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Q9BRC7

- PLCD4_HUMAN

UniProt

Q9BRC7 - PLCD4_HUMAN

Protein

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

Gene

PLCD4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      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.1 Publication

    Catalytic activityi

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

    Cofactori

    Binds 3 calcium ions per subunit. Two of the calcium ions are bound to the C2 domain By similarity.By similarity

    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
    Metal bindingi384 – 3841Calcium 1; catalyticBy similarity
    Binding sitei433 – 4331SubstrateBy similarity
    Binding sitei435 – 4351SubstrateBy similarity
    Binding sitei522 – 5221SubstrateBy similarity
    Binding sitei549 – 5491SubstrateBy similarity
    Metal bindingi650 – 6501Calcium 2; via carbonyl oxygenBy similarity
    Metal bindingi652 – 6521Calcium 2By similarity
    Metal bindingi676 – 6761Calcium 2By similarity
    Metal bindingi705 – 7051Calcium 3By similarity
    Metal bindingi706 – 7061Calcium 3; via carbonyl oxygenBy similarity
    Metal bindingi707 – 7071Calcium 3By 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: UniProtKB-EC
    3. signal transducer activity Source: UniProtKB-KW

    GO - Biological processi

    1. acrosome reaction Source: Ensembl
    2. intracellular signal transduction Source: InterPro
    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

    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
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:9062. PLCD4.

    Subcellular locationi

    Membrane By similarity; Peripheral membrane protein By similarity. Nucleus By similarity. Cytoplasm 1 Publication. Endoplasmic reticulum By similarity
    Note: Localizes primarily to intracellular membranes mostly to the endoplasmic reticulum.

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA33390.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 7627621-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4PRO_0000306824Add
    BLAST

    Proteomic databases

    PaxDbiQ9BRC7.
    PRIDEiQ9BRC7.

    PTM databases

    PhosphoSiteiQ9BRC7.

    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

    ArrayExpressiQ9BRC7.
    BgeeiQ9BRC7.
    CleanExiHS_PLCD4.
    GenevestigatoriQ9BRC7.

    Organism-specific databases

    HPAiCAB009914.

    Interactioni

    Subunit structurei

    Interacts with GRIP1.By similarity

    Protein-protein interaction databases

    BioGridi124273. 3 interactions.
    IntActiQ9BRC7. 2 interactions.
    MINTiMINT-1482361.
    STRINGi9606.ENSP00000388631.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BRC7.
    SMRiQ9BRC7. Positions 9-123, 149-755.
    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
    Domaini493 – 609117PI-PLC Y-boxPROSITE-ProRule annotationAdd
    BLAST
    Domaini614 – 719106C2PROSITE-ProRule annotationAdd
    BLAST

    Region

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

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi731 – 7344PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi440 – 47334Glu-richAdd
    BLAST
    Compositional biasi479 – 4868Poly-Lys

    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

    eggNOGiNOG149692.
    HOGENOMiHOG000006871.
    HOVERGENiHBG053610.
    InParanoidiQ9BRC7.
    KOiK05857.
    OrthoDBiEOG7V49XT.
    PhylomeDBiQ9BRC7.
    TreeFamiTF313216.

    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. 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. Align

    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

    MASLLQDQLT TDQDLLLMQE GMPMRKVRSK SWKKLRYFRL QNDGMTVWHA    50
    RQARGSAKPS FSISDVETIR NGHDSELLRS LAEELPLEQG FTIVFHGRRS 100
    NLDLMANSVE EAQIWMRGLQ LLVDLVTSMD HQERLDQWLS DWFQRGDKNQ 150
    DGKMSFQEVQ RLLHLMNVEM DQEYAFSLFQ AADTSQSGTL EGEEFVQFYK 200
    ALTKRAEVQE LFESFSADGQ KLTLLEFLDF LQEEQKERDC TSELALELID 250
    RYEPSDSGKL RHVLSMDGFL SYLCSKDGDI FNPACLPIYQ DMTQPLNHYF 300
    ICSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDVWD GPSGEPVVYH 350
    GHTLTSRILF KDVVATVAQY AFQTSDYPVI LSLETHCSWE QQQTMARHLT 400
    EILGEQLLST TLDGVLPTQL PSPEELRRKI LVKGKKLTLE EDLEYEEEEA 450
    EPELEESELA LESQFETEPE PQEQNLQNKD KKKKSKPILC PALSSLVIYL 500
    KSVSFRSFTH SKEHYHFYEI SSFSETKAKR LIKEAGNEFV QHNTWQLSRV 550
    YPSGLRTDSS NYNPQELWNA GCQMVAMNMQ TAGLEMDICD GHFRQNGGCG 600
    YVLKPDFLRD IQSSFHPEKP ISPFKAQTLL IQVISGQQLP KVDKTKEGSI 650
    VDPLVKVQIF GVRLDTARQE TNYVENNGFN PYWGQTLCFR VLVPELAMLR 700
    FVVMDYDWKS RNDFIGQYTL PWTCMQQGYR HIHLLSKDGI SLRPASIFVY 750
    ICIQEGLEGD ES 762

    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti98 – 981R → H in BAD96923. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei259 – 27214KLRHV…GFLSY → ASEEDPGEGEEVNT in isoform 2. 1 PublicationVSP_028501Add
    BLAST
    Alternative sequencei273 – 762490Missing in isoform 2. 1 PublicationVSP_028502Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    UCSCiuc021vwx.1. human. [Q9BRC7-1]

    Polymorphism databases

    DMDMi74732863.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY512961 mRNA. Translation: AAS82574.1 .
    AK223203 mRNA. Translation: BAD96923.1 .
    BC006355 mRNA. Translation: AAH06355.1 .
    CCDSi CCDS46516.1. [Q9BRC7-1 ]
    RefSeqi NP_116115.1. NM_032726.3. [Q9BRC7-1 ]
    UniGenei Hs.632528.

    3D structure databases

    ProteinModelPortali Q9BRC7.
    SMRi Q9BRC7. Positions 9-123, 149-755.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124273. 3 interactions.
    IntActi Q9BRC7. 2 interactions.
    MINTi MINT-1482361.
    STRINGi 9606.ENSP00000388631.

    PTM databases

    PhosphoSitei Q9BRC7.

    Polymorphism databases

    DMDMi 74732863.

    Proteomic databases

    PaxDbi Q9BRC7.
    PRIDEi Q9BRC7.

    Protocols and materials databases

    DNASUi 84812.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000417849 ; ENSP00000396942 ; ENSG00000115556 . [Q9BRC7-1 ]
    ENST00000450993 ; ENSP00000388631 ; ENSG00000115556 . [Q9BRC7-1 ]
    GeneIDi 84812.
    KEGGi hsa:84812.
    UCSCi uc021vwx.1. human. [Q9BRC7-1 ]

    Organism-specific databases

    CTDi 84812.
    GeneCardsi GC02P219436.
    H-InvDB HIX0002832.
    HIX0030357.
    HGNCi HGNC:9062. PLCD4.
    HPAi CAB009914.
    MIMi 605939. gene.
    neXtProti NX_Q9BRC7.
    PharmGKBi PA33390.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG149692.
    HOGENOMi HOG000006871.
    HOVERGENi HBG053610.
    InParanoidi Q9BRC7.
    KOi K05857.
    OrthoDBi EOG7V49XT.
    PhylomeDBi Q9BRC7.
    TreeFami TF313216.

    Miscellaneous databases

    ChiTaRSi PLCD4. human.
    GeneWikii PLCD4.
    GenomeRNAii 84812.
    NextBioi 74997.
    PROi Q9BRC7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9BRC7.
    Bgeei Q9BRC7.
    CleanExi HS_PLCD4.
    Genevestigatori Q9BRC7.

    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. 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 ]
    ProtoNeti Search...

    Publicationsi

    1. "Phospholipase C delta-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells."
      Leung D.W., Tompkins C., Brewer J., Ball A., Coon M., Morris V., Waggoner D., Singer J.W.
      Mol. Cancer 3:15-15(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    2. Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Kidney proximal tubule.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    4. "Assignment of the human PLC delta4 gene (PLCD4) to human chromosome band 2q35 by fluorescence in situ hybridization."
      Kim H., Suh P.-G., Ryu S.H., Park S.H.
      Cytogenet. Cell Genet. 87:254-255(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION.
    5. "Expression of phospholipases A2 and C in human corneal epithelial cells."
      Landreville S., Coulombe S., Carrier P., Gelb M.H., Guerin S.L., Salesse C.
      Invest. Ophthalmol. Vis. Sci. 45:3997-4003(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.

    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: October 1, 2014
    This is version 120 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

    External Data

    Dasty 3