NAAA_HUMAN
ID NAAA_HUMAN Reviewed; 359 AA.
AC Q02083; Q5KTF2; Q96EY2; Q9BRA8;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase {ECO:0000305};
DE EC=3.5.1.60 {ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17980170, ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22040171, ECO:0000269|PubMed:22825852, ECO:0000269|PubMed:30301806};
DE AltName: Full=Acid ceramidase-like protein;
DE AltName: Full=Acylsphingosine deacylase NAAA {ECO:0000305};
DE EC=3.5.1.23 {ECO:0000269|PubMed:15655246};
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:0000303|PubMed:30301806, ECO:0000312|HGNC:HGNC:736};
GN Synonyms=ASAHL, PLT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Placenta;
RX PubMed=10610717; DOI=10.1006/geno.1999.5953;
RA Hong S.-B., Li C.-M., Rhee H.-J., Park J.-H., He X., Levy B., Yoo O.J.,
RA Schuchman E.H.;
RT "Molecular cloning and characterization of a human cDNA and gene encoding a
RT novel acid ceramidase-like protein.";
RL Genomics 62:232-241(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, GLYCOSYLATION, SUBUNIT, AND PROTEOLYTIC CLEAVAGE.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Muscle;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 81-359 (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=1446826; DOI=10.1016/0378-1119(92)90133-a;
RA Goodchild N.L., Wilkinson D.A., Mager D.L.;
RT "A human endogenous long terminal repeat provides a polyadenylation signal
RT to a novel, alternatively spliced transcript in normal placenta.";
RL Gene 121:287-294(1992).
RN [5]
RP PROTEIN SEQUENCE OF N-TERMINUS, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, PROTEOLYTIC CLEAVAGE, GLYCOSYLATION AT ASN-37;
RP ASN-107; ASN-309 AND ASN-333, ACTIVE SITE, AND SUBUNIT.
RX PubMed=22040171; DOI=10.1021/pr200735a;
RA West J.M., Zvonok N., Whitten K.M., Wood J.T., Makriyannis A.;
RT "Mass spectrometric characterization of human N-acylethanolamine-
RT hydrolyzing acid amidase.";
RL J. Proteome Res. 11:972-981(2012).
RN [6]
RP CATALYTIC ACTIVITY, FUNCTION, PATHWAY, MUTAGENESIS OF CYS-126; ASN-309 AND
RP ASN-333, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, PROTEOLYTIC CLEAVAGE,
RP SUBUNIT, AND GLYCOSYLATION AT ASN-309 AND ASN-333.
RX PubMed=17980170; DOI=10.1016/j.bbalip.2007.10.002;
RA Zhao L.Y., Tsuboi K., Okamoto Y., Nagahata S., Ueda N.;
RT "Proteolytic activation and glycosylation of N-acylethanolamine-hydrolyzing
RT acid amidase, a lysosomal enzyme involved in the endocannabinoid
RT metabolism.";
RL Biochim. Biophys. Acta 1771:1397-1405(2007).
RN [7]
RP CATALYTIC ACTIVITY, FUNCTION, PATHWAY, MUTAGENESIS OF CYS-126; ARG-142;
RP ASP-145; GLU-195 AND ASN-287, BIOPHYSICOCHEMICAL PROPERTIES, PROTEOLYTIC
RP CLEAVAGE, SUBUNIT, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=18793752; DOI=10.1016/j.bbalip.2008.08.004;
RA Wang J., Zhao L.Y., Uyama T., Tsuboi K., Tonai T., Ueda N.;
RT "Amino acid residues crucial in pH regulation and proteolytic activation of
RT N-acylethanolamine-hydrolyzing acid amidase.";
RL Biochim. Biophys. Acta 1781:710-717(2008).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-37.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [9]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=22825852; DOI=10.1074/jbc.m112.368712;
RA Uyama T., Ikematsu N., Inoue M., Shinohara N., Jin X.H., Tsuboi K.,
RA Tonai T., Tokumura A., Ueda N.;
RT "Generation of N-acylphosphatidylethanolamine by members of the
RT phospholipase A/acyltransferase (PLA/AT) family.";
RL J. Biol. Chem. 287:31905-31919(2012).
RN [10] {ECO:0007744|PDB:6DXW, ECO:0007744|PDB:6DXX}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 29-359 OF WILD-TYPE AND MUTANT
RP ALA-126, CATALYTIC ACTIVITY, FUNCTION, PATHWAY, SUBCELLULAR LOCATION,
RP TOPOLOGY, PROTEOLYTIC CLEAVAGE, SUBUNIT, GLYCOSYLATION AT ASN-37; ASN-107;
RP ASN-309 AND ASN-333, DISULFIDE BOND, MUTAGENESIS OF VAL-116; CYS-126 AND
RP LEU-152, AND ACTIVE SITE.
RX PubMed=30301806; DOI=10.1073/pnas.1811759115;
RA Gorelik A., Gebai A., Illes K., Piomelli D., Nagar B.;
RT "Molecular mechanism of activation of the immunoregulatory amidase NAAA.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E10032-E10040(2018).
CC -!- FUNCTION: Degrades bioactive fatty acid amides to their corresponding
CC acids, with the following preference: N-palmitoylethanolamine > N-
CC myristoylethanolamine > N-lauroylethanolamine = N-stearoylethanolamine
CC > N-arachidonoylethanolamine > N-oleoylethanolamine (PubMed:15655246,
CC PubMed:17980170, PubMed:18793752, PubMed:30301806, PubMed:22825852).
CC Also exhibits weak hydrolytic activity against the ceramides N-
CC lauroylsphingosine and N-palmitoylsphingosine (PubMed:15655246).
CC {ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17980170,
CC ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22825852,
CC ECO:0000269|PubMed:30301806}.
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:15655246, ECO:0000269|PubMed:17980170,
CC ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22040171,
CC ECO:0000269|PubMed:30301806};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17506;
CC Evidence={ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17980170,
CC ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22040171,
CC ECO:0000269|PubMed:30301806};
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:15655246, ECO:0000269|PubMed:17980170,
CC ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22040171,
CC ECO:0000269|PubMed:30301806};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45065;
CC Evidence={ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17980170,
CC ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22040171,
CC ECO:0000269|PubMed:22825852, ECO:0000269|PubMed:30301806};
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:0000269|PubMed:15655246};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45457;
CC Evidence={ECO:0000269|PubMed:15655246};
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:0000269|PubMed:15655246};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45453;
CC Evidence={ECO:0000269|PubMed:15655246};
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:0000269|PubMed:15655246};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000269|PubMed:15655246};
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:0000269|PubMed:15655246};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000269|PubMed:15655246};
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:0000269|PubMed:15655246};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000269|PubMed:15655246};
CC -!- ACTIVITY REGULATION: Stimulated by DTT and Nonidet P-40.
CC {ECO:0000269|PubMed:15655246}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=97 uM for N-palmitoylethanolamine {ECO:0000269|PubMed:15655246};
CC KM=21 uM for N-palmitoylethanolamine {ECO:0000269|PubMed:22040171};
CC Vmax=5.4 nmol/min/ug enzyme with N-palmitoylethanolamine as substrate
CC {ECO:0000269|PubMed:22040171};
CC pH dependence:
CC Optimum pH is 4.5 with N-palmitoylethanolamine as substrate.
CC {ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:18793752};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17980170,
CC ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22040171,
CC ECO:0000269|PubMed:30301806}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit, produced by
CC autocatalytic cleavage. {ECO:0000269|PubMed:15655246,
CC ECO:0000269|PubMed:17980170, ECO:0000269|PubMed:18793752,
CC ECO:0000269|PubMed:22040171, ECO:0000269|PubMed:30301806}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000305|PubMed:10610717,
CC ECO:0000305|PubMed:15655246, ECO:0000305|PubMed:18793752}. Membrane
CC {ECO:0000269|PubMed:30301806}; Peripheral membrane protein
CC {ECO:0000269|PubMed:30301806}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q02083-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q02083-2; Sequence=VSP_000330;
CC Name=3;
CC IsoId=Q02083-3; Sequence=VSP_000328, VSP_000329;
CC -!- TISSUE SPECIFICITY: Expressed in numerous tissues, with highest levels
CC in liver and kidney, followed by pancreas.
CC {ECO:0000269|PubMed:10610717}.
CC -!- PTM: N-glycosylated (PubMed:17980170, PubMed:18793752,
CC PubMed:30301806). Tunicamycin treatment causes a reduction in specific
CC activity against N-palmitoylethanolamine. {ECO:0000269|PubMed:15655246,
CC ECO:0000269|PubMed:17980170, ECO:0000269|PubMed:18793752,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22040171,
CC ECO:0000269|PubMed:30301806}.
CC -!- PTM: A disulfide bond is seen in the crystal structure of the human
CC protein, but the Cys residues are not conserved in rodents.
CC {ECO:0000269|PubMed:30301806}.
CC -!- PTM: Autoproteolytic cleavage at pH 4.5 gives rise to the alpha and
CC beta subunit (PubMed:15655246, PubMed:22040171, PubMed:17980170,
CC PubMed:18793752, PubMed:30301806). Cleavage gives rise to a
CC conformation change that activates the enzyme (PubMed:17980170,
CC PubMed:18793752, PubMed:30301806, PubMed:22040171). The same catalytic
CC Cys residue mediates the autoproteolytic cleavage and subsequent
CC hydrolysis of lipid substrates (PubMed:17980170, PubMed:18793752)
CC (Probable). {ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17980170,
CC ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:22040171,
CC ECO:0000269|PubMed:30301806, ECO:0000305|PubMed:30301806}.
CC -!- SIMILARITY: Belongs to the acid ceramidase family. {ECO:0000305}.
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DR EMBL; AB161353; BAD88528.1; -; mRNA.
DR EMBL; BC006388; AAH06388.2; -; mRNA.
DR EMBL; BC011854; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M92449; AAA60119.1; -; mRNA.
DR CCDS; CCDS43239.1; -. [Q02083-1]
DR CCDS; CCDS87233.1; -. [Q02083-2]
DR RefSeq; NP_001035861.1; NM_001042402.1. [Q02083-2]
DR RefSeq; NP_055250.2; NM_014435.3. [Q02083-1]
DR RefSeq; XP_005262977.1; XM_005262920.3. [Q02083-1]
DR RefSeq; XP_005262982.1; XM_005262925.3.
DR RefSeq; XP_016863517.1; XM_017008028.1. [Q02083-1]
DR PDB; 6DXW; X-ray; 2.30 A; A/B/C/D=29-359.
DR PDB; 6DXX; X-ray; 2.70 A; A/C/E=29-125, B/D/F=126-359.
DR PDBsum; 6DXW; -.
DR PDBsum; 6DXX; -.
DR AlphaFoldDB; Q02083; -.
DR SMR; Q02083; -.
DR BioGRID; 118042; 268.
DR IntAct; Q02083; 35.
DR STRING; 9606.ENSP00000286733; -.
DR BindingDB; Q02083; -.
DR ChEMBL; CHEMBL4349; -.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB14011; Nabiximols.
DR GuidetoPHARMACOLOGY; 1402; -.
DR SwissLipids; SLP:000001125; -.
DR MEROPS; C89.002; -.
DR GlyConnect; 1534; 3 N-Linked glycans (1 site).
DR GlyGen; Q02083; 5 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q02083; -.
DR PhosphoSitePlus; Q02083; -.
DR BioMuta; NAAA; -.
DR DMDM; 116241258; -.
DR EPD; Q02083; -.
DR jPOST; Q02083; -.
DR MassIVE; Q02083; -.
DR MaxQB; Q02083; -.
DR PaxDb; Q02083; -.
DR PeptideAtlas; Q02083; -.
DR PRIDE; Q02083; -.
DR ProteomicsDB; 58044; -. [Q02083-1]
DR ProteomicsDB; 58045; -. [Q02083-2]
DR ProteomicsDB; 58046; -. [Q02083-3]
DR Antibodypedia; 24722; 193 antibodies from 25 providers.
DR DNASU; 27163; -.
DR Ensembl; ENST00000286733.9; ENSP00000286733.4; ENSG00000138744.16. [Q02083-1]
DR Ensembl; ENST00000507956.5; ENSP00000427641.1; ENSG00000138744.16. [Q02083-2]
DR GeneID; 27163; -.
DR KEGG; hsa:27163; -.
DR MANE-Select; ENST00000286733.9; ENSP00000286733.4; NM_014435.4; NP_055250.2.
DR UCSC; uc003hjb.4; human. [Q02083-1]
DR CTD; 27163; -.
DR DisGeNET; 27163; -.
DR GeneCards; NAAA; -.
DR HGNC; HGNC:736; NAAA.
DR HPA; ENSG00000138744; Low tissue specificity.
DR MIM; 607469; gene.
DR neXtProt; NX_Q02083; -.
DR OpenTargets; ENSG00000138744; -.
DR PharmGKB; PA162396672; -.
DR VEuPathDB; HostDB:ENSG00000138744; -.
DR eggNOG; ENOG502QT7H; Eukaryota.
DR GeneTree; ENSGT00530000063548; -.
DR HOGENOM; CLU_054401_0_0_1; -.
DR InParanoid; Q02083; -.
DR OMA; GQDHINM; -.
DR OrthoDB; 745108at2759; -.
DR PhylomeDB; Q02083; -.
DR TreeFam; TF313219; -.
DR BioCyc; MetaCyc:ENSG00000138744-MON; -.
DR BRENDA; 3.5.1.4; 2681.
DR BRENDA; 3.5.1.60; 2681.
DR PathwayCommons; Q02083; -.
DR Reactome; R-HSA-112310; Neurotransmitter release cycle.
DR SignaLink; Q02083; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 27163; 9 hits in 1079 CRISPR screens.
DR ChiTaRS; NAAA; human.
DR GeneWiki; ASAHL; -.
DR GenomeRNAi; 27163; -.
DR Pharos; Q02083; Tchem.
DR PRO; PR:Q02083; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q02083; protein.
DR Bgee; ENSG00000138744; Expressed in monocyte and 183 other tissues.
DR ExpressionAtlas; Q02083; baseline and differential.
DR Genevisible; Q02083; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0017064; F:fatty acid amide hydrolase activity; IDA:UniProtKB.
DR GO; GO:0016810; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds; IDA:MGI.
DR GO; GO:0047412; F:N-(long-chain-acyl)ethanolamine deacylase activity; IDA:UniProtKB.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA: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; IDA:UniProtKB.
DR GO; GO:0006670; P:sphingosine metabolic process; IDA: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 3D-structure; Alternative splicing; Autocatalytic cleavage;
KW Direct protein sequencing; Disulfide bond; Fatty acid metabolism;
KW Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism; Lysosome;
KW Membrane; Reference proteome; Signal; Zymogen.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:22040171"
FT CHAIN 29..359
FT /note="N-acylethanolamine-hydrolyzing acid amidase"
FT /id="PRO_0000002318"
FT CHAIN 29..125
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT alpha"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000419650"
FT CHAIN 126..359
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT beta"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000419651"
FT ACT_SITE 126
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:17980170,
FT ECO:0000269|PubMed:18793752, ECO:0000269|PubMed:30301806,
FT ECO:0000305|PubMed:22040171"
FT SITE 142
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000269|PubMed:18793752,
FT ECO:0000305|PubMed:30301806"
FT SITE 287
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000269|PubMed:18793752,
FT ECO:0000305|PubMed:30301806"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:22040171, ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DXW, ECO:0007744|PDB:6DXX"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22040171,
FT ECO:0000269|PubMed:30301806, ECO:0007744|PDB:6DXX"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17980170,
FT ECO:0000269|PubMed:22040171, ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DXW, ECO:0007744|PDB:6DXX"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17980170,
FT ECO:0000269|PubMed:22040171, ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DXW"
FT DISULFID 103..113
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DXX"
FT VAR_SEQ 198..199
FT /note="KG -> PE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000328"
FT VAR_SEQ 200..359
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000329"
FT VAR_SEQ 324..359
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1446826"
FT /id="VSP_000330"
FT VARIANT 107
FT /note="N -> K (in dbSNP:rs34751328)"
FT /id="VAR_048336"
FT VARIANT 151
FT /note="V -> I (in dbSNP:rs4859571)"
FT /id="VAR_028428"
FT VARIANT 334
FT /note="F -> L (in dbSNP:rs6823734)"
FT /id="VAR_048337"
FT MUTAGEN 116
FT /note="V->F: Decreased autoproteolytic cleavage and
FT strongly reduced enzyme activity with liposome-bound
FT substrate. Loss of enzyme activity with Triton-solubilized
FT substrate."
FT /evidence="ECO:0000269|PubMed:30301806"
FT MUTAGEN 126
FT /note="C->A: Loss of autoproteolytic cleavage and loss of
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:30301806"
FT MUTAGEN 126
FT /note="C->S: Loss of autoproteolytic cleavage and loss of
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:17980170,
FT ECO:0000269|PubMed:18793752"
FT MUTAGEN 142
FT /note="R->G: Loss of autoproteolytic cleavage and loss of
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:18793752"
FT MUTAGEN 145
FT /note="D->A: Loss of autoproteolytic cleavage and loss of
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:18793752"
FT MUTAGEN 152
FT /note="L->F: Strongly reduced enzyme activity both with
FT liposome-bound and Triton-solubilized substrate."
FT /evidence="ECO:0000269|PubMed:30301806"
FT MUTAGEN 195
FT /note="E->A,Q: Abolishes decrease of enzyme activity at pH
FT 6 and pH 7."
FT /evidence="ECO:0000269|PubMed:18793752"
FT MUTAGEN 287
FT /note="N->D: Loss of autoproteolytic cleavage and loss of
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:18793752"
FT MUTAGEN 309
FT /note="N->Q: Loss of one glycosylation site."
FT /evidence="ECO:0000269|PubMed:17980170"
FT MUTAGEN 333
FT /note="N->Q: Loss of one glycosylation site."
FT /evidence="ECO:0000269|PubMed:17980170"
FT CONFLICT 147
FT /note="P -> A (in Ref. 4; AAA60119)"
FT /evidence="ECO:0000305"
FT CONFLICT 240
FT /note="T -> S (in Ref. 4; AAA60119)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="V -> L (in Ref. 4; AAA60119)"
FT /evidence="ECO:0000305"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:6DXW"
FT TURN 44..48
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 57..71
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 74..88
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 110..119
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 125..132
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 138..145
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 166..174
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:6DXW"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 201..210
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 216..226
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 230..239
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 265..273
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 282..288
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 300..311
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 318..324
FT /evidence="ECO:0007829|PDB:6DXW"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 335..341
FT /evidence="ECO:0007829|PDB:6DXW"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:6DXW"
FT STRAND 350..354
FT /evidence="ECO:0007829|PDB:6DXW"
SQ SEQUENCE 359 AA; 40066 MW; A8E214DB383B872A CRC64;
MRTADREARP GLPSLLLLLL AGAGLSAASP PAAPRFNVSL DSVPELRWLP VLRHYDLDLV
RAAMAQVIGD RVPKWVHVLI GKVVLELERF LPQPFTGEIR GMCDFMNLSL ADCLLVNLAY
ESSVFCTSIV AQDSRGHIYH GRNLDYPFGN VLRKLTVDVQ FLKNGQIAFT GTTFIGYVGL
WTGQSPHKFT VSGDERDKGW WWENAIAALF RRHIPVSWLI RATLSESENF EAAVGKLAKT
PLIADVYYIV GGTSPREGVV ITRNRDGPAD IWPLDPLNGA WFRVETNYDH WKPAPKEDDR
RTSAIKALNA TGQANLSLEA LFQILSVVPV YNNFTIYTTV MSAGSPDKYM TRIRNPSRK
