Q99P84 (PLCE1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:	Plce1
Synonyms:	Plce

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	2281 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. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. Ref.5 Ref.7 Ref.8
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. Ref.1
Cofactor	Calcium. Ref.1
Enzyme regulation	Activated by the heterotrimeric G-protein subunits GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by G(i)-coupled GPCRs. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Subunit structure	Interacts with GTP-bound HRAS, RAP1A and probably with RAP2A, RAP2B and RRAS. Interacts with RHOA. Interacts with IQGAP1 By similarity. Ref.1 Ref.4 Ref.8
Subcellular location	Cytoplasm › cytosol By similarity. Cell membrane By similarity. Golgi apparatus membrane By similarity. Note: Recruited to plasma membrane by activated HRAS and RAP2. Recruited to perinuclear membrane by activated RAP1A. Associates with Golgi membranes By similarity.
Tissue specificity	Ubiquitously expressed. Detected in glomerular podocytes (at protein level). Ref.1 Ref.8
Domain	The Ras-associating domain 1 is degenerated and may not bind HRAS By similarity. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A and probably RAP2A and RAP2B and recruitment of HRAS to the cell membrane. The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway By similarity.
Sequence similarities	Contains 1 C2 domain. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain. Contains 2 Ras-associating domains. Contains 1 Ras-GEF domain.
Biophysicochemical properties	Kinetic parameters: KM=6.0 µM for PtdIns(4,5)P2 Ref.6 Vmax=10 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane
Domain	Repeat
Molecular function	Guanine-nucleotide releasing factor Hydrolase Transducer
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Inferred from direct assay Ref.1. Source: RGD activation of MAPK activity Inferred from sequence or structural similarity. Source: UniProtKB lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipase C-activating G-protein coupled receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of G-protein coupled receptor protein signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of Ras protein signal transduction Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	Ras GTPase binding Inferred from direct assay Ref.1. Source: RGD calcium ion binding Inferred from electronic annotation. Source: InterPro guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol phospholipase C activity Inferred from sequence or structural similarity. Source: UniProtKB 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 – 2281	2281	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1		PRO_0000256240
Regions
	Domain	528 – 781	254	Ras-GEF
	Domain	1373 – 1521	149	PI-PLC X-box
	Domain	1709 – 1825	117	PI-PLC Y-box
	Domain	1835 – 1935	101	C2
	Domain	1991 – 2093	103	Ras-associating 1
	Domain	2114 – 2217	104	Ras-associating 2
	Region	1667 – 1743	77	Required for activation by RHOA, RHOB, GNA12, GNA13 and G-beta gamma
Sites
	Active site	1388	1	By similarity
	Active site	1433	1	By similarity
Experimental info
	Mutagenesis	2150	1	K → A: Inhibits binding to HRAS by 59% and phospholipase stimulation by HRAS by 51%. Inhibits binding to HRAS by 97% and phospholipase stimulation by HRAS by 86%; when associated with A-2152. Ref.1
	Mutagenesis	2150	1	K → E: Inhibits binding to HRAS by 99% and phospholipase stimulation by HRAS by 94%. Inhibits binding to HRAS by 97% and phospholipase stimulation by HRAS by 94%; when associated with E-2152. Ref.1
	Mutagenesis	2152	1	K → A: Inhibits binding to HRAS by 19% and phospholipase stimulation by HRAS by 30%. Inhibits binding to HRAS by 97% and phospholipase stimulation by HRAS by 86%; when associated with A-2150. Ref.1
	Mutagenesis	2152	1	K → E: Inhibits binding to HRAS by 67% and phospholipase stimulation by HRAS by 47%. Inhibits binding to HRAS by 97% and phospholipase stimulation by HRAS by 94%; when associated with E-2150. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99P84 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 7409A739B61F69EF	FASTA	2,281	255,393
	10 20 30 40 50 60 MTSEEMAASF LIPVPQRKVA SAQSVAEERG EKVSEAGIPK TRAGRQGGLT PRTISQRNEP 70 80 90 100 110 120 EEESPRTDFS QVFSIARGEL DSDENHNERC WEENVPGSTK NHAVNCNSLL QSHQHALPPS 130 140 150 160 170 180 QLCEVCDSVT EEHLCLQPGI PSPLERKVFP GIELEMEDSP MDVSPLGNQP GIMESSGPHS 190 200 210 220 230 240 DRNMAVFHFH YAGDRTMPGA FHTLSEKFIL DDCANCVTLP GGQQNKNYMA YTCKLVELTR 250 260 270 280 290 300 TCGSKNGQLK CDHCTSLRDE YLCFESSCRK AEALSSGGGF CEDGFTHGPS AKTFLNPLEE 310 320 330 340 350 360 FSDNCEDVDD IFKGKKERST LLVRRFCKND REVKKSVYTG TRAIVRTLPS GHIGLAAWSY 370 380 390 400 410 420 VDQKKAGLMW PCGNGMRPLS TVDVRQSGRQ RLSEAQWCLI YSAVRREETE DTVGSLLHCS 430 440 450 460 470 480 TQLPTPDTAH GRIGDGPCLK QCVRDSECEY RATLQRTSIA QYITGSLLEA TTSLGARSSL 490 500 510 520 530 540 LSSFGGSTGR IMLKERQPGT SMANSSPVPS SSAGISKELI DLQPLIQFPE EVASILTEQE 550 560 570 580 590 600 QNIYRRVLPM DYLCFLTRDL SSPECQRSLP RLKACISESI LMSQSGEHNA LEDLVMRFNE 610 620 630 640 650 660 VSSWVTWLIL TAGSMEEKRE VFSYLVHVAK CCWNMGNYNA VMEFLAGLRS RKVLKMWQFM 670 680 690 700 710 720 DQSDIETMRS LKDAMAQHES SVEYKKVVTR ALHIPGCKVV PFCGVFLKEL CEVLDGASGL 730 740 750 760 770 780 LKLCPRYSSQ EEALEFVADY SGQDNFLQRV GQNGLKNPEK ELTVNSIFQI IRSCSRSLET 790 800 810 820 830 840 EDEESASEGS GSRKNSLKDK TRWQFIIGDL LDSDNDIFEK SKECDPHGSE ESQKAFDHGT 850 860 870 880 890 900 ELIPWYVLSI QADVHQFLLQ GATVIHYDQD THLSARCFLQ LQPDNSTLTW MKPPTASPAG 910 920 930 940 950 960 ARLKLGVLSN VAEPGKFPSL GNAGVSGLVE GILDLFSVKA VYMGHPGIDI HTVCVQNKLS 970 980 990 1000 1010 1020 SMLLSETGVT LLYGLQTTDN RLLHFVAPKH TAKMLFSGLL ELTTAVRKIR KFPDQRQQWL 1030 1040 1050 1060 1070 1080 RKQYVSFYQE DGRYEGPTLA HAVELFGGRR WSTRNPSPGM SAKNAEKPNM QRNNTLGIST 1090 1100 1110 1120 1130 1140 TKKKKKMLMR GESGEVTDDE MATRKAKMYR ECRSRSGSDP QEANEQEDSE ANVITNPPNP 1150 1160 1170 1180 1190 1200 LHSRRAYSLT TAGSPNLATG MSSPISAWSS SSWHGRIKGG MKGFQSFMVS DSNMSFIEFV 1210 1220 1230 1240 1250 1260 ELFKSFSIRS RKDLKDIFDI YSVPCNRSAS ESTPLYTNLT IEENTNDLQP DLDLLTRNVS 1270 1280 1290 1300 1310 1320 DLGLFMKSKQ QLSDNQRQIS DAIAAASIVT NGTGIESTSL GIFGVGILQL NDFLVNCQGE 1330 1340 1350 1360 1370 1380 HCTYDEILSI IQKFEPNISM CHQGLLSFEG FARFLMDKDN FASKNDESRE NKKDLQLPLS 1390 1400 1410 1420 1430 1440 YYYIESSHNT YLTGHQLKGE SSVELYSQVL LQGCRSIELD CWDGDDGMPI IYHGHTLTTK 1450 1460 1470 1480 1490 1500 IPFKEVVEAI DRSAFITSDL PIIISIENHC SLPQQRKMAE IFKSVFGEKL VAKFLFETDF 1510 1520 1530 1540 1550 1560 SDDPMLPSPD QLRRKVLLKN KKLKAHQTPV DILKQKAHQL ASMQTQAFTG GNANPPPASN 1570 1580 1590 1600 1610 1620 EEEEDEEDEY DYDYESLSDD NILEDRPENK SCADKLQFEY NEEVPKRIKK ADNSSGNKGK 1630 1640 1650 1660 1670 1680 VYDMELGEEF YLPQNKKESR QIAPELSDLV IYCQAVKFPG LSTLNSSGSG RGKERKSRKS 1690 1700 1710 1720 1730 1740 IFGNNPGRMS PGETASFNRT SGKSSCEGIR QIWEEPPLSP NTSLSAIIRT PKCYHISSLN 1750 1760 1770 1780 1790 1800 ENAAKRLCRR YSQKLIQHTA CQLLRTYPAA TRIDSSNPNP LMFWLHGIQL VALNYQTDDL 1810 1820 1830 1840 1850 1860 PLHLNAAMFE ANGGCGYVLK PPVLWDKSCP MYQKFSPLER DLDAMDPATY SLTIISGQNV 1870 1880 1890 1900 1910 1920 CPSNSTGSPC IEVDVLGMPL DSCHFRTKPI HRNTLNPMWN EQFLFRVHFE DLVFLRFAVV 1930 1940 1950 1960 1970 1980 ENNSSAITAQ RIIPLKALKR GYRHLQLRNL HNEILEISSL FINSRRMEDN PSGSTRPASL 1990 2000 2010 2020 2030 2040 MFNTEERKCS QTHKVTVHGV PGPEPFAVFT INEGTKAKQL LQQILAVDQD TKLTAADYFL 2050 2060 2070 2080 2090 2100 MEEKHFISKE KNECRKQPFQ RAVGPEEDIV QILNSWFPEE GYVGRIVLKP QQETLEEKNI 2110 2120 2130 2140 2150 2160 VHDDREVILS SEEESFFVQV HDVSPEQPRT VIKAPRVSTA QDVIQQTLCK AKYSYSILNN 2170 2180 2190 2200 2210 2220 PNPCDYVLLE EVMKDAPNKK SSTPKSSQRI LLDQECVFQA QSKWKGAGKF ILKLKEQVQA 2230 2240 2250 2260 2270 2280 SREDKRRGIS FASELKKLTK STKQTRGLTS PPQLVASESV QSKEEKPMGA LASGDTAGYQ S

References

[1]	"Phospholipase C(epsilon): a novel Ras effector." Kelley G.G., Reks S.E., Ondrako J.M., Smrcka A.V. EMBO J. 20:743-754(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CATALYTIC ACTIVITY, ENZYME REGULATION, COFACTOR, INTERACTION WITH HRAS AND RAP1A, MUTAGENESIS OF LYS-2150 AND LYS-2152. Tissue: Heart.
[2]	"Activation of phospholipase C-epsilon by heterotrimeric G protein betagamma-subunits." Wing M.R., Houston D., Kelley G.G., Der C.J., Siderovski D.P., Harden T.K. J. Biol. Chem. 276:48257-48261(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[3]	"Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformation." Murphy G.A., Graham S.M., Morita S., Reks S.E., Rogers-Graham K., Vojtek A., Kelley G.G., Der C.J. J. Biol. Chem. 277:9966-9975(2002) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[4]	"Direct activation of phospholipase C-epsilon by Rho." Wing M.R., Snyder J.T., Sondek J., Harden T.K. J. Biol. Chem. 278:41253-41258(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH RHOA.
[5]	"Activation of CD4 T cells by Raf-independent effectors of Ras." Czyzyk J., Brogdon J.L., Badou A., Henegariu O., Preston Hurlburt P., Flavell R., Bottomly K. Proc. Natl. Acad. Sci. U.S.A. 100:6003-6008(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"RhoA activates purified phospholipase C-epsilon by a guanine nucleotide-dependent mechanism." Seifert J.P., Wing M.R., Snyder J.T., Gershburg S., Sondek J., Harden T.K. J. Biol. Chem. 279:47992-47997(2004) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[7]	"G-protein-coupled receptor agonists activate endogenous phospholipase Cepsilon and phospholipase Cbeta3 in a temporally distinct manner." Kelley G.G., Kaproth-Joslin K.A., Reks S.E., Smrcka A.V., Wojcikiewicz R.J.H. J. Biol. Chem. 281:2639-2648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible." Hinkes B., Wiggins R.C., Gbadegesin R., Vlangos C.N., Seelow D., Nuernberg G., Garg P., Verma R., Chaib H., Hoskins B.E., Ashraf S., Becker C., Hennies H.C., Goyal M., Wharram B.L., Schachter A.D., Mudumana S., Drummond I. , Kerjaschki D., Waldherr R., Dietrich A., Ozaltin F., Bakkaloglu A., Cleper R., Basel-Vanagaite L., Pohl M., Griebel M., Tsygin A.N., Soylu A., Mueller D., Sorli C.S., Bunney T.D., Katan M., Liu J., Attanasio M., O'toole J.F., Hasselbacher K., Mucha B., Otto E.A., Airik R., Kispert A., Kelley G.G., Smrcka A.V., Gudermann T., Holzman L.B., Nuernberg P., Hildebrandt F. Nat. Genet. 38:1397-1405(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH IQGAP1.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF323615 mRNA. Translation: AAK06775.1.
IPI	IPI00325415.
RefSeq	NP_446210.1. NM_053758.2.
UniGene	Rn.64650.
3D structure databases
HSSP	HSSP built from PDB template 2C5L based on UniProtKB Q9UHV3.
ProteinModelPortal	Q99P84.
SMR	Q99P84. Positions 1985-2093, 2110-2225.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99P84. 1 interaction.
STRING	10116.ENSRNOP00000019771.
PTM databases
PhosphoSite	Q99P84.
Proteomic databases
PaxDb	Q99P84.
PRIDE	Q99P84.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	114633.
KEGG	rno:114633.
Organism-specific databases
CTD	51196.
RGD	69424. Plce1.
Phylogenomic databases
eggNOG	NOG149692.
HOGENOM	HOG000090225.
HOVERGEN	HBG059220.
InParanoid	Q99P84.
KO	K05860.
Enzyme and pathway databases
BRENDA	3.1.4.11. 5301.
Gene expression databases
ArrayExpress	Q99P84.
Genevestigator	Q99P84.
GermOnline	ENSRNOG00000014276. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.238.10. 1 hit. 1.10.840.10. 2 hits. 3.20.20.190. 3 hits.
InterPro	IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR018029. C2_membr_targeting. IPR011992. EF-hand-like_dom. IPR001192. Pinositol_PLipase_C. IPR017946. PLC-like_Pdiesterase_TIM-brl. IPR015359. PLipase_C_EF-hand-like. IPR000909. PLipase_C_PInositol-sp_X_dom. IPR001711. PLipase_C_Pinositol-sp_Y. IPR000159. Ras-assoc. IPR023578. Ras_GEF_dom. IPR001895. RasGRF_CDC25. [Graphical view]
PANTHER	PTHR10336. PTHR10336. 1 hit.
Pfam	PF00168. C2. 1 hit. PF09279. efhand_like. 1 hit. PF00388. PI-PLC-X. 1 hit. PF00387. PI-PLC-Y. 1 hit. PF00788. RA. 1 hit. PF00617. RasGEF. 1 hit. [Graphical view]
PRINTS	PR00390. PHPHLIPASEC.
SMART	SM00239. C2. 1 hit. SM00148. PLCXc. 1 hit. SM00149. PLCYc. 1 hit. SM00314. RA. 1 hit. SM00147. RasGEF. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF51695. PLC-like_Pdiesterase_TIM-brl. 1 hit. SSF48366. Ras_GEF. 1 hit.
PROSITE	PS50004. C2. 1 hit. PS50007. PIPLC_X_DOMAIN. 1 hit. PS50008. PIPLC_Y_DOMAIN. 1 hit. PS50200. RA. 1 hit. PS00720. RASGEF. False negative. PS50009. RASGEF_CAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	618799.

Entry information

Entry name

PLCE1_RAT

Accession

Primary (citable) accession number: Q99P84

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	June 1, 2001
Last modified:	April 3, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program