ID PLCD4_PONAB Reviewed; 762 AA. AC Q5RET0; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 22-FEB-2023, entry version 113. 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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; RG The German cDNA consortium; RL Submitted (NOV-2004) 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: Membrane {ECO:0000250}; Peripheral membrane CC protein {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. CC Endoplasmic reticulum {ECO:0000250}. Note=Localizes primarily to CC intracellular membranes mostly to the endoplasmic reticulum. CC {ECO:0000250}. 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}. 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; CR857436; CAH89727.1; -; mRNA. DR RefSeq; NP_001124787.1; NM_001131315.1. DR AlphaFoldDB; Q5RET0; -. DR SMR; Q5RET0; -. DR STRING; 9601.ENSPPYP00000014724; -. DR GeneID; 100171640; -. DR KEGG; pon:100171640; -. DR CTD; 84812; -. DR eggNOG; KOG0169; Eukaryota. DR InParanoid; Q5RET0; -. DR OrthoDB; 2900494at2759; -. DR Proteomes; UP000001595; Unplaced. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. 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:0004435; F:phosphatidylinositol phospholipase C activity; IEA:UniProtKB-EC. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR CDD; cd00275; C2_PLC_like; 1. DR CDD; cd13363; PH_PLC_delta; 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; PF13202; EF-hand_5; 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; Cytoplasm; Endoplasmic reticulum; Hydrolase; Lipid degradation; KW Lipid metabolism; Membrane; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Transducer. FT CHAIN 1..762 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase delta-4" FT /id="PRO_0000306828" FT DOMAIN 16..124 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 134..169 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 170..205 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 206..237 FT /note="EF-hand 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 290..435 FT /note="PI-PLC X-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT DOMAIN 493..609 FT /note="PI-PLC Y-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271" FT DOMAIN 609..736 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 26..53 FT /note="Substrate binding" FT /evidence="ECO:0000250" FT REGION 443..483 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 213..243 FT /note="GBA" FT /evidence="ECO:0000250|UniProtKB:Q9BRC7" FT MOTIF 731..734 FT /note="PDZ-binding" FT COMPBIAS 443..463 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 305 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT ACT_SITE 350 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT BINDING 147 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 149 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 151 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 153 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 183 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 185 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 187 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 189 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 306 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 335 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 337 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 384 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 433 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 435 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 522 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 549 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 650 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 652 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 676 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 705 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 706 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 707 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT MOD_RES 457 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62711" SQ SEQUENCE 762 AA; 87625 MW; 89B03949861987C2 CRC64; MASLLQDQLT TDQDLLLMQE GMPMRKVRSK SWKKLRYFRL QNDGMTVWHA RQARGSAKPS FSISDVDTIR NGHDSELLRS LAEELPLEQG FTVVFHGRRS NLDLVANSVE EAQMWMRGLQ LLVDLVTSMD HQERLDQWLS DWFQRGDKNQ DGKMSFQEVQ RLLHLMNVEM DQEYAFSLFQ AADTSQSGTL EGEEFVQFYK ALTKRAEVQE LFESFSADGQ KLTLLEFLDF LREEQKERDC TSELALELID HYEPSDSGKL RHVLSMDGFL SYLCSKDGDI FNPACLPIYQ DMTQPLNHYF ICSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDVWD GPSGEPVVYH GHTLTSRILF KDVVATVAQY AFQTSDYPVI LSLETHCSWE QQQTMARHLT EILGEQLLST TLDGVLPTQL PSPEELRRRI LVKGKKLTLE EDLEYEEEEA EPELEESELA LESQFETEPE PQEQNLQSKD KKKKSKPILC PALSSLVIYL KSVSFRSFTH SKEHYHFYEI SSFSETKAER LIKEAGNEFV QHNTWQLSRV YPSGLRTDSS NYNPQELWNA GCQMVAMNMQ TAGLEMDICD GHFRQNGGCG YVLKPDFLRD IQSSFHPERP ISPFKAQTLL IQVISGQQLP KVDKTKEGSI VDPLVKVQIF GVRLDTARQE TNYVENNGFN PYWGETLCFR VLVPELAMLR FVVMDYDWKS RNDFIGQYTL PWTCMQQGYR HIHLLSKVGI SLRPASIFVY ICIQEDLEGD ES //