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O00519 (FAAH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length579 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Cytoplasmcytoskeleton. 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

Genetic variations in FAAH can be associated with susceptibility to polysubstance abuse [MIM:606581]. At homozygosity, variant Thr-129 is strongly associated with drug and alcohol abuse, and methamphetamine dependence.

Sequence similarities

Belongs to the amidase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 579579Fatty-acid amide hydrolase 1
PRO_0000105264

Regions

Transmembrane9 – 2921Helical; Potential
Topological domain30 – 403374Cytoplasmic By similarity
Intramembrane404 – 43330 By similarity
Topological domain434 – 579146Cytoplasmic By similarity
Region238 – 2414Substrate binding By similarity

Sites

Active site1421Charge relay system By similarity
Active site2171Charge relay system By similarity
Active site2411Acyl-ester intermediate By similarity
Binding site1911Substrate; via carbonyl oxygen By similarity
Binding site2171Substrate By similarity

Natural variations

Natural variant1291P → T Polymorphism associated with susceptibility to drug abuse; the mutant enzyme is more sensitive to proteolytic degradation; displays reduced cellular expression probably due to a post-translational mechanism preceding productive folding. Ref.3 Ref.5 Ref.9 Ref.10 Ref.11 Ref.13
Corresponds to variant rs324420 [ dbSNP | Ensembl ].
VAR_013563
Natural variant3451A → D in a breast cancer sample; somatic mutation. Ref.12
VAR_035704

Experimental info

Sequence conflict471R → K in AAB58505. Ref.1
Sequence conflict471R → K in AAD13768. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O00519 [UniParc].

Last modified March 1, 2005. Version 2.
Checksum: 633A92DC36940C18

FASTA57963,066
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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: POLYMORPHISM, ASSOCIATION OF VARIANT THR-129 WITH SUSCEPTIBILITY TO POLYSUBSTANCE ABUSE, CHARACTERIZATION OF VARIANT THR-129.
[10]"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."
Chiang K.P., Gerber A.L., Sipe J.C., Cravatt B.F.
Hum. Mol. Genet. 13:2113-2119(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT THR-129.
[11]"The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an ancient missense mutation and validation of risk for drug addiction."
Flanagan J.M., Gerber A.L., Cadet J.L., Beutler E., Sipe J.C.
Hum. Genet. 120:581-588(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT THR-129 WITH SUSCEPTIBILITY TO POLYSUBSTANCE ABUSE.
[12]"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. expand/collapse author list , 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.
[13]"Association of a functional FAAH polymorphism with methamphetamine-induced symptoms and dependence in a Malaysian population."
Sim M.S., Hatim A., Reynolds G.P., Mohamed Z.
Pharmacogenomics 14:505-514(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT THR-129 WITH SUSCEPTIBILITY TO METHAMPHETAMINE DEPENDENCE.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U82535 mRNA. Translation: AAB58505.1.
AF098019 expand/collapse EMBL AC list , 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.
RefSeqNP_001432.2. NM_001441.2.
UniGeneHs.720143.

3D structure databases

ProteinModelPortalO00519.
SMRO00519. Positions 33-574.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108464. 1 interaction.
IntActO00519. 2 interactions.
STRING9606.ENSP00000243167.

Chemistry

BindingDBO00519.
ChEMBLCHEMBL2243.
DrugBankDB00818. Propofol.
DB00599. Thiopental.
GuidetoPHARMACOLOGY1400.

PTM databases

PhosphoSiteO00519.

Proteomic databases

PaxDbO00519.
PeptideAtlasO00519.
PRIDEO00519.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000243167; ENSP00000243167; ENSG00000117480.
GeneID2166.
KEGGhsa:2166.
UCSCuc001cpu.2. human.

Organism-specific databases

CTD2166.
GeneCardsGC01P046860.
H-InvDBHIX0000550.
HGNCHGNC:3553. FAAH.
HPAHPA007425.
MIM602935. gene.
606581. phenotype.
neXtProtNX_O00519.
PharmGKBPA27955.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0154.
HOGENOMHOG000016500.
HOVERGENHBG005632.
InParanoidO00519.
KOK15528.
OMAKAMKNSV.
OrthoDBEOG72JWG0.
PhylomeDBO00519.
TreeFamTF314455.

Enzyme and pathway databases

BioCycMetaCyc:HS04139-MONOMER.

Gene expression databases

BgeeO00519.
GenevestigatorO00519.

Family and domain databases

Gene3D3.90.1300.10. 1 hit.
InterProIPR000120. Amidase.
IPR020556. Amidase_CS.
IPR023631. Amidase_dom.
IPR015830. Amidase_fun.
[Graphical view]
PANTHERPTHR11895. PTHR11895. 1 hit.
PTHR11895:SF4. PTHR11895:SF4. 1 hit.
PfamPF01425. Amidase. 1 hit.
[Graphical view]
PIRSFPIRSF001221. Amidase_fungi. 1 hit.
SUPFAMSSF75304. SSF75304. 1 hit.
PROSITEPS00571. AMIDASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi2166.
NextBio8747.
PROO00519.
SOURCESearch...

Entry information

Entry nameFAAH1_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM