FAAH2_HUMAN
ID FAAH2_HUMAN Reviewed; 532 AA.
AC Q6GMR7; Q86VT2; Q96N98;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Fatty-acid amide hydrolase 2;
DE EC=3.5.1.99 {ECO:0000269|PubMed:17015445, ECO:0000269|PubMed:19926788};
DE AltName: Full=Amidase domain-containing protein;
DE AltName: Full=Anandamide amidohydrolase 2;
DE AltName: Full=Oleamide hydrolase 2;
GN Name=FAAH2; Synonyms=AMDD;
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 [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP TISSUE SPECIFICITY, 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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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).
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:17015445, PubMed:19926788). Hydrolyzes
CC monounsaturated substrate anandamide preferentially as compared to
CC polyunsaturated substrates. {ECO:0000269|PubMed:17015445,
CC ECO:0000269|PubMed:19926788}.
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26137;
CC Evidence={ECO:0000269|PubMed:17015445, ECO:0000269|PubMed:19926788};
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26507;
CC Evidence={ECO:0000269|PubMed:17015445};
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 -!- ACTIVITY REGULATION: Inhibited by O-aryl carbamates and alpha-keto
CC heterocytes. {ECO:0000269|PubMed:17015445}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.9 uM for anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC ethanolamine) {ECO:0000269|PubMed:19926788};
CC KM=4.3 uM for palmitoylethanolamine (N-hexadecanoylethanolamine)
CC {ECO:0000269|PubMed:19926788};
CC Vmax=0.20 nmol/min/mg enzyme for palmitoylethanolamine (N-
CC hexadecanoylethanolamine) (at pH 9.0) {ECO:0000269|PubMed:17015445};
CC Vmax=1.21 nmol/min/mg enzyme for palmitoylethanolamine (N-
CC hexadecanoylethanolamine) (at pH 9.0) {ECO:0000269|PubMed:19926788};
CC Vmax=0.46 nmol/min/mg enzyme for anandamide (N-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-ethanolamine) (at pH 9.0)
CC {ECO:0000269|PubMed:17015445};
CC Vmax=0.71 nmol/min/mg enzyme for anandamide (N-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-ethanolamine) (at pH 9.0)
CC {ECO:0000269|PubMed:19926788};
CC pH dependence:
CC Optimum pH is around 9.0. {ECO:0000269|PubMed:17015445};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:17015445}; Single-
CC pass membrane protein {ECO:0000305}. Lipid droplet
CC {ECO:0000269|PubMed:19926788}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, liver, lung, prostate, heart
CC and ovary. {ECO:0000269|PubMed:17015445, ECO:0000305|PubMed:19926788}.
CC -!- SIMILARITY: Belongs to the amidase family. {ECO:0000305}.
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DR EMBL; AK055766; BAB71007.1; -; mRNA.
DR EMBL; AL928898; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL606754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z83745; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048279; AAH48279.1; -; mRNA.
DR EMBL; BC073922; AAH73922.1; -; mRNA.
DR CCDS; CCDS14375.1; -.
DR RefSeq; NP_777572.2; NM_174912.3.
DR AlphaFoldDB; Q6GMR7; -.
DR SMR; Q6GMR7; -.
DR BioGRID; 127693; 4.
DR STRING; 9606.ENSP00000364035; -.
DR BindingDB; Q6GMR7; -.
DR ChEMBL; CHEMBL1628475; -.
DR GuidetoPHARMACOLOGY; 1401; -.
DR SwissLipids; SLP:000001059; -.
DR iPTMnet; Q6GMR7; -.
DR PhosphoSitePlus; Q6GMR7; -.
DR BioMuta; FAAH2; -.
DR DMDM; 74757585; -.
DR EPD; Q6GMR7; -.
DR MassIVE; Q6GMR7; -.
DR MaxQB; Q6GMR7; -.
DR PaxDb; Q6GMR7; -.
DR PeptideAtlas; Q6GMR7; -.
DR PRIDE; Q6GMR7; -.
DR ProteomicsDB; 66301; -.
DR Antibodypedia; 13026; 142 antibodies from 22 providers.
DR DNASU; 158584; -.
DR Ensembl; ENST00000374900.5; ENSP00000364035.4; ENSG00000165591.7.
DR GeneID; 158584; -.
DR KEGG; hsa:158584; -.
DR MANE-Select; ENST00000374900.5; ENSP00000364035.4; NM_174912.4; NP_777572.2.
DR UCSC; uc004dvc.4; human.
DR CTD; 158584; -.
DR DisGeNET; 158584; -.
DR GeneCards; FAAH2; -.
DR HGNC; HGNC:26440; FAAH2.
DR HPA; ENSG00000165591; Low tissue specificity.
DR MIM; 300654; gene.
DR neXtProt; NX_Q6GMR7; -.
DR OpenTargets; ENSG00000165591; -.
DR PharmGKB; PA162385543; -.
DR VEuPathDB; HostDB:ENSG00000165591; -.
DR eggNOG; KOG1212; Eukaryota.
DR GeneTree; ENSGT00940000162502; -.
DR HOGENOM; CLU_009600_16_1_1; -.
DR InParanoid; Q6GMR7; -.
DR OMA; PINFAYT; -.
DR OrthoDB; 852596at2759; -.
DR PhylomeDB; Q6GMR7; -.
DR TreeFam; TF313781; -.
DR BioCyc; MetaCyc:HS09254-MON; -.
DR BRENDA; 3.5.1.4; 2681.
DR BRENDA; 3.5.1.99; 2681.
DR PathwayCommons; Q6GMR7; -.
DR Reactome; R-HSA-2142753; Arachidonic acid metabolism.
DR BioGRID-ORCS; 158584; 7 hits in 690 CRISPR screens.
DR ChiTaRS; FAAH2; human.
DR GenomeRNAi; 158584; -.
DR Pharos; Q6GMR7; Tchem.
DR PRO; PR:Q6GMR7; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q6GMR7; protein.
DR Bgee; ENSG00000165591; Expressed in right uterine tube and 132 other tissues.
DR ExpressionAtlas; Q6GMR7; baseline and differential.
DR Genevisible; Q6GMR7; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; TAS:Reactome.
DR GO; GO:0103073; F:anandamide amidohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0017064; F:fatty acid amide hydrolase activity; TAS:Reactome.
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:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.90.1300.10; -; 1.
DR InterPro; IPR020556; Amidase_CS.
DR InterPro; IPR023631; Amidase_dom.
DR InterPro; IPR036928; AS_sf.
DR Pfam; PF01425; Amidase; 1.
DR SUPFAM; SSF75304; SSF75304; 1.
DR PROSITE; PS00571; AMIDASES; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Lipid degradation; Lipid droplet; Lipid metabolism; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..532
FT /note="Fatty-acid amide hydrolase 2"
FT /id="PRO_0000291993"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 131
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 206
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 230
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250"
FT CONFLICT 98
FT /note="K -> R (in Ref. 1; BAB71007)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 532 AA; 58304 MW; 1D83E34BFF186E5E CRC64;
MAPSFTARIQ LFLLRALGFL IGLVGRAALV LGGPKFASKT PRPVTEPLLL LSGMQLAKLI
RQRKVKCIDV VQAYINRIKD VNPMINGIVK YRFEEAMKEA HAVDQKLAEK QEDEATLENK
WPFLGVPLTV KEAFQLQGMP NSSGLMNRRD AIAKTDATVV ALLKGAGAIP LGITNCSELC
MWYESSNKIY GRSNNPYDLQ HIVGGSSGGE GCTLAAACSV IGVGSDIGGS IRMPAFFNGI
FGHKPSPGVV PNKGQFPLAV GAQELFLCTG PMCRYAEDLA PMLKVMAGPG IKRLKLDTKV
HLKDLKFYWM EHDGGSFLMS KVDQDLIMTQ KKVVVHLETI LGASVQHVKL KKMKYSFQLW
IAMMSAKGHD GKEPVKFVDL LGDHGKHVSP LWELIKWCLG LSVYTIPSIG LALLEEKLRY
SNEKYQKFKA VEESLRKELV DMLGDDGVFL YPSHPTVAPK HHVPLTRPFN FAYTGVFSAL
GLPVTQCPLG LNAKGLPLGI QVVAGPFNDH LTLAVAQYLE KTFGGWVCPG KF
