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Q62711

- PLCD4_RAT

UniProt

Q62711 - PLCD4_RAT

Protein

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

Gene

Plcd4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei305 – 3051PROSITE-ProRule annotation
    Metal bindingi306 – 3061Calcium 1; catalyticBy similarity
    Metal bindingi335 – 3351Calcium 1; catalyticBy similarity
    Metal bindingi337 – 3371Calcium 1; catalyticBy similarity
    Active sitei350 – 3501PROSITE-ProRule annotation
    Binding sitei433 – 4331SubstrateBy similarity
    Binding sitei435 – 4351SubstrateBy similarity
    Binding sitei532 – 5321SubstrateBy similarity
    Binding sitei559 – 5591SubstrateBy similarity
    Metal bindingi662 – 6621Calcium 2By similarity
    Metal bindingi686 – 6861Calcium 2By similarity
    Metal bindingi715 – 7151Calcium 3By similarity
    Metal bindingi716 – 7161Calcium 3; via carbonyl oxygenBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi147 – 158121PROSITE-ProRule annotationAdd
    BLAST
    Calcium bindingi183 – 194122PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. phosphatidylinositol phospholipase C activity Source: RGD
    3. signal transducer activity Source: UniProtKB-KW

    GO - Biological processi

    1. acrosome reaction Source: InterPro
    2. intracellular signal transduction Source: RGD
    3. lipid catabolic process Source: UniProtKB-KW
    4. phosphatidylinositol metabolic process Source: InterPro

    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.

    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
    ProteomesiUP000002494: Chromosome 9

    Organism-specific databases

    RGDi621025. Plcd4.

    Subcellular locationi

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

    GO - Cellular componenti

    1. endoplasmic reticulum Source: UniProtKB-SubCell
    2. membrane Source: UniProtKB-KW
    3. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi36 – 361R → G: Only retains weak enzyme activity and abolishes the ability of isoform 4 to act as a negative regulator. 1 Publication
    Mutagenesisi714 – 7141K → E: Abolishes affinity for POPC/POPS in the absence of Ca(2+); when associated with E-718. 1 Publication
    Mutagenesisi717 – 7171S → D: Induces a larger Ca(2+)-dependence. 1 Publication
    Mutagenesisi718 – 7181R → E: Abolishes affinity for POPC/POPS in the absence of Ca(2+); when associated with E-714. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 7727721-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4PRO_0000306829Add
    BLAST

    Proteomic databases

    PRIDEiQ62711.

    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

    ArrayExpressiQ62711.
    GenevestigatoriQ62711.

    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)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 124109PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini134 – 16936EF-hand 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini170 – 20536EF-hand 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini203 – 23735EF-hand 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini290 – 435146PI-PLC X-boxPROSITE-ProRule annotationAdd
    BLAST
    Domaini503 – 619117PI-PLC Y-boxPROSITE-ProRule annotationAdd
    BLAST
    Domaini624 – 729106C2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni26 – 5328Substrate bindingBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi741 – 7444PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi448 – 4536Poly-Glu

    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

    eggNOGiNOG149692.
    GeneTreeiENSGT00740000114979.
    HOGENOMiHOG000006871.
    HOVERGENiHBG053610.
    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.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001192. PI-PLC_fam.
    IPR028387. PLC-delta4.
    IPR017946. PLC-like_Pdiesterase_TIM-brl.
    IPR015359. PLipase_C_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.
    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]
    SUPFAMiSSF49562. SSF49562. 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. Align

    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

    MASQIQKLLT TNQDLLLMQK GTMMRKVRTK SWKKLRYFRL QDDGMTVWHG    50
    RHLESISKPT FSISDVERIR KGQDSELLRY LVEEFPLEQG FTIVFNGRRP 100
    NLDLVANSVE EAQTWMRGLQ LLVDLVARMN YQEQLDQMLR EWFQQADRNQ 150
    DSRMSFREAQ RLLLLMNVEM DEEYAFSLFQ EADVSQSNTL DSEEFVQFYK 200
    ALTKRTEIEE LFENFSSDKQ KLTLLEFVDF LREEQKESDH SSDLALKLID 250
    RYEPSENGRL LRVLSKDGFL SYLCSADGNI FNPDCLPIYQ DMTQPLSHYY 300
    INSSHNTYLL GDQFCGQSSV EGYIRALKRG CRCVEVDTWD GPDGEPVVYH 350
    GRTLTSRILF KDVLATLAQY AFQSSDYPLI LSLDNHCTWE QQKTMAHHLI 400
    AILGEQLLST TLEEQLIDIM PSPEQLRGKI LVKGKKLRTI EVVESDKEEE 450
    ELEKDEGSDL DPASAELDMQ SQPESQEQAS GNKSKNKKKF LLQSSTTILC 500
    PDLSALVVYL RTAPFCSFTH SKENYHIYDI SSFSESKAKN LIREAGNEFV 550
    QHNARQLCRV YPSGLRTDSS NYNPQEHWNV GCQMVAMNMQ TAGSAMDICD 600
    GLFRQNGGSG YVLKPEFLRD TQSSFNPMKP VSLYKAQILV VQVISGQRLP 650
    KVDKTKETTV VDPLVRVELY GVPEDTKQQE TSYVENNGIN PYWGETFYFQ 700
    IQVPELAMLR FVVKDYSRTS RNNFIGQYTL PWTCMKHGYR HVSLLSKDGT 750
    SLHPASIFVY TCMQEDLDMD EP 772
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti395 – 3951M → ML in BAA09046. (PubMed:8550586)Curated
    Sequence conflicti416 – 4161Missing in BAA09046. (PubMed:8550586)Curated
    Sequence conflicti425 – 4251Missing in BAA09046. (PubMed:8550586)Curated
    Sequence conflicti757 – 7571I → H in BAA09046. (PubMed:8550586)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei424 – 48764EQLRG…KSKNK → VMKCPMSCLLICVHVLAQAP NSIPESILLPKR in isoform 4. CuratedVSP_028507Add
    BLAST
    Alternative sequencei487 – 4871K → KVMKCPMSCLLICVHVLAQA PNSIPESILLP in isoform 2. 1 PublicationVSP_028508
    Alternative sequencei487 – 4871K → KAPNSIPESILLP in isoform 3. 1 PublicationVSP_028509

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U16655 mRNA. Translation: AAC52346.1.
    D50455 mRNA. Translation: BAA09046.1.
    RefSeqiNP_542419.1. NM_080688.1. [Q62711-1]
    XP_006245208.1. XM_006245146.1. [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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U16655 mRNA. Translation: AAC52346.1 .
    D50455 mRNA. Translation: BAA09046.1 .
    RefSeqi NP_542419.1. NM_080688.1. [Q62711-1 ]
    XP_006245208.1. XM_006245146.1. [Q62711-1 ]
    UniGenei Rn.37434.

    3D structure databases

    ProteinModelPortali Q62711.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000022234.

    Chemistry

    BindingDBi Q62711.

    Proteomic databases

    PRIDEi Q62711.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000041407 ; ENSRNOP00000039708 ; ENSRNOG00000016361 . [Q62711-1 ]
    GeneIDi 140693.
    KEGGi rno:140693.
    UCSCi RGD:621025. rat. [Q62711-1 ]

    Organism-specific databases

    CTDi 84812.
    RGDi 621025. Plcd4.

    Phylogenomic databases

    eggNOGi NOG149692.
    GeneTreei ENSGT00740000114979.
    HOGENOMi HOG000006871.
    HOVERGENi HBG053610.
    KOi K05857.
    PhylomeDBi Q62711.

    Enzyme and pathway databases

    BRENDAi 3.1.4.11. 5301.

    Miscellaneous databases

    NextBioi 620675.
    PROi Q62711.

    Gene expression databases

    ArrayExpressi Q62711.
    Genevestigatori Q62711.

    Family and domain databases

    Gene3Di 1.10.238.10. 2 hits.
    2.30.29.30. 1 hit.
    2.60.40.150. 1 hit.
    3.20.20.190. 2 hits.
    InterProi IPR000008. C2_dom.
    IPR011992. EF-hand-dom_pair.
    IPR018247. EF_Hand_1_Ca_BS.
    IPR002048. EF_hand_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001192. PI-PLC_fam.
    IPR028387. PLC-delta4.
    IPR017946. PLC-like_Pdiesterase_TIM-brl.
    IPR015359. PLipase_C_EF-hand-like.
    IPR000909. PLipase_C_PInositol-sp_X_dom.
    IPR001711. PLipase_C_Pinositol-sp_Y.
    [Graphical view ]
    PANTHERi PTHR10336. PTHR10336. 1 hit.
    PTHR10336:SF31. PTHR10336:SF31. 1 hit.
    Pfami PF00168. C2. 1 hit.
    PF09279. EF-hand_like. 1 hit.
    PF00388. PI-PLC-X. 1 hit.
    PF00387. PI-PLC-Y. 1 hit.
    [Graphical view ]
    PRINTSi PR00390. PHPHLIPASEC.
    SMARTi SM00239. C2. 1 hit.
    SM00054. EFh. 3 hits.
    SM00233. PH. 1 hit.
    SM00148. PLCXc. 1 hit.
    SM00149. PLCYc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 1 hit.
    SSF51695. SSF51695. 1 hit.
    PROSITEi PS50004. 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 ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.

    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: October 1, 2014
    This is version 109 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

    External Data

    Dasty 3