P51178 (PLCD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Phosphoinositide phospholipase C-delta-1
Phospholipase C-III
Short name=PLC-III
Phospholipase C-delta-1
Short name=PLC-delta-1

Gene names

Name:

PLCD1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. Essential for trophoblast and placental development.
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.
Involvement in disease	Nail disorder, non-syndromic congenital, 3 (NDNC3) [MIM:151600]: A nail disorder characterized by a white appearance of the nail plate (true leukonychia), the nail bed (pseudoleukonychia), or neither (apparent leukonychia). Leukonychia may involve all of the nail (leukonychia totalis) or only part of the nail (leukonychia partialis), or can appear as one or more transverse bands (leukonychia striata) or white spots (leukonychia punctata). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Contains 1 C2 domain. Contains 2 EF-hand domains. Contains 1 PH domain. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Transducer
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro labyrinthine layer blood vessel development Inferred from electronic annotation. Source: Compara lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Traceable author statement PubMed 9588182. Source: ProtInc regulation of cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay PubMed 15702972. Source: MGI cytosol Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro phosphatidylinositol phospholipase C activity Traceable author statement PubMed 9588182. Source: ProtInc phospholipid binding Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P51178-1)

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.

Isoform 2 (identifier: P51178-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-11: MDSGRDFLTLH → MQCLGIRSRSRSRELYLQERSLKVAALNGRRL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 756	756	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1		PRO_0000088504
Regions
	Domain	21 – 130	110	PH
	Domain	140 – 175	36	EF-hand 1
	Domain	176 – 211	36	EF-hand 2
	Domain	296 – 440	145	PI-PLC X-box
	Domain	492 – 609	118	PI-PLC Y-box
	Domain	616 – 720	105	C2
	Calcium binding	153 – 164	12	1 Potential
	Calcium binding	189 – 200	12	2 Potential
	Region	30 – 57	28	Substrate binding By similarity
Sites
	Active site	311	1	By similarity
	Active site	356	1	By similarity
	Metal binding	312	1	Calcium 1; catalytic By similarity
	Metal binding	341	1	Calcium 1; catalytic By similarity
	Metal binding	343	1	Calcium 1; catalytic By similarity
	Metal binding	390	1	Calcium 1; catalytic By similarity
	Metal binding	651	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	653	1	Calcium 2 By similarity
	Metal binding	677	1	Calcium 2 By similarity
	Metal binding	706	1	Calcium 3 By similarity
	Metal binding	707	1	Calcium 3; via carbonyl oxygen By similarity
	Metal binding	708	1	Calcium 3 By similarity
	Binding site	438	1	Substrate By similarity
	Binding site	440	1	Substrate By similarity
	Binding site	522	1	Substrate By similarity
	Binding site	549	1	Substrate By similarity
Natural variations
	Alternative sequence	1 – 11	11	MDSGRDFLTLH → MQCLGIRSRSRSRELYLQER SLKVAALNGRRL in isoform 2.		VSP_042919
	Natural variant	209	1	T → R in NDNC3. Ref.6		VAR_066399
	Natural variant	257	1	R → H. Corresponds to variant rs933135 [ dbSNP | Ensembl ].		VAR_046560
	Natural variant	574	1	I → T in NDNC3. Ref.6		VAR_066400
Experimental info
	Sequence conflict	224	1	S → P in AAA73567. Ref.1
	Sequence conflict	264	1	A → T in AAA73567. Ref.1
	Sequence conflict	591	1	G → D in AAA73567. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: 6C6FD7F89BA08C83	FASTA	756	85,665
	10 20 30 40 50 60 MDSGRDFLTL HGLQDDEDLQ ALLKGSQLLK VKSSSWRRER FYKLQEDCKT IWQESRKVMR 70 80 90 100 110 120 TPESQLFSIE DIQEVRMGHR TEGLEKFARD VPEDRCFSIV FKDQRNTLDL IAPSPADAQH 130 140 150 160 170 180 WVLGLHKIIH HSGSMDQRQK LQHWIHSCLR KADKNKDNKM SFKELQNFLK ELNIQVDDSY 190 200 210 220 230 240 ARKIFRECDH SQTDSLEDEE IEAFYKMLTQ RVEIDRTFAE AAGSGETLSV DQLVTFLQHQ 250 260 270 280 290 300 QREEAAGPAL ALSLIERYEP SETAKAQRQM TKDGFLMYLL SADGSAFSLA HRRVYQDMGQ 310 320 330 340 350 360 PLSHYLVSSS HNTYLLEDQL AGPSSTEAYI RALCKGCRCL ELDCWDGPNQ EPIIYHGYTF 370 380 390 400 410 420 TSKILFCDVL RAIRDYAFKA SPYPVILSLE NHCTLEQQRV MARHLHAILG PMLLNRPLDG 430 440 450 460 470 480 VTNSLPSPEQ LKGKILLKGK KLGGLLPPGG EGGPEATVVS DEDEAAEMED EAVRSRVQHK 490 500 510 520 530 540 PKEDKLRLAQ ELSDMVIYCK SVHFGGFSSP GTPGQAFYEM ASFSENRALR LLQESGNGFV 550 560 570 580 590 600 RHNVGHLSRI YPAGWRTDSS NYSPVEMWNG GCQIVALNFQ TPGPEMDVYQ GRFQDNGACG 610 620 630 640 650 660 YVLKPAFLRD PNGTFNPRAL AQGPWWARKR LNIRVISGQQ LPKVNKNKNS IVDPKVTVEI 670 680 690 700 710 720 HGVSRDVASR QTAVITNNGF NPWWDTEFAF EVVVPDLALI RFLVEDYDAS SKNDFIGQST 730 740 750 IPLNSLKQGY RHVHLMSKNG DQHPSATLFV KISLQD
	Isoform 2 [UniParc]. Checksum: 6260C76BE397266B	FASTA	777	88,135
	10 20 30 40 50 60 MQCLGIRSRS RSRELYLQER SLKVAALNGR RLGLQDDEDL QALLKGSQLL KVKSSSWRRE 70 80 90 100 110 120 RFYKLQEDCK TIWQESRKVM RTPESQLFSI EDIQEVRMGH RTEGLEKFAR DVPEDRCFSI 130 140 150 160 170 180 VFKDQRNTLD LIAPSPADAQ HWVLGLHKII HHSGSMDQRQ KLQHWIHSCL RKADKNKDNK 190 200 210 220 230 240 MSFKELQNFL KELNIQVDDS YARKIFRECD HSQTDSLEDE EIEAFYKMLT QRVEIDRTFA 250 260 270 280 290 300 EAAGSGETLS VDQLVTFLQH QQREEAAGPA LALSLIERYE PSETAKAQRQ MTKDGFLMYL 310 320 330 340 350 360 LSADGSAFSL AHRRVYQDMG QPLSHYLVSS SHNTYLLEDQ LAGPSSTEAY IRALCKGCRC 370 380 390 400 410 420 LELDCWDGPN QEPIIYHGYT FTSKILFCDV LRAIRDYAFK ASPYPVILSL ENHCTLEQQR 430 440 450 460 470 480 VMARHLHAIL GPMLLNRPLD GVTNSLPSPE QLKGKILLKG KKLGGLLPPG GEGGPEATVV 490 500 510 520 530 540 SDEDEAAEME DEAVRSRVQH KPKEDKLRLA QELSDMVIYC KSVHFGGFSS PGTPGQAFYE 550 560 570 580 590 600 MASFSENRAL RLLQESGNGF VRHNVGHLSR IYPAGWRTDS SNYSPVEMWN GGCQIVALNF 610 620 630 640 650 660 QTPGPEMDVY QGRFQDNGAC GYVLKPAFLR DPNGTFNPRA LAQGPWWARK RLNIRVISGQ 670 680 690 700 710 720 QLPKVNKNKN SIVDPKVTVE IHGVSRDVAS RQTAVITNNG FNPWWDTEFA FEVVVPDLAL 730 740 750 760 770 IRFLVEDYDA SSKNDFIGQS TIPLNSLKQG YRHVHLMSKN GDQHPSATLF VKISLQD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and identification of amino acid residues of human phospholipase C delta 1 essential for catalysis." Cheng H.F., Jiang M.J., Chen C.L., Liu S.M., Wong L.P., Lomasney J.W., King K. J. Biol. Chem. 270:5495-5505(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Aorta.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Amygdala.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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.
[6]	"Hereditary leukonychia, or porcelain nails, resulting from mutations in PLCD1." Kiuru M., Kurban M., Itoh M., Petukhova L., Shimomura Y., Wajid M., Christiano A.M. Am. J. Hum. Genet. 88:839-844(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NDNC3 ARG-209 AND THR-574.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U09117 mRNA. Translation: AAA73567.1. AK090774 mRNA. Translation: BAG52226.1. AC144536 Genomic DNA. No translation available. CH471055 Genomic DNA. Translation: EAW64507.1. BC050382 mRNA. Translation: AAH50382.2.
IPI	IPI00016461. IPI00746030.
PIR	A55943.
RefSeq	NP_001124436.1. NM_001130964.1. NP_006216.2. NM_006225.3.
UniGene	Hs.80776.
3D structure databases
ProteinModelPortal	P51178.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-107564.
STRING	9606.ENSP00000409572.
PTM databases
PhosphoSite	P51178.
Polymorphism databases
DMDM	206729887.
2D gel databases
REPRODUCTION-2DPAGE	IPI00746030.
Proteomic databases
PaxDb	P51178.
PRIDE	P51178.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334661; ENSP00000335600; ENSG00000187091. ENST00000463876; ENSP00000430344; ENSG00000187091.
GeneID	5333.
KEGG	hsa:5333.
UCSC	uc003chn.3. human.
Organism-specific databases
CTD	5333.
GeneCards	GC03M038023.
H-InvDB	HIX0003175.
HGNC	HGNC:9060. PLCD1.
HPA	CAB009913. HPA020107. HPA021677.
MIM	151600. phenotype. 602142. gene.
neXtProt	NX_P51178.
Orphanet	2387. Leukonychia totalis.
PharmGKB	PA33388.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG149692.
HOGENOM	HOG000006871.
HOVERGEN	HBG053610.
KO	K05857.
OMA	MGHRTEG.
OrthoDB	EOG4H19V6.
PhylomeDB	P51178.
Enzyme and pathway databases
BioCyc	MetaCyc:HS07195-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
Bgee	P51178.
CleanEx	HS_PLCD1.
Genevestigator	P51178.
GermOnline	ENSG00000187091. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 2 hits. 2.30.29.30. 1 hit. 3.20.20.190. 2 hits.
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. IPR002048. EF_hand_dom. IPR011993. PH_like_dom. 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]
PANTHER	PTHR10336. PTHR10336. 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. 2 hits. 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. 2 hits. PS50222. EF_HAND_2. 2 hits. PS50003. PH_DOMAIN. 1 hit. PS50007. PIPLC_X_DOMAIN. 1 hit. PS50008. PIPLC_Y_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P51178.
ChEMBL	CHEMBL3727.
GenomeRNAi	5333.
NextBio	20654.
SOURCE	Search...

Entry information

Entry name

PLCD1_HUMAN

Accession

Primary (citable) accession number: P51178
Secondary accession number(s): B3KR14, Q86VN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	September 23, 2008
Last modified:	May 1, 2013
This is version 138 of the entry and version 2 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.