FAAH1_CAEEL
ID FAAH1_CAEEL Reviewed; 572 AA.
AC Q17449; H2KY70;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Fatty acid amide hydrolase 1;
DE EC=3.5.1.99 {ECO:0000269|PubMed:21562563, ECO:0000269|PubMed:30911178};
DE AltName: Full=Anandamide amidohydrolase 1;
DE Flags: Precursor;
GN Name=faah-1 {ECO:0000312|WormBase:B0218.1};
GN ORFNames=B0218.1 {ECO:0000312|WormBase:B0218.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=21562563; DOI=10.1038/nature10007;
RA Lucanic M., Held J.M., Vantipalli M.C., Klang I.M., Graham J.B.,
RA Gibson B.W., Lithgow G.J., Gill M.S.;
RT "N-acylethanolamine signalling mediates the effect of diet on lifespan in
RT Caenorhabditis elegans.";
RL Nature 473:226-229(2011).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23072806; DOI=10.1038/ncomms2136;
RA Pastuhov S.I., Fujiki K., Nix P., Kanao S., Bastiani M., Matsumoto K.,
RA Hisamoto N.;
RT "Endocannabinoid-Goalpha signalling inhibits axon regeneration in
RT Caenorhabditis elegans by antagonizing Gqalpha-PKC-JNK signalling.";
RL Nat. Commun. 3:1136-1136(2012).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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: Catalyzes the hydrolysis of endogenous amidated lipids like
CC anandamide (AEA or N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine) and
CC eicosapentaneoyl ethanolamide (EPEA or (5Z,8Z,11Z,14Z,17Z-
CC eicosapentaenoyl) ethanolamine), as well as other fatty amides, to
CC their corresponding fatty acids, thereby regulating the signaling
CC functions of these molecules (PubMed:21562563, PubMed:30911178). EPEA
CC promotes dauer formation and may constitute a signal of high nutrient
CC availability (PubMed:21562563). Breakdown of EPEA may promote lifespan
CC extension when nutrient availability is high (PubMed:21562563).
CC Facilitates axon regeneration after injury by degradating inhibitory
CC compounds such as AEA (PubMed:23072806). FAAH cooperates with PM20D1 in
CC the hydrolysis of amino acid-conjugated fatty acids such as N-fatty
CC acyl glycine and N-fatty acyl-L-serine, thereby acting as a
CC physiological regulator of specific subsets of intracellular, but not
CC of extracellular, N-fatty acyl amino acids (By similarity).
CC {ECO:0000250|UniProtKB:O08914, ECO:0000269|PubMed:21562563,
CC ECO:0000269|PubMed:23072806, 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:21562563, ECO:0000269|PubMed:30911178};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26137;
CC Evidence={ECO:0000269|PubMed:21562563, ECO:0000269|PubMed:30911178};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenamide + H2O = (9Z)-octadecenoate + NH4(+);
CC Xref=Rhea:RHEA:26506, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:116314; EC=3.5.1.99;
CC Evidence={ECO:0000250|UniProtKB:P97612};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26507;
CC Evidence={ECO:0000250|UniProtKB:P97612};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl) ethanolamine + H2O =
CC (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + ethanolamine;
CC Xref=Rhea:RHEA:35519, ChEBI:CHEBI:15377, ChEBI:CHEBI:57603,
CC ChEBI:CHEBI:58562, ChEBI:CHEBI:71467;
CC Evidence={ECO:0000269|PubMed:21562563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35520;
CC Evidence={ECO:0000269|PubMed:21562563};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-hexadecenoyl) ethanolamine = (9Z)-hexadecenoate +
CC ethanolamine; Xref=Rhea:RHEA:35563, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:32372, ChEBI:CHEBI:57603, ChEBI:CHEBI:71465;
CC Evidence={ECO:0000269|PubMed:21562563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35564;
CC Evidence={ECO:0000269|PubMed:21562563};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl) ethanolamine = (9Z)-octadecenoate +
CC ethanolamine; Xref=Rhea:RHEA:45060, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57603, ChEBI:CHEBI:71466;
CC Evidence={ECO:0000269|PubMed:21562563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45061;
CC Evidence={ECO:0000269|PubMed:21562563};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octadecanoyl ethanolamine = ethanolamine +
CC octadecanoate; Xref=Rhea:RHEA:63124, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:57603, ChEBI:CHEBI:85299;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63125;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-docosanoyl-ethanolamine = docosanoate + ethanolamine;
CC Xref=Rhea:RHEA:63128, ChEBI:CHEBI:15377, ChEBI:CHEBI:23858,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:146186;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63129;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(15Z-tetracosenoyl)-ethanolamine = (15Z)-
CC tetracosenoate + ethanolamine; Xref=Rhea:RHEA:63144,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32392, ChEBI:CHEBI:57603,
CC ChEBI:CHEBI:146187; Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63145;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoylethanolamine = ethanolamine +
CC hexadecanoate; Xref=Rhea:RHEA:45064, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57603, ChEBI:CHEBI:71464;
CC Evidence={ECO:0000269|PubMed:21562563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45065;
CC Evidence={ECO:0000269|PubMed:21562563};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z,12Z-octadecadienoyl)-ethanolamine = (9Z,12Z)-
CC octadecadienoate + ethanolamine; Xref=Rhea:RHEA:35567,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:30245, ChEBI:CHEBI:57603,
CC ChEBI:CHEBI:64032; Evidence={ECO:0000269|PubMed:21562563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35568;
CC Evidence={ECO:0000269|PubMed:21562563};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + glycine = H2O + N-(9Z-
CC octadecenoyl)glycine; Xref=Rhea:RHEA:51316, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57305, ChEBI:CHEBI:133992;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51318;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycine; Xref=Rhea:RHEA:64108,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32395, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:59002; Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64109;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-L-serine =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + L-serine; Xref=Rhea:RHEA:64116,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32395, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:149697; Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64117;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=18.3 pmol/min/mg enzyme for the hydrolysis of arachidonoyl
CC ethanolamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine) (at 37
CC degrees Celsius) {ECO:0000269|PubMed:30911178};
CC -!- TISSUE SPECIFICITY: Expressed in the pharynx, some pharyngeal neurons,
CC the posterior intestine and anal depressor muscles.
CC {ECO:0000269|PubMed:21562563, ECO:0000269|PubMed:23072806}.
CC -!- DISRUPTION PHENOTYPE: Viable. Reduction (50 percent) in the frequency
CC of motoneuron axon regeneration in young adults but not in L4 larvae.
CC {ECO:0000269|PubMed:23072806}.
CC -!- SIMILARITY: Belongs to the amidase family. {ECO:0000305}.
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DR EMBL; BX284604; CCD61383.1; -; Genomic_DNA.
DR PIR; T29753; T29753.
DR RefSeq; NP_501368.1; NM_068967.5.
DR AlphaFoldDB; Q17449; -.
DR SMR; Q17449; -.
DR BioGRID; 42726; 1.
DR STRING; 6239.B0218.1a.4; -.
DR SwissLipids; SLP:000000044; -.
DR EPD; Q17449; -.
DR PaxDb; Q17449; -.
DR PeptideAtlas; Q17449; -.
DR EnsemblMetazoa; B0218.1.1; B0218.1.1; WBGene00015047.
DR EnsemblMetazoa; B0218.1.2; B0218.1.2; WBGene00015047.
DR EnsemblMetazoa; B0218.1.3; B0218.1.3; WBGene00015047.
DR GeneID; 177613; -.
DR KEGG; cel:CELE_B0218.1; -.
DR UCSC; B0218.1a.1; c. elegans.
DR CTD; 177613; -.
DR WormBase; B0218.1; CE06684; WBGene00015047; faah-1.
DR eggNOG; KOG1212; Eukaryota.
DR GeneTree; ENSGT00970000196322; -.
DR HOGENOM; CLU_009600_9_3_1; -.
DR InParanoid; Q17449; -.
DR OMA; EPWRPEM; -.
DR OrthoDB; 852596at2759; -.
DR PhylomeDB; Q17449; -.
DR PRO; PR:Q17449; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00015047; Expressed in larva and 4 other tissues.
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 GO; GO:0048680; P:positive regulation of axon regeneration; IMP:UniProtKB.
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 Coiled coil; Hydrolase; Lipid degradation; Lipid metabolism;
KW Phosphoprotein; Reference proteome; Signal.
FT SIGNAL 1..14
FT /evidence="ECO:0000255"
FT CHAIN 15..572
FT /note="Fatty acid amide hydrolase 1"
FT /id="PRO_0000421279"
FT COILED 32..63
FT /evidence="ECO:0000255"
FT ACT_SITE 139
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P97612"
FT ACT_SITE 214
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P97612"
FT ACT_SITE 238
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P97612"
FT BINDING 214
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 235..238
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 572 AA; 64001 MW; 4CE781426865D6E9 CRC64;
MIFYLVLLVL GAIAFYVHFS NNRKKLIERL EIVAQRRRDD LSKNVEQARK AADKLDTQRR
DWIGSLDFEQ LRDELQRGHV TCVEAIRAYF HKAILAHEKT NAVTCFILDA ERQAEELDEQ
AKLPYYVKPP LFGVPLSLKE CLKVKGYDTT RGFVQDAYHP ATEDSIQVEH YKKLGLIPFC
QTNVPQSLLS YNCSNPLFGT TTNPYDSTRT CGGSSGGEGA LIGAGGSLIG IGTDVGGSVR
IPCHFTGTAG IKPSKMRFAH RGGGASVPGK PLIDANDGPM AKDVKTNVEF LRNVWGDIDF
QSDRDPYCPP VHWNESVYSS EKKLRVGYYI DDGWFTPTPA LQRAVLESKK HLEAAGHTVI
PFYPPRLPSV MQLYFRAVCL DGGQYVLNKL LKDIIEPTIR FQVTLWMVPV WIQRILSYPV
SLVFPRMGML MQSLTRDTFE LREAYADIEA YREEFVGLMM KDNLDVILCP ASIMPAPQHD
IPSKVVSGVS YTCLYNLLDF GAGVVPVTAV SKSDEEKLIN EYPETDKWYQ ITKKATLGAV
GMPIGVQVAA PPYREEAVLR TMREIEIAVT GK
