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Protein

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

Gene

PLCD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.1 Publication

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 sitei522SubstrateBy similarity1
Binding sitei549SubstrateBy similarity1
Metal bindingi650Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi652Calcium 2By similarity1
Metal bindingi676Calcium 2By similarity1
Metal bindingi705Calcium 3By similarity1
Metal bindingi706Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi707Calcium 3By 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

BioCyciZFISH:HS03908-MONOMER.
ReactomeiR-HSA-1855204. Synthesis of IP3 and IP4 in the cytosol.
SIGNORiQ9BRC7.

Names & Taxonomyi

Protein namesi
Recommended name:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (EC:3.1.4.11)
Short name:
hPLCD4
Alternative name(s):
Phosphoinositide phospholipase C-delta-4
Phospholipase C-delta-4
Short name:
PLC-delta-4
Gene namesi
Name:PLCD4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:9062. PLCD4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi84812.
OpenTargetsiENSG00000115556.
PharmGKBiPA33390.

Polymorphism and mutation databases

BioMutaiPLCD4.
DMDMi74732863.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003068241 – 7621-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4Add BLAST762

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei457PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9BRC7.
PeptideAtlasiQ9BRC7.
PRIDEiQ9BRC7.

PTM databases

iPTMnetiQ9BRC7.
PhosphoSitePlusiQ9BRC7.

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle and kidney tissues, and at moderate level in intestinal tissue. Expressed in corneal epithelial cells.2 Publications

Gene expression databases

BgeeiENSG00000115556.
CleanExiHS_PLCD4.
ExpressionAtlasiQ9BRC7. baseline and differential.
GenevisibleiQ9BRC7. HS.

Organism-specific databases

HPAiCAB009914.
HPA038139.
HPA038140.

Interactioni

Subunit structurei

Interacts with GRIP1.By similarity

Protein-protein interaction databases

BioGridi124273. 3 interactors.
IntActiQ9BRC7. 4 interactors.
MINTiMINT-1482361.
STRINGi9606.ENSP00000388631.

Structurei

3D structure databases

ProteinModelPortaliQ9BRC7.
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
Domaini493 – 609PI-PLC Y-boxPROSITE-ProRule annotationAdd BLAST117
Domaini614 – 719C2PROSITE-ProRule annotationAdd BLAST106

Region

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi731 – 734PDZ-binding4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi440 – 473Glu-richAdd BLAST34
Compositional biasi479 – 486Poly-Lys8

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.
The PH domain is not a critical determinant of the membrane localization.

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.
InParanoidiQ9BRC7.
KOiK05857.
PhylomeDBiQ9BRC7.
TreeFamiTF313216.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 3 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.
PF13202. EF-hand_5. 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. 2 hits.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BRC7-1) [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
MASLLQDQLT TDQDLLLMQE GMPMRKVRSK SWKKLRYFRL QNDGMTVWHA
60 70 80 90 100
RQARGSAKPS FSISDVETIR NGHDSELLRS LAEELPLEQG FTIVFHGRRS
110 120 130 140 150
NLDLMANSVE EAQIWMRGLQ LLVDLVTSMD HQERLDQWLS DWFQRGDKNQ
160 170 180 190 200
DGKMSFQEVQ RLLHLMNVEM DQEYAFSLFQ AADTSQSGTL EGEEFVQFYK
210 220 230 240 250
ALTKRAEVQE LFESFSADGQ KLTLLEFLDF LQEEQKERDC TSELALELID
260 270 280 290 300
RYEPSDSGKL RHVLSMDGFL SYLCSKDGDI FNPACLPIYQ DMTQPLNHYF
310 320 330 340 350
ICSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDVWD GPSGEPVVYH
360 370 380 390 400
GHTLTSRILF KDVVATVAQY AFQTSDYPVI LSLETHCSWE QQQTMARHLT
410 420 430 440 450
EILGEQLLST TLDGVLPTQL PSPEELRRKI LVKGKKLTLE EDLEYEEEEA
460 470 480 490 500
EPELEESELA LESQFETEPE PQEQNLQNKD KKKKSKPILC PALSSLVIYL
510 520 530 540 550
KSVSFRSFTH SKEHYHFYEI SSFSETKAKR LIKEAGNEFV QHNTWQLSRV
560 570 580 590 600
YPSGLRTDSS NYNPQELWNA GCQMVAMNMQ TAGLEMDICD GHFRQNGGCG
610 620 630 640 650
YVLKPDFLRD IQSSFHPEKP ISPFKAQTLL IQVISGQQLP KVDKTKEGSI
660 670 680 690 700
VDPLVKVQIF GVRLDTARQE TNYVENNGFN PYWGQTLCFR VLVPELAMLR
710 720 730 740 750
FVVMDYDWKS RNDFIGQYTL PWTCMQQGYR HIHLLSKDGI SLRPASIFVY
760
ICIQEGLEGD ES
Note: Acceptor splice site between exons 4 and 5 is non-canonical but conserved through species for that particular gene.
Length:762
Mass (Da):87,585
Last modified:June 1, 2001 - v1
Checksum:i5444BE5CE2AEA3EF
GO
Isoform 2 (identifier: Q9BRC7-2) [UniParc]FASTAAdd to basket
Also known as: PLCD4b

The sequence of this isoform differs from the canonical sequence as follows:
     259-272: KLRHVLSMDGFLSY → ASEEDPGEGEEVNT
     273-762: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:272
Mass (Da):31,448
Checksum:iC3A83C9C8E411D88
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti98R → H in BAD96923 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028501259 – 272KLRHV…GFLSY → ASEEDPGEGEEVNT in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_028502273 – 762Missing in isoform 2. 1 PublicationAdd BLAST490

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY512961 mRNA. Translation: AAS82574.1.
AK223203 mRNA. Translation: BAD96923.1.
BC006355 mRNA. Translation: AAH06355.1.
CCDSiCCDS46516.1. [Q9BRC7-1]
RefSeqiNP_116115.1. NM_032726.3. [Q9BRC7-1]
UniGeneiHs.632528.

Genome annotation databases

EnsembliENST00000417849; ENSP00000396942; ENSG00000115556. [Q9BRC7-1]
ENST00000450993; ENSP00000388631; ENSG00000115556. [Q9BRC7-1]
GeneIDi84812.
KEGGihsa:84812.
UCSCiuc061smf.1. human. [Q9BRC7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY512961 mRNA. Translation: AAS82574.1.
AK223203 mRNA. Translation: BAD96923.1.
BC006355 mRNA. Translation: AAH06355.1.
CCDSiCCDS46516.1. [Q9BRC7-1]
RefSeqiNP_116115.1. NM_032726.3. [Q9BRC7-1]
UniGeneiHs.632528.

3D structure databases

ProteinModelPortaliQ9BRC7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124273. 3 interactors.
IntActiQ9BRC7. 4 interactors.
MINTiMINT-1482361.
STRINGi9606.ENSP00000388631.

PTM databases

iPTMnetiQ9BRC7.
PhosphoSitePlusiQ9BRC7.

Polymorphism and mutation databases

BioMutaiPLCD4.
DMDMi74732863.

Proteomic databases

PaxDbiQ9BRC7.
PeptideAtlasiQ9BRC7.
PRIDEiQ9BRC7.

Protocols and materials databases

DNASUi84812.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000417849; ENSP00000396942; ENSG00000115556. [Q9BRC7-1]
ENST00000450993; ENSP00000388631; ENSG00000115556. [Q9BRC7-1]
GeneIDi84812.
KEGGihsa:84812.
UCSCiuc061smf.1. human. [Q9BRC7-1]

Organism-specific databases

CTDi84812.
DisGeNETi84812.
GeneCardsiPLCD4.
H-InvDBHIX0002832.
HIX0030357.
HGNCiHGNC:9062. PLCD4.
HPAiCAB009914.
HPA038139.
HPA038140.
MIMi605939. gene.
neXtProtiNX_Q9BRC7.
OpenTargetsiENSG00000115556.
PharmGKBiPA33390.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0169. Eukaryota.
ENOG410XPSW. LUCA.
GeneTreeiENSGT00760000118936.
HOGENOMiHOG000006871.
HOVERGENiHBG053610.
InParanoidiQ9BRC7.
KOiK05857.
PhylomeDBiQ9BRC7.
TreeFamiTF313216.

Enzyme and pathway databases

BioCyciZFISH:HS03908-MONOMER.
ReactomeiR-HSA-1855204. Synthesis of IP3 and IP4 in the cytosol.
SIGNORiQ9BRC7.

Miscellaneous databases

ChiTaRSiPLCD4. human.
GeneWikiiPLCD4.
GenomeRNAii84812.
PROiQ9BRC7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115556.
CleanExiHS_PLCD4.
ExpressionAtlasiQ9BRC7. baseline and differential.
GenevisibleiQ9BRC7. HS.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 3 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.
PF13202. EF-hand_5. 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. 2 hits.
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_HUMAN
AccessioniPrimary (citable) accession number: Q9BRC7
Secondary accession number(s): Q53FS8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: June 1, 2001
Last modified: November 30, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.