P10686
Gene name |
Plcg1 |
Protein name |
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 |
Names |
Phosphoinositide phospholipase C-gamma-1, Phospholipase C-gamma-1, PLC-gamma-1 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:25738 |
EC number |
3.1.4.11: Phosphoric diester hydrolases |
Protein Class |
PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN (PTHR10336) |

Descriptions
Phospholipase C gamma 1 (PLCγ1) is an enzyme that plays a crucial role in intracellular signaling pathways. It hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate second messengers. The autoinhibition of PLCγ1 is mediated by the interaction of its sPH and cSH2 domains, which form extensive autoinhibitory contacts with the core of PLCγ1, thereby blocking membrane engagement and access to the PIP2 substrate. Autoinhibition is relieved by phosphorylation at Y783.
Autoinhibitory domains (AIDs)
Target domain |
320-464 (Catalytic PLC X domain) |
Relief mechanism |
PTM, Partner binding |
Assay |
Structural analysis |
Target domain |
320-464 (Catalytic PLC X domain) |
Relief mechanism |
PTM, Partner binding |
Assay |
Structural analysis |
Target domain |
320-464 (Catalytic PLC X domain) |
Relief mechanism |
PTM, Partner binding |
Assay |
Structural analysis |
Accessory elements
No accessory elements
References
- Lowe J et al. (2022) "Conformational switches that control the TEC kinase - PLCγ signaling axis", Journal of structural biology: X, 6, 100061
- Bunney TD et al. (2012) "Structural and functional integration of the PLCγ interaction domains critical for regulatory mechanisms and signaling deregulation", Structure (London, England : 1993), 20, 2062-75
- Hajicek N et al. (2019) "Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations", eLife, 8,
- Devkota S et al. (2015) "Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation", Journal of molecular biology, 427, 2734-47
- Kunze K et al. (2014) "A recurrent activating PLCG1 mutation in cardiac angiosarcomas increases apoptosis resistance and invasiveness of endothelial cells", Cancer research, 74, 6173-83
- DeBell K et al. (2007) "Intramolecular regulation of phospholipase C-gamma1 by its C-terminal Src homology 2 domain", Molecular and cellular biology, 27, 854-63
- Xie Q et al. (2013) "Substrate recognition of PLCγ1 via a specific docking surface on Itk", Journal of molecular biology, 425, 683-96
- Hajicek N et al. (2019) "Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations", eLife, 8,
- Hajicek N et al. (2013) "Autoinhibition and phosphorylation-induced activation of phospholipase C-γ isozymes", Biochemistry, 52, 4810-9
Autoinhibited structure
Activated structure
12 structures for P10686
Entry ID | Method | Resolution | Chain | Position | Source |
---|---|---|---|---|---|
1Y0M | X-ray | 120 A | A | 791-851 | PDB |
1YWO | X-ray | 181 A | A | 790-851 | PDB |
1YWP | X-ray | 160 A | A | 790-851 | PDB |
2FJL | NMR | - | PDB | ||
3GQI | X-ray | 250 A | B | 545-770 | PDB |
4K44 | X-ray | 170 A | A/B | 664-766 | PDB |
4K45 | X-ray | 150 A | PDB | ||
5EG3 | X-ray | 261 A | B | 661-773 | PDB |
6PBC | X-ray | 246 A | PDB | ||
7T8T | EM | 368 A | A | 20-1215 | PDB |
7Z3J | X-ray | 200 A | PDB | ||
AF-P10686-F1 | Predicted | AlphaFoldDB |
No variants for P10686
Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
---|---|---|---|---|---|
No variants for P10686 |
No associated diseases with P10686
14 regional properties for P10686
Type | Name | Position | InterPro Accession |
---|---|---|---|
domain | C2 domain | 1071 - 1194 | IPR000008 |
domain | Phosphatidylinositol-specific phospholipase C, X domain | 320 - 465 | IPR000909 |
domain | SH2 domain | 548 - 657 | IPR000980-1 |
domain | SH2 domain | 666 - 756 | IPR000980-2 |
domain | SH3 domain | 791 - 851 | IPR001452 |
domain | Phospholipase C, phosphatidylinositol-specific, Y domain | 953 - 1070 | IPR001711 |
domain | Pleckstrin homology domain | 27 - 144 | IPR001849-1 |
domain | Pleckstrin homology domain | 489 - 680 | IPR001849-2 |
domain | Pleckstrin homology domain | 804 - 933 | IPR001849-3 |
domain | EF-hand domain | 152 - 187 | IPR002048 |
binding_site | EF-Hand 1, calcium-binding site | 165 - 177 | IPR018247 |
domain | PLC-gamma, C-terminal SH2 domain | 663 - 765 | IPR035023 |
domain | PLC-gamma, N-terminal SH2 domain | 545 - 649 | IPR035024 |
domain | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, SH3 domain | 791 - 850 | IPR035724 |
Functions
11 GO annotations of cellular component
Name | Definition |
---|---|
cell projection | A prolongation or process extending from a cell, e.g. a flagellum or axon. |
cell-cell junction | A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects. |
clathrin-coated vesicle | A vesicle with a coat formed of clathrin connected to the membrane via one of the clathrin adaptor complexes. |
COP9 signalosome | A protein complex that catalyzes the deneddylation of proteins, including the cullin component of SCF ubiquitin E3 ligase; deneddylation increases the activity of cullin family ubiquitin ligases. The signalosome is involved in many regulatory process, including some which control development, in many species; also regulates photomorphogenesis in plants; in many species its subunits are highly similar to those of the proteasome. |
cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
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. |
ruffle | Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork. |
ruffle membrane | The portion of the plasma membrane surrounding a ruffle. |
Schaffer collateral - CA1 synapse | A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell. |
9 GO annotations of molecular function
Name | Definition |
---|---|
calcium ion binding | Binding to a calcium ion (Ca2+). |
calcium-dependent phospholipase C activity | Catalysis of the reaction: a phosphatidylcholine + H2O = 1,2-diacylglycerol + choline phosphate. This reaction requires Ca2+. |
glutamate receptor binding | Binding to a glutamate receptor. |
insulin receptor binding | Binding to an insulin receptor. |
neurotrophin TRKA receptor binding | Binding to a neurotrophin TRKA receptor. |
phosphatidylinositol phospholipase C activity | Catalysis of the reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H(2)O = 1,2-diacylglycerol + 1D-myo-inositol 1,4,5-trisphosphate + H(+). |
phosphoprotein binding | Binding to a phosphorylated protein. |
protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
receptor tyrosine kinase binding | Binding to a receptor that possesses protein tyrosine kinase activity. |
24 GO annotations of biological process
Name | Definition |
---|---|
calcium ion transport | The directed movement of calcium (Ca) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
calcium-mediated signaling | Any intracellular signal transduction in which the signal is passed on within the cell via calcium ions. |
cell migration | The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms. |
cellular response to epidermal growth factor stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epidermal growth factor stimulus. |
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. |
in utero embryonic development | The process whose specific outcome is the progression of the embryo in the uterus over time, from formation of the zygote in the oviduct, to birth. An example of this process is found in Mus musculus. |
inositol trisphosphate biosynthetic process | The chemical reactions and pathways resulting in the formation of inositol trisphosphate, 1,2,3,4,5,6-cyclohexanehexol, with three phosphate groups attached. |
modulation of chemical synaptic transmission | Any process that modulates the frequency or amplitude of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. Amplitude, in this case, refers to the change in postsynaptic membrane potential due to a single instance of synaptic transmission. |
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. |
phospholipid catabolic process | The chemical reactions and pathways resulting in the breakdown of phospholipids, any lipid containing phosphoric acid as a mono- or diester. |
positive regulation of angiogenesis | Any process that activates or increases angiogenesis. |
positive regulation of blood vessel endothelial cell migration | Any process that activates or increases the frequency, rate or extent of the migration of the endothelial cells of blood vessels. |
positive regulation of endothelial cell apoptotic process | Any process that activates or increases the frequency, rate or extent of endothelial cell apoptotic process. |
positive regulation of epithelial cell migration | Any process that activates or increases the frequency, rate or extent of epithelial cell migration. |
positive regulation of release of sequestered calcium ion into cytosol | Any process that activates or increases the frequency, rate or extent of the release into the cytosolic compartment of calcium ions sequestered in the endoplasmic reticulum or mitochondria. |
positive regulation of vascular endothelial cell proliferation | Any process that activates or increases the frequency, rate or extent of vascular endothelial cell proliferation. |
protein secretion | The controlled release of proteins from a cell. |
regulation of store-operated calcium channel activity | Any process that modulates the frequency, rate or extent of store-operated calcium channel activity. |
response to gravity | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a gravitational stimulus. |
response to hydrogen peroxide | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus. |
response to morphine | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a morphine stimulus. Morphine is an opioid alkaloid, isolated from opium, with a complex ring structure. |
response to organonitrogen compound | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organonitrogen stimulus. An organonitrogen compound is formally a compound containing at least one carbon-nitrogen bond. |
signal transduction | The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell. |
T cell receptor signaling pathway | The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell. |
17 homologous proteins in AiPD
UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
---|---|---|---|---|
P08487 | PLCG1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 | Bos taurus (Bovine) | EV SS |
P16885 | PLCG2 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 | Homo sapiens (Human) | SS |
P19174 | PLCG1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 | Homo sapiens (Human) | EV |
Q62077 | Plcg1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 | Mus musculus (Mouse) | SS |
P24135 | Plcg2 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 | Rattus norvegicus (Rat) | SS |
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 |
Q99P84 | Plce1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 | Rattus norvegicus (Rat) | EV |
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 |
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 |
10 | 20 | 30 | 40 | 50 | 60 |
MAGVGTPCAN | GCGPSAPSEA | EVLHLCRSLE | VGTVMTLFYS | KKSQRPERKT | FQVKLETRQI |
70 | 80 | 90 | 100 | 110 | 120 |
TWSRGADKIE | GSIDIREIKE | IRPGKTSRDF | DRYQEDPAFR | PDQSHCFVIL | YGMEFRLKTL |
130 | 140 | 150 | 160 | 170 | 180 |
SLQATSEDEV | NMWIKGLTWL | MEDTLQAATP | LQIERWLRKQ | FYSVDRNRED | RISAKDLKNM |
190 | 200 | 210 | 220 | 230 | 240 |
LSQVNYRVPN | MRFLRERLTD | FEQRSGDITY | GQFAQLYRSL | MYSAQKTMDL | PFLETNTLRT |
250 | 260 | 270 | 280 | 290 | 300 |
GERPELCQVS | LSEFQQFLLE | YQGELWAVDR | LQVQEFMLSF | LRDPLREIEE | PYFFLDELVT |
310 | 320 | 330 | 340 | 350 | 360 |
FLFSKENSVW | NSQLDAVCPE | TMNNPLSHYW | ISSSHNTYLT | GDQFSSESSL | EAYARCLRMG |
370 | 380 | 390 | 400 | 410 | 420 |
CRCIELDCWD | GPDGMPVIYH | GHTLTTKIKF | SDVLHTIKEH | AFVASEYPVI | LSIEDHCSIA |
430 | 440 | 450 | 460 | 470 | 480 |
QQRNMAQHFR | KVLGDTLLTK | PVDIAADGLP | SPNQLKRKIL | IKHKKLAEGS | AYEEVPTSVM |
490 | 500 | 510 | 520 | 530 | 540 |
YSENDISNSI | KNGILYLEDP | VNHEWYPHYF | VLTSSKIYYS | EETSSDQGNE | DEEEPKEASG |
550 | 560 | 570 | 580 | 590 | 600 |
STELHSSEKW | FHGKLGAGRD | GRHIAERLLT | EYCIETGAPD | GSFLVRESET | FVGDYTLSFW |
610 | 620 | 630 | 640 | 650 | 660 |
RNGKVQHCRI | HSRQDAGTPK | FFLTDNLVFD | SLYDLITHYQ | QVPLRCNEFE | MRLSEPVPQT |
670 | 680 | 690 | 700 | 710 | 720 |
NAHESKEWYH | ASLTRAQAEH | MLMRVPRDGA | FLVRKRNEPN | SYAISFRAEG | KIKHCRVQQE |
730 | 740 | 750 | 760 | 770 | 780 |
GQTVMLGNSE | FDSLVDLISY | YEKHPLYRKM | KLRYPINEEA | LEKIGTAEPD | YGALYEGRNP |
790 | 800 | 810 | 820 | 830 | 840 |
GFYVEANPMP | TFKCAVKALF | DYKAQREDEL | TFTKSAIIQN | VEKQDGGWWR | GDYGGKKQLW |
850 | 860 | 870 | 880 | 890 | 900 |
FPSNYVEEMI | NPAILEPERE | HLDENSPLGD | LLRGVLDVPA | CQIAIRPEGK | NNRLFVFSIS |
910 | 920 | 930 | 940 | 950 | 960 |
MPSVAQWSLD | VAADSQEELQ | DWVKKIREVA | QTADARLTEG | KMMERRKKIA | LELSELVVYC |
970 | 980 | 990 | 1000 | 1010 | 1020 |
RPVPFDEEKI | GTERACYRDM | SSFPETKAEK | YVNKAKGKKF | LQYNRLQLSR | IYPKGQRLDS |
1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
SNYDPLPMWI | CGSQLVALNF | QTPDKPMQMN | QALFMAGGHC | GYVLQPSTMR | DEAFDPFDKS |
1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
SLRGLEPCVI | CIEVLGARHL | PKNGRGIVCP | FVEIEVAGAE | YDSTKQKTEF | VVDNGLNPVW |
1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
PAKPFHFQIS | NPEFAFLRFV | VYEEDMFSDQ | NFLAQATFPV | KGLKTGYRAV | PLKNNYSEDL |
1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
ELASLLIKID | IFPAKENGDL | SPFSGTSLRE | RASDASSQLF | HVRAREGSFE | ARYQQPFEDF |
1270 | 1280 | ||||
RISQEHLADH | FDSRERRAPR | RTRVNGDNRL |