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Q9BRC7

- PLCD4_HUMAN

UniProt

Q9BRC7 - PLCD4_HUMAN

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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

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei305 – 3051 By similarity
Metal bindingi306 – 3061Calcium 1; catalytic By similarity
Metal bindingi335 – 3351Calcium 1; catalytic By similarity
Metal bindingi337 – 3371Calcium 1; catalytic By similarity
Active sitei350 – 3501 By similarity
Metal bindingi384 – 3841Calcium 1; catalytic By similarity
Binding sitei433 – 4331Substrate By similarity
Binding sitei435 – 4351Substrate By similarity
Binding sitei522 – 5221Substrate By similarity
Binding sitei549 – 5491Substrate By similarity
Metal bindingi650 – 6501Calcium 2; via carbonyl oxygen By similarity
Metal bindingi652 – 6521Calcium 2 By similarity
Metal bindingi676 – 6761Calcium 2 By similarity
Metal bindingi705 – 7051Calcium 3 By similarity
Metal bindingi706 – 7061Calcium 3; via carbonyl oxygen By similarity
Metal bindingi707 – 7071Calcium 3 By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi147 – 158121 Reviewed prediction
Add
BLAST
Calcium bindingi183 – 194122 Reviewed prediction
Add
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
Complete GO annotation...

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
Complete GO annotation...

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

GO - Cellular componenti

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

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-4
PRO_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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini16 – 124109PH
Add
BLAST
Domaini134 – 16936EF-hand 1
Add
BLAST
Domaini170 – 20536EF-hand 2
Add
BLAST
Domaini203 – 23735EF-hand 3
Add
BLAST
Domaini290 – 435146PI-PLC X-box
Add
BLAST
Domaini493 – 609117PI-PLC Y-box
Add
BLAST
Domaini614 – 719106C2
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni26 – 5328Substrate binding By similarity
Add
BLAST

Motif

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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi440 – 47334Glu-rich
Add
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.
Contains 3 EF-hand domains.
Contains 1 PH domain.

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei259 – 27214KLRHV…GFLSY → ASEEDPGEGEEVNT in isoform 2.
VSP_028501Add
BLAST
Alternative sequencei273 – 762490Missing in isoform 2.
VSP_028502Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti98 – 981R → H in BAD96923. 1 Publication

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...

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 119 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

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