Reviewed, UniProtKB/Swiss-Prot P13217 (PIPA_DROME)

Names and origin

Protein names

Recommended name:
    1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase
    EC=3.1.4.11
Alternative name(s):
    Phosphoinositide phospholipase C
    No receptor potential A protein

Gene names

Name:	norpA
ORF Names:	CG3620

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	1095 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. Essential component of the phototransduction pathway. Ref.1
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.
Subunit structure	Interacts with inaD.
Tissue specificity	Abundantly expressed in the adult retina. Ref.1
Disruption phenotype	Flies have no photoreceptor potential, their eyes lack phospholipase C (PLC) activity and they are completely blind. Ref.1
Sequence similarities	Contains 1 C2 domain. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain.
Caution	3D structural studies (Ref.6) were performed with a synthetic heptapeptide that contained Cys, corresponding to position 1094, therefore the detected disulfide bridge is an artifact.

Ontologies

Keywords
Biological process	Lipid degradation Sensory transduction Vision
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Transducer
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	adult locomotory behavior Inferred from mutant phenotype. Source: FlyBase calcium-mediated signaling Traceable author statement. Source: FlyBase deactivation of rhodopsin mediated signaling Inferred from direct assay. Source: FlyBase diacylglycerol biosynthetic process Traceable author statement. Source: FlyBase elevation of cytosolic calcium ion concentration during G-protein signaling, coupled to IP3 second messenger (phospholipase C activating) Traceable author statement. Source: FlyBase entrainment of circadian clock Inferred from mutant phenotype. Source: FlyBase light-induced release of internally sequestered calcium ion Traceable author statement. Source: FlyBase lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of compound eye retinal cell programmed cell death Inferred from mutant phenotype. Source: FlyBase phosphatidylinositol metabolic process Inferred from mutant phenotype. Source: FlyBase phospholipid biosynthetic process Traceable author statement. Source: FlyBase
Cellular component	inaD signaling complex Inferred from physical interaction. Source: FlyBase membrane fraction Inferred from direct assay. Source: FlyBase
Molecular function	GTPase activator activity Non-traceable author statement. Source: FlyBase calcium ion binding Inferred from electronic annotation. Source: InterPro phosphoinositide phospholipase C activity Traceable author statement. Source: FlyBase protein binding Inferred from physical interaction. Source: IntAct signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ball	Q7KRY6	1	EBI-101510,EBI-170817

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P13217-1)

Also known as: B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform C (identifier: P13217-2)

Also known as: D;

The sequence of this isoform differs from the canonical sequence as follows:
     130-154: SWQKNLRLITHNNRATNVCPRVNLM → IWLDGIRKITHNVKANNICPMMCLR

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1095	1095	1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase		PRO_0000088510
Regions
	Domain	319 – 469	151	PI-PLC X-box
	Domain	550 – 666	117	PI-PLC Y-box
	Domain	673 – 771	99	C2
Sites
	Active site	334	1	By similarity
	Active site	381	1	By similarity
	Binding site	467	1	Substrate By similarity
	Binding site	469	1	Substrate By similarity
	Binding site	579	1	Substrate By similarity
	Binding site	606	1	Substrate By similarity
Natural variations
	Alternative sequence	130 – 154	25	SWQKN…RVNLM → IWLDGIRKITHNVKANNICP MMCLR in isoform C.		VSP_034088
Experimental info
	Sequence conflict	446	1	H → R in AAA28724. Ref.1
	Sequence conflict	968	1	D → G in AAO25053. Ref.5
	Sequence conflict	1094	1	Y → C in AAA28724. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (B) [UniParc]. Last modified June 10, 2008. Version 4. Checksum: CC712ABF9B065BB6	FASTA	1,095	124,863
	10 20 30 40 50 60 MTKKYEFDWI IPVPPELTTG CVFDRWFENE KETKENDFER DALFKVDEYG FFLYWKSEGR 70 80 90 100 110 120 DGDVIELCQV SDIRAGGTPK DPKILDKVTK KNGTNIPELD KRSLTICSNT DYINITYHHV 130 140 150 160 170 180 ICPDAATAKS WQKNLRLITH NNRATNVCPR VNLMKHWMRL SYCVEKSGKI PVKTLAKTFA 190 200 210 220 230 240 SGKTEKLVYT CIKDAGLPDD KNATMTKEQF TFDKFYALYH KVCPRNDIEE LFTSITKGKQ 250 260 270 280 290 300 DFISLEQFIQ FMNDKQRDPR MNEILYPLYE EKRCTEIIND YELDEEKKKN VQMSLDGFKR 310 320 330 340 350 360 YLMSDENAPV FLDRLDFYME MDQPLAHYYI NSSHNTYLSG RQIGGKSSVE MYRQTLLAGC 370 380 390 400 410 420 RCVELDCWNG KGEDEEPIVT HGHAYCTEIL FKDCIQAIAD CAFVSSEYPV ILSFENHCNR 430 440 450 460 470 480 AQQYKLAKYC DDFFGDLLLK EPLPDHPLDP GLPLPPPCKL KRKILIKNKR MKPEVEKVEL 490 500 510 520 530 540 ELWLKGELKT DDDPEEDASA GKPPEAAAAP APAPEAAAAA EGAAEGGGGA EAEAAAANYS 550 560 570 580 590 600 GSTTNVHPWL SSMVNYAQPI KFQGFDKAIE KNIAHNMSSF AESAGMNYLK QSSIDFVNYN 610 620 630 640 650 660 KRQMSRIYPK GTRADSSNYM PQVFWNAGCQ MVSLNFQSSD LPMQLNQGKF EYNGGCGYLL 670 680 690 700 710 720 KPDFMRRADK DFDPFADAPV DGVIAAQCSV KVIAGQFLSD KKVGTYVEVD MFGLPSDTVK 730 740 750 760 770 780 KEFRTRLVAN NGLNPVYNED PFVFRKVVLP DLAVLRFGVY EESGKILGQR ILPLDGLQAG 790 800 810 820 830 840 YRHVSLRTEA NFPMSLPMLF VNIELKIYVP DGFEDFMAML SDPRGFAGAA KQQNEQMKAL 850 860 870 880 890 900 GIEEQSGGAA RDAGKAKEEE KKEPPLVFEP VTLESLRQEK GFQKVGKKQI KELDTLRKKH 910 920 930 940 950 960 AKERTSVQKT QNAAIDKLIK GKSKDDIRND ANIKNSINDQ TKQWTDMIAR HRKEEWDMLR 970 980 990 1000 1010 1020 QHVQDSQDAM KALMLTVQAA QIKQLEDRHA RDIKDLNAKQ AKMSADTAKE VQNDKTLKTK 1030 1040 1050 1060 1070 1080 NEKDRRLREK RQNNVKRFME EKKQIGVKQG RAMEKLKLAH SKQIEEFSTD VQKLMDMYKI 1090 EEEAYKTQGK TEFYA
	Isoform C (D). Checksum: 6F09204041C4FF74	FASTA	1,095	124,824
	10 20 30 40 50 60 MTKKYEFDWI IPVPPELTTG CVFDRWFENE KETKENDFER DALFKVDEYG FFLYWKSEGR 70 80 90 100 110 120 DGDVIELCQV SDIRAGGTPK DPKILDKVTK KNGTNIPELD KRSLTICSNT DYINITYHHV 130 140 150 160 170 180 ICPDAATAKI WLDGIRKITH NVKANNICPM MCLRKHWMRL SYCVEKSGKI PVKTLAKTFA 190 200 210 220 230 240 SGKTEKLVYT CIKDAGLPDD KNATMTKEQF TFDKFYALYH KVCPRNDIEE LFTSITKGKQ 250 260 270 280 290 300 DFISLEQFIQ FMNDKQRDPR MNEILYPLYE EKRCTEIIND YELDEEKKKN VQMSLDGFKR 310 320 330 340 350 360 YLMSDENAPV FLDRLDFYME MDQPLAHYYI NSSHNTYLSG RQIGGKSSVE MYRQTLLAGC 370 380 390 400 410 420 RCVELDCWNG KGEDEEPIVT HGHAYCTEIL FKDCIQAIAD CAFVSSEYPV ILSFENHCNR 430 440 450 460 470 480 AQQYKLAKYC DDFFGDLLLK EPLPDHPLDP GLPLPPPCKL KRKILIKNKR MKPEVEKVEL 490 500 510 520 530 540 ELWLKGELKT DDDPEEDASA GKPPEAAAAP APAPEAAAAA EGAAEGGGGA EAEAAAANYS 550 560 570 580 590 600 GSTTNVHPWL SSMVNYAQPI KFQGFDKAIE KNIAHNMSSF AESAGMNYLK QSSIDFVNYN 610 620 630 640 650 660 KRQMSRIYPK GTRADSSNYM PQVFWNAGCQ MVSLNFQSSD LPMQLNQGKF EYNGGCGYLL 670 680 690 700 710 720 KPDFMRRADK DFDPFADAPV DGVIAAQCSV KVIAGQFLSD KKVGTYVEVD MFGLPSDTVK 730 740 750 760 770 780 KEFRTRLVAN NGLNPVYNED PFVFRKVVLP DLAVLRFGVY EESGKILGQR ILPLDGLQAG 790 800 810 820 830 840 YRHVSLRTEA NFPMSLPMLF VNIELKIYVP DGFEDFMAML SDPRGFAGAA KQQNEQMKAL 850 860 870 880 890 900 GIEEQSGGAA RDAGKAKEEE KKEPPLVFEP VTLESLRQEK GFQKVGKKQI KELDTLRKKH 910 920 930 940 950 960 AKERTSVQKT QNAAIDKLIK GKSKDDIRND ANIKNSINDQ TKQWTDMIAR HRKEEWDMLR 970 980 990 1000 1010 1020 QHVQDSQDAM KALMLTVQAA QIKQLEDRHA RDIKDLNAKQ AKMSADTAKE VQNDKTLKTK 1030 1040 1050 1060 1070 1080 NEKDRRLREK RQNNVKRFME EKKQIGVKQG RAMEKLKLAH SKQIEEFSTD VQKLMDMYKI 1090 EEEAYKTQGK TEFYA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction." Bloomquist B.T., Shortridge R.D., Schneuwly S., Perdew M.H., Montell C., Steller H., Rubin G., Pak W.L. Cell 54:723-733(1988) [PubMed: 2457447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[2]	"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.
[3]	"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, ALTERNATIVE SPLICING.
[4]	"A Drosophila complementary DNA resource." Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M., Harvey D.A. Science 287:2222-2224(2000) [PubMed: 10731138] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: Berkeley. Tissue: Head.
[5]	Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A. , Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: Berkeley. Tissue: Head.
[6]	"Functional relevance of the disulfide-linked complex of the N-terminal PDZ domain of InaD with NorpA." Kimple M.E., Siderovski D.P., Sondek J. EMBO J. 20:4414-4422(2001) [PubMed: 11500369] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1089-1095 IN A COMPLEX WITH INAD.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

J03138 mRNA. Translation: AAA28724.1.
AE014298 Genomic DNA. Translation: AAF45942.2.
AE014298 Genomic DNA. Translation: AAN09121.1.
AE014298 Genomic DNA. Translation: AAX52474.1.
AE014298 Genomic DNA. Translation: AAX52475.1.
AF181641 mRNA. Translation: AAD55427.1.
BT003293 mRNA. Translation: AAO25053.1.

PIR

A31225.

RefSeq

NP_001014720.1.
NP_001014721.1.
NP_525069.2.
NP_726925.1.

UniGene

Dm.7394

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IHJ	X-ray	1.80	A/B	211-214	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:45N.

IntAct

P13217. 3 interactions.

STRING

P13217.

Genome annotation databases

Ensembl

FBtr0100671; FBpp0100137; FBgn0004625; Drosophila melanogaster. [Genome view]

GeneID

31376.

KEGG

dme:Dmel_CG3620.

Organism-specific databases

CTD

31376.

FlyBase

FBgn0004625. norpA.

Phylogenomic databases

HOGENOM

P13217.

OMA

FLTWRSE.

Enzyme and pathway databases

BRENDA

3.1.4.11. 48.

Gene expression databases

ArrayExpress

P13217.

Bgee

P13217.

GermOnline

CG3620. Drosophila melanogaster.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR018029. C2_membr_targeting.
IPR009535. DUF1154.
IPR011992. EF-Hand_type.
IPR015359. Phospholipase_C_EF-hand-like.
IPR001192. Phospholipase_C_Pinositol-sp_C.
IPR000909. Phospholipase_C_Pinositol-sp_X.
IPR001711. Phospholipase_C_Pinositol-sp_Y.
IPR016280. PLC-beta.
IPR017946. PLC-like_Pdiesterase_TIM-brl.
[Graphical view]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
G3DSA:3.20.20.190. PLC-like_Pdiesterase_TIM-brl. 1 hit.

Pfam

PF00168. C2. 1 hit.
PF06631. DUF1154. 1 hit.
PF09279. efhand_like. 1 hit.
PF00388. PI-PLC-X. 1 hit.
PF00387. PI-PLC-Y. 1 hit.
[Graphical view]

PIRSF

PIRSF000956. PLC-beta. 1 hit.

PRINTS

PR00390. PHPHLIPASEC.

ProDom

PD001202. PI_PLC_Y. 2 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00239. C2. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
[Graphical view]

PROSITE

PS50004. C2. 1 hit.
PS50007. PIPLC_X_DOMAIN. 1 hit.
PS50008. PIPLC_Y_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

773325.

Entry information

Entry name

PIPA_DROME

Accession

Primary (citable) accession number: P13217
Secondary accession number(s): A4V3Y2 , Q59E70, Q86P93, Q9U4G4, Q9W4K9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	June 10, 2008
Last modified:	November 3, 2009
This is version 115 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project