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Protein

Fatty-acid amide hydrolase 1

Gene

FAAH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

Activity 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

Keywordsi

Molecular functionHydrolase

Enzyme and pathway databases

BioCyciMetaCyc: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

EuPathDBiHostDB:ENSG00000117480.15
HGNCiHGNC:3553 FAAH
MIMi602935 gene
neXtProtiNX_O00519

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2166
MalaCardsiFAAH
MIMi606581 phenotype
OpenTargetsiENSG00000117480
PharmGKBiPA27955

Chemistry databases

ChEMBLiCHEMBL2243
DrugBankiDB06894 1-DODECANOL
DB08400 4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzyl)piperidine-1-carboxylic acid
DB08385 4-(quinolin-3-ylmethyl)piperidine-1-carboxylic acid
DB00316 Acetaminophen
DB02465 Methoxy arachidonyl fluorophosphonate
DB00818 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

EPDiO00519
MaxQBiO00519
PaxDbiO00519
PeptideAtlasiO00519
PRIDEiO00519
ProteomicsDBi47952

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 Expressed in 191 organ(s), highest expression level in right lobe of thyroid gland
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
OMAiMPGQEGV
OrthoDBiEOG091G05JU
PhylomeDBiO00519
TreeFamiTF314455

Family and domain databases

Gene3Di3.90.1300.10, 1 hit
InterProiView protein in InterPro
IPR000120 Amidase
IPR020556 Amidase_CS
IPR023631 Amidase_dom
IPR036928 AS_sf
IPR030560 FAAH
PANTHERiPTHR11895 PTHR11895, 1 hit
PTHR11895:SF91 PTHR11895:SF91, 1 hit
PfamiView protein in Pfam
PF01425 Amidase, 1 hit
SUPFAMiSSF75304 SSF75304, 1 hit
PROSITEiView protein in PROSITE
PS00571 AMIDASES, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WYA0A0A087WYA0_HUMAN
Fatty-acid amide hydrolase 1
FAAH
49Annotation score:

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 dbSNP:rs324420EnsemblClinVar.1
Natural variantiVAR_035704345A → D in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs772931153Ensembl.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 No translation available.
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

Similar proteinsi

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 No translation available.
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
DrugBankiDB06894 1-DODECANOL
DB08400 4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzyl)piperidine-1-carboxylic acid
DB08385 4-(quinolin-3-ylmethyl)piperidine-1-carboxylic acid
DB00316 Acetaminophen
DB02465 Methoxy arachidonyl fluorophosphonate
DB00818 Propofol
DB00599 Thiopental
GuidetoPHARMACOLOGYi1400
SwissLipidsiSLP:000000145

PTM databases

iPTMnetiO00519
PhosphoSitePlusiO00519

Polymorphism and mutation databases

BioMutaiFAAH

Proteomic databases

EPDiO00519
MaxQBiO00519
PaxDbiO00519
PeptideAtlasiO00519
PRIDEiO00519
ProteomicsDBi47952

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2166
DisGeNETi2166
EuPathDBiHostDB:ENSG00000117480.15
GeneCardsiFAAH
H-InvDBiHIX0000550
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
OMAiMPGQEGV
OrthoDBiEOG091G05JU
PhylomeDBiO00519
TreeFamiTF314455

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiFAAH human
GenomeRNAii2166
PROiPR:O00519
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117480 Expressed in 191 organ(s), highest expression level in right lobe of thyroid gland
ExpressionAtlasiO00519 baseline and differential
GenevisibleiO00519 HS

Family and domain databases

Gene3Di3.90.1300.10, 1 hit
InterProiView protein in InterPro
IPR000120 Amidase
IPR020556 Amidase_CS
IPR023631 Amidase_dom
IPR036928 AS_sf
IPR030560 FAAH
PANTHERiPTHR11895 PTHR11895, 1 hit
PTHR11895:SF91 PTHR11895:SF91, 1 hit
PfamiView protein in Pfam
PF01425 Amidase, 1 hit
SUPFAMiSSF75304 SSF75304, 1 hit
PROSITEiView protein in PROSITE
PS00571 AMIDASES, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFAAH1_HUMAN
AccessioniPrimary (citable) accession number: O00519
Secondary accession number(s): D3DQ19, Q52M86, Q5TDF8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: March 1, 2005
Last modified: November 7, 2018
This is version 158 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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