Q99P84
Gene name |
Plce1 (Plce) |
Protein name |
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 |
Names |
Phosphoinositide phospholipase C-epsilon-1, Phospholipase C-epsilon-1, PLC-epsilon-1 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:114633 |
EC number |
3.1.4.11: Phosphoric diester hydrolases |
Protein Class |
PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN (PTHR10336) |
Descriptions
PLCε is a critical regulator of calcium and DAG-dependent signaling in the cardiovascular system, where changes in its expression and/or aberrant activation result in cardiac hypertrophy and heart failure. PLCε shares four core domains common to most PLCs, including a pleckstrin homology (PH) domain, followed by four tandem EF hand repeats (EF1-4), the catalytic TIM barrel domain (split by an autoregulatory X-Y linker), and a C2 domain. In PLCε, these core domains are flanked by regions that confer responsiveness to different signal transduction pathways. The N-terminal region contains a CDC25 domain that acts as a guanine nucleotide exchange factor (GEF) for the Rap1A GTPase. This domain is essential for sustained PI hydrolysis at the perinuclear and Golgi membranes in cardiomyocytes. The C-terminal region contains two Ras association (RA) domains (RA1 and RA2) that bind activated Rap1A and Ras. PLCε is present predominantly in the cytoplasm, and is maintained in a low-activity state by the autoinhibitory X-Y linker and the C2-RA1 linker. Localization of PLCε to the perinuclear membrane through interactions between the RA1 domain and the scaffolding protein mAKAP increases lipase activity. RA1 binding to mAKAP could alter the conformation of, or displace, the C2-RA1 linker, increasing basal activity. Membrane association would also increase basal activity via interfacial activation, which may be facilitated by interactions between the αx-y helix and the membrane or, alternatively, with other domain in PLCε or proteins at the target membrane, such as activated Rap1A.
Autoinhibitory domains (AIDs)
Target domain |
1373-1522 (PI-PLC X domain); 1709-1825 (PI-PLC Y domain) |
Relief mechanism |
Ligand binding, Partner binding |
Assay |
Structural analysis, Deletion assay |
Target domain |
1825-1850 (A cleft between TIM barrel and C2 domain) |
Relief mechanism |
Ligand binding, Partner binding |
Assay |
Structural analysis, Mutagenesis experiment |
Accessory elements
No accessory elements
References
- Muralidharan K et al. (2021) "Structure and regulation of phospholipase Cβ and ε at the membrane", Chemistry and physics of lipids, 235, 105050
- Rugema NY et al. (2020) "Structure of phospholipase Cε reveals an integrated RA1 domain and previously unidentified regulatory elements", Communications biology, 3, 445
Autoinhibited structure
Activated structure
2 structures for Q99P84
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 6PMP | X-ray | 273 A | A/B/C/D | 1284-2098 | PDB |
| AF-Q99P84-F1 | Predicted | AlphaFoldDB |
No variants for Q99P84
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q99P84 | |||||
No associated diseases with Q99P84
No regional properties for Q99P84
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| No domain, repeats, and functional sites for Q99P84 | |||
Functions
| Description | ||
|---|---|---|
| EC Number | 3.1.4.11 | Phosphoric diester hydrolases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR10336 | PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN |
| PANTHER Subfamily | PTHR10336:SF6 | 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE EPSILON-1 |
| PANTHER Protein Class | phospholipase | |
| PANTHER Pathway Category |
Inflammation mediated by chemokine and cytokine signaling pathway PLCbetagamma Alpha adrenergic receptor signaling pathway PLC Oxytocin receptor mediated signaling pathway PLC beta Histamine H1 receptor mediated signaling pathway PLC 5HT2 type receptor mediated signaling pathway PLC Thyrotropin-releasing hormone receptor signaling pathway PLC |
|
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| Golgi membrane | The lipid bilayer surrounding any of the compartments of the Golgi apparatus. |
| lamellipodium | A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| enzyme binding | Binding to an enzyme, a protein with catalytic activity. |
| guanyl-nucleotide exchange factor activity | Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions. |
| metal ion binding | Binding to a metal ion. |
| phosphatidylinositol phospholipase C activity | Catalysis of the reaction |
| phospholipase C activity | Catalysis of the reaction |
| small GTPase binding | Binding to a small monomeric GTPase. |
14 GO annotations of biological process
| Name | Definition |
|---|---|
| diacylglycerol biosynthetic process | The chemical reactions and pathways resulting in the formation of diacylglycerol, a glyceride in which any two of the R groups (positions not specified) are acyl groups while the remaining R group can be either H or an alkyl group. |
| epidermal growth factor receptor signaling pathway | The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription. |
| G protein-coupled receptor signaling pathway | The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane. |
| glomerulus development | The progression of the glomerulus over time from its initial formation until its mature state. The glomerulus is a capillary tuft which forms a close network with the visceral epithelium (podocytes) and the mesangium to form the filtration barrier and is surrounded by Bowman's capsule in nephrons of the vertebrate kidney. The glomerulus is part of the nephron and is restricted to one body segment. |
| lipid catabolic process | The chemical reactions and pathways resulting in the breakdown of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. |
| phosphatidylinositol-mediated signaling | The series of molecular signals in which a cell uses a phosphatidylinositol-mediated signaling to convert a signal into a response. Phosphatidylinositols include phosphatidylinositol (PtdIns) and its phosphorylated derivatives. |
| phospholipase C-activating G protein-coupled receptor signaling pathway | A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation of phospholipase C (PLC) and a subsequent increase in the intracellular concentration of inositol trisphosphate (IP3) and diacylglycerol (DAG). |
| positive regulation of lamellipodium assembly | Any process that increases the rate, frequency or extent of the formation of a lamellipodium, a thin sheetlike extension of the surface of a migrating cell. |
| positive regulation of MAPK cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade. |
| Ras protein signal transduction | The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state. |
| regulation of G protein-coupled receptor signaling pathway | Any process that modulates the frequency, rate or extent of G protein-coupled receptor signaling pathway. |
| regulation of protein kinase activity | Any process that modulates the frequency, rate or extent of protein kinase activity. |
| regulation of Ras protein signal transduction | Any process that modulates the frequency, rate or extent of Ras protein signal transduction. |
| release of sequestered calcium ion into cytosol | The process in which calcium ions sequestered in the endoplasmic reticulum, Golgi apparatus or mitochondria are released into the cytosolic compartment. |
30 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P32383 | PLC1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| Q1RML2 | PLCZ1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 | Bos taurus (Bovine) | PR |
| P10895 | PLCD1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 | Bos taurus (Bovine) | SS |
| Q2VRL0 | PLCZ1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 | Gallus gallus (Chicken) | PR |
| Q86YW0 | PLCZ1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 | Homo sapiens (Human) | PR |
| Q9BRC7 | PLCD4 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 | Homo sapiens (Human) | SS |
| Q15111 | PLCL1 | Inactive phospholipase C-like protein 1 | Homo sapiens (Human) | PR |
| P51178 | PLCD1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 | Homo sapiens (Human) | EV |
| Q9UPR0 | PLCL2 | Inactive phospholipase C-like protein 2 | Homo sapiens (Human) | PR |
| Q8N3E9 | PLCD3 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 | Homo sapiens (Human) | SS |
| Q9P212 | PLCE1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 | Homo sapiens (Human) | SS |
| Q8R3B1 | Plcd1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 | Mus musculus (Mouse) | SS |
| Q8K394 | Plcl2 | Inactive phospholipase C-like protein 2 | Mus musculus (Mouse) | PR |
| Q8K2J0 | Plcd3 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 | Mus musculus (Mouse) | PR |
| Q8K4S1 | Plce1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 | Mus musculus (Mouse) | SS |
| Q7YRU3 | PLCZ | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 | Sus scrofa (Pig) | PR |
| P24135 | Plcg2 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 | Rattus norvegicus (Rat) | SS |
| P10686 | Plcg1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 | Rattus norvegicus (Rat) | EV |
| O89040 | Plcb2 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 | Rattus norvegicus (Rat) | PR |
| P10687 | Plcb1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 | Rattus norvegicus (Rat) | SS |
| P10688 | Plcd1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 | Rattus norvegicus (Rat) | SS |
| Q99JE6 | Plcb3 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 | Rattus norvegicus (Rat) | SS |
| Q8GV43 | PLC6 | Phosphoinositide phospholipase C 6 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q944C2 | PLC5 | Phosphoinositide phospholipase C 5 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q6NMA7 | PLC9 | Phosphoinositide phospholipase C 9 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9STZ3 | PLC8 | Phosphoinositide phospholipase C 8 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q56W08 | PLC3 | Phosphoinositide phospholipase C 3 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q39032 | PLC1 | Phosphoinositide phospholipase C 1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q944C1 | PLC4 | Phosphoinositide phospholipase C 4 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| A5D6R3 | plcd3a | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3-A | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| 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 |