Reviewed, UniProtKB/Swiss-Prot Q9VFI9 (PDE6_DROME)

Names and origin

Protein names

Recommended name:
    cGMP-specific 3',5'-cyclic phosphodiesterase
    EC=3.1.4.35
Alternative name(s):
    DmPDE5/6
      Short name=DmPDE6

Gene names

Name:	Pde6
ORF Names:	CG8279

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	1131 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Has a role regulating cGMP transport in Malpighian tubule principal cells. Ref.4
Catalytic activity	Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate. Ref.4 Ref.5
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.
Subunit structure	Interacts with PrBP. Ref.5
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side. Note: Expressed on the apical side of the Malpighian tubule principal cell polarised membrane. Loss of prenylation causes protein location to the cytoplasm. Ref.4 Ref.5
Tissue specificity	Expressed in Malpighian tubule principal cells. Ref.4
Disruption phenotype	Flies display increased active transport of cGMP. Overexpression of Pde6 confers inhibition of the active transport and efflux of cGMP by tubules. Ref.4
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. Contains 2 GAF domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Repeat
Ligand	Metal-binding cGMP
Molecular function	Hydrolase
PTM	Lipoprotein Methylation Prenylation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cGMP metabolic process Ref.4 Ref.5 Inferred from direct assay. Source: UniProtKB negative regulation of nucleobase, nucleoside, nucleotide and nucleic acid transport Ref.4 Inferred from mutant phenotype. Source: FlyBase signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell apical plasma membrane Ref.4 Ref.5 Inferred from direct assay. Source: FlyBase
Molecular function	3',5'-cyclic-GMP phosphodiesterase activity Ref.4 Ref.5 Inferred from direct assay. Source: UniProtKB protein binding Ref.5 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1128	1128	cGMP-specific 3',5'-cyclic phosphodiesterase		PRO_0000356892
	Propeptide	1129 – 1131	3	Removed in mature form Probable		PRO_0000356893
Regions
	Domain	260 – 412	153	GAF 1
	Domain	444 – 625	182	GAF 2
	Compositional bias	6 – 46	41	Ser-rich
Sites
	Active site	731	1	Proton donor By similarity
	Metal binding	735	1	Divalent metal cation 1 By similarity
	Metal binding	771	1	Divalent metal cation 1 By similarity
	Metal binding	772	1	Divalent metal cation 1 By similarity
	Metal binding	772	1	Divalent metal cation 2 By similarity
	Metal binding	882	1	Divalent metal cation 1 By similarity
Amino acid modifications
	Modified residue	1128	1	Cysteine methyl ester Probable
	Lipidation	1128	1	S-farnesyl cysteine Probable Ref.5
Experimental info
	Mutagenesis	1128	1	C → S: Impairs prenylation and membrane. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9VFI9-1 [UniParc]. Last modified October 1, 2002. Version 3. Checksum: E63183B04E5FF08A	FASTA	1,131	125,640
	10 20 30 40 50 60 MHGPVSRSSS SSNMTDVSSP AGGAASPVEM STTSSSSAAT TSASSSKPLT NGANKTAIST 70 80 90 100 110 120 AAGGVTPGAV PGPGSGAIPA SSSSGNQVKL EHHHRQSNNN RPAVTNRSSE TKLMTPTGSS 130 140 150 160 170 180 SSPSQSPSQT QASIQTQTSQ QDRLAKASTT ASQQDVDEVA RLFEEKPEAF EKWLTERAPP 190 200 210 220 230 240 EALSRLQEFI ENRKPHKRPS VTSDLFQQWM AASPTVQQKS PRSLSNSSAS SLPECRRHLM 250 260 270 280 290 300 DLDEGELFME LIRDVANELD IDVLCHKILV NVGLLTHADR GSLFLAKGTP TNKYLVAKLF 310 320 330 340 350 360 DVTQKTALKD AVTRASAEEI IIPFGIGIAG MVAQTKQMIN IKEAYKDARF NCEIDLKTGY 370 380 390 400 410 420 KTNAILCMPI CNYEGDIIGV AQIINKTNGC MEFDEHDVEI FRRYLTFCGI GIQNAQLFEM 430 440 450 460 470 480 SVQEYRRNQI LLNLARSIFE EQNNLECLVT KIMTEARELL KCERCSVFLV DLDCCEASHL 490 500 510 520 530 540 EKIIEKPNQP ATRAIKSADS FEEKKMRNRF TVLFELGGEY QAANVSRPSV SELSSSTLAQ 550 560 570 580 590 600 IAQFVATTGQ TVNICDVIEW VRDHNQIRAE DEIDSTQAIL CMPIMNAQKK VIGVAQLINK 610 620 630 640 650 660 ANGVPFTDSD ASIFEAFAIF CGLGIHNTQM YENACKLMAK QKVALECLSY HATASQDQTE 670 680 690 700 710 720 KLTQDVIAEA ESYNLYSFTF TDFELVDDDT CRAVLRMFMQ CNLVSQFQIP YDVLCRWVLS 730 740 750 760 770 780 VRKNYRPVKY HNWRHALNVA QTMFAMLKTG KMERFMTDLE ILGLLVACLC HDLDHRGTNN 790 800 810 820 830 840 AFQTKTESPL AILYTTSTME HHHFDQCVMI LNSEGNNIFQ ALSPEDYRSV MKTVESAILS 850 860 870 880 890 900 TDLAMYFKKR NAFLELVENG EFDWQGEEKK DLLCGMMMTA CDVSAIAKPW EVQHKVAKLV 910 920 930 940 950 960 ADEFFDQGDL EKLQLNTQPV AMMDRERKDE LPKMQVGFID VICLPLYRVL CDTFPWITPL 970 980 990 1000 1010 1020 YEGTLENRRN WQDLAEKVEM GLTWIDHDTI DKPVEEFAAC ADEEIKDIEF TVTTLNCNQQ 1030 1040 1050 1060 1070 1080 SQHGSEDSHT PEHQRSGSRL SMKKTGALGK AVRSKLSKTL YNSMDGSKPK TSLKLLESHV 1090 1100 1110 1120 1130 SEDMDDKSPT SPSQPQASGS MGRMSASSST SSAGGQMVDK SKKRSKLCAL L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[2]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[3]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 97-1131. Strain: Berkeley. Tissue: Head.
[4]	"A novel role for a Drosophila homologue of cGMP-specific phosphodiesterase in the active transport of cGMP." Day J.P., Houslay M.D., Davies S.-A. Biochem. J. 393:481-488(2006) [PubMed: 16232123] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[5]	"Regulation of a Drosophila melanogaster cGMP-specific phosphodiesterase by prenylation and interaction with a prenyl-binding protein." Day J.P., Cleghon V., Houslay M.D., Davies S.-A. Biochem. J. 414:363-374(2008) [PubMed: 18503409] [Abstract] Cited for: CATALYTIC ACTIVITY, INTERACTION WITH PRBP, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-1128.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AE014297 Genomic DNA. Translation: AAF55066.3. AY058470 mRNA. Translation: AAL13699.1. Different initiation.
RefSeq	NP_650369.3.
3D structure databases
HSSP	HSSP built from PDB template 1T9R based on UniProtKB O76074.
SMR	Q9VFI9. Positions 249-636, 445-690, 658-977.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9VFI9.
Genome annotation databases
Ensembl	FBtr0300330; FBpp0289559; FBgn0038237; Drosophila melanogaster. [Genome view]
GeneID	41760.
KEGG	dme:Dmel_CG8279.
Organism-specific databases
CTD	41760.
FlyBase	FBgn0038237. Pde6.
Phylogenomic databases
eggNOG	inNOG05101.
InParanoid	Q9VFI9.
OMA	REHDANK.
PhylomeDB	Q9VFI9.
Gene expression databases
ArrayExpress	Q9VFI9.
Family and domain databases
InterPro	IPR003018. GAF. IPR003607. Metal-dep_PHydrolase_HD_dom. IPR002073. PDEase. [Graphical view]
Pfam	PF01590. GAF. 2 hits. PF00233. PDEase_I. 1 hit. [Graphical view]
PRINTS	PR00387. PDIESTERASE1.
SMART	SM00065. GAF. 2 hits. SM00471. HDc. 1 hit. [Graphical view]
PROSITE	PS00126. PDEASE_I. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	825438.

Entry information

Entry name

PDE6_DROME

Accession

Primary (citable) accession number: Q9VFI9
Secondary accession number(s): Q95TW8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 16, 2008
Last sequence update:	October 1, 2002
Last modified:	February 9, 2010
This is version 63 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project