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

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Reviewed, UniProtKB/Swiss-Prot Q9BRC7 (PLCD4_HUMAN)

Last modified February 9, 2010. Version 72. History...

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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 names

Recommended name:
    1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-4
      Short name=hPLCD4
    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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	762 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.1
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H₂O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.
Cofactor	Binds 3 calcium ions per subunit. Two of the calcium ions are bound to the C2 domain By similarity.
Subunit structure	Interacts with GRIP1 By similarity.
Subcellular location	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. Ref.1
Tissue specificity	Highly expressed in skeletal muscle and kidney tissues, and at moderate level in intestinal tissue. Expressed in corneal epithelial cells. Ref.1 Ref.5
Domain	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 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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Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Transducer
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoinositide phospholipase C activity Inferred from electronic annotation. Source: EC signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BRC7-1) 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.
Note: Acceptor splice site between exons 4 and 5 is non-canonical but conserved through species for that particular gene.

Isoform 2 (identifier: Q9BRC7-2) 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.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 762

762

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

PRO_0000306824

Regions

Domain

16 – 124

109

Domain

134 – 169

EF-hand 1

Domain

170 – 205

EF-hand 2

Domain

203 – 237

EF-hand 3

Domain

290 – 435

146

PI-PLC X-box

Domain

493 – 609

117

PI-PLC Y-box

Domain

614 – 719

106

Calcium binding

147 – 158

1 Potential

Calcium binding

183 – 194

2 Potential

Region

26 – 53

Substrate binding By similarity

Motif

731 – 734

PDZ-binding

Compositional bias

440 – 473

Glu-rich

Compositional bias

479 – 486

Poly-Lys

Sites

Active site

305

By similarity

Active site

350

By similarity

Metal binding

306

Calcium 1; catalytic By similarity

Metal binding

335

Calcium 1; catalytic By similarity

Metal binding

337

Calcium 1; catalytic By similarity

Metal binding

384

Calcium 1; catalytic By similarity

Metal binding

650

Calcium 2; via carbonyl oxygen By similarity

Metal binding

652

Calcium 2 By similarity

Metal binding

676

Calcium 2 By similarity

Metal binding

705

Calcium 3 By similarity

Metal binding

706

Calcium 3; via carbonyl oxygen By similarity

Metal binding

707

Calcium 3 By similarity

Binding site

433

Substrate By similarity

Binding site

435

Substrate By similarity

Binding site

522

Substrate By similarity

Binding site

549

Substrate By similarity

Natural variations

Alternative sequence

259 – 272

KLRHV…GFLSY → ASEEDPGEGEEVNT in isoform 2.

VSP_028501

Alternative sequence

273 – 762

490

Missing in isoform 2.

VSP_028502

Experimental info

Sequence conflict

R → H in BAD96923. Ref.2

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 5444BE5CE2AEA3EF Show »	FASTA	762	87,585
10 20 30 40 50 60 MASLLQDQLT TDQDLLLMQE GMPMRKVRSK SWKKLRYFRL QNDGMTVWHA RQARGSAKPS 70 80 90 100 110 120 FSISDVETIR NGHDSELLRS LAEELPLEQG FTIVFHGRRS NLDLMANSVE EAQIWMRGLQ 130 140 150 160 170 180 LLVDLVTSMD HQERLDQWLS DWFQRGDKNQ DGKMSFQEVQ RLLHLMNVEM DQEYAFSLFQ 190 200 210 220 230 240 AADTSQSGTL EGEEFVQFYK ALTKRAEVQE LFESFSADGQ KLTLLEFLDF LQEEQKERDC 250 260 270 280 290 300 TSELALELID RYEPSDSGKL RHVLSMDGFL SYLCSKDGDI FNPACLPIYQ DMTQPLNHYF 310 320 330 340 350 360 ICSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDVWD GPSGEPVVYH GHTLTSRILF 370 380 390 400 410 420 KDVVATVAQY AFQTSDYPVI LSLETHCSWE QQQTMARHLT EILGEQLLST TLDGVLPTQL 430 440 450 460 470 480 PSPEELRRKI LVKGKKLTLE EDLEYEEEEA EPELEESELA LESQFETEPE PQEQNLQNKD 490 500 510 520 530 540 KKKKSKPILC PALSSLVIYL KSVSFRSFTH SKEHYHFYEI SSFSETKAKR LIKEAGNEFV 550 560 570 580 590 600 QHNTWQLSRV YPSGLRTDSS NYNPQELWNA GCQMVAMNMQ TAGLEMDICD GHFRQNGGCG 610 620 630 640 650 660 YVLKPDFLRD IQSSFHPEKP ISPFKAQTLL IQVISGQQLP KVDKTKEGSI VDPLVKVQIF 670 680 690 700 710 720 GVRLDTARQE TNYVENNGFN PYWGQTLCFR VLVPELAMLR FVVMDYDWKS RNDFIGQYTL 730 740 750 760 PWTCMQQGYR HIHLLSKDGI SLRPASIFVY ICIQEGLEGD ES « Hide
Isoform 2 (PLCD4b). Checksum: C3A83C9C8E411D88 Show »	FASTA	272	31,448
10 20 30 40 50 60 MASLLQDQLT TDQDLLLMQE GMPMRKVRSK SWKKLRYFRL QNDGMTVWHA RQARGSAKPS 70 80 90 100 110 120 FSISDVETIR NGHDSELLRS LAEELPLEQG FTIVFHGRRS NLDLMANSVE EAQIWMRGLQ 130 140 150 160 170 180 LLVDLVTSMD HQERLDQWLS DWFQRGDKNQ DGKMSFQEVQ RLLHLMNVEM DQEYAFSLFQ 190 200 210 220 230 240 AADTSQSGTL EGEEFVQFYK ALTKRAEVQE LFESFSADGQ KLTLLEFLDF LQEEQKERDC 250 260 270 TSELALELID RYEPSDSGAS EEDPGEGEEV NT « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 15140260] [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: 15489334] [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: 10702683] [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: 15505048] [Abstract] Cited for: TISSUE SPECIFICITY.

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Cross-references

Sequence databases
EMBL GenBank DDBJ	AY512961 mRNA. Translation: AAS82574.1. AK223203 mRNA. Translation: BAD96923.1. BC006355 mRNA. Translation: AAH06355.1.
IPI	IPI00013745. IPI00867639.
RefSeq	NP_116115.1.
UniGene	Hs.632528
3D structure databases
HSSP	HSSP built from PDB template 1QAS based on UniProtKB P10688.
SMR	Q9BRC7. Positions 194-755.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BRC7. 2 interactions.
STRING	Q9BRC7.
Proteomic databases
PRIDE	Q9BRC7.
Genome annotation databases
Ensembl	ENST00000417849; ENSP00000396942; ENSG00000115556; Homo sapiens. [Genome view] ENST00000450993; ENSP00000388631; ENSG00000115556; Homo sapiens. [Genome view]
GeneID	84812.
KEGG	hsa:84812.
Organism-specific databases
CTD	84812.
GeneCards	GC02P219180.
HGNC	HGNC:9062. PLCD4.
HPA	CAB009914.
MIM	605939. gene.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11892.
HOVERGEN	Q9BRC7.
InParanoid	Q9BRC7.
Enzyme and pathway databases
BRENDA	3.1.4.11. 247.
Gene expression databases
ArrayExpress	Q9BRC7.
Bgee	Q9BRC7.
CleanEx	HS_PLCD4.
Genevestigator	Q9BRC7.
Family and domain databases
InterPro	IPR000008. 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]
Gene3D	G3DSA: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.
Pfam	PF00168. C2. 1 hit. PF09279. efhand_like. 1 hit. PF00388. PI-PLC-X. 1 hit. PF00387. PI-PLC-Y. 1 hit. [Graphical view]
PRINTS	PR00390. PHPHLIPASEC.
SMART	SM00239. C2. 1 hit. SM00054. EFh. 3 hits. SM00233. PH. 1 hit. SM00148. PLCXc. 1 hit. SM00149. PLCYc. 1 hit. [Graphical view]
PROSITE	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]
ProtoNet	Search...
Other Resources
NextBio	74997.
SOURCE	Search...

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Entry information

Entry name

PLCD4_HUMAN

Accession

Primary (citable) accession number: Q9BRC7
Secondary accession number(s): Q53FS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	June 1, 2001
Last modified:	February 9, 2010
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents