Q8N3E9 (PLCD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-3
EC=3.1.4.11

Alternative name(s):
Phosphoinositide phospholipase C-delta-3
Phospholipase C-delta-3
Short name=PLC-delta-3

Gene names

Name:	PLCD3
Synonyms:	KIAA1964

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	789 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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. Essential for trophoblast and placental development. May participate in cytokinesis by hydrolyzing PIP2 at the cleavage furrow.
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. Ref.9
Cofactor	Binds 3 calcium ions per subunit. Two of the calcium ions are bound to the C2 domain Probable. Ref.7
Enzyme regulation	Strongly activated by phosphatidic acid. Inhibited by phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), sphingomyelin and phosphatidylserine (PtdSer). Ref.7 Ref.9
Subcellular location	Membrane; Peripheral membrane protein. Cytoplasm. Cleavage furrow. Note: Localizes at the cleavage furrow during cytokinesis. Ref.7 Ref.14
Tissue specificity	Present in corneal epithelial cells (at protein level). Ref.12
Induction	Down-regulated by Ca2+ and cAMP. Ref.7 Ref.9 Ref.10
Domain	The C2 domain is a Ca2+-dependent membrane-targeting module. Ref.9 Ref.11 The PH domain mediates interaction with the surface membrane by binding to PIP2. Ref.9 Ref.11
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.
Biophysicochemical properties	Kinetic parameters: KM=105.3 µM for PIP2 Ref.9 Vmax=28.5 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Transducer
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cleavage furrow Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro phosphatidylinositol phospholipase C activity Inferred from electronic annotation. Source: EC signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 789	789	1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-3		PRO_0000306821
Regions
	Domain	63 – 172	110	PH
	Domain	182 – 217	36	EF-hand 1
	Domain	218 – 253	36	EF-hand 2
	Domain	250 – 285	36	EF-hand 3
	Domain	337 – 482	146	PI-PLC X-box
	Domain	528 – 644	117	PI-PLC Y-box
	Domain	647 – 752	106	C2
	Calcium binding	195 – 206	12	1 Potential
	Calcium binding	231 – 242	12	2 Potential
	Region	73 – 101	29	Substrate binding By similarity
Sites
	Active site	352	1	By similarity
	Active site	397	1	By similarity
	Metal binding	353	1	Calcium 1; catalytic By similarity
	Metal binding	382	1	Calcium 1; catalytic By similarity
	Metal binding	384	1	Calcium 1; catalytic By similarity
	Metal binding	431	1	Calcium 1; catalytic By similarity
	Metal binding	683	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	685	1	Calcium 2 By similarity
	Metal binding	709	1	Calcium 2 By similarity
	Metal binding	738	1	Calcium 3 By similarity
	Metal binding	739	1	Calcium 3; via carbonyl oxygen By similarity
	Metal binding	740	1	Calcium 3 By similarity
	Binding site	480	1	Substrate By similarity
	Binding site	482	1	Substrate By similarity
	Binding site	557	1	Substrate By similarity
	Binding site	584	1	Substrate By similarity
Amino acid modifications
	Modified residue	105	1	Phosphoserine Ref.15
	Modified residue	496	1	Phosphoserine Ref.13 Ref.15
Natural variations
	Natural variant	652	1	P → L. Corresponds to variant rs734921 [ dbSNP | Ensembl ].		VAR_035316
Experimental info
	Sequence conflict	207	1	I → T in CAD39054. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8N3E9 [UniParc]. Last modified October 2, 2007. Version 3. Checksum: C6901404D2C9D070	FASTA	789	89,258
	10 20 30 40 50 60 MLCGRWRRCR RPPEEPPVAA QVAAQVAAPV ALPSPPTPSD GGTKRPGLRA LKKMGLTEDE 70 80 90 100 110 120 DVRAMLRGSR LRKIRSRTWH KERLYRLQED GLSVWFQRRI PRAPSQHIFF VQHIEAVREG 130 140 150 160 170 180 HQSEGLRRFG GAFAPARCLT IAFKGRRKNL DLAAPTAEEA QRWVRGLTKL RARLDAMSQR 190 200 210 220 230 240 ERLDHWIHSY LHRADSNQDS KMSFKEIKSL LRMVNVDMND MYAYLLFKEC DHSNNDRLEG 250 260 270 280 290 300 AEIEEFLRRL LKRPELEEIF HQYSGEDRVL SAPELLEFLE DQGEEGATLA RAQQLIQTYE 310 320 330 340 350 360 LNETAKQHEL MTLDGFMMYL LSPEGAALDN THTCVFQDMN QPLAHYFISS SHNTYLTDSQ 370 380 390 400 410 420 IGGPSSTEAY VRAFAQGCRC VELDCWEGPG GEPVIYHGHT LTSKILFRDV VQAVRDHAFT 430 440 450 460 470 480 LSPYPVILSL ENHCGLEQQA AMARHLCTIL GDMLVTQALD SPNPEELPSP EQLKGRVLVK 490 500 510 520 530 540 GKKLPAARSE DGRALSDREE EEEDDEEEEE EVEAAAQRRL AKQISPELSA LAVYCHATRL 550 560 570 580 590 600 RTLHPAPNAP QPCQVSSLSE RKAKKLIREA GNSFVRHNAR QLTRVYPLGL RMNSANYSPQ 610 620 630 640 650 660 EMWNSGCQLV ALNFQTPGYE MDLNAGRFLV NGQCGYVLKP ACLRQPDSTF DPEYPGPPRT 670 680 690 700 710 720 TLSIQVLTAQ QLPKLNAEKP HSIVDPLVRI EIHGVPADCA RQETDYVLNN GFNPRWGQTL 730 740 750 760 770 780 QFQLRAPELA LVRFVVEDYD ATSPNDFVGQ FTLPLSSLKQ GYRHIHLLSK DGASLSPATL FIQIRIQRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]	"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]. Tissue: Colon and Pancreas.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 13-789. Tissue: Amygdala.
[4]	"Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins." Nagase T., Kikuno R., Ohara O. DNA Res. 8:319-327(2001) [PubMed: 11853319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 33-789. Tissue: Brain.
[5]	"Expression, purification and kinetic properties of human recombinant phospholipase C delta 3." Pawelczyk T., Matecki A. Acta Biochim. Pol. 44:221-229(1997) [PubMed: 9360711] [Abstract] Cited for: PURIFICATION.
[6]	"Phospholipase C isoforms delta 1 and delta 3 from human fibroblasts. High-yield expression in Escherichia coli, simple purification, and properties." Ghosh S., Pawelczyk T., Lowenstein J.M. Protein Expr. Purif. 9:262-278(1997) [PubMed: 9056492] [Abstract] Cited for: PURIFICATION.
[7]	"Localization of phospholipase C delta3 in the cell and regulation of its activity by phospholipids and calcium." Pawelczyk T., Matecki A. Eur. J. Biochem. 257:169-177(1998) [PubMed: 9799116] [Abstract] Cited for: SUBCELLULAR LOCATION, COFACTOR, ENZYME REGULATION.
[8]	"Assignment of the human PLC delta3 gene (PLCD3) to human chromosome band 17q21 by fluorescence in situ hybridization." Kim H., Suh P.-G., Ryu S.H., Park S.H. Cytogenet. Cell Genet. 87:209-210(1999) [PubMed: 10702670] [Abstract] Cited for: IDENTIFICATION.
[9]	"Phospholipase C-delta3 binds with high specificity to phosphatidylinositol 4,5-bisphosphate and phosphatidic acid in bilayer membranes." Pawelczyk T., Matecki A. Eur. J. Biochem. 262:291-298(1999) [PubMed: 10336610] [Abstract] Cited for: ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, DOMAIN PH.
[10]	"Downregulation of phospholipase C delta3 by cAMP and calcium." Lin F.-G., Cheng H.-F., Lee I.-F., Kao H.-J., Loh S.-H., Lee W.-H. Biochem. Biophys. Res. Commun. 286:274-280(2001) [PubMed: 11500033] [Abstract] Cited for: INDUCTION.
[11]	"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.
[12]	"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.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-496, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Phospholipase C isoforms are localized at the cleavage furrow during cytokinesis." Naito Y., Okada M., Yagisawa H. J. Biochem. 140:785-791(2006) [PubMed: 17041247] [Abstract] Cited for: SUBCELLULAR LOCATION.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105 AND SER-496, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK074240 mRNA. Translation: BAB85029.1. BC010668 mRNA. Translation: AAH10668.2. BC072384 mRNA. Translation: AAH72384.1. AL834392 mRNA. Translation: CAD39054.2. AB075844 mRNA. Translation: BAB85550.1.
IPI	IPI00152701.
RefSeq	NP_588614.1. NM_133373.3.
UniGene	Hs.380094.
3D structure databases
HSSP	HSSP built from PDB template 1DJX based on UniProtKB P10688.
ProteinModelPortal	Q8N3E9.
SMR	Q8N3E9. Positions 55-788.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1193970.
STRING	Q8N3E9.
Polymorphism databases
DMDM	158706388.
Proteomic databases
PeptideAtlas	Q8N3E9.
PRIDE	Q8N3E9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000322765; ENSP00000313731; ENSG00000161714.
GeneID	113026.
KEGG	hsa:113026.
Organism-specific databases
CTD	113026.
GeneCards	GC17M043197.
H-InvDB	HIX0013879.
HGNC	HGNC:9061. PLCD3.
HPA	HPA025711.
MIM	608795. gene.
neXtProt	NX_Q8N3E9.
PharmGKB	PA33389.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09828.
GeneTree	ENSGT00570000078720.
HOGENOM	HBG527074.
HOVERGEN	HBG053610.
InParanoid	Q8N3E9.
OrthoDB	EOG45QHCM.
PhylomeDB	Q8N3E9.
Gene expression databases
ArrayExpress	Q8N3E9.
Bgee	Q8N3E9.
CleanEx	HS_PLCD3.
Genevestigator	Q8N3E9.
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. IPR011993. PH_type. IPR001192. Pinositol_PLipase_C. IPR017946. PLC-like_Pdiesterase_TIM-brl. IPR001849. Pleckstrin_homology. IPR015359. PLipase_C_EF-hand-like. IPR000909. PLipase_C_PInositol-sp_X_dom. IPR001711. PLipase_C_Pinositol-sp_Y. [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. 2 hits.
KO	K05857.
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. SM00233. PH. 1 hit. SM00148. PLCXc. 1 hit. SM00149. PLCYc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF51695. PLC-like_Pdiesterase_TIM-brl. 1 hit.
PROSITE	PS50004. C2. 1 hit. PS00018. EF_HAND_1. 1 hit. PS50222. EF_HAND_2. False negative. PS50003. PH_DOMAIN. False negative. PS50007. PIPLC_X_DOMAIN. 1 hit. PS50008. PIPLC_Y_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00144. Phosphatidylserine.
NextBio	78735.
SOURCE	Search...

Entry information

Entry name

PLCD3_HUMAN

Accession

Primary (citable) accession number: Q8N3E9
Secondary accession number(s): Q8TEC1, Q8TF37, Q96FL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	October 2, 2007
Last modified:	January 25, 2012
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.