Q13370 (PDE3B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	1112 AA.
Sequence status	Complete.
Protein existence	Evidence 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.9 Ref.10
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.10
Enzyme regulation	Inhibited by cGMP.
Subunit structure	Interacts with PIK3CG By similarity. Interacts with RAPGEF3 and PIK3R6. Ref.9
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 process	Angiogenesis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Metal-binding cAMP cGMP
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis 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 endocrine pancreas development Inferred from electronic annotation. Source: Compara glucose homeostasis Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of angiogenesis Inferred from mutant phenotype Ref.9. Source: UniProtKB negative regulation of cAMP-mediated signaling Inferred by curator 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: Compara
Cellular_component	Golgi 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 to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane Inferred from direct assay PubMed 18586889. Source: BHF-UCL
Molecular_function	cGMP-inhibited cyclic-nucleotide phosphodiesterase activity Traceable author statement Ref.1. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase B binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PIK3CG	P48736	3	EBI-6172856,EBI-1030384
PIK3R6	Q5UE93	3	EBI-6172856,EBI-6172907
RAPGEF3	O95398	8	EBI-6172856,EBI-6172806

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1112

1112

cGMP-inhibited 3',5'-cyclic phosphodiesterase B

PRO_0000198802

Regions

Transmembrane

88 – 108

21

Helical; Potential

Transmembrane

117 – 137

21

Helical; Potential

Transmembrane

152 – 172

21

Helical; Potential

Transmembrane

192 – 212

21

Helical; Potential

Transmembrane

220 – 240

21

Helical; Potential

Transmembrane

247 – 267

21

Helical; Potential

Region

1 – 25

25

Interaction with RAPGEF3

Region

436 – 460

25

Interaction with PIK3R6

Region

713 – 1072

360

Catalytic By similarity

Compositional bias

1077 – 1080

4

Poly-Glu

Sites

Active site

737

1

Proton donor By similarity

Metal binding

741

1

Divalent metal cation 1

Metal binding

821

1

Divalent metal cation 1

Metal binding

822

1

Divalent metal cation 1

Metal binding

822

1

Divalent metal cation 2

Metal binding

937

1

Divalent metal cation 1

Amino acid modifications

Modified residue

295

1

Phosphoserine; by PKB/AKT1 or PKB/AKT2 By similarity

Modified residue

442

1

Phosphoserine Ref.8

Modified residue

625

1

Phosphothreonine By similarity

Natural variations

Natural variant

87

1

A → V. Ref.3
Corresponds to variant rs1056584 [ dbSNP | Ensembl ].

VAR_031462

Experimental info

Mutagenesis

2

1

R → A: Abolishes interaction with RAPGEF3. Ref.9

Mutagenesis

3

1

R → A: Abolishes interaction with RAPGEF3. Ref.9

Mutagenesis

6

1

R → A: Abolishes interaction with RAPGEF3. Ref.9

Mutagenesis

8

1

A → D: Impairs interaction with RAPGEF3. Ref.9

Mutagenesis

9

1

K → A: Abolishes interaction with RAPGEF3. Ref.9

Mutagenesis

10

1

A → D: Impairss interaction with RAPGEF3. Ref.9

Mutagenesis

12

1

R → A: Abolishes interaction with RAPGEF3. Ref.9

Mutagenesis

439

1

R → A: Impairss interaction with PIK3R6. Ref.9

Mutagenesis

440

1

R → A: Impairss interaction with PIK3R6. Ref.9

Mutagenesis

445

1

S → A: Impairss interaction with PIK3R6. Ref.9

Mutagenesis

449

1

P → A: Impairss interaction with PIK3R6. Ref.9

Sequence conflict

84

1

A → D in AAC50724. Ref.1

Sequence conflict

84

1

A → D in BAA09306. Ref.2

Secondary structure

1

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1112

Helix Strand Turn

Details...

Helix

662 – 674

13

Helix

681 – 688

8

Helix

689 – 694

6

Helix

695 – 706

12

Helix

709 – 712

4

Helix

717 – 728

12

Beta strand

735 – 738

4

Helix

739 – 752

14

Helix

802 – 804

3

Helix

808 – 820

13

Turn

821 – 824

4

Helix

830 – 835

6

Helix

839 – 843

5

Turn

844 – 846

3

Helix

849 – 863

15

Helix

866 – 868

3

Turn

870 – 873

4

Helix

876 – 891

16

Helix

895 – 897

3

Helix

898 – 909

12

Beta strand

911 – 913

3

Helix

922 – 937

16

Helix

940 – 942

3

Helix

945 – 968

24

Helix

984 – 994

11

Helix

996 – 1005

10

Beta strand

1012 – 1015

4

Beta strand

1055 – 1058

4

Helix

1060 – 1072

13

Sequences

	Sequence		Length	Mass (Da)
	Q13370 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 55451C3DA142EF6A	FASTA	1,112	124,333
	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

References

	« Hide 'large scale' referencesShow '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], 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].
[5]	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. , 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].
[6]	"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].
[7]	"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.
[8]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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.
[10]	"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.
CH471064 Genomic DNA. Translation: EAW68474.1.
BC136565 mRNA. Translation: AAI36566.1.
BC136566 mRNA. Translation: AAI36567.1.

IPI

IPI00012843.

PIR

S70522.

RefSeq

NP_000913.2. NM_000922.3.

UniGene

Hs.445711.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SO2	X-ray	2.40	A/B/C/D	654-1073	[»]
1SOJ	X-ray	2.90	A/B/C/D/E/F/G/H/I/J/K/L	654-1073	[»]

ProteinModelPortal

Q13370.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13370. 3 interactions.

STRING

9606.ENSP00000282096.

PTM databases

PhosphoSite

Q13370.

Polymorphism databases

DMDM

143811435.

Proteomic databases

PaxDb

Q13370.

PRIDE

Q13370.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000282096; ENSP00000282096; ENSG00000152270.
ENST00000574273; ENSP00000459710; ENSG00000261923.

GeneID

5140.

KEGG

hsa:5140.

UCSC

uc001mln.3. human.

Organism-specific databases

CTD

5140.

GeneCards

GC11P014621.

HGNC

HGNC:8779. PDE3B.

HPA

CAB009497.
HPA024342.

MIM

602047. gene.

neXtProt

NX_Q13370.

PharmGKB

PA33127.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG145074.

HOGENOM

HOG000060144.

HOVERGEN

HBG053541.

InParanoid

Q13370.

KO

K13296.

OMA

NGYVKSC.

OrthoDB

EOG4GB75F.

PhylomeDB

Q13370.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kcibpathway. Class IB PI3K non-lipid kinase events.

Reactome

REACT_111102. Signal Transduction.
REACT_1123. Inhibition of HSL.
REACT_604. Hemostasis.

SignaLink

Q13370.

Gene expression databases

ArrayExpress

Q13370.

Bgee

Q13370.

CleanEx

HS_PDE3B.

Genevestigator

Q13370.

GermOnline

ENSG00000152270. Homo sapiens.

Family and domain databases

Gene3D

1.10.1300.10. 2 hits.

InterPro

IPR003607. HD/PDEase_dom.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]

Pfam

PF00233. PDEase_I. 1 hit.
[Graphical view]

SMART

SM00471. HDc. 1 hit.
[Graphical view]

PROSITE

PS00126. PDEASE_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q13370.

ChEMBL

CHEMBL290.

ChiTaRS

PDE3B. human.

EvolutionaryTrace

Q13370.

GenomeRNAi

5140.

NextBio

19820.

SOURCE

Search...

Entry information

Entry name

PDE3B_HUMAN

Accession

Primary (citable) accession number: Q13370
Secondary accession number(s): O00639, Q14408, Q6SEI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	April 3, 2007
Last modified:	May 29, 2013
This is version 126 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.