Reviewed, UniProtKB/Swiss-Prot Q8MLZ3 (PDE5_DICDI)

Names and origin

Protein names

Recommended name:
    cGMP-dependent 3',5'-cGMP phosphodiesterase A
    EC=3.1.4.35
Alternative name(s):
    Phosphodiesterase 5
      Short name=DdPDE5
    Phosphodiesterase D
    Cyclic GMP-binding protein A

Gene names

Name:	pdeD
Synonyms:	gbpA, pde5
ORF Names:	DDB_G0274383

Organism

Dictyostelium discoideum (Slime mold) [Complete proteome]

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	867 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphodiesterase specific for cGMP, which is activated by cGMP but not by cAMP. Involved in the degradation of intracellular cGMP. Ref.5
Catalytic activity	Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.
Cofactor	Divalent metal cation. Can use manganese and to a lower extent magnesium and zinc. Half-maximal activation occurs between 10 and 100 µM of manganese whereas maximal activation occurs with 10 mM of zinc or magnesium. Ref.2
Subcellular location	Cytoplasm › cytosol Ref.5 Ref.2 Ref.8.
Developmental stage	Expressed during growth and development, with the highest level of expression during aggregation. Ref.2
Domain	The beta lactamase-like domain catalyzes the hydrolysis of cGMP.
Sequence similarities	Belongs to the metallo-beta-lactamase superfamily. cNMP phosphodiesterase family. Contains 2 cyclic nucleotide-binding domains.
Biophysicochemical properties	Kinetic parameters: cAMP/cGMP selectivity of 0.003. KM=5.2 µM for cGMP Vmax=390 pmol/min/mg enzyme pH dependence: Optimum pH is 7.0.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	Repeat
Ligand	Magnesium Manganese Metal-binding Nucleotide-binding Zinc cGMP cGMP-binding
Molecular function	Hydrolase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cGMP catabolic process Traceable author statement. Source: dictyBase cGMP-mediated signaling Ref.5 Inferred from mutant phenotype. Source: dictyBase
Cellular component	cytosol Ref.2 Inferred from direct assay. Source: dictyBase
Molecular function	3',5'-cyclic-GMP phosphodiesterase activity Ref.2 Inferred from mutant phenotype. Source: dictyBase cGMP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 867	867	cGMP-dependent 3',5'-cGMP phosphodiesterase A		PRO_0000353105
Regions
	Nucleotide binding	607 – 721	115	cNMP 1
	Nucleotide binding	734 – 851	118	cNMP 2
	Region	357 – 503	147	Phosphodiesterase activity
	Compositional bias	124 – 127	4	Poly-Ser
	Compositional bias	142 – 145	4	Poly-Ser
	Compositional bias	151 – 154	4	Poly-Gln
	Compositional bias	155 – 158	4	Poly-Pro
	Compositional bias	178 – 185	8	Poly-His
	Compositional bias	189 – 196	8	Poly-Asn
	Compositional bias	200 – 203	4	Poly-Asn
	Compositional bias	209 – 221	13	Poly-Gln
Sites
	Metal binding	399	1	Divalent metal cation Potential
	Metal binding	401	1	Divalent metal cation Potential
	Metal binding	403	1	Divalent metal cation Potential

Sequences

	Sequence		Length	Mass (Da)
	Q8MLZ3-1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: E203EED614E6F386	FASTA	867	97,992
	10 20 30 40 50 60 MMFSKRKSIR FNPEGDYTEL PRGGYVVPSK LGGIQFGVPP ETIKDSMALK IDVPTIYVFP 70 80 90 100 110 120 EELWDRKTGI NAAEAEFPAY FNYFILKRKV SFVCTKEQEQ RIRIVFQETL LGPPEFNTGI 130 140 150 160 170 180 IINSSSSTTD TSKTSPIKKQ TSSSSPPLSP QQQQPPPPLV KQPSQQQLEE LATMDTCHYH 190 200 210 220 230 240 HHHHHQEVND NDNNNNTTTN NNNIEILEQQ QQQQQQQQQQ QDEDSTDVDE EFQKEFSSTF 250 260 270 280 290 300 PRSEIPNLEK ECKYLRTFNS VDELFDFILF DDNGIAKLSD DVEIHFQEDQ SLFKVLQFEE 310 320 330 340 350 360 TGKGNKVQTL VATIPSKILF PDMINSISTI NDNKIFDPPT FGITIIGSSH GFDPKKSTTG 370 380 390 400 410 420 FVLWINKRGI MVDPPLNSSS FLQSQGVPTR MVDHIILTHC HADHDSGTFQ KLLEEYQITV 430 440 450 460 470 480 VTTPTILGSF LRKYGALSNL STDLLRRLFI FRPVMIGEPM IISGAEFRFF YTIHTIPTIS 490 500 510 520 530 540 FEVFYGGKSI FYSGDTCYDP NRIKDMNKRG IMKTSRMKFF LRPWNHTVVL HEAGVPPIHT 550 560 570 580 590 600 PVSVLRALPD EVKNRLYLVH ISEHTLPAGS GLKIAKEGVA HTLSLDVMKS SHSEAVDILK 610 620 630 640 650 660 LVESVDIFRS IPLTQACEIL QTATKRKYSQ GSVIIARDTE PDAFYVVASG VVCVNIGELK 670 680 690 700 710 720 KNLIVGDYFG EMSLVMGGLR SANVQAVTDV EVLSFNKEDF LSITRNSTES IQFITRLWEM 730 740 750 760 770 780 RNEKSWETMS LNSVFSRCTN SQKTAIQSIL VRELIKKDET LWCKGEEALF GCLVAEGSFV 790 800 810 820 830 840 FKEDDSLESF SQGSFLGDIN AMTTQPPSIH KTTVVAKEES VIYKVLSQDL IKFFSNNPGI 850 860 QLAFLDTIFV DALRDQVQQL VNSKLTY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis in Dictyostelium." Bosgraaf L., Russcher H., Smith J.L., Wessels D., Soll D.R., Van Haastert P.J.M. EMBO J. 21:4560-4570(2002) [PubMed: 12198158] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Identification of a novel type of cGMP phosphodiesterase that is defective in the chemotactic stmF mutants." Meima M.E., Biondi R.M., Schaap P. Mol. Biol. Cell 13:3870-3877(2002) [PubMed: 12429831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, COFACTOR, DEVELOPMENTAL STAGE.
[3]	"Sequence and analysis of chromosome 2 of Dictyostelium discoideum." Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T., Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R., Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A., Noegel A.A. Nature 418:79-85(2002) [PubMed: 12097910] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[4]	"The genome of the social amoeba Dictyostelium discoideum." Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A. Nature 435:43-57(2005) [PubMed: 15875012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[5]	"Identification and characterization of two unusual cGMP-stimulated phoshodiesterases in dictyostelium." Bosgraaf L., Russcher H., Snippe H., Bader S., Wind J., Van Haastert P.J.M. Mol. Biol. Cell 13:3878-3889(2002) [PubMed: 12429832] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Identification of four candidate cGMP targets in Dictyostelium." Goldberg J.M., Bosgraaf L., Van Haastert P.J.M., Smith J.L. Proc. Natl. Acad. Sci. U.S.A. 99:6749-6754(2002) [PubMed: 12011437] [Abstract] Cited for: IDENTIFICATION.
[7]	"Characterization of a cAMP-stimulated cAMP phosphodiesterase in Dictyostelium discoideum." Meima M.E., Weening K.E., Schaap P. J. Biol. Chem. 278:14356-14362(2003) [PubMed: 12574165] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[8]	"Seven Dictyostelium discoideum phosphodiesterases degrade three pools of cAMP and cGMP." Bader S., Kortholt A., Van Haastert P.J.M. Biochem. J. 402:153-161(2007) [PubMed: 17040207] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF481921 Genomic DNA. Translation: AAM34039.1. AY047363 Genomic DNA. Translation: AAL06059.1. AAFI02000012 Genomic DNA. Translation: EAL70084.1.
RefSeq	XP_644314.1.
3D structure databases
SMR	Q8MLZ3. Positions 335-503, 592-840.
ModBase	Search...
Genome annotation databases
GeneID	8619742.
KEGG	ddi:DDB_0185054.
Organism-specific databases
dictyBase	DDB_G0274383. pdeD.
Phylogenomic databases
eggNOG	KOG1113.
HOGENOM	HBG718006.
Enzyme and pathway databases
BRENDA	3.1.4.35. 424.
Family and domain databases
InterPro	IPR001279. Blactmase-like. IPR000595. cNMP_bd. IPR018490. cNMP_bd-like. IPR018488. cNMP_bd_CS. IPR014710. RmlC-like_jellyroll. [Graphical view]
Gene3D	G3DSA:2.60.120.10. RmlC-like_jellyroll. 2 hits.
Pfam	PF00027. cNMP_binding. 2 hits. [Graphical view]
SMART	SM00100. cNMP. 2 hits. SM00849. Lactamase_B. 1 hit. [Graphical view]
PROSITE	PS00888. CNMP_BINDING_1. False negative. PS00889. CNMP_BINDING_2. 1 hit. PS50042. CNMP_BINDING_3. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PDE5_DICDI

Accession

Primary (citable) accession number: Q8MLZ3
Secondary accession number(s): Q554K9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 25, 2008
Last sequence update:	October 1, 2002
Last modified:	February 9, 2010
This is version 43 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)