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Q13370 (PDE3B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cGMP-inhibited 3',5'-cyclic phosphodiesterase B

EC=3.1.4.17
Alternative name(s):
CGIPDE1
Short name=CGIP1
Cyclic GMP-inhibited phosphodiesterase B
Short name=CGI-PDE B
Gene names
Name:PDE3B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1112 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. May play a role in fat metabolism. Regulates cAMP binding of RAPGEF3. Through simultaneous binding to RAPGEF3 and PIK3R6 assembles a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. Ref.10 Ref.11

Catalytic activity

Nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 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.11

Enzyme regulation

Inhibited by cGMP.

Subunit structure

Interacts with PIK3CG By similarity. Interacts with RAPGEF3 and PIK3R6. Ref.10

Subcellular location

Membrane; Multi-pass membrane protein Potential.

Tissue specificity

Abundant in adipose tissues.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE3 subfamily.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandcAMP
cGMP
Metal-binding
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood coagulation

Traceable author statement. Source: Reactome

cAMP catabolic process

Inferred from expression pattern PubMed 17884339PubMed 18586889. Source: BHF-UCL

cellular response to insulin stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

endocrine pancreas development

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

negative regulation of angiogenesis

Inferred from mutant phenotype Ref.10. Source: UniProtKB

negative regulation of cAMP-mediated signaling

Inferred by curator PubMed 17884339. Source: BHF-UCL

negative regulation of cell adhesion

Inferred from mutant phenotype PubMed 17884339. Source: BHF-UCL

negative regulation of cell adhesion mediated by integrin

Inferred by curator PubMed 17884339. Source: BHF-UCL

negative regulation of lipid catabolic process

Inferred from mutant phenotype PubMed 11641262. Source: BHF-UCL

regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: BHF-UCL

guanyl-nucleotide exchange factor complex

Inferred from direct assay PubMed 17884339. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 18586889. Source: BHF-UCL

   Molecular_function3',5'-cyclic-nucleotide phosphodiesterase activity

Traceable author statement PubMed 17884339. Source: BHF-UCL

cGMP-inhibited cyclic-nucleotide phosphodiesterase activity

Traceable author statement Ref.1. Source: ProtInc

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.10. Source: IntAct

protein kinase B binding

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13370-1)

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 2 (identifier: Q13370-2)

The sequence of this isoform differs from the canonical sequence as follows:
     376-426: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11121112cGMP-inhibited 3',5'-cyclic phosphodiesterase B
PRO_0000198802

Regions

Transmembrane88 – 10821Helical; Potential
Transmembrane117 – 13721Helical; Potential
Transmembrane152 – 17221Helical; Potential
Transmembrane192 – 21221Helical; Potential
Transmembrane220 – 24021Helical; Potential
Transmembrane247 – 26721Helical; Potential
Region1 – 2525Interaction with RAPGEF3
Region436 – 46025Interaction with PIK3R6
Region713 – 1072360Catalytic By similarity
Compositional bias1077 – 10804Poly-Glu

Sites

Active site7371Proton donor By similarity
Metal binding7411Divalent metal cation 1
Metal binding8211Divalent metal cation 1
Metal binding8221Divalent metal cation 1
Metal binding8221Divalent metal cation 2
Metal binding9371Divalent metal cation 1

Amino acid modifications

Modified residue2951Phosphoserine; by PKB/AKT1 or PKB/AKT2 By similarity
Modified residue4421Phosphoserine Ref.9

Natural variations

Alternative sequence376 – 42651Missing in isoform 2.
VSP_054138
Natural variant871A → V. Ref.3
Corresponds to variant rs1056584 [ dbSNP | Ensembl ].
VAR_031462

Experimental info

Mutagenesis21R → A: Abolishes interaction with RAPGEF3. Ref.10
Mutagenesis31R → A: Abolishes interaction with RAPGEF3. Ref.10
Mutagenesis61R → A: Abolishes interaction with RAPGEF3. Ref.10
Mutagenesis81A → D: Impairs interaction with RAPGEF3. Ref.10
Mutagenesis91K → A: Abolishes interaction with RAPGEF3. Ref.10
Mutagenesis101A → D: Impairss interaction with RAPGEF3. Ref.10
Mutagenesis121R → A: Abolishes interaction with RAPGEF3. Ref.10
Mutagenesis4391R → A: Impairss interaction with PIK3R6. Ref.10
Mutagenesis4401R → A: Impairss interaction with PIK3R6. Ref.10
Mutagenesis4451S → A: Impairss interaction with PIK3R6. Ref.10
Mutagenesis4491P → A: Impairss interaction with PIK3R6. Ref.10
Sequence conflict841A → D in AAC50724. Ref.1
Sequence conflict841A → D in BAA09306. Ref.2

Secondary structure

..................................................... 1112
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 3, 2007. Version 2.
Checksum: 55451C3DA142EF6A

FASTA1,112124,333
        10         20         30         40         50         60 
MRRDERDAKA MRSLQPPDGA GSPPESLRNG YVKSCVSPLR QDPPRGFFFH LCRFCNVELR 

        70         80         90        100        110        120 
PPPASPQQPR RCSPFCRARL SLGALAAFVL ALLLGAEPES WAAGAAWLRT LLSVCSHSLS 

       130        140        150        160        170        180 
PLFSIACAFF FLTCFLTRTK RGPGPGRSCG SWWLLALPAC CYLGDFLVWQ WWSWPWGDGD 

       190        200        210        220        230        240 
AGSAAPHTPP EAAAGRLLLV LSCVGLLLTL AHPLRLRHCV LVLLLASFVW WVSFTSLGSL 

       250        260        270        280        290        300 
PSALRPLLSG LVGGAGCLLA LGLDHFFQIR EAPLHPRLSS AAEEKVPVIR PRRRSSCVSL 

       310        320        330        340        350        360 
GETAASYYGS CKIFRRPSLP CISREQMILW DWDLKQWYKP HYQNSGGGNG VDLSVLNEAR 

       370        380        390        400        410        420 
NMVSDLLTDP SLPPQVISSL RSISSLMGAF SGSCRPKINP LTPFPGFYPC SEIEDPAEKG 

       430        440        450        460        470        480 
DRKLNKGLNR NSLPTPQLRR SSGTSGLLPV EQSSRWDRNN GKRPHQEFGI SSQGCYLNGP 

       490        500        510        520        530        540 
FNSNLLTIPK QRSSSVSLTH HVGLRRAGVL SSLSPVNSSN HGPVSTGSLT NRSPIEFPDT 

       550        560        570        580        590        600 
ADFLNKPSVI LQRSLGNAPN TPDFYQQLRN SDSNLCNSCG HQMLKYVSTS ESDGTDCCSG 

       610        620        630        640        650        660 
KSGEEENIFS KESFKLMETQ QEEETEKKDS RKLFQEGDKW LTEEAQSEQQ TNIEQEVSLD 

       670        680        690        700        710        720 
LILVEEYDSL IEKMSNWNFP IFELVEKMGE KSGRILSQVM YTLFQDTGLL EIFKIPTQQF 

       730        740        750        760        770        780 
MNYFRALENG YRDIPYHNRI HATDVLHAVW YLTTRPVPGL QQIHNGCGTG NETDSDGRIN 

       790        800        810        820        830        840 
HGRIAYISSK SCSNPDESYG CLSSNIPALE LMALYVAAAM HDYDHPGRTN AFLVATNAPQ 

       850        860        870        880        890        900 
AVLYNDRSVL ENHHAASAWN LYLSRPEYNF LLHLDHVEFK RFRFLVIEAI LATDLKKHFD 

       910        920        930        940        950        960 
FLAEFNAKAN DVNSNGIEWS NENDRLLVCQ VCIKLADING PAKVRDLHLK WTEGIVNEFY 

       970        980        990       1000       1010       1020 
EQGDEEANLG LPISPFMDRS SPQLAKLQES FITHIVGPLC NSYDAAGLLP GQWLEAEEDN 

      1030       1040       1050       1060       1070       1080 
DTESGDDEDG EELDTEDEEM ENNLNPKPPR RKSRRRIFCQ LMHHLTENHK IWKEIVEEEE 

      1090       1100       1110 
KCKADGNKLQ VENSSLPQAD EIQVIEEADE EE 

« Hide

Isoform 2 [UniParc].

Checksum: 755DBD55004867DC
Show »

FASTA1,061118,809

References

« Hide 'large scale' references
[1]"Characterization of the cDNA and gene encoding human PDE3B, the cGIP1 isoform of the human cyclic GMP-inhibited cyclic nucleotide phosphodiesterase family."
Miki T., Taira M., Hockman S., Shimada F., Lieman J., Napolitano M., Ward D., Taira M., Makino H., Manganiello V.C.
Genomics 36:476-485(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Adipose tissue.
[2]"Differential expression of cGMP-inhibited cyclic nucleotide phosphodiesterases in human hepatoma cell lines."
Murata T., Taira M., Manganiello V.C.
FEBS Lett. 390:29-33(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A) -- a gene involved in fat metabolism located at 11p15.1."
Loebbert R.W., Winterpacht A., Seipel B., Zabel B.U.
Genomics 37:211-218(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-87.
[4]"Importance of cAMP-response element-binding protein in regulation of expression of the murine cyclic nucleotide phosphodiesterase 3B (Pde3b) gene in differentiating 3T3-L1 preadipocytes."
Liu H., Tang J.R., Choi Y.H., Napolitano M., Hockman S., Taira M., Degerman E., Manganiello V.C.
J. Biol. Chem. 281:21096-21113(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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 1 AND 2).
[8]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"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-442, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells."
Wilson L.S., Baillie G.S., Pritchard L.M., Umana B., Terrin A., Zaccolo M., Houslay M.D., Maurice D.H.
J. Biol. Chem. 286:16285-16296(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAPGEF3 AND PIK3R6, MUTAGENESIS OF ARG-2; ARG-3; ARG-6; ALA-8; LYS-9; ALA-10; ARG-12; ARG-439; ARG-440; SER-445 AND PRO-449.
[11]"Crystal structure of human phosphodiesterase 3B: atomic basis for substrate and inhibitor specificity."
Scapin G., Patel S.B., Chung C., Varnerin J.P., Edmondson S.D., Mastracchio A., Parmee E.R., Singh S.B., Becker J.W., Van der Ploeg L.H., Tota M.R.
Biochemistry 43:6091-6100(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 654-1073 IN COMPLEX WITH METAL IONS AND INHIBITORS, FUNCTION, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U38178 Genomic DNA. Translation: AAC50724.1.
D50640 Genomic DNA. Translation: BAA09306.1.
X95520 mRNA. Translation: CAA64774.1.
AY459346 mRNA. Translation: AAR24292.1.
AC018795 Genomic DNA. No translation available.
AC087207 Genomic DNA. No translation available.
AC090835 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68474.1.
BC136565 mRNA. Translation: AAI36566.1.
BC136566 mRNA. Translation: AAI36567.1.
BC144248 mRNA. Translation: AAI44249.1.
CCDSCCDS7817.1.
PIRS70522.
RefSeqNP_000913.2. NM_000922.3. [Q13370-1]
UniGeneHs.445711.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SO2X-ray2.40A/B/C/D654-1073[»]
1SOJX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L654-1073[»]
ProteinModelPortalQ13370.
SMRQ13370. Positions 656-1073.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111166. 3 interactions.
IntActQ13370. 3 interactions.
STRING9606.ENSP00000282096.

Chemistry

BindingDBQ13370.
ChEMBLCHEMBL2095153.
GuidetoPHARMACOLOGY1299.

PTM databases

PhosphoSiteQ13370.

Polymorphism databases

DMDM143811435.

Proteomic databases

MaxQBQ13370.
PaxDbQ13370.
PRIDEQ13370.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282096; ENSP00000282096; ENSG00000152270.
ENST00000455098; ENSP00000388644; ENSG00000152270.
ENST00000574273; ENSP00000459710; ENSG00000261923.
GeneID5140.
KEGGhsa:5140.
UCSCuc001mln.3. human. [Q13370-1]

Organism-specific databases

CTD5140.
GeneCardsGC11P014621.
HGNCHGNC:8779. PDE3B.
HPACAB009497.
HPA024342.
MIM602047. gene.
neXtProtNX_Q13370.
PharmGKBPA33127.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG145074.
HOGENOMHOG000060144.
HOVERGENHBG053541.
InParanoidQ13370.
KOK13296.
OMASIHESEY.
PhylomeDBQ13370.
TreeFamTF329631.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_1123. Inhibition of HSL.
REACT_604. Hemostasis.
SignaLinkQ13370.

Gene expression databases

ArrayExpressQ13370.
BgeeQ13370.
CleanExHS_PDE3B.
GenevestigatorQ13370.

Family and domain databases

Gene3D1.10.1300.10. 2 hits.
InterProIPR003607. HD/PDEase_dom.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDE3B. human.
EvolutionaryTraceQ13370.
GenomeRNAi5140.
NextBio19820.
PROQ13370.
SOURCESearch...

Entry information

Entry namePDE3B_HUMAN
AccessionPrimary (citable) accession number: Q13370
Secondary accession number(s): B7ZM37 expand/collapse secondary AC list , O00639, Q14408, Q6SEI4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: April 3, 2007
Last modified: July 9, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM