P10688 (PLCD1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1
EC=3.1.4.11

Alternative name(s):
Phosphoinositide phospholipase C-delta-1
Phospholipase C-III
Short name=PLC-III
Phospholipase C-delta-1
Short name=PLC-delta-1

Gene names

Name:

Plcd1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
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 for trophoblast and placental development.
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.
Cofactor	Binds 3 calcium ions per subunit. Two of the calcium ions are bound to the C2 domain.
Sequence similarities	Contains 1 C2 domain. Contains 2 EF-hand domains. Contains 1 PH domain. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Transducer
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Inferred from mutant phenotype PubMed 16709602. Source: RGD intracellular signal transduction Inferred from electronic annotation. Source: InterPro lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of inositol trisphosphate biosynthetic process Inferred from mutant phenotype PubMed 16709602. Source: RGD positive regulation of norepinephrine secretion Inferred from mutant phenotype PubMed 10473563. Source: RGD response to aluminum ion Inferred from expression pattern PubMed 10814511. Source: RGD response to calcium ion Inferred from mutant phenotype PubMed 10473563. Source: RGD response to hyperoxia Inferred from expression pattern PubMed 12850505. Source: RGD response to peptide hormone stimulus Inferred from mutant phenotype PubMed 16709602. Source: RGD response to prostaglandin F stimulus Inferred from expression pattern PubMed 11517196. Source: RGD
Cellular_component	cytosol Inferred from direct assay PubMed 16709602. Source: RGD membrane raft Inferred from direct assay PubMed 18157946. Source: RGD mitochondrial membrane Inferred from direct assay PubMed 15107298. Source: RGD nucleus Inferred from direct assay PubMed 16115628. Source: RGD
Molecular_function	calcium ion binding Inferred from direct assay PubMed 9538021. Source: RGD phosphatidylinositol phospholipase C activity Inferred from direct assay PubMed 9287165. Source: RGD phosphatidylinositol-4,5-bisphosphate binding Inferred from direct assay PubMed 9804818. Source: RGD signal transducer activity 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 – 756

756

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1

PRO_0000088506

Regions

Domain

21 – 130

110

PH

Domain

140 – 175

36

EF-hand 1

Domain

176 – 211

36

EF-hand 2

Domain

296 – 440

145

PI-PLC X-box

Domain

492 – 609

118

PI-PLC Y-box

Domain

630 – 720

91

C2

Calcium binding

153 – 164

12

1 Potential

Calcium binding

189 – 200

12

2 Potential

Region

30 – 57

28

Substrate binding

Sites

Active site

311

1

Active site

356

1

Metal binding

312

1

Calcium 1; catalytic

Metal binding

341

1

Calcium 1; catalytic

Metal binding

343

1

Calcium 1; catalytic

Metal binding

390

1

Calcium 1; catalytic

Metal binding

651

1

Calcium 2; via carbonyl oxygen

Metal binding

653

1

Calcium 2

Metal binding

677

1

Calcium 2

Metal binding

706

1

Calcium 3

Metal binding

707

1

Calcium 3; via carbonyl oxygen

Metal binding

708

1

Calcium 3

Binding site

438

1

Substrate

Binding site

440

1

Substrate

Binding site

522

1

Substrate

Binding site

549

1

Substrate

Natural variations

Natural variant

412

1

I → M in SHR. Ref.2

Natural variant

423

1

T → S in SHR. Ref.2

Natural variant

463

1

V → D in SHR. Ref.2

Natural variant

668

1

G → A in SHR. Ref.2

Experimental info

Mutagenesis

311

1

H → A: Lowers activity 10000-fold. Ref.5

Mutagenesis

312

1

N → A: Lowers activity 10000-fold. Ref.5

Mutagenesis

320

1

L → A: Lowers activity 3-fold. Ref.5

Mutagenesis

341

1

E → A, H or Q: Lowers activity 200000-fold. Ref.5

Mutagenesis

343

1

D → A: Lowers activity 1000-fold. Ref.5

Mutagenesis

343

1

D → R: Lowers activity 100000-fold. Ref.5

Mutagenesis

356

1

H → A: Lowers activity 1000-fold. Ref.5

Mutagenesis

360

1

F → A: Lowers activity 4-fold. Ref.5

Mutagenesis

390

1

E → A, H or K: Lowers activity 1000-fold. Ref.5

Mutagenesis

390

1

E → Q: Lowers activity 200-fold. Ref.5

Mutagenesis

438

1

K → A: Lowers activity very slightly. Ref.5

Mutagenesis

440

1

K → A: No effect on activity towards phosphatidylinositol 4-monophosphate. Lowers activity 5-fold towards phosphatidylinositol 4,5-bisphosphate. Ref.5

Mutagenesis

522

1

S → A: Lowers activity 10000-fold. Ref.5

Mutagenesis

549

1

R → A: Lowers activity 600-fold. Ref.5

Mutagenesis

551

1

Y → A: Lowers activity 600-fold. Ref.5

Mutagenesis

555

1

W → A: Lowers activity very slightly. Ref.5

Sequence conflict

627 – 629

3

RPE → APK in AAP31521. Ref.2

Secondary structure

1

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756

Helix Strand Turn

Details...

Helix

17 – 24

8

Beta strand

26 – 35

10

Beta strand

37 – 44

8

Beta strand

48 – 53

6

Turn

62 – 65

4

Beta strand

66 – 68

3

Helix

69 – 71

3

Beta strand

72 – 79

8

Helix

82 – 87

6

Helix

93 – 95

3

Beta strand

96 – 104

9

Beta strand

108 – 111

4

Helix

115 – 129

15

Helix

203 – 208

6

Helix

212 – 222

11

Beta strand

225 – 229

5

Helix

230 – 239

10

Helix

248 – 258

11

Helix

262 – 266

5

Helix

272 – 280

9

Turn

282 – 284

3

Beta strand

285 – 287

3

Helix

289 – 292

4

Helix

302 – 304

3

Beta strand

305 – 307

3

Beta strand

309 – 312

4

Beta strand

315 – 317

3

Beta strand

319 – 321

3

Helix

326 – 334

9

Beta strand

339 – 345

7

Helix

348 – 350

3

Beta strand

353 – 355

3

Turn

357 – 360

4

Helix

366 – 376

11

Turn

377 – 379

3

Beta strand

385 – 392

8

Helix

395 – 409

15

Helix

410 – 412

3

Turn

428 – 433

6

Beta strand

435 – 439

5

Helix

490 – 493

4

Beta strand

496 – 502

7

Beta strand

509 – 514

6

Beta strand

519 – 524

6

Helix

525 – 545

21

Beta strand

548 – 551

4

Helix

565 – 568

4

Turn

569 – 571

3

Beta strand

574 – 577

4

Helix

584 – 594

11

Helix

596 – 598

3

Beta strand

600 – 603

4

Helix

606 – 609

4

Beta strand

629 – 640

12

Helix

644 – 646

3

Beta strand

648 – 650

3

Beta strand

654 – 663

10

Helix

664 – 666

3

Beta strand

668 – 671

4

Beta strand

679 – 681

3

Beta strand

683 – 693

11

Helix

695 – 697

3

Beta strand

699 – 706

8

Beta strand

709 – 711

3

Beta strand

714 – 722

9

Helix

723 – 725

3

Beta strand

729 – 736

8

Beta strand

742 – 755

14

Sequences

	Sequence		Length	Mass (Da)
	P10688 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: E33F2313AC81E9F9	FASTA	756	85,962
	10 20 30 40 50 60 MDSGRDFLTL HGLQDDPDLQ ALLKGSQLLK VKSSSWRRER FYKLQEDCKT IWQESRKVMR 70 80 90 100 110 120 SPESQLFSIE DIQEVRMGHR TEGLEKFARD IPEDRCFSIV FKDQRNTLDL IAPSPADAQH 130 140 150 160 170 180 WVQGLRKIIH HSGSMDQRQK LQHWIHSCLR KADKNKDNKM NFKELKDFLK ELNIQVDDGY 190 200 210 220 230 240 ARKIFRECDH SQTDSLEDEE IETFYKMLTQ RAEIDRAFEE AAGSAETLSV ERLVTFLQHQ 250 260 270 280 290 300 QREEEAGPAL ALSLIERYEP SETAKAQRQM TKDGFLMYLL SADGNAFSLA HRRVYQDMDQ 310 320 330 340 350 360 PLSHYLVSSS HNTYLLEDQL TGPSSTEAYI RALCKGCRCL ELDCWDGPNQ EPIIYHGYTF 370 380 390 400 410 420 TSKILFCDVL RAIRDYAFKA SPYPVILSLE NHCSLEQQRV MARHLRAILG PILLDQPLDG 430 440 450 460 470 480 VTTSLPSPEQ LKGKILLKGK KLGGLLPAGG ENGSEATDVS DEVEAAEMED EAVRSQVQHK 490 500 510 520 530 540 PKEDKLKLVP ELSDMIIYCK SVHFGGFSSP GTSGQAFYEM ASFSESRALR LLQESGNGFV 550 560 570 580 590 600 RHNVSCLSRI YPAGWRTDSS NYSPVEMWNG GCQIVALNFQ TPGPEMDVYL GCFQDNGGCG 610 620 630 640 650 660 YVLKPAFLRD PNTTFNSRAL TQGPWWRPER LRVRIISGQQ LPKVNKNKNS IVDPKVIVEI 670 680 690 700 710 720 HGVGRDTGSR QTAVITNNGF NPRWDMEFEF EVTVPDLALV RFMVEDYDSS SKNDFIGQST 730 740 750 IPWNSLKQGY RHVHLLSKNG DQHPSATLFV KISIQD

References

[1]	"Cloning and sequence of multiple forms of phospholipase C." Suh P.-G., Ryu S.H., Moon K.H., Suh H.W., Rhee S.G. Cell 54:161-169(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Phospholipase C-delta gene of the spontaneously hypertensive rat harbors point mutations causing amino acid substitutions in a catalytic domain." Yagisawa H., Tanase H., Nojima H. J. Hypertens. 9:997-1004(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SHR MET-412; SER-423; ASP-463 AND ALA-668. Tissue: Aorta.
[3]	"Putative inositol 1,4,5-trisphosphate binding proteins in rat brain cytosol." Kanematsu T., Takeya H., Watanabe Y., Ozaki S., Yoshida M., Koga T., Iwanaga S., Hirata M. J. Biol. Chem. 267:6518-6525(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 50-57; 128-140 AND 728-738. Tissue: Brain.
[4]	Lubec G., Diao W. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 61-76, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus.
[5]	"Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational analysis of residues within the active site and hydrophobic ridge of plcdelta1." Ellis M.V., James S.R., Perisic O., Downes C.P., Williams R.L., Katan M. J. Biol. Chem. 273:11650-11659(1998) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF HIS-311; ASN-312; LEU-320; GLU-341; ASP-343; HIS-356; PHE-360; GLU-390; LYS-438; LYS-440; SER-522; ARG-549; TYR-551 AND TRP-555.
[6]	"Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain." Ferguson K.M., Lemmon M.A., Schlessinger J., Sigler P.B. Cell 83:1037-1046(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 12-130.
[7]	"C2 domain conformational changes in phospholipase C-delta 1." Grobler J.A., Essen L.-O., Williams R.L., Hurley J.H. Nat. Struct. Biol. 3:788-795(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 205-756.
[8]	"Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta." Essen L.-O., Perisic O., Cheung R., Katan M., Williams R.L. Nature 380:595-602(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 133-756.
[9]	"A ternary metal binding site in the C2 domain of phosphoinositide-specific phospholipase C-delta1." Essen L.-O., Perisic O., Lynch D.E., Katan M., Williams R.L. Biochemistry 36:2753-2762(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 133-756, CALCIUM-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M20637 mRNA. Translation: AAA41886.1.
S74591 mRNA. Translation: AAP31521.1.

IPI

IPI00230949.

PIR

B28821.

RefSeq

NP_058731.1. NM_017035.1.

UniGene

Rn.12324.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DJG	X-ray	2.60	A/B	133-756	[»]
1DJH	X-ray	2.50	A/B	133-756	[»]
1DJI	X-ray	2.50	A/B	133-756	[»]
1DJW	X-ray	2.45	A/B	133-756	[»]
1DJX	X-ray	2.30	A/B	133-756	[»]
1DJY	X-ray	2.80	A/B	133-756	[»]
1DJZ	X-ray	2.95	A/B	133-756	[»]
1MAI	X-ray	1.90	A	11-140	[»]
1QAS	X-ray	2.40	A/B	135-756	[»]
1QAT	X-ray	3.00	A/B	135-756	[»]
2ISD	X-ray	2.50	A/B	133-756	[»]

DisProt

DP00055.

ProteinModelPortal

P10688.

SMR

P10688. Positions 12-130, 158-756.

ModBase

Search...

PTM databases

PhosphoSite

P10688.

Proteomic databases

PaxDb

P10688.

PRIDE

P10688.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

24655.

KEGG

rno:24655.

UCSC

RGD:3346. rat.

Organism-specific databases

CTD

5333.

RGD

3346. Plcd1.

Phylogenomic databases

eggNOG

NOG149692.

HOGENOM

HOG000006871.

HOVERGEN

HBG053610.

InParanoid

P10688.

KO

K05857.

Enzyme and pathway databases

BRENDA

3.1.4.11. 5301.

Gene expression databases

ArrayExpress

P10688.

Genevestigator

P10688.

GermOnline

ENSRNOG00000032238. Rattus norvegicus.

Family and domain databases

Gene3D

1.10.238.10. 2 hits.
2.30.29.30. 1 hit.
3.20.20.190. 2 hits.

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR011993. PH_like_dom.
IPR001192. Pinositol_PLipase_C.
IPR017946. PLC-like_Pdiesterase_TIM-brl.
IPR001849. Pleckstrin_homology.
IPR015359. PLipase_C_EF-hand-like.
IPR000909. PLipase_C_PInositol-sp_X_dom.
IPR001711. PLipase_C_Pinositol-sp_Y.
[Graphical view]

PANTHER

PTHR10336. PTHR10336. 1 hit.

Pfam

PF00168. C2. 1 hit.
PF09279. efhand_like. 1 hit.
PF00169. PH. 1 hit.
PF00388. PI-PLC-X. 1 hit.
PF00387. PI-PLC-Y. 1 hit.
[Graphical view]

PRINTS

PR00390. PHPHLIPASEC.

SMART

SM00239. C2. 1 hit.
SM00054. EFh. 2 hits.
SM00233. PH. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF51695. PLC-like_Pdiesterase_TIM-brl. 1 hit.

PROSITE

PS50004. C2. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
PS50003. PH_DOMAIN. 1 hit.
PS50007. PIPLC_X_DOMAIN. 1 hit.
PS50008. PIPLC_Y_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P10688.

ChEMBL

CHEMBL1914273.

EvolutionaryTrace

P10688.

NextBio

603990.

Entry information

Entry name

PLCD1_RAT

Accession

Primary (citable) accession number: P10688
Secondary accession number(s): Q80WI4 , Q9QVD3, Q9QVD4, Q9QVD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 141 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program