ID   FAAH1_HUMAN             Reviewed;         579 AA.
AC   O00519; D3DQ19; Q52M86; Q5TDF8;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2005, sequence version 2.
DT   29-SEP-2021, entry version 176.
DE   RecName: Full=Fatty-acid amide hydrolase 1;
DE            EC=3.5.1.99 {ECO:0000269|PubMed:17015445, ECO:0000269|PubMed:19926788, ECO:0000269|PubMed:9122178};
DE   AltName: Full=Anandamide amidohydrolase 1;
DE   AltName: Full=Fatty acid ester hydrolase {ECO:0000305|PubMed:21049984};
DE            EC=3.1.1.- {ECO:0000269|PubMed:21049984};
DE   AltName: Full=Oleamide hydrolase 1;
GN   Name=FAAH; Synonyms=FAAH1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP   REGULATION.
RC   TISSUE=Liver;
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   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9878243; DOI=10.1006/geno.1998.5597;
RA   Wan M., Cravatt B.F., Ring H.Z., Zhang X., Francke U.;
RT   "Conserved chromosomal location and genomic structure of human and mouse
RT   fatty-acid amide hydrolase genes and evaluation of clasper as a candidate
RT   neurological mutation.";
RL   Genomics 54:408-414(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-129.
RG   NIEHS SNPs program;
RL   Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-129.
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [7]
RP   PROTEIN SEQUENCE OF 456-463.
RC   TISSUE=Platelet;
RX   PubMed=12665801; DOI=10.1038/nbt810;
RA   Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA   Vandekerckhove J.;
RT   "Exploring proteomes and analyzing protein processing by mass spectrometric
RT   identification of sorted N-terminal peptides.";
RL   Nat. Biotechnol. 21:566-569(2003).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, ACTIVITY REGULATION, TISSUE
RP   SPECIFICITY, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=17015445; DOI=10.1074/jbc.m606646200;
RA   Wei B.Q., Mikkelsen T.S., McKinney M.K., Lander E.S., Cravatt B.F.;
RT   "A second fatty acid amide hydrolase with variable distribution among
RT   placental mammals.";
RL   J. Biol. Chem. 281:36569-36578(2006).
RN   [9]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=21049984; DOI=10.1021/tx1002194;
RA   Xie S., Borazjani A., Hatfield M.J., Edwards C.C., Potter P.M., Ross M.K.;
RT   "Inactivation of lipid glyceryl ester metabolism in human THP1
RT   monocytes/macrophages by activated organophosphorus insecticides: role of
RT   carboxylesterases 1 and 2.";
RL   Chem. Res. Toxicol. 23:1890-1904(2010).
RN   [10]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=19926788; DOI=10.1074/jbc.m109.058461;
RA   Kaczocha M., Glaser S.T., Chae J., Brown D.A., Deutsch D.G.;
RT   "Lipid droplets are novel sites of N-acylethanolamine inactivation by fatty
RT   acid amide hydrolase-2.";
RL   J. Biol. Chem. 285:2796-2806(2010).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   POLYMORPHISM, ASSOCIATION OF VARIANT THR-129 WITH SUSCEPTIBILITY TO
RP   POLYSUBSTANCE ABUSE, AND CHARACTERIZATION OF VARIANT THR-129.
RX   PubMed=12060782; DOI=10.1073/pnas.082235799;
RA   Sipe J.C., Chiang K., Gerber A.L., Beutler E., Cravatt B.F.;
RT   "A missense mutation in human fatty acid amide hydrolase associated with
RT   problem drug use.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:8394-8399(2002).
RN   [13]
RP   CHARACTERIZATION OF VARIANT THR-129.
RX   PubMed=15254019; DOI=10.1093/hmg/ddh216;
RA   Chiang K.P., Gerber A.L., Sipe J.C., Cravatt B.F.;
RT   "Reduced cellular expression and activity of the P129T mutant of human
RT   fatty acid amide hydrolase: evidence for a link between defects in the
RT   endocannabinoid system and problem drug use.";
RL   Hum. Mol. Genet. 13:2113-2119(2004).
RN   [14]
RP   ASSOCIATION OF VARIANT THR-129 WITH SUSCEPTIBILITY TO POLYSUBSTANCE ABUSE.
RX   PubMed=16972078; DOI=10.1007/s00439-006-0250-x;
RA   Flanagan J.M., Gerber A.L., Cadet J.L., Beutler E., Sipe J.C.;
RT   "The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis
RT   of an ancient missense mutation and validation of risk for drug
RT   addiction.";
RL   Hum. Genet. 120:581-588(2006).
RN   [15]
RP   VARIANT [LARGE SCALE ANALYSIS] ASP-345.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [16]
RP   ASSOCIATION OF VARIANT THR-129 WITH SUSCEPTIBILITY TO METHAMPHETAMINE
RP   DEPENDENCE.
RX   PubMed=23556448; DOI=10.2217/pgs.13.25;
RA   Sim M.S., Hatim A., Reynolds G.P., Mohamed Z.;
RT   "Association of a functional FAAH polymorphism with methamphetamine-induced
RT   symptoms and dependence in a Malaysian population.";
RL   Pharmacogenomics 14:505-514(2013).
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:17015445, PubMed:19926788).
CC       Hydrolyzes polyunsaturated substrate anandamide preferentially as
CC       compared to monounsaturated substrates (PubMed:9122178,
CC       PubMed:17015445). It can also catalyze the hydrolysis of the
CC       endocannabinoid 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-
CC       eicosatetraenoyl)-glycerol) (PubMed:21049984). FAAH cooperates with
CC       PM20D1 in the hydrolysis of amino acid-conjugated fatty acids such as
CC       N-fatty 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:17015445,
CC       ECO:0000269|PubMed:19926788, ECO:0000269|PubMed:21049984,
CC       ECO:0000269|PubMed:9122178}.
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:17015445, ECO:0000269|PubMed:19926788,
CC         ECO:0000269|PubMed:9122178};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26137;
CC         Evidence={ECO:0000269|PubMed:17015445, ECO:0000269|PubMed:19926788,
CC         ECO:0000269|PubMed:9122178};
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:17015445, ECO:0000269|PubMed:9122178};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26507;
CC         Evidence={ECO:0000269|PubMed:17015445, ECO:0000269|PubMed:9122178};
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:21049984};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC         Evidence={ECO:0000269|PubMed:21049984};
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:17015445};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45061;
CC         Evidence={ECO:0000269|PubMed:17015445};
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:17015445, ECO:0000269|PubMed:19926788};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45065;
CC         Evidence={ECO:0000269|PubMed:17015445, ECO:0000269|PubMed:19926788};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + hexadecanamide = hexadecanoate + NH4(+);
CC         Xref=Rhea:RHEA:62984, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:28938, ChEBI:CHEBI:74475;
CC         Evidence={ECO:0000269|PubMed:9122178};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62985;
CC         Evidence={ECO:0000269|PubMed:9122178};
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)-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:17015445};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63149;
CC         Evidence={ECO:0000269|PubMed:17015445};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62977;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63017;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63009;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63029;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62997;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63001;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63005;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63021;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63053;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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:0000250|UniProtKB:P97612};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63121;
CC         Evidence={ECO:0000250|UniProtKB:P97612};
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 O-aryl carbamates and alpha-keto
CC       heterocycles (PubMed:17015445). Inhibited by trifluoromethyl ketone
CC       (PubMed:9122178). {ECO:0000269|PubMed:17015445,
CC       ECO:0000269|PubMed:9122178}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         Vmax=9.7 nmol/min/mg enzyme for the hydrolysis of oleamide ((9Z)-
CC         octadecenamide) {ECO:0000269|PubMed:17015445};
CC         Vmax=2.1 nmol/min/mg enzyme for the hydrolysis of N-palmitoyl
CC         ethanolamine (N-hexadecanoyl ethanolamine)
CC         {ECO:0000269|PubMed:17015445};
CC         Vmax=5.6 nmol/min/mg enzyme for the hydrolysis of N-oleoyl
CC         ethanolamine (N-(9Z-octadecenoyl)-ethanolamine)
CC         {ECO:0000269|PubMed:17015445};
CC         Vmax=17 nmol/min/mg enzyme for the hydrolysis of anandamide (N-
CC         (5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine)
CC         {ECO:0000269|PubMed:17015445};
CC         Vmax=0.75 nmol/min/mg enzyme for the hydrolysis of N-oleoyltaurine
CC         (N-(9Z-octadecenoyl)-taurine) {ECO:0000269|PubMed:17015445};
CC       pH dependence:
CC         Optimum pH is around 9.0. {ECO:0000269|PubMed:17015445};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P97612}.
CC   -!- INTERACTION:
CC       O00519; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-1389829, EBI-945833;
CC   -!- SUBCELLULAR LOCATION: Endomembrane system
CC       {ECO:0000269|PubMed:17015445}; Single-pass membrane protein
CC       {ECO:0000269|PubMed:17015445}. Cytoplasm, cytoskeleton
CC       {ECO:0000269|PubMed:17015445}. Note=Seems to be attached to
CC       intracellular membranes and a portion of the cytoskeletal network.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the brain, small intestine,
CC       pancreas, skeletal muscle and testis. Also expressed in the kidney,
CC       liver, lung, placenta and prostate. {ECO:0000269|PubMed:17015445}.
CC   -!- POLYMORPHISM: Genetic variations in FAAH can be associated with
CC       susceptibility to polysubstance abuse [MIM:606581]. At homozygosity,
CC       variant Thr-129 is strongly associated with drug and alcohol abuse, and
CC       methamphetamine dependence. {ECO:0000269|PubMed:12060782,
CC       ECO:0000269|PubMed:16972078, ECO:0000269|PubMed:23556448}.
CC   -!- SIMILARITY: Belongs to the amidase family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/faah/";
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DR   EMBL; U82535; AAB58505.1; -; mRNA.
DR   EMBL; AF098019; AAD13768.1; -; Genomic_DNA.
DR   EMBL; AF098010; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098011; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098012; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098013; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098014; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098015; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098016; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098017; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AF098018; AAD13768.1; JOINED; Genomic_DNA.
DR   EMBL; AY842444; AAV88095.1; -; Genomic_DNA.
DR   EMBL; AL122001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471059; EAX06912.1; -; Genomic_DNA.
DR   EMBL; CH471059; EAX06919.1; -; Genomic_DNA.
DR   EMBL; BC093632; AAH93632.1; -; mRNA.
DR   EMBL; BC110404; AAI10405.1; -; mRNA.
DR   EMBL; BC111941; AAI11942.1; -; mRNA.
DR   CCDS; CCDS535.1; -.
DR   RefSeq; NP_001432.2; NM_001441.2.
DR   SMR; O00519; -.
DR   BioGRID; 108464; 8.
DR   IntAct; O00519; 4.
DR   STRING; 9606.ENSP00000243167; -.
DR   BindingDB; O00519; -.
DR   ChEMBL; CHEMBL2243; -.
DR   DrugBank; DB06894; 1-Dodecanol.
DR   DrugBank; DB08400; 4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzyl)piperidine-1-carboxylic acid.
DR   DrugBank; DB08385; 4-(quinolin-3-ylmethyl)piperidine-1-carboxylic acid.
DR   DrugBank; DB00316; Acetaminophen.
DR   DrugBank; DB09061; Cannabidiol.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugBank; DB14009; Medical Cannabis.
DR   DrugBank; DB02465; Methoxy arachidonyl fluorophosphonate.
DR   DrugBank; DB14011; Nabiximols.
DR   DrugBank; DB00818; Propofol.
DR   DrugBank; DB00599; Thiopental.
DR   DrugCentral; O00519; -.
DR   GuidetoPHARMACOLOGY; 1400; -.
DR   SwissLipids; SLP:000000145; -.
DR   iPTMnet; O00519; -.
DR   PhosphoSitePlus; O00519; -.
DR   BioMuta; FAAH; -.
DR   EPD; O00519; -.
DR   jPOST; O00519; -.
DR   MassIVE; O00519; -.
DR   MaxQB; O00519; -.
DR   PaxDb; O00519; -.
DR   PeptideAtlas; O00519; -.
DR   PRIDE; O00519; -.
DR   ProteomicsDB; 47952; -.
DR   Antibodypedia; 1478; 394 antibodies.
DR   DNASU; 2166; -.
DR   Ensembl; ENST00000243167; ENSP00000243167; ENSG00000117480.
DR   GeneID; 2166; -.
DR   KEGG; hsa:2166; -.
DR   UCSC; uc001cpu.3; human.
DR   CTD; 2166; -.
DR   DisGeNET; 2166; -.
DR   GeneCards; FAAH; -.
DR   HGNC; HGNC:3553; FAAH.
DR   HPA; ENSG00000117480; Low tissue specificity.
DR   MalaCards; FAAH; -.
DR   MIM; 602935; gene.
DR   MIM; 606581; phenotype.
DR   neXtProt; NX_O00519; -.
DR   OpenTargets; ENSG00000117480; -.
DR   PharmGKB; PA27955; -.
DR   VEuPathDB; HostDB:ENSG00000117480; -.
DR   eggNOG; KOG1212; Eukaryota.
DR   GeneTree; ENSGT00940000161237; -.
DR   HOGENOM; CLU_009600_9_3_1; -.
DR   InParanoid; O00519; -.
DR   OMA; MQPWKYD; -.
DR   OrthoDB; 852596at2759; -.
DR   PhylomeDB; O00519; -.
DR   TreeFam; TF314455; -.
DR   BioCyc; MetaCyc:HS04139-MONOMER; -.
DR   BRENDA; 3.5.1.4; 2681.
DR   BRENDA; 3.5.1.99; 2681.
DR   PathwayCommons; O00519; -.
DR   Reactome; R-HSA-2142753; Arachidonic acid metabolism.
DR   SIGNOR; O00519; -.
DR   BioGRID-ORCS; 2166; 18 hits in 1014 CRISPR screens.
DR   ChiTaRS; FAAH; human.
DR   GenomeRNAi; 2166; -.
DR   Pharos; O00519; Tchem.
DR   PRO; PR:O00519; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; O00519; protein.
DR   Bgee; ENSG00000117480; Expressed in right lobe of thyroid gland and 203 other tissues.
DR   ExpressionAtlas; O00519; baseline and differential.
DR   Genevisible; O00519; HS.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0031090; C:organelle membrane; ISS:UniProtKB.
DR   GO; GO:0047372; F:acylglycerol lipase activity; ISS:UniProtKB.
DR   GO; GO:0004040; F:amidase activity; IBA:GO_Central.
DR   GO; GO:0103073; F:anandamide amidohydrolase activity; ISS:UniProtKB.
DR   GO; GO:0017064; F:fatty acid amide hydrolase activity; IDA:UniProtKB.
DR   GO; GO:0102077; F:oleamide hydrolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR   GO; GO:0009062; P:fatty acid catabolic process; IDA:UniProtKB.
DR   GO; GO:0052651; P:monoacylglycerol catabolic process; ISS:UniProtKB.
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   Cytoplasm; Cytoskeleton; Direct protein sequencing; Hydrolase;
KW   Lipid degradation; Lipid metabolism; Membrane; Phosphoprotein;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..579
FT                   /note="Fatty-acid amide hydrolase 1"
FT                   /id="PRO_0000105264"
FT   TRANSMEM        9..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        30..403
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        404..433
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        434..579
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          238..241
FT                   /note="Substrate binding"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        142
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        217
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        241
FT                   /note="Acyl-ester intermediate"
FT                   /evidence="ECO:0000250"
FT   BINDING         191
FT                   /note="Substrate; via carbonyl oxygen"
FT                   /evidence="ECO:0000250"
FT   BINDING         217
FT                   /note="Substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         241
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VARIANT         129
FT                   /note="P -> T (associated with susceptibility to drug
FT                   abuse; the mutant enzyme is more sensitive to proteolytic
FT                   degradation; displays reduced cellular expression probably
FT                   due to a post-translational mechanism preceding productive
FT                   folding; dbSNP:rs324420)"
FT                   /evidence="ECO:0000269|PubMed:12060782,
FT                   ECO:0000269|PubMed:15254019, ECO:0000269|PubMed:16972078,
FT                   ECO:0000269|PubMed:23556448, ECO:0000269|Ref.3,
FT                   ECO:0000269|Ref.5"
FT                   /id="VAR_013563"
FT   VARIANT         345
FT                   /note="A -> D (in a breast cancer sample; somatic mutation;
FT                   dbSNP:rs772931153)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035704"
FT   CONFLICT        47
FT                   /note="R -> K (in Ref. 1; AAB58505 and 2; AAD13768)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   579 AA;  63066 MW;  633A92DC36940C18 CRC64;
     MVQYELWAAL PGASGVALAC CFVAAAVALR WSGRRTARGA VVRARQRQRA GLENMDRAAQ
     RFRLQNPDLD SEALLALPLP QLVQKLHSRE LAPEAVLFTY VGKAWEVNKG TNCVTSYLAD
     CETQLSQAPR QGLLYGVPVS LKECFTYKGQ DSTLGLSLNE GVPAECDSVV VHVLKLQGAV
     PFVHTNVPQS MFSYDCSNPL FGQTVNPWKS SKSPGGSSGG EGALIGSGGS PLGLGTDIGG
     SIRFPSSFCG ICGLKPTGNR LSKSGLKGCV YGQEAVRLSV GPMARDVESL ALCLRALLCE
     DMFRLDPTVP PLPFREEVYT SSQPLRVGYY ETDNYTMPSP AMRRAVLETK QSLEAAGHTL
     VPFLPSNIPH ALETLSTGGL FSDGGHTFLQ NFKGDFVDPC LGDLVSILKL PQWLKGLLAF
     LVKPLLPRLS AFLSNMKSRS AGKLWELQHE IEVYRKTVIA QWRALDLDVV LTPMLAPALD
     LNAPGRATGA VSYTMLYNCL DFPAGVVPVT TVTAEDEAQM EHYRGYFGDI WDKMLQKGMK
     KSVGLPVAVQ CVALPWQEEL CLRFMREVER LMTPEKQSS
//