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Protein

Fatty-acid amide hydrolase 1

Gene

FAAH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Active sitei142Charge relay systemBy similarity1
Binding sitei191Substrate; via carbonyl oxygenBy similarity1
Active sitei217Charge relay systemBy similarity1
Binding sitei217SubstrateBy similarity1
Active sitei241Acyl-ester intermediateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • arachidonic acid metabolic process Source: Reactome
  • fatty acid catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

BioCyciMetaCyc:HS04139-MONOMER.
ZFISH:HS04139-MONOMER.
BRENDAi3.5.1.4. 2681.
3.5.1.99. 2681.
ReactomeiR-HSA-2142753. Arachidonic acid metabolism.
SIGNORiO00519.

Chemistry databases

SwissLipidsiSLP:000000145.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:3553. FAAH.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei9 – 29HelicalSequence analysisAdd BLAST21
Topological domaini30 – 403CytoplasmicBy similarityAdd BLAST374
Intramembranei404 – 433By similarityAdd BLAST30
Topological domaini434 – 579CytoplasmicBy similarityAdd BLAST146

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2166.
MalaCardsiFAAH.
MIMi606581. phenotype.
OpenTargetsiENSG00000117480.
PharmGKBiPA27955.

Chemistry databases

ChEMBLiCHEMBL2243.
DrugBankiDB00818. Propofol.
DB00599. Thiopental.
GuidetoPHARMACOLOGYi1400.

Polymorphism and mutation databases

BioMutaiFAAH.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001052641 – 579Fatty-acid amide hydrolase 1Add BLAST579

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei241PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO00519.
PaxDbiO00519.
PeptideAtlasiO00519.
PRIDEiO00519.

PTM databases

iPTMnetiO00519.
PhosphoSitePlusiO00519.

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

BgeeiENSG00000117480.
ExpressionAtlasiO00519. baseline and differential.
GenevisibleiO00519. HS.

Organism-specific databases

HPAiHPA007425.

Interactioni

Subunit structurei

Homodimer.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
NOTCH2NLQ7Z3S93EBI-1389829,EBI-945833

Protein-protein interaction databases

BioGridi108464. 2 interactors.
IntActiO00519. 3 interactors.
STRINGi9606.ENSP00000243167.

Chemistry databases

BindingDBiO00519.

Structurei

3D structure databases

ProteinModelPortaliO00519.
SMRiO00519.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni238 – 241Substrate bindingBy similarity4

Sequence similaritiesi

Belongs to the amidase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1212. Eukaryota.
COG0154. LUCA.
GeneTreeiENSGT00550000074673.
HOGENOMiHOG000016500.
HOVERGENiHBG005632.
InParanoidiO00519.
KOiK15528.
OMAiNKETNCV.
OrthoDBiEOG091G05JU.
PhylomeDBiO00519.
TreeFamiTF314455.

Family and domain databases

Gene3Di3.90.1300.10. 1 hit.
InterProiIPR000120. Amidase.
IPR020556. Amidase_CS.
IPR023631. Amidase_dom.
IPR030560. FAAH.
[Graphical view]
PANTHERiPTHR11895. PTHR11895. 1 hit.
PTHR11895:SF91. PTHR11895:SF91. 1 hit.
PfamiPF01425. Amidase. 1 hit.
[Graphical view]
SUPFAMiSSF75304. SSF75304. 1 hit.
PROSITEiPS00571. AMIDASES. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O00519-1 [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)DescriptionActionsGraphical viewLength
Sequence conflicti47R → K in AAB58505 (PubMed:9122178).Curated1
Sequence conflicti47R → K in AAD13768 (PubMed:9878243).Curated1

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.3 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013563129P → 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. 6 PublicationsCorresponds to variant rs324420dbSNPEnsembl.1
Natural variantiVAR_035704345A → D in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs772931153dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliO00519.
SMRiO00519.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108464. 2 interactors.
IntActiO00519. 3 interactors.
STRINGi9606.ENSP00000243167.

Chemistry databases

BindingDBiO00519.
ChEMBLiCHEMBL2243.
DrugBankiDB00818. Propofol.
DB00599. Thiopental.
GuidetoPHARMACOLOGYi1400.
SwissLipidsiSLP:000000145.

PTM databases

iPTMnetiO00519.
PhosphoSitePlusiO00519.

Polymorphism and mutation databases

BioMutaiFAAH.

Proteomic databases

MaxQBiO00519.
PaxDbiO00519.
PeptideAtlasiO00519.
PRIDEiO00519.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000243167; ENSP00000243167; ENSG00000117480.
GeneIDi2166.
KEGGihsa:2166.
UCSCiuc001cpu.3. human.

Organism-specific databases

CTDi2166.
DisGeNETi2166.
GeneCardsiFAAH.
H-InvDBHIX0000550.
HGNCiHGNC:3553. FAAH.
HPAiHPA007425.
MalaCardsiFAAH.
MIMi602935. gene.
606581. phenotype.
neXtProtiNX_O00519.
OpenTargetsiENSG00000117480.
PharmGKBiPA27955.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1212. Eukaryota.
COG0154. LUCA.
GeneTreeiENSGT00550000074673.
HOGENOMiHOG000016500.
HOVERGENiHBG005632.
InParanoidiO00519.
KOiK15528.
OMAiNKETNCV.
OrthoDBiEOG091G05JU.
PhylomeDBiO00519.
TreeFamiTF314455.

Enzyme and pathway databases

BioCyciMetaCyc:HS04139-MONOMER.
ZFISH:HS04139-MONOMER.
BRENDAi3.5.1.4. 2681.
3.5.1.99. 2681.
ReactomeiR-HSA-2142753. Arachidonic acid metabolism.
SIGNORiO00519.

Miscellaneous databases

ChiTaRSiFAAH. human.
GenomeRNAii2166.
PROiO00519.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117480.
ExpressionAtlasiO00519. baseline and differential.
GenevisibleiO00519. HS.

Family and domain databases

Gene3Di3.90.1300.10. 1 hit.
InterProiIPR000120. Amidase.
IPR020556. Amidase_CS.
IPR023631. Amidase_dom.
IPR030560. FAAH.
[Graphical view]
PANTHERiPTHR11895. PTHR11895. 1 hit.
PTHR11895:SF91. PTHR11895:SF91. 1 hit.
PfamiPF01425. Amidase. 1 hit.
[Graphical view]
SUPFAMiSSF75304. SSF75304. 1 hit.
PROSITEiPS00571. AMIDASES. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 147 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.