Details of the Target

General Information of Target

Target ID LDTP05727
Target Name Secretory phospholipase A2 receptor (PLA2R1)
Gene Name PLA2R1
Gene ID 22925
Synonyms
CLEC13C; Secretory phospholipase A2 receptor; PLA2-R; PLA2R; 180 kDa secretory phospholipase A2 receptor; C-type lectin domain family 13 member C; M-type receptor) [Cleaved into: Soluble secretory phospholipase A2 receptor; Soluble PLA2-R; Soluble PLA2R)]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLLSPSLLLLLLLGAPRGCAEGVAAALTPERLLEWQDKGIFVIQSESLKKCIQAGKSVLT
LENCKQANKHMLWKWVSNHGLFNIGGSGCLGLNFSAPEQPLSLYECDSTLVSLRWRCNRK
MITGPLQYSVQVAHDNTVVASRKYIHKWISYGSGGGDICEYLHKDLHTIKGNTHGMPCMF
PFQYNHQWHHECTREGREDDLLWCATTSRYERDEKWGFCPDPTSAEVGCDTIWEKDLNSH
ICYQFNLLSSLSWSEAHSSCQMQGGTLLSITDETEENFIREHMSSKTVEVWMGLNQLDEH
AGWQWSDGTPLNYLNWSPEVNFEPFVEDHCGTFSSFMPSAWRSRDCESTLPYICKKYLNH
IDHEIVEKDAWKYYATHCEPGWNPYNRNCYKLQKEEKTWHEALRSCQADNSALIDITSLA
EVEFLVTLLGDENASETWIGLSSNKIPVSFEWSNDSSVIFTNWHTLEPHIFPNRSQLCVS
AEQSEGHWKVKNCEERLFYICKKAGHVLSDAESGCQEGWERHGGFCYKIDTVLRSFDQAS
SGYYCPPALVTITNRFEQAFITSLISSVVKMKDSYFWIALQDQNDTGEYTWKPVGQKPEP
VQYTHWNTHQPRYSGGCVAMRGRHPLGRWEVKHCRHFKAMSLCKQPVENQEKAEYEERWP
FHPCYLDWESEPGLASCFKVFHSEKVLMKRTWREAEAFCEEFGAHLASFAHIEEENFVNE
LLHSKFNWTEERQFWIGFNKRNPLNAGSWEWSDRTPVVSSFLDNTYFGEDARNCAVYKAN
KTLLPLHCGSKREWICKIPRDVKPKIPFWYQYDVPWLFYQDAEYLFHTFASEWLNFEFVC
SWLHSDLLTIHSAHEQEFIHSKIKALSKYGASWWIGLQEERANDEFRWRDGTPVIYQNWD
TGRERTVNNQSQRCGFISSITGLWGSEECSVSMPSICKRKKVWLIEKKKDTPKQHGTCPK
GWLYFNYKCLLLNIPKDPSSWKNWTHAQHFCAEEGGTLVAIESEVEQAFITMNLFGQTTS
VWIGLQNDDYETWLNGKPVVYSNWSPFDIINIPSHNTTEVQKHIPLCALLSSNPNFHFTG
KWYFEDCGKEGYGFVCEKMQDTSGHGVNTSDMYPMPNTLEYGNRTYKIINANMTWYAAIK
TCLMHKAQLVSITDQYHQSFLTVVLNRLGYAHWIGLFTTDNGLNFDWSDGTKSSFTFWKD
EESSLLGDCVFADSNGRWHSTACESFLQGAICHVPPETRQSEHPELCSETSIPWIKFKSN
CYSFSTVLDSMSFEAAHEFCKKEGSNLLTIKDEAENAFLLEELFAFGSSVQMVWLNAQFD
GNNETIKWFDGTPTDQSNWGIRKPDTDYFKPHHCVALRIPEGLWQLSPCQEKKGFICKME
ADIHTAEALPEKGPSHSIIPLAVVLTLIVIVAICTLSFCIYKHNGGFFRRLAGFRNPYYP
ATNFSTVYLEENILISDLEKSDQ
Target Type
Patented-recorded
Target Bioclass
Other
Subcellular location
Secreted; Cell membrane
Function
Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phospholipase sPLA2-IB/PLA2G1B but not sPLA2-IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in pro-inflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B. In podocytes, binding of sPLA2-IB/PLA2G1B can regulate podocyte survival and glomerular homeostasis.
TTD ID
T46702
Uniprot ID
Q13018
DrugMap ID
TTHKW7D
Ensemble ID
ENST00000283243.13
HGNC ID
HGNC:9042
ChEMBL ID
CHEMBL3713395

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A172 SNV: p.W519S .
BICR22 SNV: p.R732K .
CASKI SNV: p.D900H .
G361 SNV: p.E1245Q .
HT115 SNV: p.F838C .
IPC298 SNV: p.P1400L .
JVM3 SNV: p.I241N .
KELLY SNV: p.C1247Y .
KMCH1 SNV: p.T1019S .
MDAMB231 SNV: p.D307H; p.T1109I .
NCIH2291 SNV: p.G747C .
OVK18 SNV: p.K868N .
RKO SNV: p.S567G; p.K1089N .
SKMEL30 SNV: p.W1173Ter .
SNGM Deletion: p.A653QfsTer35
SNV: p.I806T		 .
SUPT1 SNV: p.A301T .
SW1783 SNV: p.Q988Ter .
UACC257 SNV: p.A704V .
UACC62 SNV: p.G956E .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IA-alkyne
 Probe Info  		C1354(1.09)  LDD0304  [1]
BTD
 Probe Info  		C51(0.71)  LDD2089  [2]
N1
 Probe Info  		M1133(0.00); W1135(0.00)  LDD0245  [3]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info  		N.A.  LDD0136  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0538  4-(Cyanoacetyl)morpholine MDA-MB-231 C51(0.74)  LDD2131  [2]
 LDCM0528  N-(4-bromophenyl)-2-cyano-N-phenylacetamide MDA-MB-231 C51(0.78)  LDD2121  [2]
 LDCM0496  Nucleophilic fragment 11a MDA-MB-231 C51(0.71)  LDD2089  [2]
 LDCM0513  Nucleophilic fragment 19b MDA-MB-231 C51(0.50)  LDD2106  [2]
 LDCM0131  RA190 MM1.R C1354(1.09)  LDD0304  [1]

References

1 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
4 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.