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Reviewed, UniProtKB/Swiss-Prot Q62711 (PLCD4_RAT)

Last modified February 9, 2010. Version 67. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended 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 names
Name: Plcd4
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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Protein attributes

Sequence length772 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

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 upregulates 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. Ref.1 Ref.3

Catalytic activity

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

Cofactor

Binds 3 calcium ions per subunit. Two of the calcium ions are bound to the C2 domain Probable. Ref.1

Subunit structure

Interacts with GRIP1 By similarity.

Subcellular location

Endomembrane system; Peripheral membrane protein. Nucleus. Cytoplasm. Endoplasmic reticulum. Note: Localizes primarily to intracellular membranes mostly to the endoplasmic reticulum. Ref.2 Ref.5 Ref.6

Tissue specificity

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. Ref.1 Ref.2

Developmental stage

Increases at the transition from G1- to S-phase, and the continues to the end of M-phase. Almost disappears when cells re-enter the next G1-phase. Ref.2

Induction

By serum treatment. Ref.2

Domain

The PDZ-binding motif mediates the interaction with GRIP1 By similarity. Ref.5 Ref.4

The C2 domain mediates pre-localization to the membrane prior to Ca2+ import and non-selective Ca2+-mediated targeting to various cellular membranes. Ref.5 Ref.4

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. Ref.5 Ref.4

Sequence similarities

Contains 1 C2 domain.

Contains 3 EF-hand domains.

Contains 1 PH domain.

Contains 1 PI-PLC X-box domain.

Contains 1 PI-PLC Y-box domain.

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Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q62711-1)

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.
Isoform 2 (identifier: Q62711-2)

Also known as: ALT I;

The sequence of this isoform differs from the canonical sequence as follows:
     487-487: K → KVMKCPMSCLLICVHVLAQAPNSIPESILLP
Isoform 3 (identifier: Q62711-3)

Also known as: ALT II;

The sequence of this isoform differs from the canonical sequence as follows:
     487-487: K → KAPNSIPESILLP
Isoform 4 (identifier: Q62711-4)

Also known as: ALT III;

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 7727721-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-4
PRO_0000306829

Regions

Domain16 – 124109PH
Domain134 – 16936EF-hand 1
Domain170 – 20536EF-hand 2
Domain203 – 23735EF-hand 3
Domain290 – 435146PI-PLC X-box
Domain503 – 619117PI-PLC Y-box
Domain624 – 729106C2
Calcium binding147 – 158121 Potential
Calcium binding183 – 194122 Potential
Region26 – 5328Substrate binding By similarity
Motif741 – 7444PDZ-binding
Compositional bias448 – 4536Poly-Glu

Sites

Active site3051 By similarity
Active site3501 By similarity
Metal binding3061Calcium 1; catalytic By similarity
Metal binding3351Calcium 1; catalytic By similarity
Metal binding3371Calcium 1; catalytic By similarity
Metal binding6621Calcium 2 By similarity
Metal binding6861Calcium 2 By similarity
Metal binding7151Calcium 3 By similarity
Metal binding7161Calcium 3; via carbonyl oxygen By similarity
Binding site4331Substrate By similarity
Binding site4351Substrate By similarity
Binding site5321Substrate By similarity
Binding site5591Substrate By similarity

Natural variations

Alternative sequence424 – 48764EQLRG…KSKNK → VMKCPMSCLLICVHVLAQAP NSIPESILLPKR in isoform 4.
VSP_028507
Alternative sequence4871K → KVMKCPMSCLLICVHVLAQA PNSIPESILLP in isoform 2.
VSP_028508
Alternative sequence4871K → KAPNSIPESILLP in isoform 3.
VSP_028509

Experimental info

Mutagenesis361R → G: Only retains weak enzyme activity and abolishes the ability of isoform 4 to act as a negative regulator. Ref.3
Mutagenesis7141K → E: Abolishes affinity for POPC/POPS in the absence of Ca(2+); when associated with E-718. Ref.4
Mutagenesis7171S → D: Induces a larger Ca(2+)-dependence. Ref.4
Mutagenesis7181R → E: Abolishes affinity for POPC/POPS in the absence of Ca(2+); when associated with E-714. Ref.4
Sequence conflict3951M → ML in BAA09046. Ref.2
Sequence conflict4161Missing in BAA09046. Ref.2
Sequence conflict4251Missing in BAA09046. Ref.2
Sequence conflict7571I → H in BAA09046. Ref.2

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 5DD56D1D4AA21356

FASTA77288,967
        10         20         30         40         50         60 
MASQIQKLLT TNQDLLLMQK GTMMRKVRTK SWKKLRYFRL QDDGMTVWHG RHLESISKPT 

        70         80         90        100        110        120 
FSISDVERIR KGQDSELLRY LVEEFPLEQG FTIVFNGRRP NLDLVANSVE EAQTWMRGLQ 

       130        140        150        160        170        180 
LLVDLVARMN YQEQLDQMLR EWFQQADRNQ DSRMSFREAQ RLLLLMNVEM DEEYAFSLFQ 

       190        200        210        220        230        240 
EADVSQSNTL DSEEFVQFYK ALTKRTEIEE LFENFSSDKQ KLTLLEFVDF LREEQKESDH 

       250        260        270        280        290        300 
SSDLALKLID RYEPSENGRL LRVLSKDGFL SYLCSADGNI FNPDCLPIYQ DMTQPLSHYY 

       310        320        330        340        350        360 
INSSHNTYLL GDQFCGQSSV EGYIRALKRG CRCVEVDTWD GPDGEPVVYH GRTLTSRILF 

       370        380        390        400        410        420 
KDVLATLAQY AFQSSDYPLI LSLDNHCTWE QQKTMAHHLI AILGEQLLST TLEEQLIDIM 

       430        440        450        460        470        480 
PSPEQLRGKI LVKGKKLRTI EVVESDKEEE ELEKDEGSDL DPASAELDMQ SQPESQEQAS 

       490        500        510        520        530        540 
GNKSKNKKKF LLQSSTTILC PDLSALVVYL RTAPFCSFTH SKENYHIYDI SSFSESKAKN 

       550        560        570        580        590        600 
LIREAGNEFV QHNARQLCRV YPSGLRTDSS NYNPQEHWNV GCQMVAMNMQ TAGSAMDICD 

       610        620        630        640        650        660 
GLFRQNGGSG YVLKPEFLRD TQSSFNPMKP VSLYKAQILV VQVISGQRLP KVDKTKETTV 

       670        680        690        700        710        720 
VDPLVRVELY GVPEDTKQQE TSYVENNGIN PYWGETFYFQ IQVPELAMLR FVVKDYSRTS 

       730        740        750        760        770 
RNNFIGQYTL PWTCMKHGYR HVSLLSKDGT SLHPASIFVY TCMQEDLDMD EP

« Hide

Isoform 2 (ALT I).

Checksum: 182467F673D92243
Show »

FASTA80292,170
Isoform 3 (ALT II).

Checksum: 17D1E14860897530
Show »

FASTA78490,199
Isoform 4 (ALT III).

Checksum: B0C008AAA45E7F9A
Show »

FASTA74085,314

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References

[1]"Molecular cloning, splice variants, expression, and purification of phospholipase C-delta 4."
Lee S.B., Rhee S.-G.
J. Biol. Chem. 271:25-31(1996) [PubMed: 8550568] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, ENZYME ACTIVITY, COFACTOR, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"A new phospholipase C delta 4 is induced at S-phase of the cell cycle and appears in the nucleus."
Liu N., Fukami K., Yu H., Takenawa T.
J. Biol. Chem. 271:355-360(1996) [PubMed: 8550586] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
Strain: Donryu.
[3]"A novel phospholipase C delta4 (PLCdelta4) splice variant as a negative regulator of PLC."
Nagano K., Fukami K., Minagawa T., Watanabe Y., Ozaki C., Takenawa T.
J. Biol. Chem. 274:2872-2879(1999) [PubMed: 9915823] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 4), FUNCTION (ISOFORM 4), MUTAGENESIS OF ARG-36.
[4]"Membrane targeting of C2 domains of phospholipase C-delta isoforms."
Ananthanarayanan B., Das S., Rhee S.-G., Murray D., Cho W.
J. Biol. Chem. 277:3568-3575(2002) [PubMed: 11706040] [Abstract]
Cited for: DOMAIN C2, MUTAGENESIS OF LYS-714; SER-717 AND ARG-718.
[5]"The pleckstrin homology domain of phosphoinositide-specific phospholipase Cdelta4 is not a critical determinant of the membrane localization of the enzyme."
Lee S.B., Varnai P., Balla A., Jalink K., Rhee S.G., Balla T.
J. Biol. Chem. 279:24362-24371(2004) [PubMed: 15037625] [Abstract]
Cited for: DOMAIN PH, SUBCELLULAR LOCATION.
[6]"Expression of phosphoinositide-specific phospholipase C isoenzymes in cultured astrocytes."
Lo Vasco V.R., Fabrizi C., Artico M., Cocco L., Billi A.M., Fumagalli L., Manzoli F.A.
J. Cell. Biochem. 100:952-959(2007) [PubMed: 17063484] [Abstract]
Cited for: SUBCELLULAR LOCATION.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U16655 mRNA. Translation: AAC52346.1.
D50455 mRNA. Translation: BAA09046.1.
IPIIPI00206026.
IPI00210334.
IPI00777925.
IPI00867935.
RefSeqNP_542419.1.
UniGeneRn.37434

3D structure databases

HSSPHSSP built from PDB template 1QAS based on UniProtKB P10688.
SMRQ62711. Positions 194-765.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ62711.

Genome annotation databases

EnsemblENSRNOT00000041407; ENSRNOP00000039708; ENSRNOG00000016361; Rattus norvegicus. [Genome view]
GeneID140693.
KEGGrno:140693.
UCSCNM_080688. rat.

Organism-specific databases

CTD140693.
RGD621025. Plcd4.

Phylogenomic databases

eggNOGroNOG13444.
HOVERGENQ62711.
PhylomeDBQ62711.

Enzyme and pathway databases

BRENDA3.1.4.11. 248.

Gene expression databases

ArrayExpressQ62711.
GenevestigatorQ62711.

Family and domain databases

InterProIPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR018249. EF_HAND_2.
IPR002048. EF_hand_Ca_bd.
IPR011993. PH_type.
IPR015359. Phospholipase_C_EF-hand-like.
IPR001192. Phospholipase_C_Pinositol-sp_C.
IPR001711. Phospholipase_C_Pinositol-sp_Y.
IPR017946. PLC-like_Pdiesterase_TIM-brl.
IPR001849. Pleckstrin_homology.
IPR000909. PLipase_C_PInositol-sp_X_dom.
[Graphical view]
Gene3DG3DSA:1.10.238.10. EF-Hand_type. 2 hits.
G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:3.20.20.190. PLC-like_Pdiesterase_TIM-brl. 1 hit.
PfamPF00168. C2. 1 hit.
PF09279. efhand_like. 1 hit.
PF00388. PI-PLC-X. 1 hit.
PF00387. PI-PLC-Y. 1 hit.
[Graphical view]
PRINTSPR00390. PHPHLIPASEC.
SMARTSM00239. C2. 1 hit.
SM00054. EFh. 3 hits.
SM00233. PH. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
[Graphical view]
PROSITEPS50004. 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]
ProtoNetSearch...

Other Resources

NextBio620675.

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Entry information

Entry namePLCD4_RAT
AccessionPrimary (citable) accession number: Q62711
Secondary accession number(s): Q63693
Entry history
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: November 1, 1996
Last modified: February 9, 2010
This is version 67 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents