Reviewed, UniProtKB/Swiss-Prot Q23917 (PDE2_DICDI)

Names and origin

Protein names

Recommended name:
    3',5'-cyclic-nucleotide phosphodiesterase regA
      Short name=PDEase regA
    EC=3.1.4.53
Alternative name(s):
    Response regulator protein A
    cAMP-specific 3',5'-cAMP phosphodiesterase 2
    Phosphodiesterase 2
      Short name=DdPDE2

Gene names

Name:	regA
Synonyms:	pde2
ORF Names:	DDB_G0284331

Organism

Dictyostelium discoideum (Slime mold) [Complete proteome]

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	793 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphodiesterase specific for cAMP. Involved in the degradation of intracellular cAMP. Morphological suppressor of tagB. Phosphorelay protein that accepts phosphate from rdeA or supplies phosphate from regA; depending on the relative concentration of the phosphodonor proteins. Ref.8
Catalytic activity	Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate.
Enzyme regulation	Inhibited by 3-isobutyl-1-methylxanthine (IBMX). Ref.9
Subcellular location	Cytoplasm › cytosol. Ref.8 Ref.9
Developmental stage	Expressed at low levels in vegetative cells and at high levels in prespore and prestalk cells during development. Developmentally regulated. Not observable before the end of aggregation, peaks at the mound stage and remains at a lower level thereafter.
Induction	Down-regulated by phagocytic stimuli. Ref.11
Post-translational modification	The phosphorelay mechanism involves the sequential transfer of a phosphate group from Asp-212 of pde2 to 'His-65' of rdeA. Phosphorylation of Asp-212 activates the phosphodiesterase domain.
Disruption phenotype	Rapid development. Cells are 4-fold more resistant to the antitumor agent cisplatin than are wild-type cells. Additionally it produces fruiting bodies with spore masses that cannot rise up the stalk during development. Mutant cells grow exponentially at the same rate as wild-type. Disruption of regA in a tagB null or in a tagC null background resulted in higher levels of sporulation. Disruption of regA in a dhka null background corrects the defect in stalk formation and suppresses the block to sporulation.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. Contains 1 response regulatory domain.
Biophysicochemical properties	Kinetic parameters: cAMP/cGMP selectivity of 200. KM=5 µM for cAMP Vmax=50 pmol/min/mg enzyme with cAMP as substrate

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Nucleotide-binding cAMP cAMP-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro two-component signal transduction system (phosphorelay) Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3',5'-cyclic-nucleotide phosphodiesterase activity Inferred from electronic annotation. Source: InterPro cAMP binding Inferred from electronic annotation. Source: UniProtKB-KW two-component response regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 793	793	3',5'-cyclic-nucleotide phosphodiesterase regA		PRO_0000198850
Regions
	Domain	161 – 280	120	Response regulatory
	Compositional bias	18 – 28	11	Poly-Ser
	Compositional bias	52 – 69	18	Poly-Asn
	Compositional bias	87 – 96	10	Poly-Thr
	Compositional bias	100 – 121	22	Poly-Asn
	Compositional bias	166 – 169	4	Poly-Asp
	Compositional bias	770 – 776	7	Poly-Ser
Amino acid modifications
	Modified residue	212	1	4-aspartylphosphate By similarity
Experimental info
	Mutagenesis	212	1	D → N: Loss of phosphorylation and activation.

Sequences

	Sequence		Length	Mass (Da)
	Q23917-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 6E065A96620F8C27	FASTA	793	91,176
	10 20 30 40 50 60 MNNKQEEIDQ FLSSTSTSPS PSSSSSPSNN DSTSLKSMIS GIENLNVHSK GNDNKNNNNN 70 80 90 100 110 120 NNNNNSNNNE KQKDIVSLEN NSSSNNTTTT TTTTTTSNHN SNNNSNNNNN NINNNNINNN 130 140 150 160 170 180 NYEPLVNGHN NGFGDKLNDQ PSPSSHRVSD FSDEYSPSKV RILVADDDDV QRKILNNLLK 190 200 210 220 230 240 KFHYNVTLVP NGEIAWEYIN KGQQKYDLVL TDVMMPHITG FDLLQRINDH PVHRHIPVIL 250 260 270 280 290 300 MSGTAVDYKY ANDTIKIGGQ DFLTKPIAKE LLKKKIDTVL QSIWQRRKEE EYKATLAQER 310 320 330 340 350 360 EKGNKLAKEM ELKEHEIEEL TKKVSKMSSI SKEAMESPLV SVTRNIEELL KQSSWSHYES 370 380 390 400 410 420 EIKEKLSSIL KELGSSNIYR PSFEKLIKND SVDPVTKSFL VSEFSSTTSR RNSIPTFPQT 430 440 450 460 470 480 TYNRDTKEVI KGWEFDVFKY SEDDLMPLLV DMFENFQLPE IFKIPIEKLQ RFIMTVNALY 490 500 510 520 530 540 RKNNRYHNFT HAFDVTQTVY TFLTSFNAAQ YLTHLDIFAL LISCMCHDLN HPGFNNTFQV 550 560 570 580 590 600 NAQTELSLEY NDISVLENHH AMLTFKILRN SECNILEGLN EDQYKELRRS VVQLILATDM 610 620 630 640 650 660 QNHFEHTNKF QHHLNNLPFD RNKKEDRQMI LNFLIKCGDI SNIARPWHLN FEWSLRVSDE 670 680 690 700 710 720 FFQQSHYETI CGYPVTPFMD KTKTTRARIA ADFIDFVASP LFQSMAKFLK ESQFLLKVIS 730 740 750 760 770 780 KNRENWQAYM ELQKEGKCND DDLQFMEDPT ILVKSKLPKI DEEENRDKVS SSSSSSTAPL 790 TSTSSSNNET SSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Developmental signal transduction pathways uncovered by genetic suppressors." Shaulsky G., Escalante R., Loomis W.F. Proc. Natl. Acad. Sci. U.S.A. 93:15260-15265(1996) [PubMed: 8986798] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE. Strain: AX4.
[2]	"An intersection of the cAMP/PKA and two-component signal transduction systems in Dictyostelium." Thomason P.A., Traynor D., Cavet G., Chang W.-T., Harwood A.J., Kay R.R. EMBO J. 17:2838-2845(1998) [PubMed: 9582277] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ENZYME REGULATION, MUTAGENESIS OF ASP-212. Strain: AX2.
[3]	"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.
[4]	"Histidine kinases in signal transduction pathways of eukaryotes." Loomis W.F., Shaulsky G., Wang N. J. Cell Sci. 110:1141-1145(1997) [PubMed: 9191038] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[5]	"A novel adenylyl cyclase detected in rapidly developing mutants of Dictyostelium." Kim H.-J., Chang W.-T., Meima M., Gross J.D., Schaap P. J. Biol. Chem. 273:30859-30862(1998) [PubMed: 9812977] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[6]	"The RdeA-RegA system, a eukaryotic phospho-relay controlling cAMP breakdown." Thomason P.A., Traynor D., Stock J.B., Kay R.R. J. Biol. Chem. 274:27379-27384(1999) [PubMed: 10488068] [Abstract] Cited for: ENZYME REGULATION, FUNCTION, PHOSPHORYLATION, DEVELOPMENTAL STAGE.
[7]	"Molecular basis for resistance to the anticancer drug cisplatin in Dictyostelium." Li G., Alexander H., Schneider N., Alexander S. Microbiology 146:2219-2227(2000) [PubMed: 10974109] [Abstract] Cited for: DISRUPTION PHENOTYPE. Strain: AX4.
[8]	"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.
[9]	"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, ENZYME REGULATION.
[10]	"High-throughput analysis of spatio-temporal dynamics in Dictyostelium." Sawai S., Guan X.-J., Kuspa A., Cox E.C. Genome Biol. 8:RESEARCH144.1-RESEARCH144.15(2007) [PubMed: 17659086] [Abstract] Cited for: IDENTIFICATION.
[11]	"Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium." Sillo A., Bloomfield G., Balest A., Balbo A., Pergolizzi B., Peracino B., Skelton J., Ivens A., Bozzaro S. BMC Genomics 9:291-291(2008) [PubMed: 18559084] [Abstract] Cited for: INDUCTION [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U60170 Genomic DNA. Translation: AAB03508.1. AJ005398 Genomic DNA. Translation: CAA06513.1. AAFI02000064 Genomic DNA. Translation: EAL65213.1.
RefSeq	XP_638612.1.
3D structure databases
HSSP	HSSP built from PDB template 1JBE based on UniProtKB P06143.
ModBase	Search...
Genome annotation databases
GeneID	3390184.
KEGG	ddi:DDB_0191479.
Organism-specific databases
dictyBase	DDB_G0284331. regA.
Enzyme and pathway databases
BRENDA	3.1.4.17. 424.
Family and domain databases
InterPro	IPR003607. Met-dep_phosphohydro_HD. IPR002073. PDEase. IPR001789. Sig_transdc_resp-reg_receiver. [Graphical view]
Pfam	PF00233. PDEase_I. 1 hit. PF00072. Response_reg. 1 hit. [Graphical view]
PRINTS	PR00387. PDIESTERASE1.
ProDom	PD000039. Response_reg. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00471. HDc. 1 hit. SM00448. REC. 1 hit. [Graphical view]
PROSITE	PS00126. PDEASE_I. 1 hit. PS50110. RESPONSE_REGULATORY. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PDE2_DICDI

Accession

Primary (citable) accession number: Q23917
Secondary accession number(s): Q54PP2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	July 7, 2009
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)