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P97612 (FAAH1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 By similarity.

Catalytic activity

Anandamide + H2O = arachidonic acid + ethanolamine.

Oleamide + H2O = oleic acid + NH3.

Subunit structure

Homodimer. Ref.6 Ref.7

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein. Golgi apparatus membrane; Single-pass membrane protein. Note: Seems to be associated with the endoplasmic reticulum and/or Golgi apparatus. Ref.3

Tissue specificity

Found in neuronal cells throughout the CNS. Expressed in liver and brain, and to a lesser extent in spleen, lung, kidney and testes. Ref.4

Developmental stage

In the CNS it accumulates progressively between embryonic day 14 and postnatal day 10, remains high until postnatal day 30, then decreases into adulthood.

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_0000105267

Regions

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

Sites

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

Experimental info

Mutagenesis1421K → A: Lowers activity 40000-fold. Lowers activity 70000-fold; when associated with A-217. Ref.5
Mutagenesis2171S → A: Lowers activity 3000-fold. Lowers activity 70000-fold; when associated with A-142. Ref.5

Secondary structure

1 .................................................................................................. 579
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P97612 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 606491C0B033E1AA

FASTA57963,357
        10         20         30         40         50         60 
MVLSEVWTTL SGVSGVCLAC SLLSAAVVLR WTGRQKARGA ATRARQKQRA SLETMDKAVQ 

        70         80         90        100        110        120 
RFRLQNPDLD SEALLTLPLL QLVQKLQSGE LSPEAVFFTY LGKAWEVNKG TNCVTSYLTD 

       130        140        150        160        170        180 
CETQLSQAPR QGLLYGVPVS LKECFSYKGH DSTLGLSLNE GMPSESDCVV VQVLKLQGAV 

       190        200        210        220        230        240 
PFVHTNVPQS MLSFDCSNPL FGQTMNPWKS SKSPGGSSGG EGALIGSGGS PLGLGTDIGG 

       250        260        270        280        290        300 
SIRFPSAFCG ICGLKPTGNR LSKSGLKGCV YGQTAVQLSL GPMARDVESL ALCLKALLCE 

       310        320        330        340        350        360 
HLFTLDPTVP PLPFREEVYR SSRPLRVGYY ETDNYTMPSP AMRRALIETK QRLEAAGHTL 

       370        380        390        400        410        420 
IPFLPNNIPY ALEVLSAGGL FSDGGRSFLQ NFKGDFVDPC LGDLILILRL PSWFKRLLSL 

       430        440        450        460        470        480 
LLKPLFPRLA AFLNSMRPRS AEKLWKLQHE IEMYRQSVIA QWKAMNLDVL LTPMLGPALD 

       490        500        510        520        530        540 
LNTPGRATGA ISYTVLYNCL DFPAGVVPVT TVTAEDDAQM ELYKGYFGDI WDIILKKAMK 

       550        560        570 
NSVGLPVAVQ CVALPWQEEL CLRFMREVEQ LMTPQKQPS

« Hide

References

« Hide 'large scale' references
[1]"Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides."
Cravatt B.F., Giang D.K., Mayfield S.P., Boger D.L., Lerner R.A., Gilula N.B.
Nature 384:83-87(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[2]"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: Liver.
[3]"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: SUBCELLULAR LOCATION.
[4]"Fatty acid amide hydrolase, the degradative enzyme for anandamide and oleamide, has selective distribution in neurons within the rat central nervous system."
Thomas E.A., Cravatt B.F., Danielson P.E., Gilula N.B., Sutcliffe J.G.
J. Neurosci. Res. 50:1047-1052(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[5]"Evidence for distinct roles in catalysis for residues of the serine-serine-lysine catalytic triad of fatty acid amide hydrolase."
McKinney M.K., Cravatt B.F.
J. Biol. Chem. 278:37393-37399(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF LYS-142 AND SER-217.
[6]"Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling."
Bracey M.H., Hanson M.A., Masuda K.R., Stevens R.C., Cravatt B.F.
Science 298:1793-1796(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 37-573 IN COMPLEX WITH INHIBITOR METHOXY-ARACHIDONYL FLUOROPHOSPHATE, SUBUNIT, TOPOLOGY.
[7]"Structure-guided inhibitor design for human FAAH by interspecies active site conversion."
Mileni M., Johnson D.S., Wang Z., Everdeen D.S., Liimatta M., Pabst B., Bhattacharya K., Nugent R.A., Kamtekar S., Cravatt B.F., Ahn K., Stevens R.C.
Proc. Natl. Acad. Sci. U.S.A. 105:12820-12824(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 32-579 IN COMPLEX WITH INHIBITOR PF-750, TOPOLOGY, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U72497 mRNA. Translation: AAB26961.1.
BC091148 mRNA. Translation: AAH91148.1.
IPIIPI00206396.
RefSeqNP_077046.1. NM_024132.3.
XP_003750049.1. XM_003750001.1.
UniGeneRn.89119.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MT5X-ray2.80A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P37-573[»]
2VYAX-ray2.75A/B32-579[»]
2WAPX-ray2.80A/B31-573[»]
2WJ1X-ray1.84A/B30-579[»]
2WJ2X-ray2.55A/B30-579[»]
3K7FX-ray1.95A/B30-579[»]
3K83X-ray2.25A/B30-579[»]
3K84X-ray2.25A/B30-579[»]
3LJ6X-ray2.42A/B30-579[»]
3LJ7X-ray2.30A/B30-579[»]
3OJ8X-ray1.90A/B30-579[»]
3PPMX-ray1.78A/B30-579[»]
3PR0X-ray2.20A/B30-579[»]
3QJ8X-ray2.90A/B32-579[»]
3QJ9X-ray2.30A/B32-579[»]
3QK5X-ray2.20A/B32-579[»]
3QKVX-ray3.10A/B32-579[»]
4DO3X-ray2.25A/B32-575[»]
4HBPX-ray2.91A/B30-579[»]
ProteinModelPortalP97612.
SMRP97612. Positions 37-573.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-46284N.
MINTMINT-4567335.
STRING10116.ENSRNOP00000015667.

PTM databases

PhosphoSiteP97612.

Proteomic databases

PaxDbP97612.
PRIDEP97612.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000015667; ENSRNOP00000015667; ENSRNOG00000045949.
ENSRNOT00000015961; ENSRNOP00000015961; ENSRNOG00000011019.
GeneID100911581.
29347.
KEGGrno:100911581.
rno:29347.
UCSCRGD:61808. rat.

Organism-specific databases

CTD2166.
RGD61808. Faah.

Phylogenomic databases

eggNOGCOG0154.
GeneTreeENSGT00550000074673.
HOGENOMHOG000016500.
HOVERGENHBG005632.
KOK15528.
OrthoDBEOG4PRSQP.

Gene expression databases

ArrayExpressP97612.
GenevestigatorP97612.
GermOnlineENSRNOG00000011019. Rattus norvegicus.

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. Amidase_sig_enz. 1 hit.
PROSITEPS00571. AMIDASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBP97612.
ChEMBLCHEMBL3229.
EvolutionaryTraceP97612.
NextBio608844.

Entry information

Entry nameFAAH1_RAT
AccessionPrimary (citable) accession number: P97612
Secondary accession number(s): Q5BKA3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1997
Last modified: May 29, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents