Q9P212 (PLCE1_HUMAN) 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):
Pancreas-enriched phospholipase C
Phosphoinositide phospholipase C-epsilon-1
Phospholipase C-epsilon-1
Short name=PLC-epsilon-1

Gene names

Name:	PLCE1
Synonyms:	KIAA1516, PLCE, PPLC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	2302 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.2 Ref.11 Ref.12 Ref.13 Ref.15 Ref.19 Ref.21
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. Ref.1 Ref.2
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.12 Ref.13 Ref.16 Ref.19
Subunit structure	Interacts with RHOA By similarity. Interacts with IQGAP1, HRAS, RAP1A, RAP2A, RAP2B and RRAS. Ref.1 Ref.14 Ref.19 Ref.21
Subcellular location	Cytoplasm › cytosol. Cell membrane. Golgi apparatus membrane. Note: Recruited to plasma membrane by activated HRAS and RAP2. Recruited to perinuclear membrane by activated RAP1A. Isoform 1 and isoform 2 associates with Golgi membranes. Ref.1 Ref.2 Ref.11 Ref.18
Tissue specificity	Widely expressed. Isoform 1 is broadly expressed and only absent in peripheral blood leukocytes. Isoform 2 is specifically expressed in placenta, lung and spleen. Ref.1 Ref.2 Ref.18
Induction	Overexpressed during heart failure. Ref.1 Ref.2 Ref.12 Ref.13 Ref.16 Ref.17 Ref.19
Domain	The Ras-associating domain 1 is degenerated and may not bind HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A, 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.
Involvement in disease	Nephrotic syndrome 3 (NPHS3) [MIM:610725]: A renal disease characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21
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.
Sequence caution	The sequence AAF22005.1 differs from that shown. Reason: Frameshift at position 1131. The sequence AAG17145.2 differs from that shown. Reason: Frameshift at position 2296. The sequence BAA96040.2 differs from that shown. Reason: Erroneous initiation. The sequence BAB14090.1 differs from that shown. Reason: Erroneous initiation. The sequence CAH70739.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH73288.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH73757.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI16674.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat
Molecular function	Guanine-nucleotide releasing factor Hydrolase Transducer
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Traceable author statement Ref.1. Source: UniProtKB activation of MAPK activity Inferred from direct assay Ref.2. Source: UniProtKB calcium-mediated signaling Non-traceable author statement Ref.1. Source: UniProtKB cell proliferation Non-traceable author statement Ref.1. Source: UniProtKB cytoskeleton organization Non-traceable author statement Ref.2. Source: UniProtKB diacylglycerol biosynthetic process Traceable author statement Ref.2. Source: UniProtKB elevation of cytosolic calcium ion concentration Traceable author statement Ref.2. Source: UniProtKB epidermal growth factor receptor signaling pathway Non-traceable author statement Ref.1. Source: UniProtKB glomerulus development Inferred from mutant phenotype Ref.21. Source: HGNC heart development Traceable author statement Ref.2. Source: UniProtKB inositol phosphate-mediated signaling Traceable author statement Ref.2. Source: UniProtKB lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipase C-activating G-protein coupled receptor signaling pathway Inferred from direct assay Ref.2. Source: UniProtKB phospholipid metabolic process Inferred by curator Ref.1. Source: UniProtKB protein kinase C-activating G-protein coupled receptor signaling pathway Non-traceable author statement Ref.1. Source: UniProtKB regulation of G-protein coupled receptor protein signaling pathway Inferred from direct assay Ref.2. Source: UniProtKB regulation of Ras protein signal transduction Inferred from direct assay Ref.2. Source: UniProtKB regulation of cell growth Traceable author statement Ref.2. Source: UniProtKB regulation of smooth muscle contraction Traceable author statement Ref.2. Source: UniProtKB
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay Ref.1. Source: UniProtKB plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	Ras GTPase binding Traceable author statement Ref.1. Source: UniProtKB calcium ion binding Inferred from electronic annotation. Source: InterPro guanyl-nucleotide exchange factor activity Traceable author statement Ref.2. Source: UniProtKB phosphatidylinositol phospholipase C activity Inferred from direct assay Ref.2Ref.1. Source: UniProtKB receptor signaling protein activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9P212-1)

Also known as: PLCepsilon1a;

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 2 (identifier: Q9P212-2)

Also known as: PLCepsilon1b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-308: Missing.
     309-402: DVEEDAFKSK...QRLSEAQWYP → MVSEGSAAGR...CGCWRLKEDQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2302

2302

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

PRO_0000256238

Regions

Domain

531 – 790

260

Ras-GEF

Domain

1392 – 1540

149

PI-PLC X-box

Domain

1730 – 1846

117

PI-PLC Y-box

Domain

1856 – 1956

101

C2

Domain

2012 – 2114

103

Ras-associating 1

Domain

2135 – 2238

104

Ras-associating 2

Region

1686 – 1764

79

Required for activation by RHOA, RHOB, GNA12, GNA13 and G-beta gamma By similarity

Sites

Active site

1407

1

By similarity

Active site

1452

1

By similarity

Natural variations

Alternative sequence

1 – 308

308

Missing in isoform 2.

VSP_021335

Alternative sequence

309 – 402

94

DVEED…AQWYP → MVSEGSAAGRDFAGMEEVRQ LHVRFCKGIKIWHQAWFLCS LLGREPQEREAGCQLWLCTL SAVLKVGWLFPLSEVPNFTL LKDGCGCWRLKEDQ in isoform 2.

VSP_021336

Natural variant

469

1

S → T.
Corresponds to variant rs17508082 [ dbSNP | Ensembl ].

VAR_031843

Natural variant

548

1

R → L.
Corresponds to variant rs17417407 [ dbSNP | Ensembl ].

VAR_031844

Natural variant

1484

1

S → L in NPHS3; gives rise to focal segmental glomerulosclerosis rather than diffuse mesangial sclerosis. Ref.21

VAR_029883

Natural variant

1575

1

R → P.
Corresponds to variant rs2274224 [ dbSNP | Ensembl ].

VAR_031845

Natural variant

1777

1

T → I. Ref.1 Ref.8
Corresponds to variant rs3765524 [ dbSNP | Ensembl ].

VAR_031846

Natural variant

1927

1

H → R. Ref.1 Ref.3 Ref.7 Ref.8
Corresponds to variant rs2274223 [ dbSNP | Ensembl ].

VAR_031847

Experimental info

Mutagenesis

1452

1

H → L: Loss of the phospholipase C enzymatic activity. Still activates HRAS and the MAP kinase pathway. Ref.2

Mutagenesis

2140

1

Q → E: Increases 2.8-fold the affinity for HRAS. Ref.20

Mutagenesis

2148

1

Q → E: Decreases 17.5-fold the affinity for HRAS. Ref.20

Mutagenesis

2148

1

Q → K: Increases 1.4-fold the affinity for HRAS. Ref.20

Mutagenesis

2150

1

R → L: Abolishes interaction with HRAS. Ref.20

Mutagenesis

2171

1

K → L: No effect on HRAS-binding. Ref.20

Mutagenesis

2174

1

Y → L: Reduces HRAS-binding. Ref.20

Sequence conflict

502

1

G → S in AAG28341. Ref.2

Sequence conflict

703

1

V → F in AAG28341. Ref.2

Sequence conflict

1133

1

E → K in AAG28341. Ref.2

Sequence conflict

1229 – 1230

2

SR → QA in AAF22005. Ref.8

Sequence conflict

1456

1

L → P in AAG17145. Ref.1

Sequence conflict

1571

1

N → D in BAB14090. Ref.9

Sequence conflict

1575

1

R → Q in AAG28341. Ref.2

Sequence conflict

1672

1

C → R in AAG17145. Ref.1

Sequence conflict

1705

1

P → L in BAB14090. Ref.9

Sequence conflict

2125

1

D → G in BAB14090. Ref.9

Isoform 2:

Sequence conflict

69

1

L → P in AAG28341. Ref.2

Secondary structure

1

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2302

Helix Strand Turn

Details...

Beta strand

2015 – 2020

6

Beta strand

2022 – 2031

10

Helix

2038 – 2046

9

Beta strand

2049 – 2052

4

Beta strand

2058 – 2064

7

Beta strand

2069 – 2072

4

Beta strand

2081 – 2084

4

Beta strand

2086 – 2088

3

Helix

2090 – 2096

7

Turn

2099 – 2103

5

Beta strand

2107 – 2112

6

Beta strand

2136 – 2143

8

Beta strand

2150 – 2156

7

Helix

2161 – 2171

11

Turn

2172 – 2174

3

Helix

2176 – 2180

5

Helix

2184 – 2186

3

Beta strand

2187 – 2194

8

Beta strand

2198 – 2204

7

Beta strand

2207 – 2211

5

Helix

2218 – 2223

6

Beta strand

2229 – 2235

7

Turn

2236 – 2238

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PLCepsilon1a) [UniParc]. Last modified October 31, 2006. Version 3. Checksum: 71DDE446277077A3	FASTA	2,302	258,715
	10 20 30 40 50 60 MTSEEMTASV LIPVTQRKVV SAQSAADESS EKVSDINISK AHTVRRSGET SHTISQLNKL 70 80 90 100 110 120 KEEPSGSNLP KILSIAREKI VSDENSNEKC WEKIMPDSAK NLNINCNNIL RNHQHGLPQR 130 140 150 160 170 180 QFYEMYNSVA EEDLCLETGI PSPLERKVFP GIQLELDRPS MGISPLGNQS VIIETGRAHP 190 200 210 220 230 240 DSRRAVFHFH YEVDRRMSDT FCTLSENLIL DDCGNCVPLP GGEEKQKKNY VAYTCKLMEL 250 260 270 280 290 300 AKNCDNKNEQ LQCDHCDTLN DKYFCFEGSC EKVDMVYSGD SFCRKDFTDS QAAKTFLSHF 310 320 330 340 350 360 EDFPDNCDDV EEDAFKSKKE RSTLLVRRFC KNDREVKKSV YTGTRAIVRT LPSGHIGLTA 370 380 390 400 410 420 WSYIDQKRNG PLLPCGRVME PPSTVEIRQD GSQRLSEAQW YPIYNAVRRE ETENTVGSLL 430 440 450 460 470 480 HFLTKLPASE TAHGRISVGP CLKQCVRDTV CEYRATLQRT SISQYITGSL LEATTSLGAR 490 500 510 520 530 540 SGLLSTFGGS TGRMMLKERQ PGPSVANSNA LPSSSAGISK ELIDLQPLIQ FPEEVASILM 550 560 570 580 590 600 EQEQTIYRRV LPVDYLCFLT RDLGTPECQS SLPCLKASIS ASILTTQNGE HNALEDLVMR 610 620 630 640 650 660 FNEVSSWVTW LILTAGSMEE KREVFSYLVH VAKCCWNMGN YNAVMEFLAG LRSRKVLKMW 670 680 690 700 710 720 QFMDQSDIET MRSLKDAMAQ HESSCEYRKV VTRALHIPGC KVVPFCGVFL KELCEVLDGA 730 740 750 760 770 780 SGLMKLCPRY NSQEETLEFV ADYSGQDNFL QRVGQNGLKN SEKESTVNSI FQVIRSCNRS 790 800 810 820 830 840 LETDEEDSPS EGNSSRKSSL KDKSRWQFII GDLLDSDNDI FEQSKEYDSH GSEDSQKAFD 850 860 870 880 890 900 HGTELIPWYV LSIQADVHQF LLQGATVIHY DQDTHLSARC FLQLQPDNST LTWVKPTTAS 910 920 930 940 950 960 PASSKAKLGV LNNTAEPGKF PLLGNAGLSS LTEGVLDLFA VKAVYMGHPG IDIHTVCVQN 970 980 990 1000 1010 1020 KLGSMFLSET GVTLLYGLQT TDNRLLHFVA PKHTAKMLFS GLLELTRAVR KMRKFPDQRQ 1030 1040 1050 1060 1070 1080 QWLRKQYVSL YQEDGRYEGP TLAHAVELFG GRRWSARNPS PGTSAKNAEK PNMQRNNTLG 1090 1100 1110 1120 1130 1140 ISTTKKKKKI LMRGESGEVT DDEMATRKAK MHKECRSRSG SDPQDINEQE ESEVNAIANP 1150 1160 1170 1180 1190 1200 PNPLPSRRAH SLTTAGSPNL AAGTSSPIRP VSSPVLSSSN KSPSSAWSSS SWHGRIKGGM 1210 1220 1230 1240 1250 1260 KGFQSFMVSD SNMSFVEFVE LFKSFSVRSR KDLKDLFDVY AVPCNRSGSE SAPLYTNLTI 1270 1280 1290 1300 1310 1320 DENTSDLQPD LDLLTRNVSD LGLFIKSKQQ LSDNQRQISD AIAAASIVTN GTGIESTSLG 1330 1340 1350 1360 1370 1380 IFGVGILQLN DFLVNCQGEH CTYDEILSII QKFEPSISMC HQGLMSFEGF ARFLMDKENF 1390 1400 1410 1420 1430 1440 ASKNDESQEN IKELQLPLSY YYIESSHNTY LTGHQLKGES SVELYSQVLL QGCRSVELDC 1450 1460 1470 1480 1490 1500 WDGDDGMPII YHGHTLTTKI PFKEVVEAID RSAFINSDLP IIISIENHCS LPQQRKMAEI 1510 1520 1530 1540 1550 1560 FKTVFGEKLV TKFLFETDFS DDPMLPSPDQ LRKKVLLKNK KLKAHQTPVD ILKQKAHQLA 1570 1580 1590 1600 1610 1620 SMQVQAYNGG NANPRPANNE EEEDEEDEYD YDYESLSDDN ILEDRPENKS CNDKLQFEYN 1630 1640 1650 1660 1670 1680 EEIPKRIKKA DNSACNKGKV YDMELGEEFY LDQNKKESRQ IAPELSDLVI YCQAVKFPGL 1690 1700 1710 1720 1730 1740 STLNASGSSR GKERKSRKSI FGNNPGRMSP GETASFNKTS GKSSCEGIRQ TWEESSSPLN 1750 1760 1770 1780 1790 1800 PTTSLSAIIR TPKCYHISSL NENAAKRLCR RYSQKLTQHT ACQLLRTYPA ATRIDSSNPN 1810 1820 1830 1840 1850 1860 PLMFWLHGIQ LVALNYQTDD LPLHLNAAMF EANGGCGYVL KPPVLWDKNC PMYQKFSPLE 1870 1880 1890 1900 1910 1920 RDLDSMDPAV YSLTIVSGQN VCPSNSMGSP CIEVDVLGMP LDSCHFRTKP IHRNTLNPMW 1930 1940 1950 1960 1970 1980 NEQFLFHVHF EDLVFLRFAV VENNSSAVTA QRIIPLKALK RGYRHLQLRN LHNEVLEISS 1990 2000 2010 2020 2030 2040 LFINSRRMEE NSSGNTMSAS SMFNTEERKC LQTHRVTVHG VPGPEPFTVF TINGGTKAKQ 2050 2060 2070 2080 2090 2100 LLQQILTNEQ DIKPVTTDYF LMEEKYFISK EKNECRKQPF QRAIGPEEEI MQILSSWFPE 2110 2120 2130 2140 2150 2160 EGYMGRIVLK TQQENLEEKN IVQDDKEVIL SSEEESFFVQ VHDVSPEQPR TVIKAPRVST 2170 2180 2190 2200 2210 2220 AQDVIQQTLC KAKYSYSILS NPNPSDYVLL EEVVKDTTNK KTTTPKSSQR VLLDQECVFQ 2230 2240 2250 2260 2270 2280 AQSKWKGAGK FILKLKEQVQ ASREDKKKGI SFASELKKLT KSTKQPRGLT SPSQLLTSES 2290 2300 IQTKEEKPVG GLSSSDTMDY RQ
	Isoform 2 (PLCepsilon1b) [UniParc]. Checksum: 069358CFA0D7A1CD	FASTA	1,994	223,872
	10 20 30 40 50 60 MVSEGSAAGR DFAGMEEVRQ LHVRFCKGIK IWHQAWFLCS LLGREPQERE AGCQLWLCTL 70 80 90 100 110 120 SAVLKVGWLF PLSEVPNFTL LKDGCGCWRL KEDQIYNAVR REETENTVGS LLHFLTKLPA 130 140 150 160 170 180 SETAHGRISV GPCLKQCVRD TVCEYRATLQ RTSISQYITG SLLEATTSLG ARSGLLSTFG 190 200 210 220 230 240 GSTGRMMLKE RQPGPSVANS NALPSSSAGI SKELIDLQPL IQFPEEVASI LMEQEQTIYR 250 260 270 280 290 300 RVLPVDYLCF LTRDLGTPEC QSSLPCLKAS ISASILTTQN GEHNALEDLV MRFNEVSSWV 310 320 330 340 350 360 TWLILTAGSM EEKREVFSYL VHVAKCCWNM GNYNAVMEFL AGLRSRKVLK MWQFMDQSDI 370 380 390 400 410 420 ETMRSLKDAM AQHESSCEYR KVVTRALHIP GCKVVPFCGV FLKELCEVLD GASGLMKLCP 430 440 450 460 470 480 RYNSQEETLE FVADYSGQDN FLQRVGQNGL KNSEKESTVN SIFQVIRSCN RSLETDEEDS 490 500 510 520 530 540 PSEGNSSRKS SLKDKSRWQF IIGDLLDSDN DIFEQSKEYD SHGSEDSQKA FDHGTELIPW 550 560 570 580 590 600 YVLSIQADVH QFLLQGATVI HYDQDTHLSA RCFLQLQPDN STLTWVKPTT ASPASSKAKL 610 620 630 640 650 660 GVLNNTAEPG KFPLLGNAGL SSLTEGVLDL FAVKAVYMGH PGIDIHTVCV QNKLGSMFLS 670 680 690 700 710 720 ETGVTLLYGL QTTDNRLLHF VAPKHTAKML FSGLLELTRA VRKMRKFPDQ RQQWLRKQYV 730 740 750 760 770 780 SLYQEDGRYE GPTLAHAVEL FGGRRWSARN PSPGTSAKNA EKPNMQRNNT LGISTTKKKK 790 800 810 820 830 840 KILMRGESGE VTDDEMATRK AKMHKECRSR SGSDPQDINE QEESEVNAIA NPPNPLPSRR 850 860 870 880 890 900 AHSLTTAGSP NLAAGTSSPI RPVSSPVLSS SNKSPSSAWS SSSWHGRIKG GMKGFQSFMV 910 920 930 940 950 960 SDSNMSFVEF VELFKSFSVR SRKDLKDLFD VYAVPCNRSG SESAPLYTNL TIDENTSDLQ 970 980 990 1000 1010 1020 PDLDLLTRNV SDLGLFIKSK QQLSDNQRQI SDAIAAASIV TNGTGIESTS LGIFGVGILQ 1030 1040 1050 1060 1070 1080 LNDFLVNCQG EHCTYDEILS IIQKFEPSIS MCHQGLMSFE GFARFLMDKE NFASKNDESQ 1090 1100 1110 1120 1130 1140 ENIKELQLPL SYYYIESSHN TYLTGHQLKG ESSVELYSQV LLQGCRSVEL DCWDGDDGMP 1150 1160 1170 1180 1190 1200 IIYHGHTLTT KIPFKEVVEA IDRSAFINSD LPIIISIENH CSLPQQRKMA EIFKTVFGEK 1210 1220 1230 1240 1250 1260 LVTKFLFETD FSDDPMLPSP DQLRKKVLLK NKKLKAHQTP VDILKQKAHQ LASMQVQAYN 1270 1280 1290 1300 1310 1320 GGNANPRPAN NEEEEDEEDE YDYDYESLSD DNILEDRPEN KSCNDKLQFE YNEEIPKRIK 1330 1340 1350 1360 1370 1380 KADNSACNKG KVYDMELGEE FYLDQNKKES RQIAPELSDL VIYCQAVKFP GLSTLNASGS 1390 1400 1410 1420 1430 1440 SRGKERKSRK SIFGNNPGRM SPGETASFNK TSGKSSCEGI RQTWEESSSP LNPTTSLSAI 1450 1460 1470 1480 1490 1500 IRTPKCYHIS SLNENAAKRL CRRYSQKLTQ HTACQLLRTY PAATRIDSSN PNPLMFWLHG 1510 1520 1530 1540 1550 1560 IQLVALNYQT DDLPLHLNAA MFEANGGCGY VLKPPVLWDK NCPMYQKFSP LERDLDSMDP 1570 1580 1590 1600 1610 1620 AVYSLTIVSG QNVCPSNSMG SPCIEVDVLG MPLDSCHFRT KPIHRNTLNP MWNEQFLFHV 1630 1640 1650 1660 1670 1680 HFEDLVFLRF AVVENNSSAV TAQRIIPLKA LKRGYRHLQL RNLHNEVLEI SSLFINSRRM 1690 1700 1710 1720 1730 1740 EENSSGNTMS ASSMFNTEER KCLQTHRVTV HGVPGPEPFT VFTINGGTKA KQLLQQILTN 1750 1760 1770 1780 1790 1800 EQDIKPVTTD YFLMEEKYFI SKEKNECRKQ PFQRAIGPEE EIMQILSSWF PEEGYMGRIV 1810 1820 1830 1840 1850 1860 LKTQQENLEE KNIVQDDKEV ILSSEEESFF VQVHDVSPEQ PRTVIKAPRV STAQDVIQQT 1870 1880 1890 1900 1910 1920 LCKAKYSYSI LSNPNPSDYV LLEEVVKDTT NKKTTTPKSS QRVLLDQECV FQAQSKWKGA 1930 1940 1950 1960 1970 1980 GKFILKLKEQ VQASREDKKK GISFASELKK LTKSTKQPRG LTSPSQLLTS ESIQTKEEKP 1990 VGGLSSSDTM DYRQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras." Song C., Hu C.-D., Masago M., Kariya K., Yamawaki-Kataoka Y., Shibatohge M., Wu D., Satoh T., Kataoka T. J. Biol. Chem. 276:2752-2757(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH HRAS AND RAP1A, SUBCELLULAR LOCATION, ENZYME REGULATION, VARIANTS ILE-1777 AND ARG-1927. Tissue: Fetal brain.
[2]	"A novel bifunctional phospholipase C that is regulated by Galpha 12 and stimulates the Ras/mitogen-activated protein kinase pathway." Lopez I., Mak E.C., Ding J., Hamm H.E., Lomasney J.W. J. Biol. Chem. 276:2758-2765(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ENZYME REGULATION, MUTAGENESIS OF HIS-1452. Tissue: Heart.
[3]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-1927. Tissue: Brain.
[4]	Ohara O., Nagase T., Kikuno R. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-1927. Tissue: Brain.
[8]	"A novel phospholipase C enriched in pancreas." Kawasaki H., Chen E.J., Springett G.M., Graybiel A.M., Housman D.E. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1098-2302 (ISOFORMS 1/2), VARIANTS ILE-1777 AND ARG-1927. Tissue: Pancreas.
[9]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1383 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1475-2302 (ISOFORMS 1/2). Tissue: Brain and Teratocarcinoma.
[10]	"Sequence of cDNA clone MPMGp800D13530." Buessow K. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1987-2302 (ISOFORMS 1/2). Tissue: Brain.
[11]	"Role of the CDC25 homology domain of phospholipase Cepsilon in amplification of Rap1-dependent signaling." Jin T.-G., Satoh T., Liao Y., Song C., Gao X., Kariya K., Hu C.-D., Kataoka T. J. Biol. Chem. 276:30301-30307(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]	"A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase." Schmidt M., Evellin S., Weernink P.A.O., von Dorp F., Rehmann H., Lomasney J.W., Jakobs K.H. Nat. Cell Biol. 3:1020-1024(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[13]	"Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B." Evellin S., Nolte J., Tysack K., vom Dorp F., Thiel M., Weernink P.A.O., Jakobs K.H., Webb E.J., Lomasney J.W., Schmidt M. J. Biol. Chem. 277:16805-16813(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[14]	"Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase C epsilon." Song C., Satoh T., Edamatsu H., Wu D., Tadano M., Gao X., Kataoka T. Oncogene 21:8105-8113(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAP1A; RAP2A AND RAP2B.
[15]	"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.
[16]	"Inhibition of phospholipase C-epsilon by Gi-coupled receptors." vom Dorp F., Sari A.Y., Sanders H., Keiper M., Oude Weernink P.A., Jakobs K.H., Schmidt M. Cell. Signal. 16:921-928(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[17]	"Phospholipase C epsilon modulates beta-adrenergic receptor-dependent cardiac contraction and inhibits cardiac hypertrophy." Wang H., Oestreich E.A., Maekawa N., Bullard T.A., Vikstrom K.L., Dirksen R.T., Kelley G.G., Blaxall B.C., Smrcka A.V. Circ. Res. 97:1305-1313(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[18]	"Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants." Sorli S.C., Bunney T.D., Sugden P.H., Paterson H.F., Katan M. Oncogene 24:90-100(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[19]	"The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLCepsilon." Ada-Nguema A.S., Xenias H., Sheetz M.P., Keely P.J. J. Cell Sci. 119:1307-1319(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RRAS, ENZYME REGULATION.
[20]	"Structural and mechanistic insights into ras association domains of phospholipase C epsilon." Bunney T.D., Harris R., Gandarillas N.L., Josephs M.B., Roe S.M., Sorli S.C., Paterson H.F., Rodrigues-Lima F., Esposito D., Ponting C.P., Gierschik P., Pearl L.H., Driscoll P.C., Katan M. Mol. Cell 21:495-507(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2131-2246 OF MUTANT LEU-2176 IN COMPLEX WITH HRAS, STRUCTURE BY NMR OF 2006-2114 AND 2131-2246, MUTAGENESIS OF GLN-2140; GLN-2148; ARG-2150; LYS-2171 AND TYR-2174.
[21]	"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: VARIANT NPHS3 LEU-1484, FUNCTION, INTERACTION WITH IQGAP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF190642 mRNA. Translation: AAG17145.2. Frameshift.
AF170071 mRNA. Translation: AAG28341.1.
AB040949 mRNA. Translation: BAA96040.2. Different initiation.
AL139118 , AL139124, AL365510, AL389885 Genomic DNA. Translation: CAH70739.1. Sequence problems.
AL139118 , AL139124, AL365510, AL389885 Genomic DNA. Translation: CAH70740.1.
AL389885 , AL139118, AL139124, AL365510 Genomic DNA. Translation: CAH73288.1. Sequence problems.
AL389885 , AL139118, AL139124, AL365510 Genomic DNA. Translation: CAH73289.1.
AL365510 , AL139118, AL139124, AL389885 Genomic DNA. Translation: CAH73757.1. Sequence problems.
AL365510 , AL139118, AL139124, AL389885 Genomic DNA. Translation: CAH73758.1.
AL139124 , AL139118, AL365510, AL389885 Genomic DNA. Translation: CAI16674.1. Sequence problems.
AL139124 , AL139118, AL365510, AL389885 Genomic DNA. Translation: CAI16675.1.
CH471066 Genomic DNA. Translation: EAW50042.1.
CH471066 Genomic DNA. Translation: EAW50043.1.
BC140705 mRNA. Translation: AAI40706.1.
BC151854 mRNA. Translation: AAI51855.1.
AF117948 mRNA. Translation: AAF22005.1. Frameshift.
AK022543 mRNA. Translation: BAB14090.1. Different initiation.
AK289852 mRNA. Translation: BAF82541.1.
AY995135 mRNA. Translation: AAY45890.1.

IPI

IPI00010604.
IPI00791109.

RefSeq

NP_001159451.1. NM_001165979.1.
NP_057425.3. NM_016341.3.

UniGene

Hs.655033.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BYE	NMR	-	A	2006-2114	[»]
2BYF	NMR	-	A	2131-2246	[»]
2C5L	X-ray	1.90	C/D	2131-2246	[»]

ProteinModelPortal

Q9P212.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P212. 3 interactions.

MINT

MINT-1420367.

PTM databases

PhosphoSite

Q9P212.

Polymorphism databases

DMDM

118595723.

Proteomic databases

PaxDb

Q9P212.

PRIDE

Q9P212.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260766; ENSP00000260766; ENSG00000138193.
ENST00000371375; ENSP00000360426; ENSG00000138193.
ENST00000371380; ENSP00000360431; ENSG00000138193.
ENST00000371385; ENSP00000360438; ENSG00000138193.

GeneID

51196.

KEGG

hsa:51196.

UCSC

uc001kjk.3. human.
uc001kjm.3. human.

Organism-specific databases

CTD

51196.

GeneCards

GC10P095753.

H-InvDB

HIX0009051.
HIX0035415.

HGNC

HGNC:17175. PLCE1.

HPA

HPA015597.
HPA015598.

MIM

608414. gene.
610725. phenotype.

neXtProt

NX_Q9P212.

Orphanet

99977. Esophageal squamous cell carcinoma.
93217. Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis.
93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.

PharmGKB

PA33391.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG149692.

HOVERGEN

HBG059220.

InParanoid

Q9P212.

KO

K05860.

OrthoDB

EOG4BG8V4.

Enzyme and pathway databases

BioCyc

MetaCyc:HS06473-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9P212.

Bgee

Q9P212.

Genevestigator

Q9P212.

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

ChEMBL

CHEMBL3282.

ChiTaRS

PLCE1. human.

EvolutionaryTrace

Q9P212.

GenomeRNAi

51196.

NextBio

54210.

SOURCE

Search...

Entry information

Entry name

PLCE1_HUMAN

Accession

Primary (citable) accession number: Q9P212
Secondary accession number(s): A6NGW0 , A6NLA1, A7MBN7, A8K1D7, B9EIJ6, Q1X6H8, Q5VWL4, Q5VWL5, Q9H9X8, Q9HBX6, Q9HC53, Q9UHV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	October 31, 2006
Last modified:	May 1, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.