PLCE1

Protein identityUniProt · HPA

UniProt accession

Q9P212

Gene

PLCE1

Ensembl

ENSG00000138193

Chromosome

10

Canonical length

2302 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, RAS pathway related proteins

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

2302 residues, UniProt reviewed canonical sequence.

>Q9P212|PLCE1
     1  MTSEEMTASV LIPVTQRKVV SAQSAADESS EKVSDINISK AHTVRRSGET SHTISQLNKL
    61  KEEPSGSNLP KILSIAREKI VSDENSNEKC WEKIMPDSAK NLNINCNNIL RNHQHGLPQR
   121  QFYEMYNSVA EEDLCLETGI PSPLERKVFP GIQLELDRPS MGISPLGNQS VIIETGRAHP
   181  DSRRAVFHFH YEVDRRMSDT FCTLSENLIL DDCGNCVPLP GGEEKQKKNY VAYTCKLMEL
   241  AKNCDNKNEQ LQCDHCDTLN DKYFCFEGSC EKVDMVYSGD SFCRKDFTDS QAAKTFLSHF
   301  EDFPDNCDDV EEDAFKSKKE RSTLLVRRFC KNDREVKKSV YTGTRAIVRT LPSGHIGLTA
   361  WSYIDQKRNG PLLPCGRVME PPSTVEIRQD GSQRLSEAQW YPIYNAVRRE ETENTVGSLL
   421  HFLTKLPASE TAHGRISVGP CLKQCVRDTV CEYRATLQRT SISQYITGSL LEATTSLGAR
   481  SGLLSTFGGS TGRMMLKERQ PGPSVANSNA LPSSSAGISK ELIDLQPLIQ FPEEVASILM
   541  EQEQTIYRRV LPVDYLCFLT RDLGTPECQS SLPCLKASIS ASILTTQNGE HNALEDLVMR
   601  FNEVSSWVTW LILTAGSMEE KREVFSYLVH VAKCCWNMGN YNAVMEFLAG LRSRKVLKMW
   661  QFMDQSDIET MRSLKDAMAQ HESSCEYRKV VTRALHIPGC KVVPFCGVFL KELCEVLDGA
   721  SGLMKLCPRY NSQEETLEFV ADYSGQDNFL QRVGQNGLKN SEKESTVNSI FQVIRSCNRS
   781  LETDEEDSPS EGNSSRKSSL KDKSRWQFII GDLLDSDNDI FEQSKEYDSH GSEDSQKAFD
   841  HGTELIPWYV LSIQADVHQF LLQGATVIHY DQDTHLSARC FLQLQPDNST LTWVKPTTAS
   901  PASSKAKLGV LNNTAEPGKF PLLGNAGLSS LTEGVLDLFA VKAVYMGHPG IDIHTVCVQN
   961  KLGSMFLSET GVTLLYGLQT TDNRLLHFVA PKHTAKMLFS GLLELTRAVR KMRKFPDQRQ
  1021  QWLRKQYVSL YQEDGRYEGP TLAHAVELFG GRRWSARNPS PGTSAKNAEK PNMQRNNTLG
  1081  ISTTKKKKKI LMRGESGEVT DDEMATRKAK MHKECRSRSG SDPQDINEQE ESEVNAIANP
  1141  PNPLPSRRAH SLTTAGSPNL AAGTSSPIRP VSSPVLSSSN KSPSSAWSSS SWHGRIKGGM
  1201  KGFQSFMVSD SNMSFVEFVE LFKSFSVRSR KDLKDLFDVY AVPCNRSGSE SAPLYTNLTI
  1261  DENTSDLQPD LDLLTRNVSD LGLFIKSKQQ LSDNQRQISD AIAAASIVTN GTGIESTSLG
  1321  IFGVGILQLN DFLVNCQGEH CTYDEILSII QKFEPSISMC HQGLMSFEGF ARFLMDKENF
  1381  ASKNDESQEN IKELQLPLSY YYIESSHNTY LTGHQLKGES SVELYSQVLL QGCRSVELDC
  1441  WDGDDGMPII YHGHTLTTKI PFKEVVEAID RSAFINSDLP IIISIENHCS LPQQRKMAEI
  1501  FKTVFGEKLV TKFLFETDFS DDPMLPSPDQ LRKKVLLKNK KLKAHQTPVD ILKQKAHQLA
  1561  SMQVQAYNGG NANPRPANNE EEEDEEDEYD YDYESLSDDN ILEDRPENKS CNDKLQFEYN
  1621  EEIPKRIKKA DNSACNKGKV YDMELGEEFY LDQNKKESRQ IAPELSDLVI YCQAVKFPGL
  1681  STLNASGSSR GKERKSRKSI FGNNPGRMSP GETASFNKTS GKSSCEGIRQ TWEESSSPLN
  1741  PTTSLSAIIR TPKCYHISSL NENAAKRLCR RYSQKLTQHT ACQLLRTYPA ATRIDSSNPN
  1801  PLMFWLHGIQ LVALNYQTDD LPLHLNAAMF EANGGCGYVL KPPVLWDKNC PMYQKFSPLE
  1861  RDLDSMDPAV YSLTIVSGQN VCPSNSMGSP CIEVDVLGMP LDSCHFRTKP IHRNTLNPMW
  1921  NEQFLFHVHF EDLVFLRFAV VENNSSAVTA QRIIPLKALK RGYRHLQLRN LHNEVLEISS
  1981  LFINSRRMEE NSSGNTMSAS SMFNTEERKC LQTHRVTVHG VPGPEPFTVF TINGGTKAKQ
  2041  LLQQILTNEQ DIKPVTTDYF LMEEKYFISK EKNECRKQPF QRAIGPEEEI MQILSSWFPE
  2101  EGYMGRIVLK TQQENLEEKN IVQDDKEVIL SSEEESFFVQ VHDVSPEQPR TVIKAPRVST
  2161  AQDVIQQTLC KAKYSYSILS NPNPSDYVLL EEVVKDTTNK KTTTPKSSQR VLLDQECVFQ
  2221  AQSKWKGAGK FILKLKEQVQ ASREDKKKGI SFASELKKLT KSTKQPRGLT SPSQLLTSES
  2281  IQTKEEKPVG GLSSSDTMDY RQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLCE1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.44

Highest tissue expression

7.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PLCE1.

Disease | AllUniProt

Conditions PLCE1 is implicated in, by any mechanism.

• Nephrotic syndrome 3 (NPHS3) MIM:610725

Disease | GeneticClinVar

64 pathogenic / likely-pathogenic of 1,011 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Nephrotic syndrome, type 3
• Nephrotic syndrome
• PLCE1-related disorder
• Focal segmental glomerulosclerosis
• Finnish congenital nephrotic syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.46

gnomAD pLI

0

gnomAD missense Z

1.38

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium-mediated signaling
• diacylglycerol biosynthetic process
• epidermal growth factor receptor signaling pathway
• G protein-coupled receptor signaling pathway
• glomerulus development
• intracellular signal transduction
• lipid catabolic process
• phosphatidylinositol metabolic process
• phosphatidylinositol-mediated signaling
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of lamellipodium assembly
• Ras protein signal transduction
• release of sequestered calcium ion into cytosol

Molecular functions

• enzyme binding
• guanyl-nucleotide exchange factor activity
• metal ion binding
• phosphatidylinositol-4,5-bisphosphate phospholipase C activity
• phospholipase C activity
• small GTPase binding

Cellular components

• cytosol
• Golgi membrane
• lamellipodium
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• C2 domain
• Ras-associating domain
• Phosphatidylinositol-specific phospholipase C, X domain
• Phosphoinositide phospholipase C family
• Phospholipase C, phosphatidylinositol-specific, Y domain
• Ras guanine-nucleotide exchange factors catalytic domain
• EF-hand domain pair
• Phosphoinositide-specific phospholipase C, EF-hand-like domain
• PLC-like phosphodiesterase, TIM beta/alpha-barrel domain superfamily
• Ras guanine nucleotide exchange factor domain superfamily
• Ubiquitin-like domain superfamily
• C2 domain superfamily
• Ras guanine-nucleotide exchange factor, catalytic domain superfamily
• C2 domain
• Phosphatidylinositol-specific phospholipase C, Y domain
• Phosphatidylinositol-specific phospholipase C, X domain
• RasGEF domain
• Ras association (RalGDS/AF-6) domain
• Phosphoinositide-specific phospholipase C, efhand-like
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, RA domain 2
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, catalytic domain
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, EF-hand domain

KeywordsUniProt

• Calcium
• Cell membrane
• Cell projection
• Cytoplasm
• Golgi apparatus
• Guanine-nucleotide releasing factor
• Hydrolase
• Lipid degradation
• Lipid metabolism
• Membrane
• Metal-binding
• Phosphoprotein
• Repeat
• Transducer

InteractionsUniProt · HPA

Protein binding partners of PLCE1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AVIL
• IQGAP1
• RAP1A
• RAP2A
• RAP2B
• RHOA
• RRAS
• HRAS