Fatty-acid amide hydrolase 1

Function

Catalyzes the hydrolysis of endogenous amidated lipids like the sleep-inducing lipid oleamide ((9Z)-octadecenamide), the endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), as well as other fatty amides, to their corresponding fatty acids, thereby regulating the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates. It can also catalyze the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol). FAAH cooperates with PM20D1 in the hydrolysis of amino acid-conjugated fatty acids such as N-fatty acyl glycine and N-fatty acyl-L-serine, thereby acting as a physiological regulator of specific subsets of intracellular, but not of extracellular, N-fatty acyl amino acids (By similarity).

Classification

Family (Pfam)

PF01425 Amidase

InterPro

Amidase_CS, Amidase_dom, AS_sf, Endocannabinoid_amidase

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Gene Ontology · 18

• GO:0005856 cytoskeleton
• GO:0005789 endoplasmic reticulum membrane
• GO:0098978 glutamatergic synapse
• GO:0031090 organelle membrane
• GO:0098794 postsynapse
• GO:0098793 presynapse
• GO:0004040 amidase activity
• GO:0017064 fatty acid amide hydrolase activity
• GO:0042802 identical protein binding
• GO:0047372 monoacylglycerol lipase activity
• GO:0005543 phospholipid binding
• GO:0019369 arachidonate metabolic process
• GO:0009062 fatty acid catabolic process
• GO:0052651 monoacylglycerol catabolic process
• GO:0045907 positive regulation of vasoconstriction
• GO:0150036 regulation of trans-synaptic signaling by endocannabinoid, modulating synaptic transmission
• GO:0045471 response to ethanol
• GO:0035902 response to immobilization stress

Disease associations

• polysubstance abuse, susceptibility to MONDO:0011685

Drugs targeting this protein · 3

• ACETAMINOPHEN inhibitor
• REDAFAMDASTAT inhibitor
• JNJ-42165279 inhibitor

Related proteins · sequence + function similarity

• Fatty-acid amide hydrolase 1 0.98
• Fatty-acid amide hydrolase 1 0.98
• Fatty-acid amide hydrolase 1 0.97
• Vitamin D3 hydroxylase-associated protein 0.87
• Fatty-acid amide hydrolase 2-A 0.86
• Fatty-acid amide hydrolase 2-B 0.86
• Fatty-acid amide hydrolase 2 0.73
• Fatty acid amide hydrolase 1 0.65
• Lysophospholipid acyltransferase LPCAT4 0.64
• Lysophospholipid acyltransferase LPCAT4 0.64
• Lipid droplet-regulating VLDL assembly factor AUP1 0.62
• GH3 domain-containing protein 0.62

Co-cited proteins · studied together in the literature

• Fatty-acid amide hydrolase 2 2 shared papers
• Fatty-acid amide hydrolase 1 2 shared papers
• Fatty-acid amide hydrolase 1 1 shared papers
• Cocaine esterase 1 shared papers
• Monoglyceride lipase 1 shared papers
• Liver carboxylesterase 1 1 shared papers

Literature · 14 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Association of a functional FAAH polymorphism with methamphetamine-induced symptoms and dependence in a Malaysian population. Pharmacogenomics · 2013
• Inactivation of lipid glyceryl ester metabolism in human THP1 monocytes/macrophages by activated organophosphorus insecticides: role of carboxylesterases 1 and 2. Chem. Res. Toxicol. · 2010
• Lipid droplets are novel sites of N-acylethanolamine inactivation by fatty acid amide hydrolase-2. J. Biol. Chem. · 2010
• A second fatty acid amide hydrolase with variable distribution among placental mammals. J. Biol. Chem. · 2006
• The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an ancient missense mutation and validation of risk for drug addiction. Hum. Genet. · 2006
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use. Hum. Mol. Genet. · 2004
• Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat. Biotechnol. · 2003
• A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc. Natl. Acad. Sci. U.S.A. · 2002
• … and 2 more in the literature graph