NAAA_RAT
ID NAAA_RAT Reviewed; 362 AA.
AC Q5KTC7; Q3KRD3;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase {ECO:0000305};
DE EC=3.5.1.60 {ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:15655246};
DE AltName: Full=Acylsphingosine deacylase NAAA {ECO:0000250|UniProtKB:Q02083};
DE EC=3.5.1.23 {ECO:0000250|UniProtKB:Q02083};
DE AltName: Full=N-acylsphingosine amidohydrolase-like;
DE Short=ASAH-like protein;
DE Contains:
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase subunit alpha;
DE Contains:
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase subunit beta;
DE Flags: Precursor;
GN Name=Naaa {ECO:0000312|RGD:1307267}; Synonyms=Asahl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 131-143, CATALYTIC
RP ACTIVITY, FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Lung;
RX PubMed=15655246; DOI=10.1074/jbc.m413473200;
RA Tsuboi K., Sun Y.-X., Okamoto Y., Araki N., Tonai T., Ueda N.;
RT "Molecular characterization of N-acylethanolamine-hydrolyzing acid amidase,
RT a novel member of the choloylglycine hydrolase family with structural and
RT functional similarity to acid ceramidase.";
RL J. Biol. Chem. 280:11082-11092(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=11463796; DOI=10.1074/jbc.m106261200;
RA Ueda N., Yamanaka K., Yamamoto S.;
RT "Purification and characterization of an acid amidase selective for N-
RT palmitoylethanolamine, a putative endogenous anti-inflammatory substance.";
RL J. Biol. Chem. 276:35552-35557(2001).
RN [4]
RP FUNCTION, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=22860206; DOI=10.1021/cn300007s;
RA Tai T., Tsuboi K., Uyama T., Masuda K., Cravatt B.F., Houchi H., Ueda N.;
RT "Endogenous molecules stimulating N-acylethanolamine-hydrolyzing acid
RT amidase (NAAA).";
RL ACS Chem. Neurosci. 3:379-385(2012).
CC -!- FUNCTION: Degrades bioactive fatty acid amides to their corresponding
CC acids, with the following preference: N-palmitoylethanolamine > N-
CC myristoylethanolamine > N-stearoylethanolamine > N-oleoylethanolamine >
CC N-linoleoylethanolamine > N-arachidonoylethanolamine.
CC {ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:15655246,
CC ECO:0000269|PubMed:22860206}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoylethanolamine = ethanolamine +
CC hexadecanoate; Xref=Rhea:RHEA:45064, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57603, ChEBI:CHEBI:71464;
CC Evidence={ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:15655246,
CC ECO:0000269|PubMed:22860206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45065;
CC Evidence={ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:15655246,
CC ECO:0000305|PubMed:22860206};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(long-chain fatty acyl)ethanolamine = a long-chain
CC fatty acid + ethanolamine; Xref=Rhea:RHEA:17505, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15897, ChEBI:CHEBI:57560, ChEBI:CHEBI:57603; EC=3.5.1.60;
CC Evidence={ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:15655246,
CC ECO:0000269|PubMed:22860206, ECO:0000305|PubMed:22860206};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17506;
CC Evidence={ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:15655246};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoylethanolamine = dodecanoate + ethanolamine;
CC Xref=Rhea:RHEA:45456, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:85263;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45457;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-tetradecanoylethanolamine = ethanolamine +
CC tetradecanoate; Xref=Rhea:RHEA:45452, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57603, ChEBI:CHEBI:85262;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45453;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + H2O = a fatty acid + sphing-4-enine;
CC Xref=Rhea:RHEA:20856, ChEBI:CHEBI:15377, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57756; EC=3.5.1.23;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoylsphing-4-enine = hexadecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:38891, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72959;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoylsphing-4-enine = dodecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:41291, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72956;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
CC -!- ACTIVITY REGULATION: Stimulated by DTT (PubMed:11463796,
CC PubMed:22860206). Stimulated by nonionic detergent of the
CC polyoxyethylenep-t-octylphenylether type (Triton X-100 or Nonidet P-40)
CC whereas 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate
CC (CHAPS) and octyl alpha-D-glucopyranoside decrease the N-(long-chain-
CC acyl)ethanolamine deacylase activity (PubMed:22860206). Polysorbate 20
CC (Tween 20) is inhibitory (PubMed:11463796). Stimulated by endogenous
CC phospholipids such as choline- or ethanolamine-containing
CC phospholipids, and dihydrolipoic acid (PubMed:22860206).
CC {ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:22860206}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=35 uM for N-palmitoylethanolamine {ECO:0000269|PubMed:11463796};
CC pH dependence:
CC Optimum pH is 5 with N-palmitoylethanolamine as substrate.
CC {ECO:0000269|PubMed:11463796};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:11463796, ECO:0000269|PubMed:15655246}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit, produced by
CC autocatalytic cleavage. {ECO:0000250|UniProtKB:Q02083}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q02083}. Membrane
CC {ECO:0000250|UniProtKB:Q02083}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q02083}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, cecum, colon, heart, ileum,
CC kidney, liver, lung, spleen, stomach, submaxillary gland, testis and
CC thymus. {ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:22860206}.
CC -!- PTM: N-glycosylated. Tunicamycin treatment causes a reduction in
CC specific activity against N-palmitoylethanolamine.
CC {ECO:0000250|UniProtKB:Q02083}.
CC -!- PTM: Autoproteolytic cleavage at pH 4.5 gives rise to the alpha and
CC beta subunit. Cleavage gives rise to a conformation change that
CC activates the enzyme. The same catalytic Cys residue mediates the
CC autoproteolytic cleavage and subsequent hydrolysis of lipid substrates.
CC {ECO:0000250|UniProtKB:Q02083}.
CC -!- SIMILARITY: Belongs to the acid ceramidase family. {ECO:0000305}.
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DR EMBL; AB162193; BAD88529.1; -; mRNA.
DR EMBL; BC105771; AAI05772.1; -; mRNA.
DR RefSeq; NP_001010967.1; NM_001010967.2.
DR AlphaFoldDB; Q5KTC7; -.
DR SMR; Q5KTC7; -.
DR STRING; 10116.ENSRNOP00000003102; -.
DR BindingDB; Q5KTC7; -.
DR ChEMBL; CHEMBL2034805; -.
DR GuidetoPHARMACOLOGY; 1402; -.
DR MEROPS; C89.002; -.
DR GlyGen; Q5KTC7; 4 sites.
DR PhosphoSitePlus; Q5KTC7; -.
DR PaxDb; Q5KTC7; -.
DR Ensembl; ENSRNOT00000003102; ENSRNOP00000003102; ENSRNOG00000002273.
DR GeneID; 497009; -.
DR KEGG; rno:497009; -.
DR UCSC; RGD:1307267; rat.
DR CTD; 27163; -.
DR RGD; 1307267; Naaa.
DR eggNOG; ENOG502QT7H; Eukaryota.
DR GeneTree; ENSGT00530000063548; -.
DR HOGENOM; CLU_054401_0_0_1; -.
DR InParanoid; Q5KTC7; -.
DR OMA; GQDHINM; -.
DR OrthoDB; 745108at2759; -.
DR PhylomeDB; Q5KTC7; -.
DR TreeFam; TF313219; -.
DR BRENDA; 3.5.1.4; 5301.
DR BRENDA; 3.5.1.60; 5301.
DR Reactome; R-RNO-112310; Neurotransmitter release cycle.
DR UniPathway; UPA00199; -.
DR PRO; PR:Q5KTC7; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000002273; Expressed in lung and 20 other tissues.
DR Genevisible; Q5KTC7; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0017064; F:fatty acid amide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0016810; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds; ISO:RGD.
DR GO; GO:0047412; F:N-(long-chain-acyl)ethanolamine deacylase activity; IDA:UniProtKB.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; ISS:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0070291; P:N-acylethanolamine metabolic process; IDA:UniProtKB.
DR GO; GO:0070292; P:N-acylphosphatidylethanolamine metabolic process; ISS:UniProtKB.
DR GO; GO:0006670; P:sphingosine metabolic process; ISS:UniProtKB.
DR InterPro; IPR016699; Acid_ceramidase-like.
DR InterPro; IPR029130; Acid_ceramidase_N.
DR InterPro; IPR029132; CBAH/NAAA_C.
DR Pfam; PF02275; CBAH; 1.
DR Pfam; PF15508; NAAA-beta; 1.
DR PIRSF; PIRSF017632; Acid_ceramidase-like; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Direct protein sequencing; Fatty acid metabolism;
KW Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism; Lysosome;
KW Membrane; Reference proteome; Signal; Zymogen.
FT SIGNAL 1..33
FT /evidence="ECO:0000250"
FT CHAIN 34..362
FT /note="N-acylethanolamine-hydrolyzing acid amidase"
FT /id="PRO_0000002320"
FT CHAIN 34..130
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT alpha"
FT /id="PRO_0000419654"
FT CHAIN 131..362
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT beta"
FT /id="PRO_0000419655"
FT ACT_SITE 131
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT SITE 147
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT SITE 292
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 362 AA; 40313 MW; A9B6AB03F1668FA4 CRC64;
MGTPAIRAAC HGAHLALALL LLLSLSDPWL WATAPGTPPL FNVSLDAAPE LRWLPMLQHY
DPDFVRAAVA QVIGDRVPQW ILEMIGEIVQ KVESFLPQPF TSEIRGICDY LNLSLAEGVL
VNLAYEASAF CTSIVAQDSQ GRIYHGRNLD YPFGNALRKL TADVQFVKNG QIVFTATTFV
GYVGLWTGQS PHKFTISGDE RDKGWWWENM IAALSLGHSP ISWLIRKTLT ESEDFEAAVY
TLAKTPLIAD VYYIVGGTSP QEGVVITRDR GGPADIWPLD PLNGAWFRVE TNYDHWEPVP
KRDDRRTPAI KALNATGQAH LSLETLFQVL SVFPVYNNYT IYTTVMSAAE PDKYMTMIRN
PS