FAAH1_RAT
ID FAAH1_RAT Reviewed; 579 AA.
AC P97612; Q5BKA3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Fatty-acid amide hydrolase 1;
DE EC=3.5.1.99 {ECO:0000269|PubMed:10526230, ECO:0000269|PubMed:11128635, ECO:0000269|PubMed:17649977, ECO:0000269|PubMed:9122178, ECO:0000269|PubMed:9299394, ECO:0000269|PubMed:9790682};
DE AltName: Full=Anandamide amidase;
DE AltName: Full=Anandamide amidohydrolase 1;
DE AltName: Full=Fatty acid ester hydrolase;
DE EC=3.1.1.- {ECO:0000269|PubMed:10526230, ECO:0000269|PubMed:15533037, ECO:0000269|PubMed:17649977};
DE AltName: Full=Oleamide hydrolase 1;
GN Name=Faah; Synonyms=Faah1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=8900284; DOI=10.1038/384083a0;
RA Cravatt B.F., Giang D.K., Mayfield S.P., Boger D.L., Lerner R.A.,
RA Gilula N.B.;
RT "Molecular characterization of an enzyme that degrades neuromodulatory
RT fatty-acid amides.";
RL Nature 384:83-87(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9122178; DOI=10.1073/pnas.94.6.2238;
RA Giang D.K., Cravatt B.F.;
RT "Molecular characterization of human and mouse fatty acid amide
RT hydrolases.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2238-2242(1997).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=9452020;
RX DOI=10.1002/(sici)1097-4547(19971215)50:6<1047::aid-jnr16>3.0.co;2-1;
RA Thomas E.A., Cravatt B.F., Danielson P.E., Gilula N.B., Sutcliffe J.G.;
RT "Fatty acid amide hydrolase, the degradative enzyme for anandamide and
RT oleamide, has selective distribution in neurons within the rat central
RT nervous system.";
RL J. Neurosci. Res. 50:1047-1052(1997).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9299394; DOI=10.1006/bbrc.1997.7180;
RA Kurahashi Y., Ueda N., Suzuki H., Suzuki M., Yamamoto S.;
RT "Reversible hydrolysis and synthesis of anandamide demonstrated by
RT recombinant rat fatty-acid amide hydrolase.";
RL Biochem. Biophys. Res. Commun. 237:512-515(1997).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=9790682; DOI=10.1021/bi981733n;
RA Patricelli M.P., Lashuel H.A., Giang D.K., Kelly J.W., Cravatt B.F.;
RT "Comparative characterization of a wild type and transmembrane domain-
RT deleted fatty acid amide hydrolase: identification of the transmembrane
RT domain as a site for oligomerization.";
RL Biochemistry 37:15177-15187(1998).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10526230; DOI=10.1016/s1388-1981(99)00143-2;
RA Goparaju S.K., Kurahashi Y., Suzuki H., Ueda N., Yamamoto S.;
RT "Anandamide amidohydrolase of porcine brain: cDNA cloning, functional
RT expression and site-directed mutagenesis.";
RL Biochim. Biophys. Acta 1441:77-84(1999).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11128635; DOI=10.1016/s0960-894x(00)00528-x;
RA Boger D.L., Fecik R.A., Patterson J.E., Miyauchi H., Patricelli M.P.,
RA Cravatt B.F.;
RT "Fatty acid amide hydrolase substrate specificity.";
RL Bioorg. Med. Chem. Lett. 10:2613-2616(2000).
RN [9]
RP CHARACTERIZATION, AND MUTAGENESIS OF LYS-142 AND SER-217.
RX PubMed=12734197; DOI=10.1074/jbc.m303922200;
RA McKinney M.K., Cravatt B.F.;
RT "Evidence for distinct roles in catalysis for residues of the serine-
RT serine-lysine catalytic triad of fatty acid amide hydrolase.";
RL J. Biol. Chem. 278:37393-37399(2003).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15533037; DOI=10.1021/bi0480335;
RA Saghatelian A., Trauger S.A., Want E.J., Hawkins E.G., Siuzdak G.,
RA Cravatt B.F.;
RT "Assignment of endogenous substrates to enzymes by global metabolite
RT profiling.";
RL Biochemistry 43:14332-14339(2004).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17649977; DOI=10.1021/bi7005898;
RA Vila A., Rosengarth A., Piomelli D., Cravatt B., Marnett L.J.;
RT "Hydrolysis of prostaglandin glycerol esters by the endocannabinoid-
RT hydrolyzing enzymes, monoacylglycerol lipase and fatty acid amide
RT hydrolase.";
RL Biochemistry 46:9578-9585(2007).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 37-573 IN COMPLEX WITH INHIBITOR
RP METHOXY-ARACHIDONYL FLUOROPHOSPHATE, SUBUNIT, AND TOPOLOGY.
RX PubMed=12459591; DOI=10.1126/science.1076535;
RA Bracey M.H., Hanson M.A., Masuda K.R., Stevens R.C., Cravatt B.F.;
RT "Structural adaptations in a membrane enzyme that terminates
RT endocannabinoid signaling.";
RL Science 298:1793-1796(2002).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 32-579 IN COMPLEX WITH INHIBITOR
RP PF-750, TOPOLOGY, AND SUBUNIT.
RX PubMed=18753625; DOI=10.1073/pnas.0806121105;
RA Mileni M., Johnson D.S., Wang Z., Everdeen D.S., Liimatta M., Pabst B.,
RA Bhattacharya K., Nugent R.A., Kamtekar S., Cravatt B.F., Ahn K.,
RA Stevens R.C.;
RT "Structure-guided inhibitor design for human FAAH by interspecies active
RT site conversion.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12820-12824(2008).
CC -!- FUNCTION: Catalyzes the hydrolysis of endogenous amidated lipids like
CC the sleep-inducing lipid oleamide ((9Z)-octadecenamide), the
CC endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC ethanolamine), as well as other fatty amides, to their corresponding
CC fatty acids, thereby regulating the signaling functions of these
CC molecules (PubMed:9122178, PubMed:9299394, PubMed:9790682,
CC PubMed:10526230, PubMed:11128635, PubMed:15533037, PubMed:17649977).
CC Hydrolyzes polyunsaturated substrate anandamide preferentially as
CC compared to monounsaturated substrates (PubMed:9122178,
CC PubMed:11128635). It can also catalyze the hydrolysis of the
CC endocannabinoid 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-glycerol) (PubMed:10526230, PubMed:15533037,
CC PubMed:17649977). FAAH cooperates with PM20D1 in the hydrolysis of
CC amino acid-conjugated fatty acids such as N-fatty acyl glycine and N-
CC fatty acyl-L-serine, thereby acting as a physiological regulator of
CC specific subsets of intracellular, but not of extracellular, N-fatty
CC acyl amino acids (By similarity). {ECO:0000250|UniProtKB:O08914,
CC ECO:0000269|PubMed:10526230, ECO:0000269|PubMed:11128635,
CC ECO:0000269|PubMed:15533037, ECO:0000269|PubMed:17649977,
CC ECO:0000269|PubMed:9122178, ECO:0000269|PubMed:9299394,
CC ECO:0000269|PubMed:9790682}.
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:10526230, ECO:0000269|PubMed:11128635,
CC ECO:0000269|PubMed:17649977, ECO:0000269|PubMed:9122178,
CC ECO:0000269|PubMed:9299394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26137;
CC Evidence={ECO:0000269|PubMed:10526230, ECO:0000269|PubMed:11128635,
CC ECO:0000269|PubMed:17649977, ECO:0000269|PubMed:9122178,
CC ECO:0000269|PubMed:9299394};
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:0000269|PubMed:10526230, ECO:0000269|PubMed:11128635,
CC ECO:0000269|PubMed:9122178, ECO:0000269|PubMed:9299394,
CC ECO:0000269|PubMed:9790682};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26507;
CC Evidence={ECO:0000269|PubMed:10526230, ECO:0000269|PubMed:11128635,
CC ECO:0000269|PubMed:9122178, ECO:0000269|PubMed:9299394,
CC ECO:0000269|PubMed:9790682};
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:10526230, ECO:0000269|PubMed:15533037,
CC ECO:0000269|PubMed:17649977};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000269|PubMed:10526230, ECO:0000269|PubMed:15533037,
CC ECO:0000269|PubMed:17649977};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z)-octadecatrienamide + H2O = (9Z,12Z,15Z)-
CC octadecatrienoate + NH4(+); Xref=Rhea:RHEA:62976, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:32387, ChEBI:CHEBI:142684;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62977;
CC Evidence={ECO:0000269|PubMed:11128635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenamide + H2O = (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + NH4(+); Xref=Rhea:RHEA:63016, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:32395, ChEBI:CHEBI:137830;
CC Evidence={ECO:0000269|PubMed:11128635, ECO:0000269|PubMed:9299394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63017;
CC Evidence={ECO:0000269|PubMed:11128635, ECO:0000269|PubMed:9299394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6Z)-octadecenamide + H2O = (6Z)-octadecenoate + NH4(+);
CC Xref=Rhea:RHEA:63008, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:32375, ChEBI:CHEBI:146168;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63009;
CC Evidence={ECO:0000269|PubMed:11128635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15Z)-tetracosenamide + H2O = (15Z)-tetracosenoate + NH4(+);
CC Xref=Rhea:RHEA:63028, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:32392, ChEBI:CHEBI:146166;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63029;
CC Evidence={ECO:0000269|PubMed:11128635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienamide + H2O = (8Z,11Z,14Z)-
CC eicosatrienoate + NH4(+); Xref=Rhea:RHEA:62996, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:71589, ChEBI:CHEBI:146163;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62997;
CC Evidence={ECO:0000269|PubMed:11128635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11Z,14Z,17Z)-eicosatrienamide + H2O = (11Z,14Z,17Z)-
CC eicosatrienoate + NH4(+); Xref=Rhea:RHEA:63000, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:77223, ChEBI:CHEBI:146164;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63001;
CC Evidence={ECO:0000269|PubMed:11128635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11Z,14Z)-eicosadienamide + H2O = (11Z,14Z)-eicosadienoate +
CC NH4(+); Xref=Rhea:RHEA:63004, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:77220, ChEBI:CHEBI:146165;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63005;
CC Evidence={ECO:0000269|PubMed:11128635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienamide + H2O = (9Z,12Z)-octadecadienoate +
CC NH4(+); Xref=Rhea:RHEA:63020, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:82984;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63021;
CC Evidence={ECO:0000269|PubMed:11128635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + tetradecamide = NH4(+) + tetradecanoate;
CC Xref=Rhea:RHEA:62992, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:137125;
CC Evidence={ECO:0000269|PubMed:9122178};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62993;
CC Evidence={ECO:0000269|PubMed:9122178};
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:15533037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45061;
CC Evidence={ECO:0000269|PubMed:15533037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-taurine = (9Z)-octadecenoate +
CC taurine; Xref=Rhea:RHEA:63148, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:146191, ChEBI:CHEBI:507393;
CC Evidence={ECO:0000269|PubMed:15533037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63149;
CC Evidence={ECO:0000269|PubMed:15533037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H2O =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + methanol;
CC Xref=Rhea:RHEA:63052, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17790, ChEBI:CHEBI:32395, ChEBI:CHEBI:78033;
CC Evidence={ECO:0000269|PubMed:9299394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63053;
CC Evidence={ECO:0000269|PubMed:9299394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11Z)-eicosenamide + H2O = (11Z)-eicosenoate + NH4(+);
CC Xref=Rhea:RHEA:63120, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:32426, ChEBI:CHEBI:146167;
CC Evidence={ECO:0000269|PubMed:11128635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63121;
CC Evidence={ECO:0000269|PubMed:11128635};
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:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35564;
CC Evidence={ECO:0000250|UniProtKB:O08914};
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-tetracosanoyl-taurine = taurine + tetracosanoate;
CC Xref=Rhea:RHEA:63140, ChEBI:CHEBI:15377, ChEBI:CHEBI:31014,
CC ChEBI:CHEBI:132049, ChEBI:CHEBI:507393;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63141;
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-docosanoyl-taurine = docosanoate + taurine;
CC Xref=Rhea:RHEA:63156, ChEBI:CHEBI:15377, ChEBI:CHEBI:23858,
CC ChEBI:CHEBI:146196, ChEBI:CHEBI:507393;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63157;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(15Z-tetracosenoyl)-taurine = (15Z)-tetracosenoate +
CC taurine; Xref=Rhea:RHEA:63160, ChEBI:CHEBI:15377, ChEBI:CHEBI:32392,
CC ChEBI:CHEBI:146198, ChEBI:CHEBI:507393;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63161;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-tricosanoyl-taurine = taurine + tricosanoate;
CC Xref=Rhea:RHEA:63164, ChEBI:CHEBI:15377, ChEBI:CHEBI:79007,
CC ChEBI:CHEBI:146197, ChEBI:CHEBI:507393;
CC Evidence={ECO:0000250|UniProtKB:O08914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63165;
CC Evidence={ECO:0000250|UniProtKB:O08914};
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 -!- ACTIVITY REGULATION: inhibited by trifluoromethyl ketone.
CC {ECO:0000269|PubMed:9122178}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=23 uM for oleamide ((9Z)-octadecenamide)
CC {ECO:0000269|PubMed:9790682};
CC KM=100 uM for arachidonamide ((5Z,8Z,11Z,14Z)-eicosatetraenamide)
CC {ECO:0000269|PubMed:9299394};
CC KM=45 uM for methyl arachidonate (1-O-methyl-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate) {ECO:0000269|PubMed:9299394};
CC KM=18 uM for anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC ethanolamine) {ECO:0000269|PubMed:9299394};
CC KM=34 uM for anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC ethanolamine) {ECO:0000269|PubMed:17649977};
CC KM=89 uM for 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-glycerol) {ECO:0000269|PubMed:17649977};
CC Vmax=0.11 umol/min/mg enzyme for the hydrolysis of anandamide (N-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine)
CC {ECO:0000269|PubMed:10526230};
CC Note=kcat is 7.1 sec(-1) with oleamide ((9Z)-octadecenamide)
CC (PubMed:9790682). kcat is 28 min(-1) with 2-arachidonoylglycerol (2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol) (PubMed:17649977). kcat is
CC 16 min(-1) with anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC ethanolamine) (PubMed:17649977). {ECO:0000269|PubMed:17649977,
CC ECO:0000269|PubMed:9790682};
CC pH dependence:
CC Optimum pH is 9.5. {ECO:0000269|PubMed:9790682};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12459591,
CC ECO:0000269|PubMed:18753625}.
CC -!- INTERACTION:
CC P97612; P97612: Faah; NbExp=2; IntAct=EBI-15726093, EBI-15726093;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9122178, ECO:0000269|PubMed:9790682}; Single-pass
CC membrane protein {ECO:0000269|PubMed:9122178}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:9122178, ECO:0000269|PubMed:9790682}; Single-pass
CC membrane protein {ECO:0000269|PubMed:9122178}. Note=Seems to be
CC associated with the endoplasmic reticulum and/or Golgi apparatus.
CC -!- TISSUE SPECIFICITY: Found in neuronal cells throughout the CNS.
CC Expressed in liver and brain, and to a lesser extent in spleen, lung,
CC kidney and testes. {ECO:0000269|PubMed:9452020}.
CC -!- DEVELOPMENTAL STAGE: In the CNS it accumulates progressively between
CC embryonic day 14 and postnatal day 10, remains high until postnatal day
CC 30, then decreases into adulthood.
CC -!- SIMILARITY: Belongs to the amidase family. {ECO:0000305}.
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DR EMBL; U72497; AAB26961.1; -; mRNA.
DR EMBL; BC091148; AAH91148.1; -; mRNA.
DR RefSeq; NP_077046.1; NM_024132.3.
DR RefSeq; XP_003750049.1; XM_003750001.4.
DR RefSeq; XP_008774266.1; XM_008776044.2.
DR PDB; 1MT5; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=37-573.
DR PDB; 2VYA; X-ray; 2.75 A; A/B=32-579.
DR PDB; 2WAP; X-ray; 2.80 A; A/B=31-573.
DR PDB; 2WJ1; X-ray; 1.84 A; A/B=30-579.
DR PDB; 2WJ2; X-ray; 2.55 A; A/B=30-579.
DR PDB; 3K7F; X-ray; 1.95 A; A/B=30-579.
DR PDB; 3K83; X-ray; 2.25 A; A/B=30-579.
DR PDB; 3K84; X-ray; 2.25 A; A/B=30-579.
DR PDB; 3LJ6; X-ray; 2.42 A; A/B=30-579.
DR PDB; 3LJ7; X-ray; 2.30 A; A/B=30-579.
DR PDB; 3OJ8; X-ray; 1.90 A; A/B=30-579.
DR PDB; 3PPM; X-ray; 1.78 A; A/B=30-579.
DR PDB; 3PR0; X-ray; 2.20 A; A/B=30-579.
DR PDB; 3QJ8; X-ray; 2.90 A; A/B=32-579.
DR PDB; 3QJ9; X-ray; 2.30 A; A/B=32-579.
DR PDB; 3QK5; X-ray; 2.20 A; A/B=32-579.
DR PDB; 3QKV; X-ray; 3.10 A; A/B=32-579.
DR PDB; 4DO3; X-ray; 2.25 A; A/B=32-575.
DR PDB; 4HBP; X-ray; 2.91 A; A/B=30-579.
DR PDB; 4J5P; X-ray; 2.30 A; A/B=30-579.
DR PDB; 6MRG; X-ray; 2.77 A; A/B/C/D=32-579.
DR PDBsum; 1MT5; -.
DR PDBsum; 2VYA; -.
DR PDBsum; 2WAP; -.
DR PDBsum; 2WJ1; -.
DR PDBsum; 2WJ2; -.
DR PDBsum; 3K7F; -.
DR PDBsum; 3K83; -.
DR PDBsum; 3K84; -.
DR PDBsum; 3LJ6; -.
DR PDBsum; 3LJ7; -.
DR PDBsum; 3OJ8; -.
DR PDBsum; 3PPM; -.
DR PDBsum; 3PR0; -.
DR PDBsum; 3QJ8; -.
DR PDBsum; 3QJ9; -.
DR PDBsum; 3QK5; -.
DR PDBsum; 3QKV; -.
DR PDBsum; 4DO3; -.
DR PDBsum; 4HBP; -.
DR PDBsum; 4J5P; -.
DR PDBsum; 6MRG; -.
DR AlphaFoldDB; P97612; -.
DR SMR; P97612; -.
DR DIP; DIP-46284N; -.
DR IntAct; P97612; 1.
DR STRING; 10116.ENSRNOP00000015667; -.
DR BindingDB; P97612; -.
DR ChEMBL; CHEMBL3229; -.
DR DrugCentral; P97612; -.
DR GuidetoPHARMACOLOGY; 1400; -.
DR SwissLipids; SLP:000001428; -.
DR iPTMnet; P97612; -.
DR PhosphoSitePlus; P97612; -.
DR jPOST; P97612; -.
DR PaxDb; P97612; -.
DR PRIDE; P97612; -.
DR Ensembl; ENSRNOT00000015667; ENSRNOP00000015667; ENSRNOG00000045949.
DR GeneID; 100911581; -.
DR GeneID; 29347; -.
DR UCSC; RGD:61808; rat.
DR CTD; 2166; -.
DR CTD; 29347; -.
DR RGD; 61808; Faah.
DR eggNOG; KOG1212; Eukaryota.
DR GeneTree; ENSGT00940000161237; -.
DR HOGENOM; CLU_009600_9_3_1; -.
DR InParanoid; P97612; -.
DR OMA; GMQPWKY; -.
DR OrthoDB; 852596at2759; -.
DR BRENDA; 3.5.1.4; 5301.
DR BRENDA; 3.5.1.99; 5301.
DR Reactome; R-RNO-2142753; Arachidonic acid metabolism.
DR SABIO-RK; P97612; -.
DR EvolutionaryTrace; P97612; -.
DR PRO; PR:P97612; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000011019; Expressed in jejunum and 13 other tissues.
DR Genevisible; P97612; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IC:RGD.
DR GO; GO:0031090; C:organelle membrane; IDA:UniProtKB.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:UniProtKB.
DR GO; GO:0004040; F:amidase activity; IDA:RGD.
DR GO; GO:0103073; F:anandamide amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0017064; F:fatty acid amide hydrolase activity; IDA:UniProtKB.
DR GO; GO:0016788; F:hydrolase activity, acting on ester bonds; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IMP:RGD.
DR GO; GO:0008289; F:lipid binding; IDA:RGD.
DR GO; GO:0102077; F:oleamide hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0005543; F:phospholipid binding; IMP:RGD.
DR GO; GO:0009062; P:fatty acid catabolic process; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IMP:RGD.
DR GO; GO:0052651; P:monoacylglycerol catabolic process; IDA:UniProtKB.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR Gene3D; 3.90.1300.10; -; 1.
DR InterPro; IPR020556; Amidase_CS.
DR InterPro; IPR023631; Amidase_dom.
DR InterPro; IPR036928; AS_sf.
DR InterPro; IPR030560; FAAH.
DR PANTHER; PTHR45847:SF3; PTHR45847:SF3; 1.
DR Pfam; PF01425; Amidase; 1.
DR SUPFAM; SSF75304; SSF75304; 1.
DR PROSITE; PS00571; AMIDASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum;
KW Golgi apparatus; Hydrolase; Lipid degradation; Lipid metabolism; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..579
FT /note="Fatty-acid amide hydrolase 1"
FT /id="PRO_0000105267"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 404..433
FT /evidence="ECO:0000305"
FT TOPO_DOM 434..579
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 142
FT /note="Charge relay system"
FT ACT_SITE 217
FT /note="Charge relay system"
FT ACT_SITE 241
FT /note="Acyl-ester intermediate"
FT BINDING 191
FT /ligand="substrate"
FT BINDING 217
FT /ligand="substrate"
FT BINDING 238..241
FT /ligand="substrate"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00519"
FT MUTAGEN 142
FT /note="K->A: Lowers activity 40000-fold. Lowers activity
FT 70000-fold; when associated with A-217."
FT /evidence="ECO:0000269|PubMed:12734197"
FT MUTAGEN 217
FT /note="S->A: Lowers activity 3000-fold. Lowers activity
FT 70000-fold; when associated with A-142."
FT /evidence="ECO:0000269|PubMed:12734197"
FT HELIX 35..65
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 71..76
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 79..87
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:3OJ8"
FT HELIX 93..111
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 121..127
FT /evidence="ECO:0007829|PDB:3PPM"
FT TURN 133..136
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:3QK5"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:3PPM"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 219..226
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 231..240
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 243..249
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 252..255
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 287..297
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 300..305
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 326..329
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 340..355
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 368..373
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 375..380
FT /evidence="ECO:0007829|PDB:3PPM"
FT TURN 382..385
FT /evidence="ECO:0007829|PDB:1MT5"
FT HELIX 386..389
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 404..408
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 412..422
FT /evidence="ECO:0007829|PDB:3PPM"
FT TURN 423..425
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 427..435
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 436..438
FT /evidence="ECO:0007829|PDB:3LJ7"
FT HELIX 441..464
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 468..473
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 484..486
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 488..491
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 492..499
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 504..511
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 514..520
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 530..538
FT /evidence="ECO:0007829|PDB:3PPM"
FT STRAND 546..552
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 558..572
FT /evidence="ECO:0007829|PDB:3PPM"
FT HELIX 574..576
FT /evidence="ECO:0007829|PDB:3PR0"
SQ SEQUENCE 579 AA; 63357 MW; 606491C0B033E1AA CRC64;
MVLSEVWTTL SGVSGVCLAC SLLSAAVVLR WTGRQKARGA ATRARQKQRA SLETMDKAVQ
RFRLQNPDLD SEALLTLPLL QLVQKLQSGE LSPEAVFFTY LGKAWEVNKG TNCVTSYLTD
CETQLSQAPR QGLLYGVPVS LKECFSYKGH DSTLGLSLNE GMPSESDCVV VQVLKLQGAV
PFVHTNVPQS MLSFDCSNPL FGQTMNPWKS SKSPGGSSGG EGALIGSGGS PLGLGTDIGG
SIRFPSAFCG ICGLKPTGNR LSKSGLKGCV YGQTAVQLSL GPMARDVESL ALCLKALLCE
HLFTLDPTVP PLPFREEVYR SSRPLRVGYY ETDNYTMPSP AMRRALIETK QRLEAAGHTL
IPFLPNNIPY ALEVLSAGGL FSDGGRSFLQ NFKGDFVDPC LGDLILILRL PSWFKRLLSL
LLKPLFPRLA AFLNSMRPRS AEKLWKLQHE IEMYRQSVIA QWKAMNLDVL LTPMLGPALD
LNTPGRATGA ISYTVLYNCL DFPAGVVPVT TVTAEDDAQM ELYKGYFGDI WDIILKKAMK
NSVGLPVAVQ CVALPWQEEL CLRFMREVEQ LMTPQKQPS
