ID PLCD4_PIG Reviewed; 772 AA. AC Q8SPR7; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 02-SEP-2026, entry version 162. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4; DE EC=3.1.4.11 {ECO:0000250|UniProtKB:Q9BRC7}; DE AltName: Full=Phosphoinositide phospholipase C-delta-4; DE AltName: Full=Phospholipase C-delta-4; DE Short=PLC-delta-4; GN Name=PLCD4; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Smith T.P.L.; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) CC to generate 2 second messenger molecules diacylglycerol (DAG) and CC inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of CC protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular CC stores. Required for acrosome reaction in sperm during fertilization, CC probably by acting as an important enzyme for intracellular Ca(2+) CC mobilization in the zona pellucida-induced acrosome reaction. May play CC a role in cell growth. Modulates the liver regeneration in cooperation CC with nuclear PKC. Overexpression up-regulates the Erk signaling pathway CC and proliferation (By similarity). {ECO:0000250}. 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:Q9BRC7}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; CC Evidence={ECO:0000250|UniProtKB:Q9BRC7}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = CC 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+); CC Xref=Rhea:RHEA:43484, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17815, ChEBI:CHEBI:57880, ChEBI:CHEBI:58433; CC Evidence={ECO:0000250|UniProtKB:Q9BRC7}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43485; CC Evidence={ECO:0000250|UniProtKB:Q9BRC7}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041}; CC Note=Binds 5 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound CC to the C2 domain. {ECO:0000250}; CC -!- SUBUNIT: Interacts with GRIP1 (By similarity). Interacts (via GBA CC motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 CC (inactive GDP-bound form); low-affinity interaction (By similarity). CC {ECO:0000250|UniProtKB:Q8K3R3, ECO:0000250|UniProtKB:Q9BRC7}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q62711}; CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q62711}; Cytoplasmic CC side {ECO:0000250|UniProtKB:Q62711}. Nucleus CC {ECO:0000250|UniProtKB:Q62711}. Cytoplasm CC {ECO:0000250|UniProtKB:Q9BRC7}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:Q62711}. Note=The C2 domain mediates pre- CC localization to the membrane prior to Ca(2+) import and non-selective CC Ca(2+)-mediated targeting to various cellular membranes (By CC similarity). Localizes primarily to intracellular membranes mostly to CC the endoplasmic reticulum (By similarity). CC {ECO:0000250|UniProtKB:Q62711}. CC -!- DOMAIN: The PDZ-binding motif mediates the interaction with GRIP1. CC {ECO:0000250}. CC -!- DOMAIN: The C2 domain mediates pre-localization to the membrane prior CC to Ca(2+) import and non-selective Ca(2+)-mediated targeting to various CC cellular membranes. {ECO:0000250|UniProtKB:Q9BRC7}. CC -!- DOMAIN: The PH domain is not a critical determinant of the membrane CC localization. {ECO:0000250}. CC -!- DOMAIN: The GBA (G-alpha binding and activating) motif mediates binding CC to the alpha subunits of guanine nucleotide-binding proteins (G CC proteins). {ECO:0000250|UniProtKB:Q9BRC7}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF498759; AAM18122.1; -; mRNA. DR RefSeq; NP_999217.1; NM_214052.1. DR AlphaFoldDB; Q8SPR7; -. DR SMR; Q8SPR7; -. DR FunCoup; Q8SPR7; 104. DR STRING; 9823.ENSSSCP00000073871; -. DR PaxDb; 9823-ENSSSCP00000073871; -. DR PeptideAtlas; Q8SPR7; -. DR Ensembl; ENSSSCT00000017632.3; ENSSSCP00000017154.3; ENSSSCG00000016192.5. DR Ensembl; ENSSSCT00085014442; ENSSSCP00085010404; ENSSSCG00085007585. DR GeneID; 397119; -. DR KEGG; ssc:397119; -. DR CTD; 84812; -. DR eggNOG; KOG0169; Eukaryota. DR GeneTree; ENSGT00940000156180; -. DR HOGENOM; CLU_002738_0_2_1; -. DR InParanoid; Q8SPR7; -. DR OrthoDB; 269822at2759; -. DR Reactome; R-SSC-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Proteomes; UP000008227; Chromosome 15. DR Bgee; ENSSSCG00000016192; Expressed in longissimus lumborum muscle and 31 other cell types or tissues. DR ExpressionAtlas; Q8SPR7; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB. DR GO; GO:0120548; F:phosphatidylinositol phospholipase C activity; ISS:UniProtKB. DR GO; GO:0004435; F:phosphatidylinositol-4,5-bisphosphate phospholipase C activity; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0006629; P:lipid metabolic process; IEA:InterPro. DR CDD; cd00275; C2_PLC_like; 1. DR CDD; cd13363; PH_PLC_delta; 1. DR FunFam; 1.10.238.10:FF:000005; Phosphoinositide phospholipase C; 1. DR FunFam; 1.10.238.10:FF:000145; Phosphoinositide phospholipase C; 1. DR FunFam; 2.30.29.30:FF:000088; Phosphoinositide phospholipase C; 1. DR FunFam; 2.60.40.150:FF:000058; Phosphoinositide phospholipase C; 1. DR FunFam; 3.20.20.190:FF:000020; Phosphoinositide phospholipase C; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.238.10; EF-hand; 2. DR Gene3D; 3.20.20.190; Phosphatidylinositol (PI) phosphodiesterase; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR001192; PI-PLC_fam. DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl. DR InterPro; IPR015359; PLC_EF-hand-like. DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom. DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y. DR PANTHER; PTHR10336:SF31; 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE DELTA-4; 1. DR PANTHER; PTHR10336; PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF09279; EF-hand_like; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00388; PI-PLC-X; 1. DR Pfam; PF00387; PI-PLC-Y; 1. DR PRINTS; PR00390; PHPHLIPASEC. DR SMART; SM00239; C2; 1. DR SMART; SM00054; EFh; 3. DR SMART; SM00233; PH; 1. DR SMART; SM00148; PLCXc; 1. DR SMART; SM00149; PLCYc; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF51695; PLC-like phosphodiesterases; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 3. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1. DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1. PE 2: Evidence at transcript level; KW Calcium; Cell membrane; Cytoplasm; Endoplasmic reticulum; Hydrolase; KW Lipid degradation; Lipid metabolism; Membrane; Metal-binding; Nucleus; KW Reference proteome; Repeat; Transducer. FT CHAIN 1..772 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase delta-4" FT /id="PRO_0000306827" FT DOMAIN 23..131 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 141..176 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 177..212 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 213..244 FT /note="EF-hand 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 297..442 FT /note="PI-PLC X-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT DOMAIN 503..619 FT /note="PI-PLC Y-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271" FT DOMAIN 619..746 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 33..60 FT /note="Substrate binding" FT /evidence="ECO:0000250" FT REGION 448..470 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 220..250 FT /note="GBA" FT /evidence="ECO:0000250|UniProtKB:Q9BRC7" FT MOTIF 741..744 FT /note="PDZ-binding" FT COMPBIAS 449..470 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 312 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT ACT_SITE 357 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT BINDING 154 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 156 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 160 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 165 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 190 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 192 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 194 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 196 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 201 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 313 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 342 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 344 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 391 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 440 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 442 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 532 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 559 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 660 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 662 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 686 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 715 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 716 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 717 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" SQ SEQUENCE 772 AA; 88075 MW; 86E5706A74247548 CRC64; MASLLQGLSA SPGSGLPINQ DLLLMQKGML MRKVRSKSWK KLRYYRLQDD GMTVWHARQA GGRAKPSFSI SDVETVRGGH ESELLRNLAE EFPLEQGFTI VFHGRRSNLD LVANSVEEAQ VWMQGLQLLV DFVTNMDQQE RLDQWLSDWF QRGDKNQDGR MSFGEVQRLL HLMNVEMDQE HAFQLFQTAD TSQSGTLEGE EFVEFYKSLT KRAEVQELFE NFSSDGQKLT LLEFVDFLQE EQKEGERASD LALELIDRHE PSDSGKLRHV LSLDGFLSYL CSKDGDIFNP TCLPIYQDMT QPLNHYFINS SHNTYLVGDQ LCGQSSVEGY IRALKRGCRC VEVDIWDGPN GEPVVYHGHT LTSRIPFKDV VAAIAQYAFQ TSDYPVILSL ENHCSWEQQE MIAHHLTEIL GEQLLSTTLD GQLPTQLPSP EELRRKILVK GKKLRTLEED LEEEEEEPEE SELEGEQEAE LELEAQFESE PQELSPRSKD KKKKVKAILC PALSALVVYL KAVSFYSFAH SREHYRFYEI SSFSEAKAKS LIKESGNEFV QHNTWQLSRV YPGGLRTDSS NYNPQEFWNA GCQMVAMNMQ TAGLEMDLCD GLFRQNAGCG YVLKPDFLRD AQSSFHPERP ISPSKAQTLL IQVISGQQLP KVDDSKEGSI VDPLVRVEIF GVRPDTARQE TSYVENNGFN PYWGQTLCFR VLVPELALLR FVVKDYDWKS RNDFVGQYTL PWNCMQQGYR HIHLLSKDGI SLHPASIFVH ICIREGIEGV ES //