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Reviewed, UniProtKB/Swiss-Prot Q07343 (PDE4B_HUMAN)

Last modified February 9, 2010. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4B
    EC=3.1.4.17
Alternative name(s):
    DPDE4
    PDE32
Gene names
Name: PDE4B
Synonyms: DPDE4
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length736 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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.

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.

Enzyme regulation

Inhibited by rolipram.

Pathway

Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.

Tissue specificity

Expressed in brain, heart, lung and skeletal muscle.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMetal-binding
cAMP
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processsignal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular componentcytosol Ref.2

Inferred from Experiment. Source: Reactome

insoluble fraction Ref.2

Traceable author statement. Source: ProtInc

soluble fraction Ref.2

Traceable author statement. Source: ProtInc

   Molecular function3',5'-cyclic-AMP phosphodiesterase activity Ref.2

Inferred from Experiment. Source: Reactome

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform PDE4B1 (identifier: Q07343-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform PDE4B2 (identifier: Q07343-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-211: MKKSRSVMTV...QPPVSRVNPQ → MKKEHGGTFS...PNYMPVCLFA
Isoform PDE4B3 (identifier: Q07343-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736cAMP-specific 3',5'-cyclic phosphodiesterase 4B
PRO_0000198809

Regions

Nucleotide binding406 – 4105cAMP

Sites

Active site4061Proton donor
Metal binding4101Divalent metal cation 1
Metal binding4461Divalent metal cation 1
Metal binding4471Divalent metal cation 1
Metal binding4471Divalent metal cation 2
Metal binding5641Divalent metal cation 1
Binding site4471cAMP
Binding site5641cAMP
Binding site6151cAMP
Site5671Binds AMP, but not cAMP By similarity

Amino acid modifications

Modified residue1841Phosphothreonine By similarity
Modified residue2721Phosphoserine By similarity
Modified residue2741Phosphotyrosine By similarity

Natural variations

Alternative sequence1 – 211211MKKSR…RVNPQ → MKKEHGGTFSSTGISGGSGD SAMDSLQPLQPNYMPVCLFA in isoform PDE4B2.
VSP_004572
Alternative sequence1 – 9393MKKSR…TVSQE → MTAKDSSKELTASEPEVCIK TFKEQMHLELELPRLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform PDE4B3.
VSP_004571
Natural variant7031S → C: dbSNP rs2227297.
VAR_034373

Secondary structure

...................................................... 736
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform PDE4B1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 208FCE9CD40EF5EB

FASTA73683,343
        10         20         30         40         50         60 
MKKSRSVMTV MADDNVKDYF ECSLSKSYSS SSNTLGIDLW RGRRCCSGNL QLPPLSQRQS 

        70         80         90        100        110        120 
ERARTPEGDG ISRPTTLPLT TLPSIAITTV SQECFDVENG PSPGRSPLDP QASSSAGLVL 

       130        140        150        160        170        180 
HATFPGHSQR RESFLYRSDS DYDLSPKAMS RNSSLPSEQH GDDLIVTPFA QVLASLRSVR 

       190        200        210        220        230        240 
NNFTILTNLH GTSNKRSPAA SQPPVSRVNP QEESYQKLAM ETLEELDWCL DQLETIQTYR 

       250        260        270        280        290        300 
SVSEMASNKF KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQNDVEIPS PTQKDREKKK 

       310        320        330        340        350        360 
KQQLMTQISG VKKLMHSSSL NNTSISRFGV NTENEDHLAK ELEDLNKWGL NIFNVAGYSH 

       370        380        390        400        410        420 
NRPLTCIMYA IFQERDLLKT FRISSDTFIT YMMTLEDHYH SDVAYHNSLH AADVAQSTHV 

       430        440        450        460        470        480 
LLSTPALDAV FTDLEILAAI FAAAIHDVDH PGVSNQFLIN TNSELALMYN DESVLENHHL 

       490        500        510        520        530        540 
AVGFKLLQEE HCDIFMNLTK KQRQTLRKMV IDMVLATDMS KHMSLLADLK TMVETKKVTS 

       550        560        570        580        590        600 
SGVLLLDNYT DRIQVLRNMV HCADLSNPTK SLELYRQWTD RIMEEFFQQG DKERERGMEI 

       610        620        630        640        650        660 
SPMCDKHTAS VEKSQVGFID YIVHPLWETW ADLVQPDAQD ILDTLEDNRN WYQSMIPQSP 

       670        680        690        700        710        720 
SPPLDEQNRD CQGLMEKFQF ELTLDEEDSE GPEKEGEGHS YFSSTKTLCV IDPENRDSLG 

       730 
ETDIDIATED KSPVDT 

« Hide

Isoform PDE4B2.

Checksum: 5087570D9EB3711E
Show »

FASTA56564,480
Isoform PDE4B3.

Checksum: 49618FFEAFF33D30
Show »

FASTA72182,096

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: 8413254] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE4B1 AND PDE4B2).
Tissue: Brain.
[2]"Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3."
Huston E., Lumb S., Russell A., Catterall C., Ross A.H., Steele M.R., Bolger G.B., Perry M.J., Owens R.J., Houslay M.D.
Biochem. J. 328:549-558(1997) [PubMed: 9371714] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4B3).
[3]"A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human brain. Cloning and expression of cDNA, biochemical characterization of recombinant protein, and tissue distribution of mRNA."
McLaughlin M.M., Cieslinski L.B., Burman M., Torphy T.J., Livi G.P.
J. Biol. Chem. 268:6470-6476(1993) [PubMed: 8384210] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4B2).
Tissue: Brain.
[4]"Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity."
Xu R.X., Hassell A.M., Vanderwall D., Lambert M.H., Holmes W.D., Luther M.A., Rocque W.J., Milburn M.V., Zhao Y., Ke H., Nolte R.T.
Science 288:1822-1825(2000) [PubMed: 10846163] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 324-700 IN COMPLEX WITH METAL IONS, FUNCTION, COFACTOR.
[5]"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: 15003452] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 324-700 IN COMPLEX WITH AMP; METAL IONS AND THE INHIBITOR ROLIPRAM, FUNCTION, COFACTOR.
[6]"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: 15260978] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 324-700 IN COMPLEX WITH AMP AND METAL IONS.
[7]"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: 15576036] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 324-700 IN COMPLEX WITH METAL IONS AND INHIBITORS.
[8]"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: 15685167] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 324-700 IN COMPLEX WITH METAL IONS AND INHIBITORS.
[9]"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: 17727341] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 324-659 IN COMPLEX WITH METAL IONS AND THE INHIBITOR NVP.
[10]"Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors."
Hamblin J.N., Angell T.D.R., Ballantine S.P., Cook C.M., Cooper A.W.J., Dawson J., Delves C.J., Jones P.S., Lindvall M., Lucas F.S., Mitchell C.J., Neu M.Y., Ranshaw L.E., Solanke Y.E., Somers D.O., Wiseman J.O.
Bioorg. Med. Chem. Lett. 18:4237-4241(2008) [PubMed: 18539455] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 324-675 IN COMPLEX WITH METAL IONS AND INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L20966 mRNA. Translation: AAA03589.1.
L20971 mRNA. Translation: AAA03593.1.
M97515 mRNA. Translation: AAA36426.1.
U85048 mRNA. Translation: AAB96381.1.
IPIIPI00016604.
IPI00183599.
IPI00220621.
PIRI61354.
RefSeqNP_001032416.1.
NP_001032417.1.
NP_001032418.1.
NP_002591.2.
UniGeneHs.198072

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
3HC8X-ray1.79A451-474[»]
3HDZX-ray1.80A451-474[»]
3KKTX-ray2.48A/B324-700[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ07343. 3 interactions.
STRINGQ07343.

PTM databases

PhosphoSiteQ07343.

Proteomic databases

PRIDEQ07343.

Genome annotation databases

EnsemblENST00000329654; ENSP00000332116; ENSG00000184588; Homo sapiens. [Genome view]
ENST00000371049; ENSP00000360088; ENSG00000184588; Homo sapiens. [Genome view]
GeneID5142.
KEGGhsa:5142.
UCSCuc001dcn.1. human.

Organism-specific databases

CTD5142.
GeneCardsGC01P065970.
H-InvDBHIX0000677.
HGNCHGNC:8781. PDE4B.
HPAHPA003005.
MIM600127. gene.
PharmGKBPA33129.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14687.
HOGENOMHBG315913.
HOVERGENQ07343.
InParanoidQ07343.
OMAGEGHNYF.
OrthoDBEOG9BK7PW.
PhylomeDBQ07343.

Enzyme and pathway databases

BRENDA3.1.4.17. 247.
ReactomeREACT_14797. Signaling by GPCR.
REACT_15295. Opioid Signalling.

Gene expression databases

ArrayExpressQ07343.
BgeeQ07343.
CleanExHS_PDE4B.
GenevestigatorQ07343.
GermOnlineENSG00000184588. Homo sapiens.

Family and domain databases

InterProIPR003607. Metal-dep_PHydrolase_HD_dom.
IPR002073. PDEase.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00131. Adenosine monophosphate.
DB01427. Amrinone.
DB00201. Caffeine.
DB01166. Cilostazol.
DB00651. Dyphylline.
DB00824. Enprofylline.
DB01113. Papaverine.
DB00806. Pentoxifylline.
DB00277. Theophylline.
NextBio19828.
SOURCESearch...

Entry information

Entry namePDE4B_HUMAN
AccessionPrimary (citable) accession number: Q07343
Secondary accession number(s): O15443
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: February 9, 2010
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents