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Protein

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

Gene

PDE4B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.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.

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 8A (PDE8A), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B)
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 sitei406Proton donor1
Metal bindingi410Divalent metal cation 11
Metal bindingi446Divalent metal cation 11
Metal bindingi447Divalent metal cation 11
Metal bindingi447Divalent metal cation 21
Binding sitei447cAMP1
Metal bindingi564Divalent metal cation 11
Binding sitei564cAMP1
Sitei567Binds AMP, but not cAMPBy similarity1
Binding sitei615cAMP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi406 – 410cAMP5

GO - Molecular functioni

  • 3',5'-cyclic-AMP phosphodiesterase activity Source: BHF-UCL
  • cAMP binding Source: BHF-UCL
  • gamma-tubulin binding Source: Ensembl
  • ion channel binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

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
SIGNORiQ07343
UniPathwayiUPA00762; UER00747

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4B (EC:3.1.4.53)
Alternative name(s):
DPDE4
PDE32
Gene namesi
Name:PDE4B
Synonyms:DPDE4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000184588.17
HGNCiHGNC:8781 PDE4B
MIMi600127 gene
neXtProtiNX_Q07343

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi5142
OpenTargetsiENSG00000184588
PharmGKBiPA33129

Chemistry databases

ChEMBLiCHEMBL275
DrugBankiDB01647 (R)-Mesopram
DB04149 (R)-Rolipram
DB03606 (S)-Rolipram
DB03349 8-Bromo-Adenosine-5'-Monophosphate
DB00131 Adenosine monophosphate
DB01427 Amrinone
DB05676 Apremilast
DB00201 Caffeine
DB03849 Cilomilast
DB05219 Crisaborole
DB00651 Dyphylline
DB00824 Enprofylline
DB02660 Filaminast
DB05266 Ibudilast
DB01088 Iloprost
DB01113 Papaverine
DB00806 Pentoxifylline
DB01791 Piclamilast
DB01656 Roflumilast
DB01954 Rolipram
DB01412 Theobromine
DB00277 Theophylline
GuidetoPHARMACOLOGYi1301

Polymorphism and mutation databases

BioMutaiPDE4B
DMDMi729163

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988091 – 736cAMP-specific 3',5'-cyclic phosphodiesterase 4BAdd BLAST736

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei290PhosphoserineBy similarity1
Modified residuei659PhosphoserineBy similarity1
Modified residuei661PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ07343
PeptideAtlasiQ07343
PRIDEiQ07343
ProteomicsDBi58512
58513 [Q07343-2]
58514 [Q07343-3]

PTM databases

iPTMnetiQ07343
PhosphoSitePlusiQ07343

Expressioni

Tissue specificityi

Expressed in brain, heart, lung and skeletal muscle.

Gene expression databases

BgeeiENSG00000184588
CleanExiHS_PDE4B
ExpressionAtlasiQ07343 baseline and differential
GenevisibleiQ07343 HS

Organism-specific databases

HPAiHPA003005

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111168, 11 interactors
CORUMiQ07343
ELMiQ07343
IntActiQ07343, 4 interactors
STRINGi9606.ENSP00000332116

Chemistry databases

BindingDBiQ07343

Structurei

Secondary structure

1736
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi168 – 183Combined sources16
Helixi217 – 235Combined sources19
Helixi239 – 264Combined sources26
Helixi266 – 279Combined sources14
Helixi324 – 327Combined sources4
Beta strandi328 – 330Combined sources3
Turni332 – 334Combined sources3
Helixi335 – 342Combined sources8
Turni343 – 346Combined sources4
Helixi352 – 358Combined sources7
Turni359 – 361Combined sources3
Helixi363 – 374Combined sources12
Helixi377 – 380Combined sources4
Helixi385 – 397Combined sources13
Beta strandi403 – 407Combined sources5
Helixi408 – 422Combined sources15
Helixi425 – 427Combined sources3
Turni428 – 430Combined sources3
Helixi433 – 445Combined sources13
Turni446 – 449Combined sources4
Helixi455 – 460Combined sources6
Helixi464 – 468Combined sources5
Turni469 – 471Combined sources3
Helixi474 – 486Combined sources13
Helixi490 – 492Combined sources3
Turni494 – 497Combined sources4
Helixi500 – 515Combined sources16
Helixi519 – 521Combined sources3
Helixi522 – 534Combined sources13
Beta strandi540 – 542Combined sources3
Helixi549 – 564Combined sources16
Helixi567 – 569Combined sources3
Helixi572 – 595Combined sources24
Helixi602 – 604Combined sources3
Turni606 – 608Combined sources3
Helixi611 – 621Combined sources11
Helixi623 – 633Combined sources11
Turni634 – 638Combined sources5
Helixi639 – 654Combined sources16
Beta strandi656 – 658Combined sources3
Beta strandi659 – 662Combined sources4
Helixi664 – 666Combined sources3
Helixi671 – 677Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1F0JX-ray1.77A/B324-700[»]
1JP1model-A324-700[»]
1JP2model-A324-700[»]
1RO6X-ray2.00A/B324-700[»]
1RO9X-ray2.13A/B324-700[»]
1RORX-ray2.00A/B324-700[»]
1TB5X-ray2.15A/B324-700[»]
1XLXX-ray2.19A/B324-700[»]
1XLZX-ray2.06A/B324-700[»]
1XM4X-ray2.31A/B324-700[»]
1XM6X-ray1.92A/B324-700[»]
1XMUX-ray2.30A/B324-700[»]
1XMYX-ray2.40A/B324-700[»]
1XN0X-ray2.31A/B324-700[»]
1XOSX-ray2.28A324-700[»]
1XOTX-ray2.34A/B324-700[»]
1Y2HX-ray2.40A/B324-700[»]
1Y2JX-ray2.55A/B324-700[»]
2CHMX-ray1.60A450-475[»]
2QYLX-ray1.95A324-659[»]
3D3PX-ray1.75A324-675[»]
3FRGX-ray1.70A324-675[»]
3G45X-ray2.63A/B241-289[»]
A/B305-659[»]
3GWTX-ray1.75A324-675[»]
3HC8X-ray1.79A451-474[»]
3HDZX-ray1.80A451-474[»]
3HMVX-ray2.23A/B324-700[»]
3KKTX-ray2.48A/B324-700[»]
3LY2X-ray2.60A/B/C/D/E/F/G/H324-659[»]
3O0JX-ray1.95A334-656[»]
3O56X-ray2.42A324-675[»]
3O57X-ray2.00A324-675[»]
3W5EX-ray2.30A/B324-700[»]
3WD9X-ray2.50A/B324-700[»]
4KP6X-ray1.50A324-659[»]
4MYQX-ray1.90A324-691[»]
4NW7X-ray2.15A324-691[»]
4WZIX-ray2.58A/B122-736[»]
4X0FX-ray3.22A/B122-736[»]
5K6JX-ray1.86A334-656[»]
5LAQX-ray2.40A241-289[»]
A305-659[»]
5OHJX-ray1.60A/B241-659[»]
ProteinModelPortaliQ07343
SMRiQ07343
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ07343

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini330 – 659PDEasePROSITE-ProRule annotationAdd BLAST330

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000118889
HOGENOMiHOG000236297
HOVERGENiHBG108239
KOiK13293
OMAiTCFDVEN
OrthoDBiEOG091G06CD
PhylomeDBiQ07343
TreeFamiTF314638

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform PDE4B1 (identifier: Q07343-1) [UniParc]FASTAAdd to basket

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
MKKSRSVMTV MADDNVKDYF ECSLSKSYSS SSNTLGIDLW RGRRCCSGNL
60 70 80 90 100
QLPPLSQRQS ERARTPEGDG ISRPTTLPLT TLPSIAITTV SQECFDVENG
110 120 130 140 150
PSPGRSPLDP QASSSAGLVL HATFPGHSQR RESFLYRSDS DYDLSPKAMS
160 170 180 190 200
RNSSLPSEQH GDDLIVTPFA QVLASLRSVR NNFTILTNLH GTSNKRSPAA
210 220 230 240 250
SQPPVSRVNP QEESYQKLAM ETLEELDWCL DQLETIQTYR SVSEMASNKF
260 270 280 290 300
KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQNDVEIPS PTQKDREKKK
310 320 330 340 350
KQQLMTQISG VKKLMHSSSL NNTSISRFGV NTENEDHLAK ELEDLNKWGL
360 370 380 390 400
NIFNVAGYSH NRPLTCIMYA IFQERDLLKT FRISSDTFIT YMMTLEDHYH
410 420 430 440 450
SDVAYHNSLH AADVAQSTHV LLSTPALDAV FTDLEILAAI FAAAIHDVDH
460 470 480 490 500
PGVSNQFLIN TNSELALMYN DESVLENHHL AVGFKLLQEE HCDIFMNLTK
510 520 530 540 550
KQRQTLRKMV IDMVLATDMS KHMSLLADLK TMVETKKVTS SGVLLLDNYT
560 570 580 590 600
DRIQVLRNMV HCADLSNPTK SLELYRQWTD RIMEEFFQQG DKERERGMEI
610 620 630 640 650
SPMCDKHTAS VEKSQVGFID YIVHPLWETW ADLVQPDAQD ILDTLEDNRN
660 670 680 690 700
WYQSMIPQSP SPPLDEQNRD CQGLMEKFQF ELTLDEEDSE GPEKEGEGHS
710 720 730
YFSSTKTLCV IDPENRDSLG ETDIDIATED KSPVDT
Length:736
Mass (Da):83,343
Last modified:February 1, 1995 - v1
Checksum:i208FCE9CD40EF5EB
GO
Isoform PDE4B2 (identifier: Q07343-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-211: MKKSRSVMTV...QPPVSRVNPQ → MKEHGGTFSS...PNYMPVCLFA

Show »
Length:564
Mass (Da):64,352
Checksum:iA4F9FA0C5DB43380
GO
Isoform PDE4B3 (identifier: Q07343-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MKKSRSVMTV...SIAITTVSQE → MTAKDSSKEL...QRRRFTVAHT

Show »
Length:721
Mass (Da):82,096
Checksum:i49618FFEAFF33D30
GO
Isoform PDE4B5 (identifier: Q07343-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MKKSRSVMTVMADDN → MPEANYLLSVSWGYI
     16-248: Missing.

Note: Brain-specific isoform.
Show »
Length:503
Mass (Da):57,709
Checksum:i23AF122BAF338C42
GO

Sequence cautioni

The sequence AAA35643 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034373703S → C. Corresponds to variant dbSNP:rs2227297Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045721 – 211MKKSR…RVNPQ → MKEHGGTFSSTGISGGSGDS AMDSLQPLQPNYMPVCLFA in isoform PDE4B2. 3 PublicationsAdd BLAST211
Alternative sequenceiVSP_0045711 – 93MKKSR…TVSQE → MTAKDSSKELTASEPEVCIK TFKEQMHLELELPRLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform PDE4B3. 2 PublicationsAdd BLAST93
Alternative sequenceiVSP_0477231 – 15MKKSR…MADDN → MPEANYLLSVSWGYI in isoform PDE4B5. 2 PublicationsAdd BLAST15
Alternative sequenceiVSP_04772416 – 248Missing in isoform PDE4B5. 2 PublicationsAdd BLAST233

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12686 mRNA Translation: AAA35643.1 Different initiation.
L20966 mRNA Translation: AAA03589.1
L20971 mRNA Translation: AAA03593.1
U85048 mRNA Translation: AAB96381.1
M97515 mRNA Translation: AAA36426.1
EF595686 mRNA Translation: ABQ85407.1
AK289969 mRNA Translation: BAF82658.1
AK290006 mRNA Translation: BAF82695.1
AK290206 mRNA Translation: BAF82895.1
AL592285 Genomic DNA No translation available.
AL357273 Genomic DNA No translation available.
AL109926 Genomic DNA No translation available.
AL359701 Genomic DNA No translation available.
AL513493 Genomic DNA No translation available.
AL590783 Genomic DNA No translation available.
AL591487 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06524.1
BC101480 mRNA Translation: AAI01481.1
BC105040 mRNA Translation: AAI05041.1
CCDSiCCDS30742.1 [Q07343-3]
CCDS30743.1 [Q07343-2]
CCDS632.1 [Q07343-1]
CCDS72802.1 [Q07343-4]
PIRiI61354
RefSeqiNP_001032416.1, NM_001037339.2 [Q07343-2]
NP_001032417.1, NM_001037340.2 [Q07343-3]
NP_001032418.1, NM_001037341.1 [Q07343-1]
NP_001284369.1, NM_001297440.1
NP_001284370.1, NM_001297441.1
NP_001284371.1, NM_001297442.1 [Q07343-4]
NP_002591.2, NM_002600.3 [Q07343-1]
UniGeneiHs.198072

Genome annotation databases

EnsembliENST00000329654; ENSP00000332116; ENSG00000184588 [Q07343-1]
ENST00000341517; ENSP00000342637; ENSG00000184588 [Q07343-1]
ENST00000371045; ENSP00000360084; ENSG00000184588 [Q07343-2]
ENST00000423207; ENSP00000392947; ENSG00000184588 [Q07343-3]
ENST00000480109; ENSP00000432592; ENSG00000184588 [Q07343-4]
GeneIDi5142
KEGGihsa:5142
UCSCiuc001dcp.4 human [Q07343-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPDE4B_HUMAN
AccessioniPrimary (citable) accession number: Q07343
Secondary accession number(s): A5YW33
, O15443, Q13945, Q5TEK4, Q5TEK5, Q5TEK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: June 20, 2018
This is version 180 of the entry and version 1 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

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