Reviewed, UniProtKB/Swiss-Prot Q14432 (PDE3A_HUMAN)

Names and origin

Protein names

Recommended name:
    cGMP-inhibited 3',5'-cyclic phosphodiesterase A
    EC=3.1.4.17
Alternative name(s):
    Cyclic GMP-inhibited phosphodiesterase A
      Short name=CGI-PDE A

Gene names

Name:

PDE3A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1141 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 By similarity.
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 By similarity.
Enzyme regulation	Inhibited by cGMP.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. PDE3 subfamily.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Ligand	Metal-binding cAMP cGMP
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	lipid metabolic process Traceable author statement. Source: ProtInc signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cGMP-inhibited cyclic-nucleotide phosphodiesterase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1141

1141

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

PRO_0000198799

Regions

Transmembrane

61 – 81

21

Potential

Transmembrane

130 – 150

21

Potential

Transmembrane

160 – 180

21

Potential

Transmembrane

185 – 205

21

Potential

Transmembrane

210 – 230

21

Potential

Transmembrane

232 – 252

21

Potential

Region

728 – 1086

359

Catalytic By similarity

Compositional bias

95 – 98

4

Poly-Ala

Compositional bias

99 – 102

4

Poly-Glu

Compositional bias

288 – 291

4

Poly-Arg

Compositional bias

440 – 445

6

Poly-Thr

Compositional bias

870 – 873

4

Poly-Ala

Compositional bias

1040 – 1045

6

Poly-Glu

Compositional bias

1121 – 1125

5

Poly-Glu

Sites

Active site

752

1

Proton donor By similarity

Metal binding

756

1

Divalent metal cation 1 By similarity

Metal binding

836

1

Divalent metal cation 1 By similarity

Metal binding

837

1

Divalent metal cation 1 By similarity

Metal binding

837

1

Divalent metal cation 2 By similarity

Metal binding

950

1

Divalent metal cation 1 By similarity

Amino acid modifications

Modified residue

312

1

Phosphoserine Ref.8 Ref.10

Modified residue

428

1

Phosphoserine Ref.10 Ref.7

Modified residue

440

1

Phosphothreonine Ref.9

Modified residue

495

1

Phosphoserine By similarity

Natural variations

Natural variant

12

1

D → N: dbSNP rs12305038. Ref.3

VAR_059543

Experimental info

Sequence conflict

69

1

S → C in AAB18673. Ref.3

Sequence conflict

110

1

G → A in AAB18673. Ref.3

Sequence conflict

354 – 371

18

HGLIT…PPNVC → TASLPTSWQTLLFHQTCA Ref.3

Sequence conflict

354 – 371

18

HGLIT…PPNVC → TASLPTSWQTLLFHQTCA Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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1141

Helix Strand Turn

Details...

Helix

815 – 817

3

Helix

823 – 835

13

Turn

836 – 839

4

Helix

845 – 850

6

Helix

854 – 858

5

Turn

859 – 861

3

Helix

864 – 876

13

Turn

877 – 879

3

Turn

885 – 888

4

Helix

891 – 906

16

Helix

910 – 912

3

Helix

913 – 918

6

Helix

939 – 950

12

Helix

953 – 955

3

Helix

958 – 981

24

Helix

997 – 1007

11

Helix

1009 – 1016

8

Sequences

	Sequence		Length	Mass (Da)
	Q14432-1 [UniParc]. Last modified May 10, 2004. Version 3. Checksum: E69504130F39EFEA	FASTA	1,141	124,979
	10 20 30 40 50 60 MAVPGDAARV RDKPVHSGVS QAPTAGRDCH HRADPASPRD SGCRGCWGDL VLQPLRSSRK 70 80 90 100 110 120 LSSALCAGSL SFLLALLVRL VRGEVGCDLE QCKEAAAAEE EEAAPGAEGG VFPGPRGGAP 130 140 150 160 170 180 GGGARLSPWL QPSALLFSLL CAFFWMGLYL LRAGVRLPLA VALLAACCGG EALVQIGLGV 190 200 210 220 230 240 GEDHLLSLPA AGVVLSCLAA ATWLVLRLRL GVLMIALTSA VRTVSLISLE RFKVAWRPYL 250 260 270 280 290 300 AYLAGVLGIL LARYVEQILP QSAEAAPREH LGSQLIAGTK EDIPVFKRRR RSSSVVSAEM 310 320 330 340 350 360 SGCSSKSHRR TSLPCIPREQ LMGHSEWDHK RGPRGSQSSG TSITVDIAVM GEAHGLITDL 370 380 390 400 410 420 LADPSLPPNV CTSLRAVSNL LSTQLTFQAI HKPRVNPVTS LSENYTCSDS EESSEKDKLA 430 440 450 460 470 480 IPKRLRRSLP PGLLRRVSST WTTTTSATGL PTLEPAPVRR DRSTSIKLQE APSSSPDSWN 490 500 510 520 530 540 NPVMMTLTKS RSFTSSYAIS AANHVKAKKQ SRPGALAKIS PLSSPCSSPL QGTPASSLVS 550 560 570 580 590 600 KISAVQFPES ADTTAKQSLG SHRALTYTQS APDLSPQILT PPVICSSCGR PYSQGNPADE 610 620 630 640 650 660 PLERSGVATR TPSRTDDTAQ VTSDYETNNN SDSSDIVQNE DETECLREPL RKASACSTYA 670 680 690 700 710 720 PETMMFLDKP ILAPEPLVMD NLDSIMEQLN TWNFPIFDLV ENIGRKCGRI LSQVSYRLFE 730 740 750 760 770 780 DMGLFEAFKI PIREFMNYFH ALEIGYRDIP YHNRIHATDV LHAVWYLTTQ PIPGLSTVIN 790 800 810 820 830 840 DHGSTSDSDS DSGFTHGHMG YVFSKTYNVT DDKYGCLSGN IPALELMALY VAAAMHDYDH 850 860 870 880 890 900 PGRTNAFLVA TSAPQAVLYN DRSVLENHHA AAAWNLFMSR PEYNFLINLD HVEFKHFRFL 910 920 930 940 950 960 VIEAILATDL KKHFDFVAKF NGKVNDDVGI DWTNENDRLL VCQMCIKLAD INGPAKCKEL 970 980 990 1000 1010 1020 HLQWTDGIVN EFYEQGDEEA SLGLPISPFM DRSAPQLANL QESFISHIVG PLCNSYDSAG 1030 1040 1050 1060 1070 1080 LMPGKWVEDS DESGDTDDPE EEEEEAPAPN EEETCENNES PKKKTFKRRK IYCQITQHLL 1090 1100 1110 1120 1130 1140 QNHKMWKKVI EEEQRLAGIE NQSLDQTPQS HSSEQIQAIK EEEEEKGKPR GEEIPTQKPD Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of human myocardial cGMP-inhibited cAMP phosphodiesterase." Meacci E., Taira M., Moos M. Jr., Smith C.J., Movsesian M.A., Degerman E., Belfrage P., Manganiello V. Proc. Natl. Acad. Sci. U.S.A. 89:3721-3725(1992) [PubMed: 1315035] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Myocardium.
[2]	Liu H., Manganiello V. Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 12; 63-64 AND 354-371.
[3]	"Human platelet cGI-PDE: expression in yeast and localization of the catalytic domain by deletion mutagenesis." Cheung P.P., Xu H., McLaughlin M.M., Ghazaleh F.A., Livi G.P., Colman R.W. Blood 88:1321-1329(1996) [PubMed: 8695850] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-12. Tissue: Blood.
[4]	"Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum." Kuthe A., Eckel H., Stief C.G., Uckert S., Forssmann W.-G., Jonas U., Maegert H.-J. Chem. Biol. Interact. 119:593-598(1999) [PubMed: 10421499] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Penis.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[6]	"Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase." Degerman E., Moos M. Jr., Rascon A., Vasta V., Meacci E., Smith C.J., Lindgren S., Andersson K.-E., Belfrage P., Manganiello V. Biochim. Biophys. Acta 1205:189-198(1994) [PubMed: 8155697] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, MASS SPECTROMETRY. Tissue: Platelet.
[9]	"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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-440, MASS SPECTROMETRY.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312 AND SER-428, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

Wikipedia

PDE3 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M91667 mRNA. Translation: AAA35912.2.
U36798 mRNA. Translation: AAB18673.1.
AJ005036 mRNA. Translation: CAA06304.1.
BC117369 mRNA. Translation: AAI17370.1.
BC117371 mRNA. Translation: AAI17372.1.

IPI

IPI00291205.

PIR

A44093.

RefSeq

NP_000912.3.

UniGene

Hs.591150

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LRC	model	-	A	812-1017	[»]

SMR

Q14432. Positions 677-1087.

ModBase

Search...

Protein-protein interaction databases

STRING

Q14432.

PTM databases

PhosphoSite

Q14432.

Proteomic databases

PRIDE

Q14432.

Genome annotation databases

Ensembl

ENST00000359062; ENSP00000351957; ENSG00000172572; Homo sapiens. [Genome view]

GeneID

5139.

KEGG

hsa:5139.

UCSC

uc001reh.1. human.

Organism-specific databases

CTD

5139.

GeneCards

GC12P020413.

HGNC

HGNC:8778. PDE3A.

HPA

HPA014492.

MIM

123805. gene.

PharmGKB

PA33126.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12959.

HOGENOM

HBG712991.

HOVERGEN

Q14432.

InParanoid

Q14432.

OMA

YSQGNPA.

OrthoDB

EOG91NX56.

PhylomeDB

Q14432.

Enzyme and pathway databases

BRENDA

3.1.4.17. 247.

Reactome

REACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpress

Q14432.

Bgee

Q14432.

CleanEx

HS_PDE3A.

Genevestigator

Q14432.

GermOnline

ENSG00000172572. Homo sapiens.

Family and domain databases

InterPro

IPR003607. Metal-dep_PHydrolase_HD_dom.
IPR002073. PDEase.
[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 Resources

DrugBank

DB01223. Aminophylline.
DB01427. Amrinone.
DB00261. Anagrelide.
DB01166. Cilostazol.
DB04880. Enoximone.
DB00235. Milrinone.
DB00277. Theophylline.

NextBio

19816.

SOURCE

Search...

Entry information

Entry name

PDE3A_HUMAN

Accession

Primary (citable) accession number: Q14432
Secondary accession number(s): O60865, Q13348, Q17RD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 10, 2004
Last modified:	January 19, 2010
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.