQDRA
260 270 280 290 300
PSKRSPMCNQ PSINKATITE EAYQKLASET LEELDWCLDQ LETLQTRHSV
310 320 330 340 350
SEMASNKFKR MLNRELTHLS EMSRSGNQVS EFISNTFLDK QHEVEIPSPT
360 370 380 390 400
QKEKEKKKRP MSQISGVKKL MHSSSLTNSS IPRFGVKTEQ EDVLAKELED
410 420 430 440 450
VNKWGLHVFR IAELSGNRPL TVIMHTIFQE RDLLKTFKIP VDTLITYLMT
460 470 480 490 500
LEDHYHADVA YHNNIHAADV VQSTHVLLST PALEAVFTDL EILAAIFASA
510 520 530 540 550
IHDVDHPGVS NQFLINTNSE LALMYNDSSV LENHHLAVGF KLLQEENCDI
560 570 580 590 600
FQNLTKKQRQ SLRKMVIDIV LATDMSKHMN LLADLKTMVE TKKVTSSGVL
610 620 630 640 650
LLDNYSDRIQ VLQNMVHCAD LSNPTKPLQL YRQWTDRIME EFFRQGDRER
660 670 680 690 700
ERGMEISPMC DKHNASVEKS QVGFIDYIVH PLWETWADLV HPDAQDILDT
710 720 730 740 750
LEDNREWYQS TIPQSPSPAP DDPEEGRQGQ TEKFQFELTL EEDGESDTEK
760 770 780 790 800
DSGSQVEEDT SCSDSKTLCT QDSESTEIPL DEQVEEEAVG EEEESQPEAC

VIDDRSPDT
Length:809
Mass (Da):91,115
Last modified:December 1, 2000 - v2
Checksum:i7A4773DD3A044F57
GO
Isoform 3 (identifier: Q08499-2) [UniParc]FASTAAdd to basket
Also known as: hPDE4D3

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

Note: Activated by phosphorylation at Ser-53. Mutagenesis of Ser-53 abolishes activation.1 Publication
Show »
Length:673
Mass (Da):76,467
Checksum:iBDC04171BA91A297
GO
Isoform 10 (identifier: Q08499-3) [UniParc]FASTAAdd to basket

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

Show »
Length:604
Mass (Da):68,607
Checksum:i446D0C31C86399AB
GO
Isoform 1 (identifier: Q08499-4) [UniParc]FASTAAdd to basket
Also known as: hPDE4D1

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

Show »
Length:584
Mass (Da):66,376
Checksum:iC1761886FF962102
GO
Isoform 2 (identifier: Q08499-5) [UniParc]FASTAAdd to basket
Also known as: hPDE4D2

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

Show »
Length:507
Mass (Da):57,792
Checksum:i6C07C949952EE5DF
GO
Isoform 5 (identifier: Q08499-6) [UniParc]FASTAAdd to basket
Also known as: hPDE4D5

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

Show »
Length:745
Mass (Da):84,428
Checksum:iD136AE2B7132DAAC
GO
Isoform N3 (identifier: Q08499-7) [UniParc]FASTAAdd to basket
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.

Show »
Length:215
Mass (Da):23,839
Checksum:i255EF7985DB75353
GO
Isoform 6 (identifier: Q08499-8) [UniParc]FASTAAdd to basket
Also known as: PDE4D6

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

Show »
Length:518
Mass (Da):59,113
Checksum:i069F18EB90BAAF4B
GO
Isoform 8 (identifier: Q08499-9) [UniParc]FASTAAdd to basket
Also known as: PDE4D8

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

Show »
Length:687
Mass (Da):77,705
Checksum:i90B1ED110D7ED77C
GO
Isoform 9 (identifier: Q08499-10) [UniParc]FASTAAdd to basket
Also known as: PDE4D9

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

Show »
Length:679
Mass (Da):76,816
Checksum:iD35B0A2D975C5705
GO
Isoform 7 (identifier: Q08499-11) [UniParc]FASTAAdd to basket
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

Show »
Length:748
Mass (Da):84,662
Checksum:iD10CF5036B1EA7C8
GO
Isoform 12 (identifier: Q08499-12) [UniParc]FASTAAdd to basket

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.

Show »
Length:219
Mass (Da):24,429
Checksum:i04C84B400D6F7D2C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti510S → F in AAH36319 (PubMed:15489334).Curated1
Sequence conflicti549D → G in AAN10119 (PubMed:12834813).Curated1
Sequence conflicti644R → P (PubMed:8797812).Curated1
Sequence conflicti769C → R in AAA97890 (PubMed:8125310).Curated1
Sequence conflicti769C → R in AAA97891 (PubMed:8125310).Curated1
Sequence conflicti769C → R in AAA97892 (PubMed:8125310).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068242190S → A in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514466Ensembl.1
Natural variantiVAR_068243225P → T in ACRDYS2. 2 PublicationsCorresponds to variant dbSNP:rs397514464Ensembl.1
Natural variantiVAR_068244226F → S in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514465Ensembl.1
Natural variantiVAR_069448227A → S in ACRDYS2. 1 Publication1
Natural variantiVAR_069449228Q → E in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514468Ensembl.1
Natural variantiVAR_069450301S → T in ACRDYS2. 1 Publication1
Natural variantiVAR_069451304A → V in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397515433Ensembl.1
Natural variantiVAR_069452329V → A in ACRDYS2. 1 Publication1
Natural variantiVAR_068245587T → P in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514467Ensembl.1
Natural variantiVAR_069453590E → A in ACRDYS2. 2 Publications1
Natural variantiVAR_069454673G → D in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs397514469Ensembl.1
Natural variantiVAR_069455678I → T in ACRDYS2. 1 PublicationCorresponds to variant dbSNP:rs587777188Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045801 – 302Missing in isoform 2. 2 PublicationsAdd BLAST302
Alternative sequenceiVSP_0123831 – 291Missing in isoform 6. 2 PublicationsAdd BLAST291
Alternative sequenceiVSP_0045791 – 269MEAEG…KATIT → MKEQPSCAGTGHPMAGYGRM APFELASGPVKRLRTESPFP CLFA in isoform 1. 2 PublicationsAdd BLAST269
Alternative sequenceiVSP_0045781 – 205Missing in isoform 10. 2 PublicationsAdd BLAST205
Alternative sequenceiVSP_0045771 – 152MEAEG…QGLRR → MMHVNNFPFRRHSWIC in isoform 3. 2 PublicationsAdd BLAST152
Alternative sequenceiVSP_0123841 – 152MEAEG…QGLRR → MAQQTSPDTLTVPEVDNPHC PNPWLNEDLVKSLRENLLQH EKSKTARKSVSPKLSPVISP RNSPRLLRRMLLSSNIPKQR RFTVAHTC in isoform 5, isoform N3 and isoform 12. 4 PublicationsAdd BLAST152
Alternative sequenceiVSP_0123851 – 130Missing in isoform 9. 2 PublicationsAdd BLAST130
Alternative sequenceiVSP_0123861 – 122Missing in isoform 8. 1 PublicationAdd BLAST122
Alternative sequenceiVSP_0123871 – 61Missing in isoform 7. 2 PublicationsAdd BLAST61
Alternative sequenceiVSP_01238862 – 152PPSPQ…QGLRR → MKRNTCDLLSRSKSASEETL HSSNEEEDPFRGMEPYLVRR LSCRNIQLPPLAFRQLEQAD LKSESENIQRPTSLPLKILP LIAITSAESSG in isoform 7. 2 PublicationsAdd BLAST91
Alternative sequenceiVSP_012389123 – 152RTSYA…QGLRR → MAFVWDPLGATVPGPSTRAK SRLRFSKSYS in isoform 8. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_012390131 – 152GHRPG…QGLRR → MSIIMKPRSRSTSSLRTAEA VC in isoform 9. 2 PublicationsAdd BLAST22
Alternative sequenceiVSP_023326270 – 283EEAYQ…ETLEE → GSWMELNPYTLLDM in isoform 12. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_012391270 – 279EEAYQKLASE → GLYNGIIAFL in isoform N3. 1 Publication10
Alternative sequenceiVSP_012392280 – 809Missing in isoform N3. 1 PublicationAdd BLAST530
Alternative sequenceiVSP_023327284 – 809Missing in isoform 12. 2 PublicationsAdd BLAST526
Alternative sequenceiVSP_012393292 – 306ETLQT…EMASN → MPEANYLLSVSWGYI in isoform 6. 2 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47213.1. [Q08499-1]
CCDS54858.1. [Q08499-2]
CCDS54859.1. [Q08499-11]
CCDS56369.1. [Q08499-8]
CCDS56370.1. [Q08499-5]
CCDS56371.1. [Q08499-10]
CCDS56372.1. [Q08499-9]
CCDS56373.1. [Q08499-6]
PIRiI61358.
RefSeqiNP_001098101.1. NM_001104631.1. [Q08499-1]
NP_001159371.1. NM_001165899.1. [Q08499-11]
NP_001184147.1. NM_001197218.1. [Q08499-6]
NP_001184148.1. NM_001197219.1. [Q08499-9]
NP_001184149.1. NM_001197220.1. [Q08499-10]
NP_001184150.1. NM_001197221.1. [Q08499-5]
NP_001184151.1. NM_001197222.1.
NP_001184152.1. NM_001197223.1. [Q08499-8]
NP_006194.2. NM_006203.4. [Q08499-2]
XP_005248595.1. XM_005248538.4. [Q08499-2]
XP_011541773.1. XM_011543471.1. [Q08499-11]
XP_011541775.1. XM_011543473.1. [Q08499-11]
XP_016865055.1. XM_017009566.1. [Q08499-11]
UniGeneiHs.117545.

Genome annotation databases

EnsembliENST00000309641; ENSP00000308485; ENSG00000113448. [Q08499-7]
ENST00000317118; ENSP00000321739; ENSG00000113448. [Q08499-8]
ENST00000340635; ENSP00000345502; ENSG00000113448. [Q08499-1]
ENST00000358923; ENSP00000351800; ENSG00000113448. [Q08499-5]
ENST00000360047; ENSP00000353152; ENSG00000113448. [Q08499-2]
ENST00000405755; ENSP00000384806; ENSG00000113448. [Q08499-9]
ENST00000502484; ENSP00000423094; ENSG00000113448. [Q08499-11]
ENST00000502575; ENSP00000425917; ENSG00000113448. [Q08499-12]
ENST00000503258; ENSP00000425605; ENSG00000113448. [Q08499-10]
ENST00000507116; ENSP00000424852; ENSG00000113448. [Q08499-6]
GeneIDi5144.
KEGGihsa:5144.
UCSCiuc003jrs.4. human. [Q08499-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) (PDE4D)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47213.1. [Q08499-1]
CCDS54858.1. [Q08499-2]
CCDS54859.1. [Q08499-11]
CCDS56369.1. [Q08499-8]
CCDS56370.1. [Q08499-5]
CCDS56371.1. [Q08499-10]
CCDS56372.1. [Q08499-9]
CCDS56373.1. [Q08499-6]
PIRiI61358.
RefSeqiNP_001098101.1. NM_001104631.1. [Q08499-1]
NP_001159371.1. NM_001165899.1. [Q08499-11]
NP_001184147.1. NM_001197218.1. [Q08499-6]
NP_001184148.1. NM_001197219.1. [Q08499-9]
NP_001184149.1. NM_001197220.1. [Q08499-10]
NP_001184150.1. NM_001197221.1. [Q08499-5]
NP_001184151.1. NM_001197222.1.
NP_001184152.1. NM_001197223.1. [Q08499-8]
NP_006194.2. NM_006203.4. [Q08499-2]
XP_005248595.1. XM_005248538.4. [Q08499-2]
XP_011541773.1. XM_011543471.1. [Q08499-11]
XP_011541775.1. XM_011543473.1. [Q08499-11]
XP_016865055.1. XM_017009566.1. [Q08499-11]
UniGeneiHs.117545.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1E9KNMR-A-[»]
1MKDX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L388-715[»]
1OYNX-ray2.00A/B/C/D381-740[»]
1PTWX-ray2.30A/B/C/D381-740[»]
1Q9MX-ray2.30A/B/C/D381-740[»]
1TB7X-ray1.63A/B388-715[»]
1TBBX-ray1.60A/B388-715[»]
1XOMX-ray1.55A/B388-715[»]
1XONX-ray1.72A/B388-715[»]
1XOQX-ray1.83A/B388-715[»]
1XORX-ray1.54A/B388-715[»]
1Y2BX-ray1.40A/B388-715[»]
1Y2CX-ray1.67A/B388-715[»]
1Y2DX-ray1.70A/B388-715[»]
1Y2EX-ray2.10A/B388-715[»]
1Y2KX-ray1.36A/B388-715[»]
1ZKNX-ray2.10A/B/C/D381-714[»]
2FM0X-ray2.00A/B/C/D381-741[»]
2FM5X-ray2.03A/B/C/D381-741[»]
2PW3X-ray1.56A/B388-714[»]
2QYNX-ray1.57A/B388-715[»]
3G4GX-ray2.30A/B/C/D299-347[»]
A/B/C/D360-714[»]
3G4IX-ray1.90A/B/C/D380-753[»]
3G4KX-ray1.95A/B/C/D380-753[»]
3G4LX-ray2.50A/B/C/D380-753[»]
3G58X-ray2.05A/B/C/D380-753[»]
3IADX-ray2.65A/B/C/D326-339[»]
A/B/C/D380-714[»]
3IAKX-ray2.80A388-715[»]
3K4SX-ray2.05A388-715[»]
3SL3X-ray2.10A/B/C/D381-741[»]
3SL4X-ray1.90A/B/C/D381-741[»]
3SL5X-ray2.65A/B/C/D381-714[»]
3SL6X-ray2.44A/B/C/D381-741[»]
3SL8X-ray2.60A/B/C/D381-741[»]
3V9BX-ray2.10A/B/C/D381-740[»]
4OGBX-ray2.03A/B/C/D381-741[»]
4W1OX-ray2.20A/B/C/D381-739[»]
4WCUX-ray2.35A/B/C/D381-739[»]
5K1IX-ray2.61A/B/C/D/E/F/G/H388-713[»]
5K32X-ray1.99A/B390-713[»]
5TKBX-ray2.16A/B/C/D380-753[»]
5WQAX-ray2.30A/B381-714[»]
ProteinModelPortaliQ08499.
SMRiQ08499.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111170. 48 interactors.
DIPiDIP-29709N.
DIP-41115N.
IntActiQ08499. 24 interactors.
MINTiMINT-92262.
STRINGi9606.ENSP00000345502.

Chemistry databases

BindingDBiQ08499.
ChEMBLiCHEMBL288.
DrugBankiDB06842. (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one.
DB04149. (R)-Rolipram.
DB03606. (S)-Rolipram.
DB07954. 3-isobutyl-1-methyl-7H-xanthine.
DB02918. 6-(4-Difluoromethoxy-3-Methoxy-Phenyl)-2h-Pyridazin-3-One.
DB00131. Adenosine monophosphate.
DB05676. Apremilast.
DB00201. Caffeine.
DB03849. Cilomilast.
DB05219. Crisaborole.
DB00651. Dyphylline.
DB05266. Ibudilast.
DB01088. Iloprost.
DB05298. OPC-6535.
DB01791. Piclamilast.
DB01656. Roflumilast.
DB01954. Rolipram.
GuidetoPHARMACOLOGYi1303.

PTM databases

iPTMnetiQ08499.
PhosphoSitePlusiQ08499.

Polymorphism and mutation databases

BioMutaiPDE4D.
DMDMi12644392.

Proteomic databases

MaxQBiQ08499.
PaxDbiQ08499.
PeptideAtlasiQ08499.
PRIDEiQ08499.

Protocols and materials databases

DNASUi5144.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309641; ENSP00000308485; ENSG00000113448. [Q08499-7]
ENST00000317118; ENSP00000321739; ENSG00000113448. [Q08499-8]
ENST00000340635; ENSP00000345502; ENSG00000113448. [Q08499-1]
ENST00000358923; ENSP00000351800; ENSG00000113448. [Q08499-5]
ENST00000360047; ENSP00000353152; ENSG00000113448. [Q08499-2]
ENST00000405755; ENSP00000384806; ENSG00000113448. [Q08499-9]
ENST00000502484; ENSP00000423094; ENSG00000113448. [Q08499-11]
ENST00000502575; ENSP00000425917; ENSG00000113448. [Q08499-12]
ENST00000503258; ENSP00000425605; ENSG00000113448. [Q08499-10]
ENST00000507116; ENSP00000424852; ENSG00000113448. [Q08499-6]
GeneIDi5144.
KEGGihsa:5144.
UCSCiuc003jrs.4. human. [Q08499-1]

Organism-specific databases

CTDi5144.
DisGeNETi5144.
GeneCardsiPDE4D.
HGNCiHGNC:8783. PDE4D.
HPAiHPA045895.
MalaCardsiPDE4D.
MIMi600129. gene.
614613. phenotype.
neXtProtiNX_Q08499.
OpenTargetsiENSG00000113448.
Orphaneti950. Acrodysostosis.
280651. Acrodysostosis with multiple hormone resistance.
PharmGKBiPA33130.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOVERGENiHBG108239.
KOiK13293.
OMAiQHEVEMP.
OrthoDBiEOG091G06CD.
PhylomeDBiQ08499.
TreeFamiTF314638.

Enzyme and pathway databases

UniPathwayiUPA00762; UER00747.
BRENDAi3.1.4.53. 2681.
ReactomeiR-HSA-180024. DARPP-32 events.
R-HSA-418555. G alpha (s) signalling events.
SignaLinkiQ08499.
SIGNORiQ08499.

Miscellaneous databases

ChiTaRSiPDE4D. human.
EvolutionaryTraceiQ08499.
GeneWikiiPDE4D.
GenomeRNAii5144.
PROiPR:Q08499.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113448.
ExpressionAtlasiQ08499. baseline and differential.
GenevisibleiQ08499. HS.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiView protein in InterPro
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
PfamiView protein in Pfam
PF00233. PDEase_I. 1 hit.
PRINTSiPR00387. PDIESTERASE1.
PROSITEiView protein in PROSITE
PS00126. PDEASE_I. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPDE4D_HUMAN
AccessioniPrimary (citable) accession number: Q08499
Secondary accession number(s): O43433
, Q13549, Q13550, Q13551, Q7Z2L8, Q8IV84, Q8IVA9, Q8IVD2, Q8IVD3, Q96HL4, Q9HCX7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 1, 2000
Last modified: June 7, 2017
This is version 189 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.