PLCD4_BOVIN
ID PLCD4_BOVIN Reviewed; 791 AA.
AC P21671; Q2KIZ7;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4;
DE EC=3.1.4.11 {ECO:0000250|UniProtKB:Q9BRC7};
DE AltName: Full=PLC-85;
DE AltName: Full=Phosphoinositide phospholipase C-delta-4;
DE AltName: Full=Phospholipase C-delta-2;
DE Short=PLC-delta-2;
DE AltName: Full=Phospholipase C-delta-4;
DE Short=PLC-delta-4;
GN Name=PLCD4; Synonyms=PLCD2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 560-584 AND 685-696.
RX PubMed=2753038; DOI=10.1111/j.1432-1033.1989.tb14878.x;
RA Meldrum E., Katan M., Parker P.;
RT "A novel inositol-phospholipid-specific phospholipase C. Rapid purification
RT and characterization.";
RL Eur. J. Biochem. 182:673-677(1989).
RN [3]
RP IDENTIFICATION.
RX PubMed=15219862; DOI=10.1016/j.bbrc.2004.05.206;
RA Irino Y., Cho H., Nakamura Y., Nakahara M., Furutani M., Suh P.-G.,
RA Takenawa T., Fukami K.;
RT "Phospholipase C delta-type consists of three isozymes: bovine PLCdelta2 is
RT a homologue of human/mouse PLCdelta4.";
RL Biochem. Biophys. Res. Commun. 320:537-543(2004).
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}.
CC -!- CAUTION: Was initially (PubMed:2753038) named PLCD2 and was thought to
CC be a new member of the PLC-delta family. It was later shown that it
CC corresponds to PLCD4 (PubMed:15219862). {ECO:0000305|PubMed:15219862,
CC ECO:0000305|PubMed:2753038}.
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DR EMBL; BC112449; AAI12450.1; -; mRNA.
DR RefSeq; NP_001039954.1; NM_001046489.2.
DR AlphaFoldDB; P21671; -.
DR SMR; P21671; -.
DR STRING; 9913.ENSBTAP00000041545; -.
DR PaxDb; P21671; -.
DR GeneID; 540771; -.
DR KEGG; bta:540771; -.
DR CTD; 84812; -.
DR eggNOG; KOG0169; Eukaryota.
DR InParanoid; P21671; -.
DR OrthoDB; 368239at2759; -.
DR Proteomes; UP000009136; 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; 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 1: Evidence at protein level;
KW Calcium; Cytoplasm; Direct protein sequencing; Endoplasmic reticulum;
KW Hydrolase; Lipid degradation; Lipid metabolism; Membrane; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transducer.
FT CHAIN 1..791
FT /note="1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase delta-4"
FT /id="PRO_0000088508"
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 207..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 522..638
FT /note="PI-PLC Y-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271"
FT DOMAIN 638..765
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 26..53
FT /note="Substrate binding"
FT /evidence="ECO:0000250"
FT MOTIF 213..243
FT /note="GBA"
FT /evidence="ECO:0000250|UniProtKB:Q9BRC7"
FT MOTIF 760..763
FT /note="PDZ-binding"
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 551
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 578
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 679
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 681
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="4"
FT /evidence="ECO:0000250"
FT BINDING 734
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 735
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 736
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
SQ SEQUENCE 791 AA; 90581 MW; 33E4C4278F280CD2 CRC64;
MAYLLQGRLP INQDLLLMQK GTMMRKVRSK SWKKLRFFRL QDDGMTVWHA RQAGGRAKPS
FSISDVDTVR EDHESELLRN LAEEFPLEQG FTIVFHGRRS NLDLVANSVQ EAQTWMQGLQ
LLVGFVTNMD QQERLDQWLS DWFQRGDKNQ DGRMSFGEVQ RLLHLMNVEM DQEYAFQLFQ
TADTSQSGTL EGEEFVEFYK SLTQRPEVQE LFEKFSSDGQ KLTLLEFVDF LQEEQKEGER
ASDLALELID RYEPSESGKL RHVLSMDGFL GYLCSKDGDI FNPTCHPLYQ DMTQPLNHYY
INSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDIWD GPSGEPIVYH GHTLTSRIPF
KDVVAAIGQY AFQTSDYPVI LSLENHCSWE QQEIIVRHLT EILGDQLLTT ALDGQPPTQL
PSPEDLRGKI LVKGKKLMLE EEEEEPEAEL EAEQEARLDL EAQLESEPQD LSPRSEDKKK
VVMCPLLCRP LCCQIMAQAP ISKPGLLLFP KQKPKAILCP ALSALVVYLK AVTFYSFTHS
REHYHFYETS SFSETKAKSL IKEAGDEFVQ HNAWQLSRVY PSGLRTDSSN YNPQEFWNAG
CQMVAMNMQT AGLEMDLCDG LFRQNAGCGY VLKPDFLRDA QSSFHPERPI SPFKAQTLII
QVISGQQLPK VDNTKEQSIV DPLVRVEIFG VRPDTTRQET SYVENNGFNP YWGQTLCFRI
LVPELALLRF VVKDYDWKSR NDFIGQYTLP WSCMQQGYRH IHLLSKDGLS LHPASIFVHI
CTQEVSEEAE S
