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Protein

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4

Gene

Plcd4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca2+ from intracellular stores. Required for acrosome reaction in sperm during fertilization, probably by acting as an important enzyme for intracellular Ca2+ mobilization in the zona pellucida-induced acrosome reaction. May play a role in cell growth. Modulates the liver regeneration in cooperation with nuclear PKC. Overexpression up-regulates the Erk signaling pathway and proliferation.3 Publications

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.

Cofactori

Ca2+By similarityNote: Binds 3 Ca2+ ions per subunit. Two of the Ca2+ ions are bound to the C2 domain.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei305PROSITE-ProRule annotation1
Metal bindingi306Calcium 1; catalyticBy similarity1
Metal bindingi335Calcium 1; catalyticBy similarity1
Metal bindingi337Calcium 1; catalyticBy similarity1
Active sitei350PROSITE-ProRule annotation1
Metal bindingi384Calcium 1; catalyticBy similarity1
Binding sitei433SubstrateBy similarity1
Binding sitei435SubstrateBy similarity1
Binding sitei567SubstrateBy similarity1
Binding sitei594SubstrateBy similarity1
Metal bindingi697Calcium 2By similarity1
Metal bindingi721Calcium 2By similarity1
Metal bindingi750Calcium 3By similarity1
Metal bindingi751Calcium 3; via carbonyl oxygenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi147 – 1581PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi183 – 1942PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

GO - Biological processi

  • acrosome reaction Source: MGI
  • intracellular signal transduction Source: InterPro
  • lipid catabolic process Source: UniProtKB-KW
  • phosphatidylinositol metabolic process Source: MGI
  • signal transduction Source: MGI

Keywordsi

Molecular functionHydrolase, Transducer
Biological processLipid degradation, Lipid metabolism
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-1855204 Synthesis of IP3 and IP4 in the cytosol

Names & Taxonomyi

Protein namesi
Recommended name:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (EC:3.1.4.11)
Alternative name(s):
Phosphoinositide phospholipase C-delta-4
Phospholipase C-delta-4
Short name:
PLC-delta-4
Gene namesi
Name:Plcd4
Synonyms:Plcd
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:107469 Plcd4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are either sterile or produce few small litters. In these mice, fewer eggs become activated and the Ca2+ transients associated with fertilization are absent or delayed. Sperm are unable to initiate the acrosome reaction.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003068261 – 8071-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4Add BLAST807

Proteomic databases

PaxDbiQ8K3R3
PRIDEiQ8K3R3

PTM databases

iPTMnetiQ8K3R3
PhosphoSitePlusiQ8K3R3

Expressioni

Inductioni

By treatment with growth factors such as bradykinin, lysophosphatidic acid, and Ca2+ ionophore in addition to serum.1 Publication

Gene expression databases

BgeeiENSMUSG00000026173
CleanExiMM_PLCD4
ExpressionAtlasiQ8K3R3 baseline and differential
GenevisibleiQ8K3R3 MM

Interactioni

Subunit structurei

Interacts with GRIP1.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000027362

Structurei

3D structure databases

ProteinModelPortaliQ8K3R3
SMRiQ8K3R3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 124PHPROSITE-ProRule annotationAdd BLAST109
Domaini134 – 169EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini170 – 205EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini203 – 237EF-hand 3PROSITE-ProRule annotationAdd BLAST35
Domaini290 – 435PI-PLC X-boxPROSITE-ProRule annotationAdd BLAST146
Domaini538 – 654PI-PLC Y-boxPROSITE-ProRule annotationAdd BLAST117
Domaini659 – 764C2PROSITE-ProRule annotationAdd BLAST106

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni26 – 53Substrate bindingBy similarityAdd BLAST28

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi776 – 779PDZ-binding4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi445 – 456Poly-GluAdd BLAST12

Domaini

The PDZ-binding motif mediates the interaction with GRIP1.
The C2 domain mediates pre-localization to the membrane prior to Ca2+ import and non-selective Ca2+-mediated targeting to various cellular membranes.By similarity
The PH domain is not a critical determinant of the membrane localization.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0169 Eukaryota
ENOG410XPSW LUCA
GeneTreeiENSGT00760000118936
HOGENOMiHOG000006871
HOVERGENiHBG053610
InParanoidiQ8K3R3
KOiK05857
OMAiQLCGQSS
OrthoDBiEOG091G02KH
PhylomeDBiQ8K3R3
TreeFamiTF313216

Family and domain databases

Gene3Di2.30.29.30, 1 hit
2.60.40.150, 1 hit
3.20.20.190, 2 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR011992 EF-hand-dom_pair
IPR002048 EF_hand_dom
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR001192 PI-PLC_fam
IPR028387 PLC-delta4
IPR017946 PLC-like_Pdiesterase_TIM-brl
IPR015359 PLC_EF-hand-like
IPR000909 PLipase_C_PInositol-sp_X_dom
IPR001711 PLipase_C_Pinositol-sp_Y
PANTHERiPTHR10336 PTHR10336, 1 hit
PTHR10336:SF31 PTHR10336:SF31, 1 hit
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF09279 EF-hand_like, 1 hit
PF00169 PH, 1 hit
PF00388 PI-PLC-X, 1 hit
PF00387 PI-PLC-Y, 1 hit
PRINTSiPR00390 PHPHLIPASEC
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00054 EFh, 3 hits
SM00233 PH, 1 hit
SM00148 PLCXc, 1 hit
SM00149 PLCYc, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
SSF51695 SSF51695, 2 hits
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50222 EF_HAND_2, 3 hits
PS50003 PH_DOMAIN, 1 hit
PS50007 PIPLC_X_DOMAIN, 1 hit
PS50008 PIPLC_Y_DOMAIN, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8K3R3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTSQIQDLLA TDQDLLLMQE GTMMRKVRTK SWKKLRYFRL QNDGMTVWHG
60 70 80 90 100
SQPESMPKPT FSISDVERIR KGQDSELLRY LVEEFPLEQG FTVVFHGRRP
110 120 130 140 150
NLDLVANSVE EAQIWMRGLQ LLVDLVASMD HQEQMDQMLN EWFQQADRNQ
160 170 180 190 200
DGRMSFREAQ RLLLLMNVEM DEEYAFSLFQ EADVTQSDDL GSEEFVQFYK
210 220 230 240 250
ALTKRTEIEE IFEDFSSDKQ KLTLLEFVDF LRKEQKEKDH APDLALELID
260 270 280 290 300
RYEPSENGRL LHVLSKDGFL KYLCSKDGNI FNSDCLPIYQ DMTQPLSHYY
310 320 330 340 350
INSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDTWD GPDGEPVVYH
360 370 380 390 400
GHTLTSRILF KDVLATLAQY AFQSSDYPLI LSLENHCTWE QQRTMAHHLT
410 420 430 440 450
EILGEQLLRN TLEGLLVDSM PSPEQLRGKI LVKGKKLRTI EVDKEEEEEE
460 470 480 490 500
EEEELEKDEG PDLDPASPEL DTQPQPETQG QAAGNKKERK KKVMKCPMSC
510 520 530 540 550
LLICGHVMAQ APSSIPESIL LSKQFLLLSS TTIMCPDLSA LVVYLRTVPF
560 570 580 590 600
CSFTHSKENY HIYDISSFSE SKAKNLIKEA GNEFVQHNAR QLCRVYPSGL
610 620 630 640 650
RTDSSNFNPQ EHWNVGCQMV AMNMQTAGSA MDICDGLFRQ NGGSGYVLKP
660 670 680 690 700
EFLRDTQSSF NPERPISLYK AQILVVQVIS GQQLPKVDKT KETTVVDPLV
710 720 730 740 750
KVELYGVPED TKEQETSHVE NNGINPYWGE TFYFRLQVPE LAMLRFVVKD
760 770 780 790 800
YSRKSRNNFI GQYTLPWTCM KQGYRHVSLL SRDGTSLNPA SIFVYTCMQE

DLDMDEP
Length:807
Mass (Da):92,694
Last modified:October 2, 2007 - v2
Checksum:iC109F6255CED45F7
GO
Isoform 2 (identifier: Q8K3R3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     493-524: Missing.

Note: No experimental confirmation available.
Show »
Length:775
Mass (Da):89,296
Checksum:iEFA6651F8635BBF7
GO
Isoform 3 (identifier: Q8K3R3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     493-524: Missing.
     773-807: GYRHVSLLSRDGTSLNPASIFVYTCMQEDLDMDEP → EMALASIQLP...LKIQSQPKDQ

Note: No experimental confirmation available.
Show »
Length:798
Mass (Da):92,091
Checksum:i5D5EEC1B9028824D
GO
Isoform 4 (identifier: Q8K3R3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     494-496: MKC → SQD
     497-807: Missing.

Note: No experimental confirmation available.
Show »
Length:496
Mass (Da):57,480
Checksum:i85050CCD6471FB72
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti180Q → R in BAE24292 (PubMed:16141072).Curated1
Sequence conflicti310V → A in AAH66156 (PubMed:15489334).Curated1
Sequence conflicti372F → L in AAH66156 (PubMed:15489334).Curated1
Sequence conflicti445Missing in BAE24292 (PubMed:16141072).Curated1
Sequence conflicti470L → F in AAK61537 (Ref. 1) Curated1
Sequence conflicti594R → C in AAH66156 (PubMed:15489334).Curated1
Sequence conflicti653L → V in AAK61537 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028503493 – 524Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST32
Alternative sequenceiVSP_028504494 – 496MKC → SQD in isoform 4. 1 Publication3
Alternative sequenceiVSP_028505497 – 807Missing in isoform 4. 1 PublicationAdd BLAST311
Alternative sequenceiVSP_028506773 – 807GYRHV…DMDEP → EMALASIQLPSLYTPACRKT WIWMSPEKHREGLEEQSTDA QSFPTYNFLKIQSQPKDQ in isoform 3. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY033991 mRNA Translation: AAK61537.1
AK016945 mRNA Translation: BAB30513.1
AK039149 mRNA Translation: BAC30256.1
AK140231 mRNA Translation: BAE24292.1
BC066156 mRNA Translation: AAH66156.1
CCDSiCCDS35616.1 [Q8K3R3-1]
CCDS35617.1 [Q8K3R3-2]
RefSeqiNP_001074925.1, NM_001081456.1 [Q8K3R3-2]
NP_683739.2, NM_148937.2 [Q8K3R3-1]
XP_006495851.1, XM_006495788.3 [Q8K3R3-1]
UniGeneiMm.290731

Genome annotation databases

EnsembliENSMUST00000027362; ENSMUSP00000027362; ENSMUSG00000026173 [Q8K3R3-1]
ENSMUST00000067916; ENSMUSP00000064413; ENSMUSG00000026173 [Q8K3R3-2]
ENSMUST00000113747; ENSMUSP00000109376; ENSMUSG00000026173 [Q8K3R3-2]
ENSMUST00000113749; ENSMUSP00000109378; ENSMUSG00000026173 [Q8K3R3-1]
ENSMUST00000113750; ENSMUSP00000109379; ENSMUSG00000026173 [Q8K3R3-3]
GeneIDi18802
KEGGimmu:18802
UCSCiuc007bmg.1 mouse [Q8K3R3-2]
uc007bmh.1 mouse [Q8K3R3-1]
uc007bmi.1 mouse [Q8K3R3-4]
uc011wnb.1 mouse [Q8K3R3-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPLCD4_MOUSE
AccessioniPrimary (citable) accession number: Q8K3R3
Secondary accession number(s): Q3USN9
, Q6NZF7, Q8CAB1, Q9CUC1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: March 28, 2018
This is version 133 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health