Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

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

Gene

Plcd4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Isoform 4 has no enzyme activity and acts as a negative regulator of phospholipases C, with a preference for PLC-delta family.1 Publication

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.2 Publications

Cofactori

Ca2+1 PublicationNote: Binds 3 Ca2+ ions per subunit. Two of the Ca2+ ions are bound to the C2 domain.1 Publication

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
Binding sitei433SubstrateBy similarity1
Binding sitei435SubstrateBy similarity1
Binding sitei532SubstrateBy similarity1
Binding sitei559SubstrateBy similarity1
Metal bindingi662Calcium 2By similarity1
Metal bindingi686Calcium 2By similarity1
Metal bindingi715Calcium 3By similarity1
Metal bindingi716Calcium 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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transducer

Keywords - Biological processi

Lipid degradation, Lipid metabolism

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.11. 5301.
ReactomeiR-RNO-1855204. Synthesis of IP3 and IP4 in the cytosol.

Chemistry databases

SwissLipidsiSLP:000001069.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi621025. Plcd4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi36R → G: Only retains weak enzyme activity and abolishes the ability of isoform 4 to act as a negative regulator. 1 Publication1
Mutagenesisi714K → E: Abolishes affinity for POPC/POPS in the absence of Ca(2+); when associated with E-718. 1 Publication1
Mutagenesisi717S → D: Induces a larger Ca(2+)-dependence. 1 Publication1
Mutagenesisi718R → E: Abolishes affinity for POPC/POPS in the absence of Ca(2+); when associated with E-714. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003068291 – 7721-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4Add BLAST772

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei445PhosphoserineCombined sources1
Modified residuei458PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ62711.
PRIDEiQ62711.

PTM databases

iPTMnetiQ62711.
PhosphoSitePlusiQ62711.

Expressioni

Tissue specificityi

Present at high level in testis. Also present in brain > skeletal muscle > thyroid gland > stomach > thymus > aorta > heart (at protein level). Highly expressed in regenerating liver. Isoform 4 is weakly expressed compared to other isoforms but is expressed at high level in some neural cells.2 Publications

Developmental stagei

Increases at the transition from G1- to S-phase, and the continues to the end of M-phase. Almost disappears when cells reenter the next G1-phase.1 Publication

Inductioni

By serum treatment.1 Publication

Gene expression databases

BgeeiENSRNOG00000016361.
ExpressionAtlasiQ62711. baseline and differential.
GenevisibleiQ62711. RN.

Interactioni

Subunit structurei

Interacts with GRIP1.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022234.

Structurei

3D structure databases

ProteinModelPortaliQ62711.
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
Domaini503 – 619PI-PLC Y-boxPROSITE-ProRule annotationAdd BLAST117
Domaini624 – 729C2PROSITE-ProRule annotationAdd BLAST106

Region

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi741 – 744PDZ-binding4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi448 – 453Poly-Glu6

Domaini

The PDZ-binding motif mediates the interaction with GRIP1.By similarity
The C2 domain mediates pre-localization to the membrane prior to Ca2+ import and non-selective Ca2+-mediated targeting to various cellular membranes.
The PH domain is not a critical determinant of the membrane localization. The PH domain of isoform 4 is necessary and sufficient to inhibit enzyme activity of other PLC-delta enzymes.

Sequence similaritiesi

Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 3 EF-hand domains.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 PI-PLC X-box domain.PROSITE-ProRule annotation
Contains 1 PI-PLC Y-box domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0169. Eukaryota.
ENOG410XPSW. LUCA.
GeneTreeiENSGT00760000118936.
HOGENOMiHOG000006871.
HOVERGENiHBG053610.
InParanoidiQ62711.
KOiK05857.
PhylomeDBiQ62711.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
2.30.29.30. 1 hit.
2.60.40.150. 1 hit.
3.20.20.190. 2 hits.
InterProiIPR000008. C2_dom.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR011993. PH_dom-like.
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.
[Graphical view]
PANTHERiPTHR10336. PTHR10336. 1 hit.
PTHR10336:SF31. PTHR10336:SF31. 1 hit.
PfamiPF00168. 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.
[Graphical view]
PRINTSiPR00390. PHPHLIPASEC.
SMARTiSM00239. C2. 1 hit.
SM00054. EFh. 3 hits.
SM00233. PH. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF51695. SSF51695. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS00018. EF_HAND_1. 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.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q62711-1) [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
MASQIQKLLT TNQDLLLMQK GTMMRKVRTK SWKKLRYFRL QDDGMTVWHG
60 70 80 90 100
RHLESISKPT FSISDVERIR KGQDSELLRY LVEEFPLEQG FTIVFNGRRP
110 120 130 140 150
NLDLVANSVE EAQTWMRGLQ LLVDLVARMN YQEQLDQMLR EWFQQADRNQ
160 170 180 190 200
DSRMSFREAQ RLLLLMNVEM DEEYAFSLFQ EADVSQSNTL DSEEFVQFYK
210 220 230 240 250
ALTKRTEIEE LFENFSSDKQ KLTLLEFVDF LREEQKESDH SSDLALKLID
260 270 280 290 300
RYEPSENGRL LRVLSKDGFL SYLCSADGNI FNPDCLPIYQ DMTQPLSHYY
310 320 330 340 350
INSSHNTYLL GDQFCGQSSV EGYIRALKRG CRCVEVDTWD GPDGEPVVYH
360 370 380 390 400
GRTLTSRILF KDVLATLAQY AFQSSDYPLI LSLDNHCTWE QQKTMAHHLI
410 420 430 440 450
AILGEQLLST TLEEQLIDIM PSPEQLRGKI LVKGKKLRTI EVVESDKEEE
460 470 480 490 500
ELEKDEGSDL DPASAELDMQ SQPESQEQAS GNKSKNKKKF LLQSSTTILC
510 520 530 540 550
PDLSALVVYL RTAPFCSFTH SKENYHIYDI SSFSESKAKN LIREAGNEFV
560 570 580 590 600
QHNARQLCRV YPSGLRTDSS NYNPQEHWNV GCQMVAMNMQ TAGSAMDICD
610 620 630 640 650
GLFRQNGGSG YVLKPEFLRD TQSSFNPMKP VSLYKAQILV VQVISGQRLP
660 670 680 690 700
KVDKTKETTV VDPLVRVELY GVPEDTKQQE TSYVENNGIN PYWGETFYFQ
710 720 730 740 750
IQVPELAMLR FVVKDYSRTS RNNFIGQYTL PWTCMKHGYR HVSLLSKDGT
760 770
SLHPASIFVY TCMQEDLDMD EP
Length:772
Mass (Da):88,967
Last modified:November 1, 1996 - v1
Checksum:i5DD56D1D4AA21356
GO
Isoform 2 (identifier: Q62711-2) [UniParc]FASTAAdd to basket
Also known as: ALT I

The sequence of this isoform differs from the canonical sequence as follows:
     487-487: K → KVMKCPMSCLLICVHVLAQAPNSIPESILLP

Show »
Length:802
Mass (Da):92,170
Checksum:i182467F673D92243
GO
Isoform 3 (identifier: Q62711-3) [UniParc]FASTAAdd to basket
Also known as: ALT II

The sequence of this isoform differs from the canonical sequence as follows:
     487-487: K → KAPNSIPESILLP

Show »
Length:784
Mass (Da):90,199
Checksum:i17D1E14860897530
GO
Isoform 4 (identifier: Q62711-4) [UniParc]FASTAAdd to basket
Also known as: ALT III

The sequence of this isoform differs from the canonical sequence as follows:
     424-487: EQLRGKILVK...QASGNKSKNK → VMKCPMSCLLICVHVLAQAPNSIPESILLPKR

Note: Inactive.
Show »
Length:740
Mass (Da):85,314
Checksum:iB0C008AAA45E7F9A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti395M → ML in BAA09046 (PubMed:8550586).Curated1
Sequence conflicti416Missing in BAA09046 (PubMed:8550586).Curated1
Sequence conflicti425Missing in BAA09046 (PubMed:8550586).Curated1
Sequence conflicti757I → H in BAA09046 (PubMed:8550586).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028507424 – 487EQLRG…KSKNK → VMKCPMSCLLICVHVLAQAP NSIPESILLPKR in isoform 4. CuratedAdd BLAST64
Alternative sequenceiVSP_028508487K → KVMKCPMSCLLICVHVLAQA PNSIPESILLP in isoform 2. 1 Publication1
Alternative sequenceiVSP_028509487K → KAPNSIPESILLP in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16655 mRNA. Translation: AAC52346.1.
D50455 mRNA. Translation: BAA09046.1.
RefSeqiNP_542419.1. NM_080688.1. [Q62711-1]
UniGeneiRn.37434.

Genome annotation databases

EnsembliENSRNOT00000041407; ENSRNOP00000039708; ENSRNOG00000016361. [Q62711-1]
GeneIDi140693.
KEGGirno:140693.
UCSCiRGD:621025. rat. [Q62711-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16655 mRNA. Translation: AAC52346.1.
D50455 mRNA. Translation: BAA09046.1.
RefSeqiNP_542419.1. NM_080688.1. [Q62711-1]
UniGeneiRn.37434.

3D structure databases

ProteinModelPortaliQ62711.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022234.

Chemistry databases

SwissLipidsiSLP:000001069.

PTM databases

iPTMnetiQ62711.
PhosphoSitePlusiQ62711.

Proteomic databases

PaxDbiQ62711.
PRIDEiQ62711.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000041407; ENSRNOP00000039708; ENSRNOG00000016361. [Q62711-1]
GeneIDi140693.
KEGGirno:140693.
UCSCiRGD:621025. rat. [Q62711-1]

Organism-specific databases

CTDi84812.
RGDi621025. Plcd4.

Phylogenomic databases

eggNOGiKOG0169. Eukaryota.
ENOG410XPSW. LUCA.
GeneTreeiENSGT00760000118936.
HOGENOMiHOG000006871.
HOVERGENiHBG053610.
InParanoidiQ62711.
KOiK05857.
PhylomeDBiQ62711.

Enzyme and pathway databases

BRENDAi3.1.4.11. 5301.
ReactomeiR-RNO-1855204. Synthesis of IP3 and IP4 in the cytosol.

Miscellaneous databases

PROiQ62711.

Gene expression databases

BgeeiENSRNOG00000016361.
ExpressionAtlasiQ62711. baseline and differential.
GenevisibleiQ62711. RN.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
2.30.29.30. 1 hit.
2.60.40.150. 1 hit.
3.20.20.190. 2 hits.
InterProiIPR000008. C2_dom.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR011993. PH_dom-like.
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.
[Graphical view]
PANTHERiPTHR10336. PTHR10336. 1 hit.
PTHR10336:SF31. PTHR10336:SF31. 1 hit.
PfamiPF00168. 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.
[Graphical view]
PRINTSiPR00390. PHPHLIPASEC.
SMARTiSM00239. C2. 1 hit.
SM00054. EFh. 3 hits.
SM00233. PH. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF51695. SSF51695. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS00018. EF_HAND_1. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPLCD4_RAT
AccessioniPrimary (citable) accession number: Q62711
Secondary accession number(s): Q63693
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.