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O00519

- FAAH1_HUMAN

UniProt

O00519 - FAAH1_HUMAN

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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

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
Complete GO annotation...

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-KW
  3. integral component of membrane Source: UniProtKB-KW
  4. organelle membrane Source: UniProtKB
Complete GO annotation...

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.
GeneTreeiENSGT00550000074673.
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 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVQYELWAAL PGASGVALAC CFVAAAVALR WSGRRTARGA VVRARQRQRA
60 70 80 90 100
GLENMDRAAQ RFRLQNPDLD SEALLALPLP QLVQKLHSRE LAPEAVLFTY
110 120 130 140 150
VGKAWEVNKG TNCVTSYLAD CETQLSQAPR QGLLYGVPVS LKECFTYKGQ
160 170 180 190 200
DSTLGLSLNE GVPAECDSVV VHVLKLQGAV PFVHTNVPQS MFSYDCSNPL
210 220 230 240 250
FGQTVNPWKS SKSPGGSSGG EGALIGSGGS PLGLGTDIGG SIRFPSSFCG
260 270 280 290 300
ICGLKPTGNR LSKSGLKGCV YGQEAVRLSV GPMARDVESL ALCLRALLCE
310 320 330 340 350
DMFRLDPTVP PLPFREEVYT SSQPLRVGYY ETDNYTMPSP AMRRAVLETK
360 370 380 390 400
QSLEAAGHTL VPFLPSNIPH ALETLSTGGL FSDGGHTFLQ NFKGDFVDPC
410 420 430 440 450
LGDLVSILKL PQWLKGLLAF LVKPLLPRLS AFLSNMKSRS AGKLWELQHE
460 470 480 490 500
IEVYRKTVIA QWRALDLDVV LTPMLAPALD LNAPGRATGA VSYTMLYNCL
510 520 530 540 550
DFPAGVVPVT TVTAEDEAQM EHYRGYFGDI WDKMLQKGMK KSVGLPVAVQ
560 570
CVALPWQEEL CLRFMREVER LMTPEKQSS
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.
GeneTreei ENSGT00550000074673.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 126 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