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Q99P84 (PLCE1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length2281 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Cytoplasmcytosol 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 processLipid degradation
Lipid metabolism
   Cellular componentCell membrane
Cytoplasm
Golgi apparatus
Membrane
   DomainRepeat
   Molecular functionGuanine-nucleotide releasing factor
Hydrolase
Transducer
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from mutant phenotype Ref.7. Source: RGD

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

regulation of protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 1651229. Source: RGD

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRas GTPase binding

Inferred from direct assay Ref.1. Source: RGD

calcium ion binding

Inferred from electronic annotation. Source: InterPro

enzyme binding

Inferred from sequence or structural similarity. Source: UniProtKB

guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatidylinositol phospholipase C activity

Inferred from sequence or structural similarity. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 228122811-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1
PRO_0000256240

Regions

Domain528 – 781254Ras-GEF
Domain1373 – 1521149PI-PLC X-box
Domain1709 – 1825117PI-PLC Y-box
Domain1835 – 1935101C2
Domain1991 – 2093103Ras-associating 1
Domain2114 – 2217104Ras-associating 2
Region1667 – 174377Required for activation by RHOA, RHOB, GNA12, GNA13 and G-beta gamma

Sites

Active site13881 By similarity
Active site14331 By similarity

Experimental info

Mutagenesis21501K → 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
Mutagenesis21501K → 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
Mutagenesis21521K → 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
Mutagenesis21521K → 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 LengthMass (Da)Tools
Q99P84 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 7409A739B61F69EF

FASTA2,281255,393
        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 

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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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF323615 mRNA. Translation: AAK06775.1.
RefSeqNP_446210.1. NM_053758.2.
UniGeneRn.64650.

3D structure databases

ProteinModelPortalQ99P84.
SMRQ99P84. Positions 1985-2093, 2110-2225.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ99P84. 1 interaction.
STRING10116.ENSRNOP00000019771.

PTM databases

PhosphoSiteQ99P84.

Proteomic databases

PaxDbQ99P84.
PRIDEQ99P84.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID114633.
KEGGrno:114633.

Organism-specific databases

CTD51196.
RGD69424. Plce1.

Phylogenomic databases

eggNOGNOG149692.
HOGENOMHOG000090225.
HOVERGENHBG059220.
InParanoidQ99P84.
KOK05860.

Enzyme and pathway databases

BRENDA3.1.4.11. 5301.

Gene expression databases

GenevestigatorQ99P84.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.10.840.10. 2 hits.
2.60.40.150. 1 hit.
3.20.20.190. 3 hits.
InterProIPR000008. C2_dom.
IPR011992. EF-hand-dom_pair.
IPR001192. PI-PLC_fam.
IPR028398. PLC-epsilon1.
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.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERPTHR10336. PTHR10336. 1 hit.
PTHR10336:SF6. PTHR10336:SF6. 1 hit.
PfamPF00168. C2. 1 hit.
PF09279. EF-hand_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]
PRINTSPR00390. PHPHLIPASEC.
SMARTSM00239. C2. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
SM00314. RA. 1 hit.
SM00147. RasGEF. 1 hit.
[Graphical view]
SUPFAMSSF48366. SSF48366. 2 hits.
SSF49562. SSF49562. 1 hit.
SSF51695. SSF51695. 3 hits.
SSF54236. SSF54236. 2 hits.
PROSITEPS50004. C2. 1 hit.
PS50007. PIPLC_X_DOMAIN. 1 hit.
PS50008. PIPLC_Y_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio618799.
PROQ99P84.

Entry information

Entry namePLCE1_RAT
AccessionPrimary (citable) accession number: Q99P84
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: June 1, 2001
Last modified: June 11, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families