Reviewed,
UniProtKB/Swiss-Prot Q8K4S1 (PLCE1_MOUSE)
Last modified
February 9, 2010.
Version 63.
History...
Clusters with 100%,
90%,
50% identity |
Documents (2) |
Third-party data |
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Names and origin
| Protein names | Recommended name: 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1 EC=3.1.4.11 Alternative name(s): Phosphoinositide phospholipase C-epsilon-1 Phospholipase C-epsilon-1 Short name=PLC-epsilon-1 | ||||
| Gene names |
| ||||
| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 2282 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. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. Ref.6 Ref.7 Ref.8 Ref.9 |
| Catalytic activity | 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. Ref.1 |
| Cofactor | Calcium By similarity. |
| Enzyme regulation | Activated by the heterotrimeric G-protein subunits GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by G(i)-coupled GPCRs By similarity. |
| Subunit structure | Interacts with GTP-bound HRAS, RAP1A, RAP2A, RAP2B and RHOA By similarity. Interacts with IQGAP1. Ref.10 |
| Subcellular location | Cytoplasm › cytosol By similarity. Cell membrane By similarity. Golgi apparatus membrane By similarity. Note: Recruited to plasma membrane by activated HRAS and RAP2. Recruited to perinuclear membrane by activated RAP1A. Associates with Golgi membranes By similarity. |
| Tissue specificity | Highly expressed in neurons and to a lower extent in skin, skeletal muscle and heart (at protein level). Expressed in the epidermis. Ref.7 Ref.9 |
| Developmental stage | Specifically expressed in cells committed to the neuronal lineage (at protein level). Weakly expressed at E7, expression strongly increases at later embryonic stages. Expressed abundantly in almost all neural tissues at E12.5 and also detected in tongue muscles, genital tubercle and hand plate. At E15.5 a strong expression in skeletal muscles is detected together with the strong expression in neural tissues. Ref.1 |
| Induction | Up-regulated during the differentiation of neural precursor cells into neurons and not glial cells. Up-regulated in heart upon induced hypertrophy. Ref.8 Ref.1 |
| Domain | The Ras-associating domain 1 is degenerated and may not bind HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell membrane By similarity. The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway By similarity. |
| Disruption phenotype | Mice exhibit delayed onset and markedly reduced incidence of chemically induced skin squamous tumors. They also display cardiac malformations which mainly affects aortic and pulmonary valves and enhanced susceptibility to cardiac hypertrophy and fibrosis in response to chronic stress. Ref.7 Ref.9 |
| Sequence similarities | Contains 1 C2 domain. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain. Contains 2 Ras-associating domains. Contains 1 Ras-GEF domain. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q8K4S1-1) 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: Q8K4S1-2) The sequence of this isoform differs from the canonical sequence as follows: 1-1150: Missing. 1151-1165: TAGSPNLATGMSSPI → MAWGLHLPVTAMFLC | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2282 | 2282 | 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1 | PRO_0000256239 | |||||
Regions | |||||||||
| Domain | 528 – 781 | 254 | Ras-GEF | ||||||
| Domain | 1373 – 1521 | 149 | PI-PLC X-box | ||||||
| Domain | 1710 – 1826 | 117 | PI-PLC Y-box | ||||||
| Domain | 1836 – 1936 | 101 | C2 | ||||||
| Domain | 1992 – 2094 | 103 | Ras-associating 1 | ||||||
| Domain | 2115 – 2218 | 104 | Ras-associating 2 | ||||||
| Region | 1667 – 1744 | 78 | Required for activation by RHOA, RHOB, GNA12, GNA13 and G-beta gamma By similarity | ||||||
Sites | |||||||||
| Active site | 1388 | 1 | By similarity | ||||||
| Active site | 1433 | 1 | By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 1150 | 1150 | Missing in isoform 2. | VSP_021337 | |||||
| Alternative sequence | 1151 – 1165 | 15 | TAGSP…MSSPI → MAWGLHLPVTAMFLC in isoform 2. | VSP_021338 | |||||
Experimental info | |||||||||
| Sequence conflict | 1798 | 1 | T → A in AAF40208. Ref.4 | ||||||
| Sequence conflict | 1829 | 1 | S → N in AAF40208. Ref.4 | ||||||
| Sequence conflict | 2215 – 2217 | 3 | LKE → VKD in BAC29099. Ref.2 | ||||||
| Sequence conflict | 2233 | 1 | A → G in BAC29099. Ref.2 | ||||||
| Sequence conflict | 2236 | 1 | L → V in BAC29099. Ref.2 | ||||||
| Sequence conflict | 2239 | 1 | L → V in BAC29099. Ref.2 | ||||||
| Sequence conflict | 2275 | 1 | S → T in BAC29099. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Neuronal lineage-specific induction of phospholipase Cepsilon expression in the developing mouse brain." Wu D., Tadano M., Edamatsu H., Masago-Toda M., Yamawaki-Kataoka Y., Terashima T., Mizoguchi A., Minami Y., Satoh T., Kataoka T. Eur. J. Neurosci. 17:1571-1580(2003) [PubMed: 12752375] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, INDUCTION. Tissue: Embryo. |
| [2] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Egg and Urinary bladder. |
| [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] | "A novel transgenic marker for migrating limb muscle precursors and for vascular smooth muscle cells." Tidhar A., Reichenstein M., Cohen D., Faerman A., Copeland N.G., Gilbert D.J., Jenkins N.A., Shani M. Dev. Dyn. 220:60-73(2001) [PubMed: 11146508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 919-2282 (ISOFORMS 1/2). |
| [5] | "Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H. DNA Res. 10:35-48(2003) [PubMed: 12693553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 919-2282 (ISOFORMS 1/2). Tissue: Brain. |
| [6] | "Activation of CD4 T cells by Raf-independent effectors of Ras." Czyzyk J., Brogdon J.L., Badou A., Henegariu O., Preston Hurlburt P., Flavell R., Bottomly K. Proc. Natl. Acad. Sci. U.S.A. 100:6003-6008(2003) [PubMed: 12721365] [Abstract] Cited for: FUNCTION. |
| [7] | "Crucial role of phospholipase Cepsilon in chemical carcinogen-induced skin tumor development." Bai Y., Edamatsu H., Maeda S., Saito H., Suzuki N., Satoh T., Kataoka T. Cancer Res. 64:8808-8810(2004) [PubMed: 15604236] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE. |
| [8] | "Phospholipase C epsilon modulates beta-adrenergic receptor-dependent cardiac contraction and inhibits cardiac hypertrophy." Wang H., Oestreich E.A., Maekawa N., Bullard T.A., Vikstrom K.L., Dirksen R.T., Kelley G.G., Blaxall B.C., Smrcka A.V. Circ. Res. 97:1305-1313(2005) [PubMed: 16293787] [Abstract] Cited for: FUNCTION, INDUCTION. |
| [9] | "Congenital semilunar valvulogenesis defect in mice deficient in phospholipase C epsilon." Tadano M., Edamatsu H., Minamisawa S., Yokoyama U., Ishikawa Y., Suzuki N., Saito H., Wu D., Masago-Toda M., Yamawaki-Kataoka Y., Setsu T., Terashima T., Maeda S., Satoh T., Kataoka T. Mol. Cell. Biol. 25:2191-2199(2005) [PubMed: 15743817] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE. |
| [10] | "Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible." Hinkes B., Wiggins R.C., Gbadegesin R., Vlangos C.N., Seelow D., Nuernberg G., Garg P., Verma R., Chaib H., Hoskins B.E., Ashraf S., Becker C., Hennies H.C., Goyal M., Wharram B.L., Schachter A.D., Mudumana S., Drummond I. Hildebrandt F.Nat. Genet. 38:1397-1405(2006) [PubMed: 17086182] [Abstract] Cited for: INTERACTION WITH IQGAP1. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AB076247 mRNA. Translation: BAC00906.1. AK035546 mRNA. Translation: BAC29099.1. AK162236 mRNA. Translation: BAE36807.1. BC138349 mRNA. Translation: AAI38350.1. BC138350 mRNA. Translation: AAI38351.1. AF233885 mRNA. Translation: AAF40208.1. Different initiation. AK122521 mRNA. Translation: BAC65803.1. |
| IPI | IPI00170268. IPI00798586. |
| RefSeq | NP_062534.2. |
| UniGene | Mm.34031 |
3D structure databases | |
| HSSP | HSSP built from PDB template 2C5L based on UniProtKB Q9UHV3. |
| SMR | Q8K4S1. Positions 528-827, 1309-1966, 1986-2094, 2111-2226. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q8K4S1. |
PTM databases | |
| PhosphoSite | Q8K4S1. |
Proteomic databases | |
| PRIDE | Q8K4S1. |
Genome annotation databases | |
| Ensembl | ENSMUST00000025962; ENSMUSP00000025962; ENSMUSG00000024998; Mus musculus. [Genome view] |
| GeneID | 74055. |
| KEGG | mmu:74055. |
| UCSC | uc008hjp.1. mouse. uc008hjq.1. mouse. |
Organism-specific databases | |
| CTD | 74055. |
| MGI | MGI:1921305. Plce1. |
| Rouge | Search... |
Phylogenomic databases | |
| eggNOG | roNOG11704. |
| HOVERGEN | Q8K4S1. |
| InParanoid | Q8K4S1. |
| PhylomeDB | Q8K4S1. |
Enzyme and pathway databases | |
| BRENDA | 3.1.4.11. 244. |
Gene expression databases | |
| ArrayExpress | Q8K4S1. |
| Bgee | Q8K4S1. |
| CleanEx | MM_PLCE1. |
| Genevestigator | Q8K4S1. |
| GermOnline | ENSMUSG00000024998. Mus musculus. |
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. IPR015359. Phospholipase_C_EF-hand-like. IPR001192. Phospholipase_C_Pinositol-sp_C. IPR001711. Phospholipase_C_Pinositol-sp_Y. IPR017946. PLC-like_Pdiesterase_TIM-brl. IPR000909. PLipase_C_PInositol-sp_X_dom. IPR000159. Ras-assoc. IPR008937. Ras_GEF. IPR001895. RasGRF_CDC25. [Graphical view] |
| Gene3D | G3DSA:1.10.238.10. EF-Hand_type. 1 hit. G3DSA:3.20.20.190. PLC-like_Pdiesterase_TIM-brl. 2 hits. G3DSA:1.10.840.10. RasGRF_CDC25. 1 hit. |
| Pfam | PF00168. C2. 1 hit. PF09279. efhand_like. 1 hit. PF00388. PI-PLC-X. 1 hit. PF00387. PI-PLC-Y. 1 hit. PF00788. RA. 1 hit. PF00617. RasGEF. 1 hit. [Graphical view] |
| PRINTS | PR00390. PHPHLIPASEC. |
| SMART | SM00239. C2. 1 hit. SM00148. PLCXc. 1 hit. SM00149. PLCYc. 1 hit. SM00314. RA. 1 hit. SM00147. RasGEF. 1 hit. [Graphical view] |
| PROSITE | PS50004. C2. 1 hit. PS50007. PIPLC_X_DOMAIN. 1 hit. PS50008. PIPLC_Y_DOMAIN. 1 hit. PS50200. RA. 1 hit. PS00720. RASGEF. False negative. PS50009. RASGEF_CAT. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 339656. |
| SOURCE | Search... |
Entry information
| Entry name | PLCE1_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q8K4S1 Secondary accession number(s): B9EHS1 Q9JKM2 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


