FAAH1_HUMAN
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 03-AUG-2022, entry version 179.
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 AlphaFoldDB; O00519; -.
DR SMR; O00519; -.
DR BioGRID; 108464; 27.
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; 400 antibodies from 36 providers.
DR DNASU; 2166; -.
DR Ensembl; ENST00000243167.9; ENSP00000243167.8; ENSG00000117480.16.
DR GeneID; 2166; -.
DR KEGG; hsa:2166; -.
DR MANE-Select; ENST00000243167.9; ENSP00000243167.8; NM_001441.3; NP_001432.2.
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; GMQPWKY; -.
DR OrthoDB; 852596at2759; -.
DR PhylomeDB; O00519; -.
DR TreeFam; TF314455; -.
DR BioCyc; MetaCyc:HS04139-MON; -.
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 SignaLink; O00519; -.
DR SIGNOR; O00519; -.
DR BioGRID-ORCS; 2166; 22 hits in 1079 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 154 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:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0102077; F:oleamide hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0005543; F:phospholipid binding; IEA:Ensembl.
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 GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
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 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 /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 238..241
FT /ligand="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
