NAAA_CAEEL
ID NAAA_CAEEL Reviewed; 355 AA.
AC Q9GUI1;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase;
DE EC=3.5.1.60 {ECO:0000250|UniProtKB:Q5KTC7};
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 ORFNames=Y55D5A.3 {ECO:0000312|WormBase:Y55D5A.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0007744|PDB:6DY3}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 19-121 AND 122-355, PROTEOLYTIC
RP CLEAVAGE, SUBUNIT, AND GLYCOSYLATION AT ASN-150.
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, such as N-
CC palmitoylethanolamine, to ethanolamine and free fatty acids.
CC {ECO:0000250|UniProtKB:Q5KTC7}.
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:0000250|UniProtKB:Q5KTC7};
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:0000250|UniProtKB:Q5KTC7};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000250|UniProtKB:Q02083}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit, produced by
CC autocatalytic cleavage. {ECO:0000269|PubMed:30301806}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q02083}. Membrane
CC {ECO:0000250|UniProtKB:Q02083}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q02083}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:30301806}.
CC -!- PTM: Autoproteolytic cleavage at pH 4.5 gives rise to the alpha and
CC beta subunit (PubMed:30301806). Cleavage gives rise to a conformation
CC change that activates the enzyme. The same catalytic Cys residue
CC mediates the autoproteolytic cleavage and subsequent hydrolysis of
CC lipid substrates (By similarity). {ECO:0000250|UniProtKB:Q02083,
CC ECO:0000269|PubMed:30301806}.
CC -!- SIMILARITY: Belongs to the acid ceramidase family. {ECO:0000305}.
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DR EMBL; BX284603; CCD72199.1; -; Genomic_DNA.
DR RefSeq; NP_497647.1; NM_065246.1.
DR PDB; 6DY3; X-ray; 2.70 A; A/C/E/G=19-121, B/D/F/H=122-355.
DR PDBsum; 6DY3; -.
DR AlphaFoldDB; Q9GUI1; -.
DR SMR; Q9GUI1; -.
DR STRING; 6239.Y55D5A.3; -.
DR MEROPS; C89.002; -.
DR iPTMnet; Q9GUI1; -.
DR EPD; Q9GUI1; -.
DR PaxDb; Q9GUI1; -.
DR PeptideAtlas; Q9GUI1; -.
DR EnsemblMetazoa; Y55D5A.3.1; Y55D5A.3.1; WBGene00021917.
DR GeneID; 190304; -.
DR KEGG; cel:CELE_Y55D5A.3; -.
DR UCSC; Y55D5A.3; c. elegans.
DR CTD; 190304; -.
DR WormBase; Y55D5A.3; CE27498; WBGene00021917; -.
DR eggNOG; ENOG502QT7H; Eukaryota.
DR GeneTree; ENSGT00530000063548; -.
DR HOGENOM; CLU_054401_0_0_1; -.
DR InParanoid; Q9GUI1; -.
DR OMA; WWIDENI; -.
DR OrthoDB; 745108at2759; -.
DR PhylomeDB; Q9GUI1; -.
DR Reactome; R-CEL-112310; Neurotransmitter release cycle.
DR UniPathway; UPA00199; -.
DR PRO; PR:Q9GUI1; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00021917; Expressed in embryo and 3 other tissues.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0047412; F:N-(long-chain-acyl)ethanolamine deacylase activity; IEA:UniProtKB-EC.
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; 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 3D-structure; Autocatalytic cleavage; Fatty acid metabolism; Glycoprotein;
KW Hydrolase; Lipid degradation; Lipid metabolism; Lysosome; Membrane;
KW Reference proteome; Signal; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..355
FT /note="N-acylethanolamine-hydrolyzing acid amidase"
FT /id="PRO_5004330692"
FT CHAIN 18..121
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT alpha"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000446530"
FT CHAIN 122..355
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT beta"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000446531"
FT ACT_SITE 122
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT SITE 138
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT SITE 284
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q02083"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DY3"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT STRAND 23..28
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 38..44
FT /evidence="ECO:0007829|PDB:6DY3"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 48..56
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 80..93
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 97..105
FT /evidence="ECO:0007829|PDB:6DY3"
FT TURN 107..111
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 134..141
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 145..149
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 162..170
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:6DY3"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 185..191
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 197..210
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 213..223
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 227..234
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 242..248
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 287..291
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 294..306
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 313..320
FT /evidence="ECO:0007829|PDB:6DY3"
FT TURN 323..325
FT /evidence="ECO:0007829|PDB:6DY3"
FT STRAND 330..336
FT /evidence="ECO:0007829|PDB:6DY3"
FT HELIX 343..347
FT /evidence="ECO:0007829|PDB:6DY3"
SQ SEQUENCE 355 AA; 40567 MW; FAB51D5F49393A73 CRC64;
MLLLQIILLL LPVICSAGDR KPRHYEINLD EPPSQRWNQV IKDHLEYLPG VVEETKKYIP
KPLQPFVWWA ASKIDRYFTT EIQEELKGIA SESGLPIGEI VGMNILYDVA AFDRRHIFGL
GCTSIVAQNS AGQIIHGRNL DYDMTELLKN ITIHVDFVRN GTIQYSGLTF ALYNGVLTGQ
RPGEYSVSLN ARYSGAYIDN ILMEFYTKFK RPVSFFIRDV LENQATYTEA VDAFSRTHLF
SPSYIIVAGI KKNEGVVISR NRWSAANVYP LNVDANQWFL VETNFDNWKK QGDDRRITAI
QKLKELGRRN FDEKSMVEVL STVPVRNNLT VFSTVMVPGL PDSADYFRQS TWILP
