O00519 (FAAH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fatty-acid amide hydrolase 1
EC=3.5.1.99

Alternative name(s):
Anandamide amidohydrolase 1
Oleamide hydrolase 1

Gene names

Name:	FAAH
Synonyms:	FAAH1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	579 AA.
Sequence status	Complete.
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.8
Catalytic activity	Anandamide + H2O = arachidonic acid + ethanolamine. Oleamide + H2O = oleic acid + NH3.
Enzyme regulation	Inhibited by O-aryl carbamates and alpha-keto heterocytes. Ref.8
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. Ref.8
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.8
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 Transmembrane helix
Molecular function	Hydrolase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid catabolic process Inferred from direct assay Ref.1. Source: UniProtKB
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 organelle membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	acylglycerol lipase activity Inferred from electronic annotation. Source: Compara carbon-nitrogen ligase activity, with glutamine as amido-N-donor Inferred from electronic annotation. Source: InterPro fatty acid amide hydrolase activity Inferred from direct assay Ref.1. Source: UniProtKB
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	Helical; Potential
	Topological domain	30 – 403	374	Cytoplasmic By similarity
	Intramembrane	404 – 433	30	By similarity
	Topological domain	434 – 579	146	Cytoplasmic By similarity
	Region	238 – 241	4	Substrate binding 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
Natural variations
	Natural variant	129	1	P → T Strongly associated with drug use. Ref.3 Ref.5 Ref.9 Corresponds to variant rs324420 [ dbSNP | Ensembl ].		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 in AAB58505. Ref.1
	Sequence conflict	47	1	R → K in AAD13768. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O00519 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-129.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 456-463. Tissue: Platelet.
[8]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, ENZYME REGULATION, TISSUE SPECIFICITY.
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-345.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. CH471059 Genomic DNA. Translation: EAX06912.1. CH471059 Genomic DNA. Translation: EAX06919.1. BC093632 mRNA. Translation: AAH93632.1. BC110404 mRNA. Translation: AAI10405.1. BC111941 mRNA. Translation: AAI11942.1.
IPI	IPI00012107.
RefSeq	NP_001432.2. NM_001441.2.
UniGene	Hs.720143.
3D structure databases
ProteinModelPortal	O00519.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00519. 2 interactions.
STRING	9606.ENSP00000243167.
PTM databases
PhosphoSite	O00519.
Proteomic databases
PaxDb	O00519.
PeptideAtlas	O00519.
PRIDE	O00519.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000243167; ENSP00000243167; ENSG00000117480.
GeneID	2166.
KEGG	hsa:2166.
UCSC	uc001cpu.2. human.
Organism-specific databases
CTD	2166.
GeneCards	GC01P046860.
H-InvDB	HIX0000550.
HGNC	HGNC:3553. FAAH.
HPA	HPA007425.
MIM	602935. gene+phenotype.
neXtProt	NX_O00519.
PharmGKB	PA27955.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0154.
HOGENOM	HOG000016500.
HOVERGEN	HBG005632.
InParanoid	O00519.
KO	K15528.
OMA	FGQTVNP.
OrthoDB	EOG4PRSQP.
PhylomeDB	O00519.
Enzyme and pathway databases
BioCyc	MetaCyc:HS04139-MONOMER.
Gene expression databases
Bgee	O00519.
Genevestigator	O00519.
GermOnline	ENSG00000117480. Homo sapiens.
Family and domain databases
Gene3D	3.90.1300.10. 1 hit.
InterPro	IPR000120. Amidase. IPR020556. Amidase_CS. IPR023631. Amidase_dom. IPR015830. Amidase_fun. [Graphical view]
PANTHER	PTHR11895. PTHR11895. 1 hit. PTHR11895:SF4. PTHR11895:SF4. 1 hit.
Pfam	PF01425. Amidase. 1 hit. [Graphical view]
PIRSF	PIRSF001221. Amidase_fungi. 1 hit.
SUPFAM	SSF75304. Amidase_sig_enz. 1 hit.
PROSITE	PS00571. AMIDASES. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O00519.
ChEMBL	CHEMBL2243.
DrugBank	DB00818. Propofol. DB00599. Thiopental.
GenomeRNAi	2166.
NextBio	8747.
SOURCE	Search...

Entry information

Entry name

FAAH1_HUMAN

Accession

Primary (citable) accession number: O00519
Secondary accession number(s): D3DQ19, Q52M86, Q5TDF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	March 1, 2005
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.