PLCD4_PONAB
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 03-AUG-2022, entry version 111.
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;
CC Evidence={ECO:0000255|PROSITE-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}.
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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; 368239at2759; -.
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:0007340; P:acrosome reaction; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IEA:InterPro.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR Gene3D; 3.20.20.190; -; 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; IPR028387; PLC-delta4.
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; PTHR10336; 1.
DR PANTHER; PTHR10336:SF31; PTHR10336:SF31; 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; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51695; SSF51695; 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
