FAAH4_CAEEL
ID FAAH4_CAEEL Reviewed; 647 AA.
AC Q9U217; Q8I4C5; Q9U216;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Monoglyceride lipase faah-4 {ECO:0000305};
DE EC=3.1.1.23 {ECO:0000269|PubMed:30911178};
DE AltName: Full=Fatty acid amide hydrolase 4 {ECO:0000305};
DE EC=3.5.1.99 {ECO:0000269|PubMed:30911178};
GN Name=faah-4 {ECO:0000312|WormBase:Y56A3A.12a};
GN ORFNames=Y56A3A.12 {ECO:0000312|WormBase:Y56A3A.12a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30911178; DOI=10.1038/s41589-019-0243-4;
RA Chen A.L., Lum K.M., Lara-Gonzalez P., Ogasawara D., Cognetta A.B. III,
RA To A., Parsons W.H., Simon G.M., Desai A., Petrascheck M., Bar-Peled L.,
RA Cravatt B.F.;
RT "Pharmacological convergence reveals a lipid pathway that regulates C.
RT elegans lifespan.";
RL Nat. Chem. Biol. 15:453-462(2019).
CC -!- FUNCTION: Converts monoacylglycerides to free fatty acids and glycerol
CC (PubMed:30911178). Hydrolyzes the endocannabinoid 2-
CC arachidonoylglycerol (2-AG), and thereby regulates the degradation of
CC endocannabinoid-related monoacylglycerides (PubMed:30911178). Also
CC hydrolyzes arachidonoyl ethanolamide (anandamide, or AEA), but with low
CC efficiency (PubMed:30911178). Plays a role in the regulation of
CC longevity and resistance to oxidative stress (PubMed:30911178).
CC {ECO:0000269|PubMed:30911178}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000269|PubMed:30911178};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + ethanolamine;
CC Xref=Rhea:RHEA:26136, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57603; EC=3.5.1.99;
CC Evidence={ECO:0000269|PubMed:30911178};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+);
CC Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392;
CC Evidence={ECO:0000269|PubMed:30911178};
CC -!- ACTIVITY REGULATION: Inhibited by the benzodioxole 4-[bis(1,3-
CC benzodioxol-5-yl)-hydroxymethyl]-1-piperidinecarboxylic acid (4-
CC nitrophenyl) ester (JZL184). {ECO:0000269|PubMed:30911178}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=19.4 pmol/min/mg enzyme towards arachidonoyl ethanolamide (at 37
CC degrees Celsius) {ECO:0000269|PubMed:30911178};
CC Vmax=1200.8 pmol/min/mg enzyme towards endocannabinoid 2-
CC arachidonoylglycerol (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:30911178};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:Y56A3A.12a};
CC IsoId=Q9U217-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y56A3A.12b};
CC IsoId=Q9U217-2; Sequence=VSP_060464;
CC -!- DISRUPTION PHENOTYPE: Extended lifespan, increased food consumption and
CC increased resistance to oxidative stress induced by paraquat
CC (PubMed:30911178). Increased levels of mono- and polyunsaturated
CC monoacylglycerides, including endocannabinoid 2-arachidonoylglycerol
CC (PubMed:30911178). Lifespan is further extended following treatment
CC with the benzodioxole 4-[bis(1,3-benzodioxol-5-yl)-hydroxymethyl]-1-
CC piperidinecarboxylic acid (4-nitrophenyl) ester (JZL184)
CC (PubMed:30911178). {ECO:0000269|PubMed:30911178}.
CC -!- SIMILARITY: Belongs to the amidase family. {ECO:0000305}.
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DR EMBL; BX284603; CAB60524.1; -; Genomic_DNA.
DR EMBL; BX284603; CAB60525.1; -; Genomic_DNA.
DR RefSeq; NP_499544.1; NM_067143.4.
DR RefSeq; NP_499545.1; NM_067144.3. [Q9U217-1]
DR AlphaFoldDB; Q9U217; -.
DR SMR; Q9U217; -.
DR IntAct; Q9U217; 1.
DR STRING; 6239.Y56A3A.12a.1; -.
DR EPD; Q9U217; -.
DR PaxDb; Q9U217; -.
DR EnsemblMetazoa; Y56A3A.12a.1; Y56A3A.12a.1; WBGene00013232. [Q9U217-1]
DR EnsemblMetazoa; Y56A3A.12a.2; Y56A3A.12a.2; WBGene00013232. [Q9U217-1]
DR EnsemblMetazoa; Y56A3A.12a.3; Y56A3A.12a.3; WBGene00013232. [Q9U217-1]
DR EnsemblMetazoa; Y56A3A.12b.1; Y56A3A.12b.1; WBGene00013232. [Q9U217-2]
DR EnsemblMetazoa; Y56A3A.12b.2; Y56A3A.12b.2; WBGene00013232. [Q9U217-2]
DR GeneID; 176620; -.
DR UCSC; Y56A3A.12b.1; c. elegans.
DR CTD; 176620; -.
DR WormBase; Y56A3A.12a; CE24467; WBGene00013232; faah-4. [Q9U217-1]
DR WormBase; Y56A3A.12b; CE24468; WBGene00013232; faah-4. [Q9U217-2]
DR eggNOG; KOG1212; Eukaryota.
DR GeneTree; ENSGT00970000196598; -.
DR HOGENOM; CLU_009600_9_3_1; -.
DR InParanoid; Q9U217; -.
DR OMA; LTPVMPH; -.
DR OrthoDB; 852596at2759; -.
DR PhylomeDB; Q9U217; -.
DR PRO; PR:Q9U217; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00013232; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0047372; F:acylglycerol lipase activity; IEA:UniProtKB-EC.
DR GO; GO:0004040; F:amidase activity; IBA:GO_Central.
DR GO; GO:0103073; F:anandamide amidohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0017064; F:fatty acid amide hydrolase activity; IBA:GO_Central.
DR GO; GO:0102077; F:oleamide hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0009062; P:fatty acid catabolic process; IBA:GO_Central.
DR Gene3D; 3.90.1300.10; -; 1.
DR InterPro; IPR020556; Amidase_CS.
DR InterPro; IPR023631; Amidase_dom.
DR InterPro; IPR036928; AS_sf.
DR Pfam; PF01425; Amidase; 1.
DR SUPFAM; SSF75304; SSF75304; 1.
DR PROSITE; PS00571; AMIDASES; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Lipid degradation; Lipid metabolism;
KW Reference proteome; Serine esterase.
FT CHAIN 1..647
FT /note="Monoglyceride lipase faah-4"
FT /id="PRO_0000448890"
FT ACT_SITE 165
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P97612"
FT ACT_SITE 240
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P97612"
FT ACT_SITE 264
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P97612"
FT VAR_SEQ 4..35
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060464"
SQ SEQUENCE 647 AA; 71729 MW; 4168A44EF8C19B5A CRC64;
MGNNFWSTWS PSQRIFSLIW PATILYLIMK LLIEKMWGKN RGAVERFQTR REALFDDFKS
RSAPASLVNN PRIVKGNETA EQIETTFNEI LKLDLIALKS ALQTDKYNAY TVLCAFVWRA
IDVNSEINCI TEVIREAFNT AEALDDNYAQ TGEKGQLFGL PFSVKSNFYM ENYDVTVGLA
KLLEQPKTTT CPMVQFLSDQ GAVPFCLTNV PQGLLSYVSS NPIYGTTKNP WDFSRTPGGS
SGGEAALLAA GGAAFGIGSD LAGSLRIPAA FCGLVTLKPT QDRLCVTDTH GGLPGRGRLG
LSFGFYTRSV KEQEFLLGLI VGRSEYLELC PMSSPAKLEK HIEKDQKLVI GWFVDDGFNP
VVPSNRRAVE ETVKSLQAKG HQVVELKLAD VSEEFPPFAV ADMLFRNVMP DNGAYMSEMY
AGEQYDEHMK LFIRLVCLKQ NFLVSFLLRY GVMPFAKLAL SKRLACIGSA YNSDLAACRQ
NQENTDSYKL QWIRYWKSKK IDALICPSFI TPAQPFEYPA QLSNGAFITG LFNMLDVPAG
VVPVSPVNQK DVDQLIDGFS TEGDLLLKKQ REAARGTTGL PNAVQVVTLP NCEEMCLRVM
RLVEESAEGV QRLQWRVGAS AAPIDVENTP AGVVSSLEHF ERVNLLH
