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O00519

- FAAH1_HUMAN

UniProt

O00519 - FAAH1_HUMAN

Protein

Fatty-acid amide hydrolase 1

Gene

FAAH

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 2 (01 Mar 2005)
      Previous versions | rss
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    Functioni

    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.1 Publication

    Catalytic activityi

    Anandamide + H2O = arachidonic acid + ethanolamine.
    Oleamide + H2O = oleic acid + NH3.

    Enzyme regulationi

    Inhibited by O-aryl carbamates and alpha-keto heterocytes.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei142 – 1421Charge relay systemBy similarity
    Binding sitei191 – 1911Substrate; via carbonyl oxygenBy similarity
    Active sitei217 – 2171Charge relay systemBy similarity
    Binding sitei217 – 2171SubstrateBy similarity
    Active sitei241 – 2411Acyl-ester intermediateBy similarity

    GO - Molecular functioni

    1. acylglycerol lipase activity Source: Ensembl
    2. carbon-nitrogen ligase activity, with glutamine as amido-N-donor Source: InterPro
    3. fatty acid amide hydrolase activity Source: UniProtKB

    GO - Biological processi

    1. fatty acid catabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04139-MONOMER.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fatty-acid amide hydrolase 1 (EC:3.5.1.99)
    Alternative name(s):
    Anandamide amidohydrolase 1
    Oleamide hydrolase 1
    Gene namesi
    Name:FAAH
    Synonyms:FAAH1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:3553. FAAH.

    Subcellular locationi

    Endomembrane system 1 Publication; Single-pass membrane protein 1 Publication. Cytoplasmcytoskeleton 1 Publication
    Note: Seems to be attached to intracellular membranes and a portion of the cytoskeletal network.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-KW
    2. cytoskeleton Source: UniProtKB-SubCell
    3. endomembrane system Source: UniProtKB-SubCell
    4. integral component of membrane Source: UniProtKB-KW
    5. organelle membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Membrane

    Pathology & Biotechi

    Organism-specific databases

    MIMi606581. phenotype.
    PharmGKBiPA27955.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 579579Fatty-acid amide hydrolase 1PRO_0000105264Add
    BLAST

    Proteomic databases

    MaxQBiO00519.
    PaxDbiO00519.
    PeptideAtlasiO00519.
    PRIDEiO00519.

    PTM databases

    PhosphoSiteiO00519.

    Expressioni

    Tissue specificityi

    Highly expressed in the brain, small intestine, pancreas, skeletal muscle and testis. Also expressed in the kidney, liver, lung, placenta and prostate.1 Publication

    Gene expression databases

    BgeeiO00519.
    GenevestigatoriO00519.

    Organism-specific databases

    HPAiHPA007425.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi108464. 1 interaction.
    IntActiO00519. 2 interactions.
    STRINGi9606.ENSP00000243167.

    Structurei

    3D structure databases

    ProteinModelPortaliO00519.
    SMRiO00519. Positions 33-574.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini30 – 403374CytoplasmicBy similarityAdd
    BLAST
    Topological domaini434 – 579146CytoplasmicBy similarityAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei404 – 43330By similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei9 – 2921HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni238 – 2414Substrate bindingBy similarity

    Sequence similaritiesi

    Belongs to the amidase family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0154.
    HOGENOMiHOG000016500.
    HOVERGENiHBG005632.
    InParanoidiO00519.
    KOiK15528.
    OMAiCCFVAAA.
    OrthoDBiEOG72JWG0.
    PhylomeDBiO00519.
    TreeFamiTF314455.

    Family and domain databases

    Gene3Di3.90.1300.10. 1 hit.
    InterProiIPR000120. Amidase.
    IPR020556. Amidase_CS.
    IPR023631. Amidase_dom.
    IPR015830. Amidase_fun_type.
    [Graphical view]
    PANTHERiPTHR11895. PTHR11895. 1 hit.
    PfamiPF01425. Amidase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001221. Amidase_fungi. 1 hit.
    SUPFAMiSSF75304. SSF75304. 1 hit.
    PROSITEiPS00571. AMIDASES. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O00519-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVQYELWAAL PGASGVALAC CFVAAAVALR WSGRRTARGA VVRARQRQRA    50
    GLENMDRAAQ RFRLQNPDLD SEALLALPLP QLVQKLHSRE LAPEAVLFTY 100
    VGKAWEVNKG TNCVTSYLAD CETQLSQAPR QGLLYGVPVS LKECFTYKGQ 150
    DSTLGLSLNE GVPAECDSVV VHVLKLQGAV PFVHTNVPQS MFSYDCSNPL 200
    FGQTVNPWKS SKSPGGSSGG EGALIGSGGS PLGLGTDIGG SIRFPSSFCG 250
    ICGLKPTGNR LSKSGLKGCV YGQEAVRLSV GPMARDVESL ALCLRALLCE 300
    DMFRLDPTVP PLPFREEVYT SSQPLRVGYY ETDNYTMPSP AMRRAVLETK 350
    QSLEAAGHTL VPFLPSNIPH ALETLSTGGL FSDGGHTFLQ NFKGDFVDPC 400
    LGDLVSILKL PQWLKGLLAF LVKPLLPRLS AFLSNMKSRS AGKLWELQHE 450
    IEVYRKTVIA QWRALDLDVV LTPMLAPALD LNAPGRATGA VSYTMLYNCL 500
    DFPAGVVPVT TVTAEDEAQM EHYRGYFGDI WDKMLQKGMK KSVGLPVAVQ 550
    CVALPWQEEL CLRFMREVER LMTPEKQSS 579
    Length:579
    Mass (Da):63,066
    Last modified:March 1, 2005 - v2
    Checksum:i633A92DC36940C18
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti47 – 471R → K in AAB58505. (PubMed:9122178)Curated
    Sequence conflicti47 – 471R → K in AAD13768. (PubMed:9878243)Curated

    Polymorphismi

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti129 – 1291P → 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. 2 Publications
    Corresponds to variant rs324420 [ dbSNP | Ensembl ].
    VAR_013563
    Natural varianti345 – 3451A → D in a breast cancer sample; somatic mutation. 1 Publication
    VAR_035704

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS535.1.
    RefSeqiNP_001432.2. NM_001441.2.
    UniGeneiHs.720143.

    Genome annotation databases

    EnsembliENST00000243167; ENSP00000243167; ENSG00000117480.
    GeneIDi2166.
    KEGGihsa:2166.
    UCSCiuc001cpu.2. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS535.1.
    RefSeqi NP_001432.2. NM_001441.2.
    UniGenei Hs.720143.

    3D structure databases

    ProteinModelPortali O00519.
    SMRi O00519. Positions 33-574.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108464. 1 interaction.
    IntActi O00519. 2 interactions.
    STRINGi 9606.ENSP00000243167.

    Chemistry

    BindingDBi O00519.
    ChEMBLi CHEMBL2243.
    DrugBanki DB00818. Propofol.
    DB00599. Thiopental.
    GuidetoPHARMACOLOGYi 1400.

    PTM databases

    PhosphoSitei O00519.

    Proteomic databases

    MaxQBi O00519.
    PaxDbi O00519.
    PeptideAtlasi O00519.
    PRIDEi O00519.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000243167 ; ENSP00000243167 ; ENSG00000117480 .
    GeneIDi 2166.
    KEGGi hsa:2166.
    UCSCi uc001cpu.2. human.

    Organism-specific databases

    CTDi 2166.
    GeneCardsi GC01P046860.
    H-InvDB HIX0000550.
    HGNCi HGNC:3553. FAAH.
    HPAi HPA007425.
    MIMi 602935. gene.
    606581. phenotype.
    neXtProti NX_O00519.
    PharmGKBi PA27955.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0154.
    HOGENOMi HOG000016500.
    HOVERGENi HBG005632.
    InParanoidi O00519.
    KOi K15528.
    OMAi CCFVAAA.
    OrthoDBi EOG72JWG0.
    PhylomeDBi O00519.
    TreeFami TF314455.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS04139-MONOMER.

    Miscellaneous databases

    GenomeRNAii 2166.
    NextBioi 8747.
    PROi O00519.
    SOURCEi Search...

    Gene expression databases

    Bgeei O00519.
    Genevestigatori O00519.

    Family and domain databases

    Gene3Di 3.90.1300.10. 1 hit.
    InterProi IPR000120. Amidase.
    IPR020556. Amidase_CS.
    IPR023631. Amidase_dom.
    IPR015830. Amidase_fun_type.
    [Graphical view ]
    PANTHERi PTHR11895. PTHR11895. 1 hit.
    Pfami PF01425. Amidase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001221. Amidase_fungi. 1 hit.
    SUPFAMi SSF75304. SSF75304. 1 hit.
    PROSITEi PS00571. AMIDASES. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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.

    Entry informationi

    Entry nameiFAAH1_HUMAN
    AccessioniPrimary (citable) accession number: O00519
    Secondary accession number(s): D3DQ19, Q52M86, Q5TDF8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: March 1, 2005
    Last modified: October 1, 2014
    This is version 125 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3