NAAA_CAVPO
ID NAAA_CAVPO Reviewed; 354 AA.
AC H0VCJ6;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 3.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=N-acylethanolamine-hydrolyzing acid amidase {ECO:0000250|UniProtKB:Q5KTC7};
DE EC=3.5.1.60 {ECO:0000250|UniProtKB:Q5KTC7};
DE AltName: Full=Acylsphingosine deacylase NAAA {ECO:0000250|UniProtKB:Q5KTC7};
DE EC=3.5.1.23 {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 Name=NAAA {ECO:0000303|PubMed:30301806};
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2N;
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0007744|PDB:6DY2}
RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 28-122 AND 123-354 IN COMPLEX
RP WITH INHIBITOR, ACTIVE SITE, SUBUNIT, PROTEOLYTIC CLEAVAGE, AND
RP GLYCOSYLATION AT ASN-35; ASN-104 AND ASN-306.
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-stearoylethanolamine > N-oleoylethanolamine >
CC N-linoleoylethanolamine > N-arachidonoylethanolamine.
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:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45065;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
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:Q02083};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17506;
CC Evidence={ECO:0000250|UniProtKB:Q02083};
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 -!- 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 (PubMed:30301806). Tunicamycin treatment causes a
CC reduction in specific activity against N-palmitoylethanolamine (By
CC similarity). {ECO:0000250|UniProtKB:Q02083,
CC 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; AAKN02008187; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 6DY2; X-ray; 2.71 A; A/C=28-122, B/D=123-354.
DR PDBsum; 6DY2; -.
DR AlphaFoldDB; H0VCJ6; -.
DR SMR; H0VCJ6; -.
DR STRING; 10141.ENSCPOP00000007657; -.
DR iPTMnet; H0VCJ6; -.
DR eggNOG; ENOG502QT7H; Eukaryota.
DR HOGENOM; CLU_054401_0_0_1; -.
DR InParanoid; H0VCJ6; -.
DR TreeFam; TF313219; -.
DR BRENDA; 3.5.1.60; 1225.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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:0017064; F:fatty acid amide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0047412; F:N-(long-chain-acyl)ethanolamine deacylase activity; ISS: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; ISS: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 3D-structure; Autocatalytic cleavage; Fatty acid metabolism; Glycoprotein;
KW Hydrolase; Lipid degradation; Lipid metabolism; Lysosome; Membrane;
KW Reference proteome; Signal; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..354
FT /note="N-acylethanolamine-hydrolyzing acid amidase"
FT /id="PRO_0000446524"
FT CHAIN 23..122
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT alpha"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000446525"
FT CHAIN 123..354
FT /note="N-acylethanolamine-hydrolyzing acid amidase subunit
FT beta"
FT /evidence="ECO:0000305|PubMed:30301806"
FT /id="PRO_0000446526"
FT ACT_SITE 123
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:30301806"
FT SITE 139
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 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DY2"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DY2"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30301806,
FT ECO:0007744|PDB:6DY2"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 55..69
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 72..83
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 107..114
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 135..142
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 146..152
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 161..171
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:6DY2"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 199..208
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 213..223
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 227..236
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 262..270
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 298..308
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 315..321
FT /evidence="ECO:0007829|PDB:6DY2"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 332..338
FT /evidence="ECO:0007829|PDB:6DY2"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:6DY2"
FT STRAND 347..350
FT /evidence="ECO:0007829|PDB:6DY2"
SQ SEQUENCE 354 AA; 39035 MW; 3681353E3C8A0FAD CRC64;
MRSPGIVLLL LLLLLLPPGA APCPADLCPA PPRVNVSLDA APAARWLPVL RLFDPGLLRA
AVARIVGDRV PKWRDVIGKL VAEMESFLPQ PYTKEIRGIS DFLNLSLADG FIVNLAYEAS
AFCTSVVAQD SRGHIYHGRN LDYPFGDLLR KMTVDVQFLK NGQIAFTGTT FIGYVGLWTG
QSPYKFTVSG DERDKGWWWE NMIAALFQGH SPVSWLIRTT LSESEDFEAS VYKLAKTPLI
ADVYYIVGGT APGEGVVVTR NRGGPADIWP LDPLNGAWFR VETNYDHWKP VPKSDDRRTP
AIKALNATGQ ANLSLEALFQ VLSVVPVCNK ITVYTTVMSA ATPDKYMTRI RNLS
