UniProtKB - Q3MJ16 (PA24E_HUMAN)
Protein
Cytosolic phospholipase A2 epsilon
Gene
PLA2G4E
Organism
Homo sapiens (Human)
Status
Functioni
Calcium-dependent N-acyltransferase involved in the biosynthesis of N-acyl ethanolamines (NAEs) in the brain (PubMed:29447909). Transfers the sn-1 fatty acyl chain of phosphatidylcholine (fatty acyl donor) to the amine group of phosphatidylethanolamine (fatty acyl acceptor) to generate N-acyl phosphatidylethanolamine (NAPE). Similarly can use plasmenylethanolamine as a fatty acyl acceptor to form N-acyl plasmenylethanolamine (N-Acyl-PlsEt). Both NAPE and N-Acyl-PlsEt can serve as precursors of bioactive NAEs like N-arachidonoyl phosphatidylethanolamine also called anandamide (PubMed:29447909, PubMed:30517655). Has weak phospholipase A2 and lysophospholipase activities (By similarity). Regulates intracellular membrane trafficking that requires modulation of membrane curvature as it occurs by enrichment in lysophospholipids. Promotes tubule formation involved in clathrin-independent endocytotic trafficking and cargo recycling (By similarity).By similarity2 Publications
Catalytic activityi
- a 1,2-diacyl-sn-glycero-3-phosphocholine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine = a 2-acyl-sn-glycero-3-phosphocholine + H+ + N-acyl-1,2-diacyl-sn-glycero-3-phosphoethanolamine2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine = 2-octadecanoyl-sn-glycero-3-phosphocholine + H+ + N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + 1-octadecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine = 2-hexadecanoyl-sn-glycero-3-phosphocholine + H+ + N-octadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine = 2-hexadecanoyl-sn-glycero-3-phosphocholine + H+ + N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine = 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H+ + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H+ + N,1,2-tri-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + 1-(1Z-octadecenyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine = 1-(1Z-octadecenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-N-hexadecanoyl-ethanolamine + 2-hexadecanoyl-sn-glycero-3-phosphocholine + H+By similarityThis reaction proceeds in the forwardBy similarity direction.
- a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H+By similarityEC:3.1.1.4By similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+By similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H+ + hexadecanoate + sn-glycerol 3-phosphocholineBy similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Ca2+PROSITE-ProRule annotation1 Publication
Activity regulationi
Stimulated by cytosolic Ca2+. Stimulated by anionic phospholipids such as phosphatidylserines, phosphatidates and phosphatidylinositols.2 Publications
pH dependencei
Optimum pH is 8.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 84 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 84 | Calcium 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 90 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 140 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 140 | Calcium 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 142 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 142 | Calcium 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 148 | Calcium 2PROSITE-ProRule annotation | 1 | |
Active sitei | 412 | NucleophileBy similarity | 1 | |
Active sitei | 700 | Proton acceptorBy similarity | 1 |
GO - Molecular functioni
- calcium-dependent phospholipase A2 activity Source: GO_Central
- calcium-dependent phospholipid binding Source: GO_Central
- calcium ion binding Source: GO_Central
- N-acyltransferase activity Source: UniProtKB
- phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
- phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
- phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
- phosphatidylinositol-3-phosphate binding Source: UniProtKB
- phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
- phosphatidylinositol-4-phosphate binding Source: UniProtKB
- phosphatidylinositol-5-phosphate binding Source: UniProtKB
- phospholipase A2 activity Source: GO_Central
- phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine) Source: UniProtKB-EC
- phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine) Source: UniProtKB-EC
GO - Biological processi
- glycerophospholipid catabolic process Source: GO_Central
- N-acylphosphatidylethanolamine metabolic process Source: UniProtKB
- phosphatidylcholine acyl-chain remodeling Source: Reactome
- phosphatidylethanolamine acyl-chain remodeling Source: Reactome
- phosphatidylinositol acyl-chain remodeling Source: Reactome
- phosphatidylserine acyl-chain remodeling Source: Reactome
- phospholipid metabolic process Source: Reactome
- positive regulation of endocytic recycling Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Transferase |
Biological process | Lipid degradation, Lipid metabolism |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q3MJ16 |
Reactomei | R-HSA-1482788, Acyl chain remodelling of PC R-HSA-1482801, Acyl chain remodelling of PS R-HSA-1482839, Acyl chain remodelling of PE R-HSA-1482922, Acyl chain remodelling of PI R-HSA-1483115, Hydrolysis of LPC |
Names & Taxonomyi
Protein namesi | Recommended name: Cytosolic phospholipase A2 epsilon1 Publication (EC:3.1.1.4By similarity)Short name: cPLA2-epsilon1 Publication Alternative name(s): Calcium-dependent N-acyltransferase1 Publication Phospholipase A2 group IVE |
Gene namesi | Name:PLA2G4EImported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:24791, PLA2G4E |
neXtProti | NX_Q3MJ16 |
VEuPathDBi | HostDB:ENSG00000188089.13 |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol By similarity
Plasma membrane
- Cell membrane By similarity; Peripheral membrane protein ; Cytoplasmic side By similarity
Endosome
- Early endosome membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
Lysosome
- Lysosome membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
Note: Targeted to clathrin-independent endocytotic vesicles through binding to phosphoinositides, especially phosphatidylinositol 4,5-bisphosphates.By similarity
Cytosol
- cytosol Source: GO_Central
Endosome
- early endosome membrane Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Endosome, Lysosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 412 | S → A: Impairs localization at membrane structures and N-acyl transferase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 123745 |
OpenTargetsi | ENSG00000188089 |
Miscellaneous databases
Pharosi | Q3MJ16, Tdark |
Genetic variation databases
BioMutai | PLA2G4E |
DMDMi | 325511387 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000247025 | 1 – 868 | Cytosolic phospholipase A2 epsilonAdd BLAST | 868 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 800 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q3MJ16 |
jPOSTi | Q3MJ16 |
MassIVEi | Q3MJ16 |
PeptideAtlasi | Q3MJ16 |
PRIDEi | Q3MJ16 |
ProteomicsDBi | 61802 [Q3MJ16-2] 6312 |
PTM databases
PhosphoSitePlusi | Q3MJ16 |
Expressioni
Gene expression databases
Bgeei | ENSG00000188089, Expressed in zone of skin and 57 other tissues |
Organism-specific databases
HPAi | ENSG00000188089, Tissue enriched (skin) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 125832, 3 interactors |
IntActi | Q3MJ16, 3 interactors |
STRINGi | 9606.ENSP00000382434 |
Miscellaneous databases
RNActi | Q3MJ16, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 46 – 170 | C2PROSITE-ProRule annotationAdd BLAST | 125 | |
Domaini | 324 – 856 | PLA2cPROSITE-ProRule annotationAdd BLAST | 533 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 857 – 868 | Required for localization at membrane structures1 PublicationAdd BLAST | 12 |
Domaini
The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca2+ (By similarity).By similarity
Phylogenomic databases
eggNOGi | KOG1028, Eukaryota KOG1325, Eukaryota |
GeneTreei | ENSGT01000000214525 |
InParanoidi | Q3MJ16 |
OMAi | YELHMKS |
OrthoDBi | 302848at2759 |
PhylomeDBi | Q3MJ16 |
TreeFami | TF325228 |
Family and domain databases
CDDi | cd04036, C2_cPLA2, 1 hit |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR016035, Acyl_Trfase/lysoPLipase IPR041847, C2_cPLA2 IPR000008, C2_dom IPR035892, C2_domain_sf IPR040723, cPLA2_C2 IPR002642, LysoPLipase_cat_dom |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF18695, cPLA2_C2, 1 hit PF01735, PLA2_B, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00022, PLAc, 1 hit |
SUPFAMi | SSF52151, SSF52151, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS51210, PLA2C, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q3MJ16-3) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSLQASEGCP GLGTNVFVPQ SPQTDEEGSR SGRSFSEFED TQDLDTPGLP
60 70 80 90 100
PFCPMAPWGS EEGLSPCHLL TVRVIRMKNV RQADMLSQTD CFVSLWLPTA
110 120 130 140 150
SQKKLRTRTI SNCPNPEWNE SFNFQIQSRV KNVLELSVCD EDTVTPDDHL
160 170 180 190 200
LTVLYDLTKL CFRKKTHVKF PLNPQGMEEL EVEFLLEESP SPPETLVTNG
210 220 230 240 250
VLVSRQVSCL EVHAQSRRRR KREKMKDLLV MVNESFENTQ RVRPCLEPCC
260 270 280 290 300
PTSACFQTAA CFHYPKYFQS QVHVEVPKSH WSCGLCCRSR KKGPISQPLD
310 320 330 340 350
CLSDGQVMTL PVGESYELHM KSTPCPETLD VRLGFSLCPA ELEFLQKRKV
360 370 380 390 400
VVAKALKQVL QLEEDLQEDE VPLIAIMATG GGTRSMTSMY GHLLGLQKLN
410 420 430 440 450
LLDCASYITG LSGATWTMAT LYRDPDWSSK NLEPAIFEAR RHVVKDKLPS
460 470 480 490 500
LFPDQLRKFQ EELRQRSQEG YRVTFTDFWG LLIETCLGDE RNECKLSDQR
510 520 530 540 550
AALSCGQNPL PIYLTINVKD DVSNQDFREW FEFSPYEVGL QKYGAFIPSE
560 570 580 590 600
LFGSEFFMGR LVKRIPESRI CYMLGLWSSI FSLNLLDAWN LSHTSEEFFH
610 620 630 640 650
RWTREKVQDI EDEPILPEIP KCDANILETT VVIPGSWLSN SFREILTHRS
660 670 680 690 700
FVSEFHNFLS GLQLHTNYLQ NGQFSRWKDT VLDGFPNQLT ESANHLCLLD
710 720 730 740 750
TAFFVNSSYP PLLRPERKAD LIIHLNYCAG SQTKPLKQTC EYCTVQNIPF
760 770 780 790 800
PKYELPDENE NLKECYLMEN PQEPDAPIVT FFPLINDTFR KYKAPGVERS
810 820 830 840 850
PEELEQGQVD IYGPKTPYAT KELTYTEATF DKLVKLSEYN ILNNKDTLLQ
860
ALRLAVEKKK RLKGQCPS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 389 | M → V in BAC87034 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 502 | A → P in BAC87034 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 690 | T → A in BAC87034 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 765 | C → Y in BAC87034 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_027052 | 400 | N → S. Corresponds to variant dbSNP:rs4924595Ensembl. | 1 | |
Natural variantiVAR_027053 | 693 | A → T. Corresponds to variant dbSNP:rs8030775Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_019883 | 1 – 376 | Missing in isoform 2. 1 PublicationAdd BLAST | 376 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK127558 mRNA Translation: BAC87034.1 AC039056 Genomic DNA No translation available. BC101584 mRNA Translation: AAI01585.2 BC101612 mRNA Translation: AAI01613.2 |
CCDSi | CCDS55962.1 [Q3MJ16-3] |
RefSeqi | NP_001193599.1, NM_001206670.1 [Q3MJ16-3] XP_011519540.1, XM_011521238.1 [Q3MJ16-2] |
Genome annotation databases
Ensembli | ENST00000399518; ENSP00000382434; ENSG00000188089 [Q3MJ16-3] |
GeneIDi | 123745 |
KEGGi | hsa:123745 |
UCSCi | uc021sjp.2, human |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK127558 mRNA Translation: BAC87034.1 AC039056 Genomic DNA No translation available. BC101584 mRNA Translation: AAI01585.2 BC101612 mRNA Translation: AAI01613.2 |
CCDSi | CCDS55962.1 [Q3MJ16-3] |
RefSeqi | NP_001193599.1, NM_001206670.1 [Q3MJ16-3] XP_011519540.1, XM_011521238.1 [Q3MJ16-2] |
3D structure databases
SMRi | Q3MJ16 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 125832, 3 interactors |
IntActi | Q3MJ16, 3 interactors |
STRINGi | 9606.ENSP00000382434 |
PTM databases
PhosphoSitePlusi | Q3MJ16 |
Genetic variation databases
BioMutai | PLA2G4E |
DMDMi | 325511387 |
Proteomic databases
EPDi | Q3MJ16 |
jPOSTi | Q3MJ16 |
MassIVEi | Q3MJ16 |
PeptideAtlasi | Q3MJ16 |
PRIDEi | Q3MJ16 |
ProteomicsDBi | 61802 [Q3MJ16-2] 6312 |
Protocols and materials databases
Antibodypediai | 42114, 71 antibodies |
Genome annotation databases
Ensembli | ENST00000399518; ENSP00000382434; ENSG00000188089 [Q3MJ16-3] |
GeneIDi | 123745 |
KEGGi | hsa:123745 |
UCSCi | uc021sjp.2, human |
Organism-specific databases
CTDi | 123745 |
DisGeNETi | 123745 |
GeneCardsi | PLA2G4E |
HGNCi | HGNC:24791, PLA2G4E |
HPAi | ENSG00000188089, Tissue enriched (skin) |
neXtProti | NX_Q3MJ16 |
OpenTargetsi | ENSG00000188089 |
VEuPathDBi | HostDB:ENSG00000188089.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1028, Eukaryota KOG1325, Eukaryota |
GeneTreei | ENSGT01000000214525 |
InParanoidi | Q3MJ16 |
OMAi | YELHMKS |
OrthoDBi | 302848at2759 |
PhylomeDBi | Q3MJ16 |
TreeFami | TF325228 |
Enzyme and pathway databases
PathwayCommonsi | Q3MJ16 |
Reactomei | R-HSA-1482788, Acyl chain remodelling of PC R-HSA-1482801, Acyl chain remodelling of PS R-HSA-1482839, Acyl chain remodelling of PE R-HSA-1482922, Acyl chain remodelling of PI R-HSA-1483115, Hydrolysis of LPC |
Miscellaneous databases
BioGRID-ORCSi | 123745, 12 hits in 982 CRISPR screens |
GenomeRNAii | 123745 |
Pharosi | Q3MJ16, Tdark |
PROi | PR:Q3MJ16 |
RNActi | Q3MJ16, protein |
Gene expression databases
Bgeei | ENSG00000188089, Expressed in zone of skin and 57 other tissues |
Family and domain databases
CDDi | cd04036, C2_cPLA2, 1 hit |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR016035, Acyl_Trfase/lysoPLipase IPR041847, C2_cPLA2 IPR000008, C2_dom IPR035892, C2_domain_sf IPR040723, cPLA2_C2 IPR002642, LysoPLipase_cat_dom |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF18695, cPLA2_C2, 1 hit PF01735, PLA2_B, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00022, PLAc, 1 hit |
SUPFAMi | SSF52151, SSF52151, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS51210, PLA2C, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PA24E_HUMAN | |
Accessioni | Q3MJ16Primary (citable) accession number: Q3MJ16 Secondary accession number(s): B7WPN2, Q6ZSC0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 25, 2006 |
Last sequence update: | March 28, 2018 | |
Last modified: | April 7, 2021 | |
This is version 125 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports