Q8K4S1

SS
Gene name
Plce1 (Kiaa1516, Plce)
Protein name
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1
Names
EC 3.1.4.11 , Phosphoinositide phospholipase C-epsilon-1 , Phospholipase C-epsilon-1 , PLC-epsilon-1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:74055
EC number
3.1.4.11: Phosphoric diester hydrolases
Protein Class

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)

1522-1643 (X-Y linker) SS

Target domain

1373-1522 (PI-PLC X domain);1709-1826 (PI-PLC Y domain)

Relief mechanism

Ligand binding, Partner binding

Assay

1973-1990 (C2-RA1 linker) SS

Target domain

1826-1851 (A cleft between TIM barrel and C2 domain)

Relief mechanism

Ligand binding, Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q8K4S1

Entry ID Method Resolution Chain Position Source
AF-Q8K4S1-F1 Predicted AlphaFoldDB

125 variants for Q8K4S1

Variant ID(s) Position Change Description Diseaes Association Provenance
rs253280628 24 S>L No EVA
rs3389530903 26 A>V No EVA
rs3389529609 27 E>D No EVA
rs3389539245 30 S>N No EVA
rs3389550371 34 S>L No EVA
rs3389529636 47 G>D No EVA
rs3389503599 59 K>E No EVA
rs213131754 79 E>D No EVA
rs235865647 82 C>G No EVA
rs254131378 86 S>P No EVA
rs223306819 86 S>Y No EVA
rs259059980 99 P>T No EVA
rs3389538330 134 C>S No EVA
rs3389445347 139 I>F No EVA
rs48812424 170 R>G No EVA
rs260044125 176 G>R No EVA
rs3389532184 178 H>Y No EVA
rs231779205 202 T>N No EVA
rs3389516414 204 S>* No EVA
rs3389493918 206 N>D No EVA
rs3389445407 217 T>S No EVA
rs262394709 223 Q>H No EVA
rs3389445354 223 Q>K No EVA
rs51753162 229 A>V No EVA
rs50967683 276 G>S No EVA
rs3389538285 283 G>D No EVA
rs30559618 295 N>S No EVA
rs50749515 351 C>R No EVA
rs3554102562 355 A>V No EVA
rs218680208 360 V>I No EVA
rs50029846 376 G>V No EVA
rs3554102478 390 R>C No EVA
rs581861627 390 R>H No EVA
rs246604299 391 L>Q No EVA
rs3389484754 404 R>I No EVA
rs3389530848 412 T>M No EVA
rs3389484827 421 T>S No EVA
rs49946911 434 E>G No EVA
rs3389530844 448 C>Y No EVA
rs3389538342 471 T>I No EVA
rs3408097056 492 M>I No EVA
rs52056572 498 L>P No EVA
rs3389493840 581 L>H No EVA
rs50946241 588 H>R No EVA
rs3389445403 630 K>Q No EVA
rs3389536621 631 C>* No EVA
rs3389536663 657 W>* No EVA
rs3389446252 667 T>I No EVA
rs3389536693 668 M>T No EVA
rs3389532185 671 L>V No EVA
rs221869272 682 V>L No EVA
rs3389553072 711 C>Y No EVA
rs3389532260 740 Y>N No EVA
rs3389493889 748 Q>* No EVA
rs3408837807 840 T>I No EVA
rs584345423 925 V>M No EVA
rs3389516392 941 V>M No EVA
rs3409283354 955 V>I No EVA
rs3407231787 956 Q>K No EVA
rs3389532230 1020 L>F No EVA
rs3389530834 1033 R>W No EVA
rs3412937779 1049 R>K No EVA
rs245015568 1135 T>S No EVA
rs264025823 1140 P>T No EVA
rs3389547189 1165 I>T No EVA
rs3407231805 1171 S>C No EVA
rs3407231840 1172 S>C No EVA
rs233449367 1181 M>L No EVA
rs243069838 1197 V>L No EVA
rs3389547196 1257 R>* No EVA
rs3389493852 1257 R>K No EVA
rs3389532181 1259 V>* No EVA
rs3389530364 1259 V>L No EVA
rs3389516363 1260 S>T No EVA
rs3409162672 1269 K>E No EVA
rs3389542027 1270 Q>H No EVA
rs3389538313 1310 L>H No EVA
rs3389530832 1338 V>I No EVA
rs3389484836 1423 D>V No EVA
rs3408174787 1436 T>P No EVA
rs3389536674 1447 V>M No EVA
rs3389538269 1453 S>C No EVA
rs3389550362 1460 L>M No EVA
rs3389547203 1463 I>N No EVA
rs3389530362 1468 N>S No EVA
rs3410769811 1487 G>* No EVA
rs3389493828 1500 F>Y No EVA
rs3389484782 1546 Q>L No EVA
rs3389538249 1558 A>P No EVA
rs244800560 1614 S>T No EVA
rs3389539240 1621 V>L No EVA
rs3389484803 1649 L>I No EVA
rs3389530297 1673 K>E No EVA
rs3389493919 1697 F>L No EVA
rs3389550359 1701 S>Y No EVA
rs3389536613 1750 R>H No EVA
rs3389542054 1799 D>H No EVA
rs3389539171 1829 S>G No EVA
rs214205915 1845 N>T No EVA
rs3389484748 1864 S>I No EVA
rs3389532216 1881 L>P No EVA
rs3389538320 1910 F>I No EVA
rs3389503622 1950 N>S No EVA
rs3389550424 1955 I>V No EVA
rs3389538300 1965 S>R No EVA
rs3408175672 1973 S>A No EVA
rs3389542033 1981 L>S No EVA
rs258938443 2034 C>R No EVA
rs3389530902 2070 I>T No EVA
rs3389539174 2076 S>N No EVA
rs3389530880 2081 E>D No EVA
rs3389536645 2085 G>S No EVA
rs3389539194 2109 I>F No EVA
rs3389503635 2150 C>G No EVA
rs3389553055 2186 K>M No EVA
rs3389446278 2186 K>N No EVA
rs3389553055 2186 K>R No EVA
rs3389547265 2188 S>P No EVA
rs3389516375 2194 D>Y No EVA
rs3409323289 2195 Q>H No EVA
rs215041587 2227 R>K No EVA
rs3389484807 2236 L>R No EVA
rs3389550356 2250 P>L No EVA
rs3389530301 2261 V>I No EVA
rs261776603 2273 S>A No EVA

No associated diseases with Q8K4S1

9 regional properties for Q8K4S1

Type Name Position InterPro Accession
domain C2 domain 1831 - 1956 IPR000008
domain Ras-associating domain 2115 - 2218 IPR000159
domain Phosphatidylinositol-specific phospholipase C, X domain 1373 - 1522 IPR000909
domain Phospholipase C, phosphatidylinositol-specific, Y domain 1710 - 1826 IPR001711
domain Ras guanine-nucleotide exchange factors catalytic domain 525 - 828 IPR001895
domain Phosphoinositide-specific phospholipase C, EF-hand-like domain 1308 - 1359 IPR015359
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, RA domain 2 2114 - 2216 IPR028398
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, catalytic domain 1372 - 1813 IPR046973
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, EF-hand domain 1179 - 1359 IPR046974

Functions

Description
EC Number 3.1.4.11 Phosphoric diester hydrolases
Subcellular Localization
  • Cytoplasm, cytosol
  • Cell membrane
  • Golgi apparatus membrane
  • Cell projection, lamellipodium
  • 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
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

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.

11 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.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
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 metabolic process The chemical reactions and pathways involving phosphatidylinositol, any glycophospholipid in which a sn-glycerol 3-phosphate residue is esterified to the 1-hydroxyl group of 1D-myo-inositol.
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.
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.
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.

29 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
Q8K2J0 Plcd3 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 Mus musculus (Mouse) PR
Q8K394 Plcl2 Inactive phospholipase C-like protein 2 Mus musculus (Mouse) PR
Q8R3B1 Plcd1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 Mus musculus (Mouse) SS
P51432 Plcb3 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 Mus musculus (Mouse) SS
Q62077 Plcg1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 Mus musculus (Mouse) SS
A3KGF7 Plcb2 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 Mus musculus (Mouse) PR
Q9Z1B3 Plcb1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 Mus musculus (Mouse) SS
Q7YRU3 PLCZ 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 Sus scrofa (Pig) PR
P10688 Plcd1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 Rattus norvegicus (Rat) SS
Q99P84 Plce1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 Rattus norvegicus (Rat) EV
Q39032 PLC1 Phosphoinositide phospholipase C 1 Arabidopsis thaliana (Mouse-ear cress) PR
Q56W08 PLC3 Phosphoinositide phospholipase C 3 Arabidopsis thaliana (Mouse-ear cress) PR
Q6NMA7 PLC9 Phosphoinositide phospholipase C 9 Arabidopsis thaliana (Mouse-ear cress) PR
Q8GV43 PLC6 Phosphoinositide phospholipase C 6 Arabidopsis thaliana (Mouse-ear cress) PR
Q944C2 PLC5 Phosphoinositide phospholipase C 5 Arabidopsis thaliana (Mouse-ear cress) PR
Q9STZ3 PLC8 Phosphoinositide phospholipase C 8 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
MTSEEMAASV LIPVTQRKVA SAQSVAEERS VKVSDAGIPR ARAGRQGALI PPTISQWNKH
70 80 90 100 110 120
KEESSRSDLS KVFSIARGEL VCDENSNEEG WEENAPDSPE NHAMNGNSLV QSHQHQFPRS
130 140 150 160 170 180
QLCEARDSVT EDPCLQPGIP SPLERKVLPG IQLEMEDSPM DVSPAGSQPR IMESSGPHSD
190 200 210 220 230 240
RNTAVFHFHY EADRTMSDAF HTLSENLILD DCANCVTLPG GQQNKNCMAY ACKLVELTRT
250 260 270 280 290 300
CGSKNGQVQC EHCTSLRDEY LCFESSCSKA DEVCSGGGFC EDGFAHGPAA KTFLNPLEDF
310 320 330 340 350 360
SDNCEDVDDF FKSKKERSTL LVRRFCKNDR EVKKSVYTGT RAIMRTLPSG CIGPAAWNYV
370 380 390 400 410 420
DQKKAGLLWP CGNVMGTLSA MDIRQSGSQR LSEAQWCLIY SAVRRGEEIE DTVGSLLHCS
430 440 450 460 470 480
TQLPNSETAH GRIEDGPCLK QCVRDTECEF RATLQRTSIA QYITGSLLEA TTSLGARSGL
490 500 510 520 530 540
LSSFGGSTGR IMLKERQLGT SMANSNPVPS SSAGISKELI DLQPLIQFPE EVASILTEQE
550 560 570 580 590 600
QNIYRRVLPM DYLCFLTRDL SSPECQRSLP RLKASISESI LTSQSGEHNA 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 GQNGLKNSEK ELTVNSIFQV IRSCSRSLEM
790 800 810 820 830 840
EEEDSASEGS GSRKNSLKDK ARWQFIIGDL LDSENDIFEK SKECDPHGSE ESQKAFDHGT
850 860 870 880 890 900
ELIPWYVLSI QADVHQFLLQ GATVIHYDQD THLSARCFLQ LQPDNSTLTW MKPPTASPAG
910 920 930 940 950 960
ARPKLGVLSN MAEPGKFPSP GNAGVSGLAE GILDLFSVKA VYMGHPGIDI HTVCVQNKLS
970 980 990 1000 1010 1020
SMLLSETGVT LLYGLQTTDN RLLHFVAPKH TAEMLFSGLL ELTTAVRKIR RFPDQRQQWL
1030 1040 1050 1060 1070 1080
RKQYVSLYQE DGRYEGPTLA HAVELFGGRR WSTRNPSPGM SAKNAEKPNM QRNNTLGIST
1090 1100 1110 1120 1130 1140
TKKKKKMLMR GESGEVTDDE MATRKAKMYR ECRSRSGSDP QDVNEQEESE ANVITNPPNP
1150 1160 1170 1180 1190 1200
LHSRRAYSLT TAGSPNLATG MSSPISAWSS SSWHGRIRGG MQGFQSFMVS DSNMSFVEFV
1210 1220 1230 1240 1250 1260
ELFKSFSIRS RKDLKDIFDI YSVPCNRSAS ESAPLYTNLT IEENTSDLQP DLDLLTRNVS
1270 1280 1290 1300 1310 1320
DLGLFIKSKQ QLSDNQRQIS DAIAAASIVT NGTGIESTSL GIFGVGILQL NDFLVNCQGE
1330 1340 1350 1360 1370 1380
HCTYDEILSI IQKFEPSVSM CHQGLLSFEG FARFLMDKDN FASKNDESRE NKKELQLPLS
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 ASMQAQAFTG GNANPPPASN
1570 1580 1590 1600 1610 1620
EEEEDEEDEY DYDYESLSDD NILEDRPENK SCADKLQFEY NEEVPKRIKK ADNSSGNKGK
1630 1640 1650 1660 1670 1680
VYDMELGEEF YLPQNKKESR QIAPELSDLV IYCQAVKFPG LSTLNSSGSS RGKERKSRKS
1690 1700 1710 1720 1730 1740
IFGNNPGRMS PGETAPFNRT SGKGSCEGMR HTWEESSPLS PSTSLSAIIR TPKCYHISSL
1750 1760 1770 1780 1790 1800
NENAAKRLCR RGSQKLIQHT AYQLLRTYPA ATRIDSSNPN PIMFWLHGIQ LVALNYQTDD
1810 1820 1830 1840 1850 1860
LPLHLNAAMF EANGGCGYVL KPPVLWDKSC PMYQKFSPLE RDLDNLDPAI YSLTIISGQN
1870 1880 1890 1900 1910 1920
VCPSNSTGSP CIEVDVLGMP LDSCHFRTKP IHRNTLNPMW NEQFLFRVHF EDLVFLRFAV
1930 1940 1950 1960 1970 1980
VENNSSAITA QRIIPLRALK RGYRHLQLRN LHNEILEISS LFINSRRMEE NPSGSSMPAS
1990 2000 2010 2020 2030 2040
LMFNTEERKC SQTHKVTVHG VPGPEPFAVF TINEGTKAKQ LLQQVLAVDQ DTKCTATDYF
2050 2060 2070 2080 2090 2100
LMEEKHFISK EKNECRKQPF QRAVGPEEDI VQILNSWFPE EGYVGRIVLK PQQETLEEKS
2110 2120 2130 2140 2150 2160
IVFDDKEVIL SSEEESFFVQ VHDVSPEQPR TVIKAPRVST AQDVIQQTLC KAKYSYSILN
2170 2180 2190 2200 2210 2220
NPNPCDYVLL EEVLKDAANK KSSTPKSSQR ILLDQECVFQ AQSKWKGAGK FILKLKEQVQ
2230 2240 2250 2260 2270 2280
ASREDKRRGI SFASELKKLT KSTKQSRGLP SPPQLVASES VQSKEEKPVG ALSSSDTVGY
QQ