Reviewed, UniProtKB/Swiss-Prot O00519 (FAAH1_HUMAN)

Names and origin

Protein names

Recommended name:
    Fatty-acid amide hydrolase 1
    EC=3.5.1.n2
Alternative name(s):
    Oleamide hydrolase 1
    Anandamide amidohydrolase 1

Gene names

Name:	FAAH
Synonyms:	FAAH1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	579 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates. Ref.7
Enzyme regulation	Inhibited by O-aryl carbamates and alpha-keto heterocytes. Ref.7
Subunit structure	Homodimer By similarity.
Subcellular location	Endomembrane system; Single-pass membrane protein. Cytoplasm › cytoskeleton. Note: Seems to be attached to intracellular membranes and a portion of the cytoskeletal network.
Tissue specificity	Highly expressed in the brain, small intestine, pancreas, skeletal muscle and testis. Also expressed in the kidney, liver, lung, placenta and prostate. Ref.7
Polymorphism	Variant Thr-129 seems to be strongly associated with illegal drug use and dependence. This variant displays normal catalytic properties but an enhanced sensitivity to proteolytic degradation.
Sequence similarities	Belongs to the amidase family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from direct assay. Source: HPA cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	carbon-nitrogen ligase activity, with glutamine as amido-N-donor Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 579	579	Fatty-acid amide hydrolase 1		PRO_0000105264
Regions
	Transmembrane	9 – 29	21	Potential
	Topological domain	30 – 403	374	Cytoplasmic By similarity
	Topological domain	434 – 579	146	Cytoplasmic By similarity
	Region	238 – 241	4	Substrate binding By similarity
	Region	404 – 433	30	In membrane By similarity
Sites
	Active site	142	1	Charge relay system By similarity
	Active site	217	1	Charge relay system By similarity
	Active site	241	1	Acyl-ester intermediate By similarity
	Binding site	191	1	Substrate; via carbonyl oxygen By similarity
	Binding site	217	1	Substrate By similarity
Amino acid modifications
	Modified residue	329	1	Phosphotyrosine Ref.8
	Modified residue	335	1	Phosphotyrosine Ref.8
Natural variations
	Natural variant	129	1	P → T Strongly associated with drug use. dbSNP rs324420. Ref.3 Ref.9		VAR_013563
	Natural variant	345	1	A → D in a breast cancer sample; somatic mutation. Ref.10		VAR_035704
Experimental info
	Sequence conflict	47	1	R → K Ref.1
	Sequence conflict	47	1	R → K Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O00519-1 [UniParc]. Last modified March 1, 2005. Version 2. Checksum: 633A92DC36940C18	FASTA	579	63,066
	10 20 30 40 50 60 MVQYELWAAL PGASGVALAC CFVAAAVALR WSGRRTARGA VVRARQRQRA GLENMDRAAQ 70 80 90 100 110 120 RFRLQNPDLD SEALLALPLP QLVQKLHSRE LAPEAVLFTY VGKAWEVNKG TNCVTSYLAD 130 140 150 160 170 180 CETQLSQAPR QGLLYGVPVS LKECFTYKGQ DSTLGLSLNE GVPAECDSVV VHVLKLQGAV 190 200 210 220 230 240 PFVHTNVPQS MFSYDCSNPL FGQTVNPWKS SKSPGGSSGG EGALIGSGGS PLGLGTDIGG 250 260 270 280 290 300 SIRFPSSFCG ICGLKPTGNR LSKSGLKGCV YGQEAVRLSV GPMARDVESL ALCLRALLCE 310 320 330 340 350 360 DMFRLDPTVP PLPFREEVYT SSQPLRVGYY ETDNYTMPSP AMRRAVLETK QSLEAAGHTL 370 380 390 400 410 420 VPFLPSNIPH ALETLSTGGL FSDGGHTFLQ NFKGDFVDPC LGDLVSILKL PQWLKGLLAF 430 440 450 460 470 480 LVKPLLPRLS AFLSNMKSRS AGKLWELQHE IEVYRKTVIA QWRALDLDVV LTPMLAPALD 490 500 510 520 530 540 LNAPGRATGA VSYTMLYNCL DFPAGVVPVT TVTAEDEAQM EHYRGYFGDI WDKMLQKGMK 550 560 570 KSVGLPVAVQ CVALPWQEEL CLRFMREVER LMTPEKQSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of human and mouse fatty acid amide hydrolases." Giang D.K., Cravatt B.F. Proc. Natl. Acad. Sci. U.S.A. 94:2238-2242(1997) [PubMed: 9122178] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Conserved chromosomal location and genomic structure of human and mouse fatty-acid amide hydrolase genes and evaluation of clasper as a candidate neurological mutation." Wan M., Cravatt B.F., Ring H.Z., Zhang X., Francke U. Genomics 54:408-414(1998) [PubMed: 9878243] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	NIEHS SNPs program Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-129.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 456-463. Tissue: Platelet.
[7]	"A second fatty acid amide hydrolase with variable distribution among placental mammals." Wei B.Q., Mikkelsen T.S., McKinney M.K., Lander E.S., Cravatt B.F. J. Biol. Chem. 281:36569-36578(2006) [PubMed: 17015445] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, ENZYME REGULATION, TISSUE SPECIFICITY.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-329 AND TYR-335, MASS SPECTROMETRY.
[9]	"A missense mutation in human fatty acid amide hydrolase associated with problem drug use." Sipe J.C., Chiang K., Gerber A.L., Beutler E., Cravatt B.F. Proc. Natl. Acad. Sci. U.S.A. 99:8394-8399(2002) [PubMed: 12060782] [Abstract] Cited for: VARIANT THR-129.
[10]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-345.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U82535 mRNA. Translation: AAB58505.1. AF098019 , AF098010, AF098011, AF098012, AF098013, AF098014, AF098015, AF098016, AF098017, AF098018 Genomic DNA. Translation: AAD13768.1. AY842444 Genomic DNA. Translation: AAV88095.1. AL122001 Genomic DNA. Translation: CAI21960.1. BC093632 mRNA. Translation: AAH93632.1. BC110404 mRNA. Translation: AAI10405.1. BC111941 mRNA. Translation: AAI11942.1.
IPI	IPI00012107.
RefSeq	NP_001432.2.
UniGene	Hs.714801
3D structure databases
HSSP	HSSP built from PDB template 1MT5 based on UniProtKB P97612.
SMR	O00519. Positions 37-573.
ModBase	Search...
PTM databases
PhosphoSite	O00519.
Proteomic databases
PeptideAtlas	O00519.
PRIDE	O00519.
Genome annotation databases
Ensembl	ENSG00000117480. Homo sapiens. [Contig view]
GeneID	2166.
KEGG	hsa:2166.
NMPDR	fig|9606.3.peg.1092.
Organism-specific databases
GeneCards	GC01P046632.
HGNC	HGNC:3553. FAAH.
HPA	HPA007425.
MIM	602935. gene+phenotype.
PharmGKB	PA27955.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O00519.
HOVERGEN	O00519.
OMA	O00519. FGQTVNP.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000117480-MON.
Gene expression databases
ArrayExpress	O00519.
Bgee	O00519.
GermOnline	ENSG00000117480. Homo sapiens.
Family and domain databases
InterPro	IPR015830. Amidase_fun_type. IPR000120. Amidase_sig_enz. [Graphical view]
Gene3D	G3DSA:3.90.1300.10. Amidase_sig_enz. 1 hit.
PANTHER	PTHR11895. Amidase. 1 hit.
Pfam	PF01425. Amidase. 1 hit. [Graphical view]
PIRSF	PIRSF001221. Amidase_fungi. 1 hit.
PROSITE	PS00571. AMIDASES. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00818. Propofol. DB00599. Thiopental.
NextBio	8747.
SOURCE	Search...

Entry information

Entry name

FAAH1_HUMAN

Accession

Primary (citable) accession number: O00519
Secondary accession number(s): Q52M86, Q5TDF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	March 1, 2005
Last modified:	June 16, 2009
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)