PLCG2_RAT
ID PLCG2_RAT Reviewed; 1265 AA.
AC P24135;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 {ECO:0000305};
DE EC=3.1.4.11 {ECO:0000250|UniProtKB:P16885};
DE AltName: Full=Phosphoinositide phospholipase C-gamma-2;
DE AltName: Full=Phospholipase C-IV;
DE Short=PLC-IV;
DE AltName: Full=Phospholipase C-gamma-2;
DE Short=PLC-gamma-2;
GN Name=Plcg2 {ECO:0000312|RGD:3348};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=2557343; DOI=10.1016/s0021-9258(20)88267-2;
RA Emori Y., Homma Y., Sorimachi H., Kawasaki H., Nakanishi O., Suzuki K.,
RA Takenawa T.;
RT "A second type of rat phosphoinositide-specific phospholipase C containing
RT a src-related sequence not essential for phosphoinositide-hydrolyzing
RT activity.";
RL J. Biol. Chem. 264:21885-21890(1989).
RN [2]
RP PHOSPHORYLATION AT TYR-1197.
RX PubMed=10498607;
RA Hashimoto S., Iwamatsu A., Ishiai M., Okawa K., Yamadori T., Matsushita M.,
RA Baba Y., Kishimoto T., Kurosaki T., Tsukada S.;
RT "Identification of the SH2 domain binding protein of Bruton's tyrosine
RT kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen
RT receptor-coupled calcium signaling.";
RL Blood 94:2357-2364(1999).
RN [3]
RP STRUCTURE BY NMR OF 633-744.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the second SH2 domain from rat PLC gamma-2.";
RL Submitted (APR-2008) to the PDB data bank.
CC -!- FUNCTION: The production of the second messenger molecules
CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated
CC by activated phosphatidylinositol-specific phospholipase C enzymes. It
CC is a crucial enzyme in transmembrane signaling.
CC {ECO:0000250|UniProtKB:P16885}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-
CC diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456,
CC ChEBI:CHEBI:203600; EC=3.1.4.11;
CC Evidence={ECO:0000250|UniProtKB:P16885};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180;
CC Evidence={ECO:0000250|UniProtKB:P16885};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC -!- SUBUNIT: Interacts (via SH2 domain) with CSF1R (tyrosine
CC phosphorylated). Interacts constitutively with THEMIS2.
CC {ECO:0000250|UniProtKB:Q8CIH5}.
CC -!- PTM: Phosphorylated on tyrosine residues by CSF1R (By similarity).
CC Phosphorylated on tyrosine residues by BTK and SYK; upon ligand-induced
CC activation of a variety of growth factor receptors and immune system
CC receptors. Phosphorylation leads to increased phospholipase activity
CC (By similarity). {ECO:0000250|UniProtKB:P16885,
CC ECO:0000250|UniProtKB:Q8CIH5}.
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DR EMBL; J05155; AAA41896.1; -; mRNA.
DR PIR; A34163; A34163.
DR RefSeq; NP_058864.1; NM_017168.1.
DR PDB; 2EOB; NMR; -; A=633-743.
DR PDBsum; 2EOB; -.
DR AlphaFoldDB; P24135; -.
DR BMRB; P24135; -.
DR SMR; P24135; -.
DR IntAct; P24135; 5.
DR STRING; 10116.ENSRNOP00000018678; -.
DR ChEMBL; CHEMBL5230; -.
DR iPTMnet; P24135; -.
DR PhosphoSitePlus; P24135; -.
DR PaxDb; P24135; -.
DR PRIDE; P24135; -.
DR GeneID; 29337; -.
DR KEGG; rno:29337; -.
DR UCSC; RGD:3348; rat.
DR CTD; 5336; -.
DR RGD; 3348; Plcg2.
DR eggNOG; KOG1264; Eukaryota.
DR InParanoid; P24135; -.
DR OrthoDB; 368239at2759; -.
DR PhylomeDB; P24135; -.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR Reactome; R-RNO-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-RNO-202433; Generation of second messenger molecules.
DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-RNO-2424491; DAP12 signaling.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-RNO-5621480; Dectin-2 family.
DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR EvolutionaryTrace; P24135; -.
DR PRO; PR:P24135; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0097708; C:intracellular vesicle; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISO:RGD.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:RGD.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; ISO:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0032237; P:activation of store-operated calcium channel activity; ISO:RGD.
DR GO; GO:0061760; P:antifungal innate immune response; ISO:RGD.
DR GO; GO:0030183; P:B cell differentiation; ISO:RGD.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD.
DR GO; GO:0001775; P:cell activation; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR GO; GO:1990858; P:cellular response to lectin; ISO:RGD.
DR GO; GO:0071396; P:cellular response to lipid; ISO:RGD.
DR GO; GO:0002316; P:follicular B cell differentiation; ISO:RGD.
DR GO; GO:0032959; P:inositol trisphosphate biosynthetic process; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:ARUK-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISO:RGD.
DR GO; GO:0043069; P:negative regulation of programmed cell death; ISO:RGD.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009395; P:phospholipid catabolic process; IEA:InterPro.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:RGD.
DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; IDA:ARUK-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:0002732; P:positive regulation of dendritic cell cytokine production; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:ARUK-UCL.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISO:RGD.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:RGD.
DR GO; GO:0032747; P:positive regulation of interleukin-23 production; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; ISO:RGD.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:RGD.
DR GO; GO:0070884; P:regulation of calcineurin-NFAT signaling cascade; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISO:RGD.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:0033198; P:response to ATP; IDA:RGD.
DR GO; GO:0048678; P:response to axon injury; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0032026; P:response to magnesium ion; IDA:RGD.
DR GO; GO:0001878; P:response to yeast; ISO:RGD.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:RGD.
DR CDD; cd09932; SH2_C-SH2_PLC_gamma_like; 1.
DR CDD; cd10341; SH2_N-SH2_PLC_gamma_like; 1.
DR CDD; cd11969; SH3_PLCgamma2; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR Gene3D; 3.20.20.190; -; 2.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR001192; PI-PLC_fam.
DR InterPro; IPR016279; PLC-gamma.
DR InterPro; IPR028381; PLC-gamma2.
DR InterPro; IPR035023; PLC-gamma_C-SH2.
DR InterPro; IPR035024; PLC-gamma_N-SH2.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR InterPro; IPR035723; PLCgamma2_SH3.
DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom.
DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10336; PTHR10336; 1.
DR PANTHER; PTHR10336:SF25; PTHR10336:SF25; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00388; PI-PLC-X; 1.
DR Pfam; PF00387; PI-PLC-Y; 1.
DR Pfam; PF00017; SH2; 2.
DR Pfam; PF00018; SH3_1; 1.
DR PIRSF; PIRSF000952; PLC-gamma; 1.
DR PRINTS; PR00390; PHPHLIPASEC.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00239; C2; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00148; PLCXc; 1.
DR SMART; SM00149; PLCYc; 1.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF51695; SSF51695; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Hydrolase; Lipid degradation; Lipid metabolism;
KW Phosphoprotein; Reference proteome; Repeat; SH2 domain; SH3 domain;
KW Transducer.
FT CHAIN 1..1265
FT /note="1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase gamma-2"
FT /id="PRO_0000088502"
FT DOMAIN 20..131
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 312..456
FT /note="PI-PLC X-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT DOMAIN 532..635
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 646..735
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 769..829
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 930..1044
FT /note="PI-PLC Y-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271"
FT DOMAIN 1038..1169
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT ACT_SITE 327
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT ACT_SITE 372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT MOD_RES 753
FT /note="Phosphotyrosine; by BTK"
FT /evidence="ECO:0000250|UniProtKB:P16885"
FT MOD_RES 759
FT /note="Phosphotyrosine; by BTK"
FT /evidence="ECO:0000250|UniProtKB:P16885"
FT MOD_RES 1197
FT /note="Phosphotyrosine; by BTK"
FT /evidence="ECO:0000269|PubMed:10498607"
FT MOD_RES 1217
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P16885"
FT MOD_RES 1245
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P16885"
FT TURN 641..643
FT /evidence="ECO:0007829|PDB:2EOB"
FT STRAND 647..650
FT /evidence="ECO:0007829|PDB:2EOB"
FT HELIX 653..662
FT /evidence="ECO:0007829|PDB:2EOB"
FT STRAND 665..672
FT /evidence="ECO:0007829|PDB:2EOB"
FT STRAND 680..686
FT /evidence="ECO:0007829|PDB:2EOB"
FT STRAND 689..700
FT /evidence="ECO:0007829|PDB:2EOB"
FT STRAND 702..707
FT /evidence="ECO:0007829|PDB:2EOB"
FT STRAND 710..712
FT /evidence="ECO:0007829|PDB:2EOB"
FT HELIX 713..720
FT /evidence="ECO:0007829|PDB:2EOB"
FT STRAND 725..728
FT /evidence="ECO:0007829|PDB:2EOB"
FT HELIX 737..742
FT /evidence="ECO:0007829|PDB:2EOB"
SQ SEQUENCE 1265 AA; 147735 MW; 2C34910D43572723 CRC64;
MTTMVNVDTL PEYEKSQIKR ALELGTVMTV FSARKSTPER RTVQMIMETR QVAWSKTADK
IEGFLDIMEI KEIRPGKNSK DFERAKAVRH KADCCFTIFY GTQFVLSTLS LATDSKEDAV
KWLSGLKILH QEAMNASTPT MIESWLRKQI YSVDQTRRNS ISLRELKTIL PLVNFKVSGI
KFLKDKLVEI GAQKDELSFE QFHLFYKKLM FEQQKSILDE FKKDSSVFIL GNTDRPDASA
VYLQDFQRFL LHEQQELWAQ DLNKVRERMT KFIDDTMRET AEPFLFVDEF LTYLFSRENS
IWDEKYDAVD MQDMNNPLSH YWISSSHNTY LTGDQLRSES STEAYIRCLR AGCRCIELDC
WDGPDGKPII YHGWTRTTKI KFDDVVQAIR DHAFVTSSFP VILSIEEHCS VEQQRHMAKV
FKEVLGDLLL TKPTEASADQ LPSPSQLREK IIIKHKKLGP RGDVDVNVED KKDEHKTQGE
LYMWDSIDQK WTRHYCAIAD AKLSFSDDIE QTVEEDPVQD TPPTELHFGE KWFHKKVESR
TSAEKLLQEY CAETGAKDGT FLVRESETFP NDYTLSFWRS GRVQHCRIRS TMEGGVMKYY
LTDNLTFNSI YALIQHYREA HLRCAEFELR LTDPVPNPNP HESKPWYYDR LSRGEAEDML
MRIPRDGAFL IRKREGTDSY AITFRARGKV KHCRINRDGR HFVLGTSAYF ESLVELVSYY
EKHALYRKMR LRYPVTPELL ERYNMERDIN SLYDVSRMYV DPSEINPSMP QRTVKALYDY
KAKRSDELTF CRGALIHNVS KEPGGWWKGD YGTRIQQYFP SNYVEDISAG DAEEMEKQII
EDNPLGSLCR GILDLNTYNV VKAPQGKNQK AFVFILEPKK QGDPPVEFAT DRVEELFEWF
QSIREITWKI DTKENNMKYW ERNQSIAIEL SDLVVYCKPT SKTKDHLENP DFREIRSFVE
TKADSIVRQK PVDLLRYNQK GLTRVYPKGQ RVDSSNYDPF RLWLCGSQMV ALNFQTPDKY
MQMNHALFSL NGRTGYVLQP ESMRSEKYDP MPPESQRKIL MTLTVKVLGA RHLPKLGRSI
ACPFVEVEIC GAEYDSNKFK TTVVNDNGLS PVWAPTQEKV TFEIYDPNLA FLRFLVYEED
MFSDPNFLAH ATYPIKGIKS GFRSVPLKNG YSEDIELASL LVFCEMRPVL ESEEELYSSC
RQLRRRQEEL NNQLFLYDTH QNLRGANRDA LVKEFNVNEN QLRLYQEKCN RRLREKRVSN
SRFYS
